title: Dietary protein and calcium interact to influence calcium retention: a controlled feeding study. Consumption of a high calcium mineral water lowers biochemical indices of bone remodeling in postmenopausal women with low calcium intake NaHCO(3) and KHCO(3) ingestion rapidly increases renal electrolyte excretion in humans. Protein consumption and bone fractures in women. High phosphorus intake only slightly affects serum minerals, urinary pyridinium crosslinks and renal function in young women Carbonated beverages and urinary calcium excretion. Short-term changes in calcium but not protein intake alter the rate of bone resorption in healthy subjects as assessed by urinary pyridinium cross-link excretion. A comparison of the effects of feeding sulfur amino acids and protein on urine calcium in man. Calcium supplements and milk: effects on acid-base balance and on retention of calcium, magnesium, and phosphorus. Acute effects of oral phosphate-salt ingestion on serum phosphorus, serum ionized calcium, and parathyroid hormone in young adults. A high ratio of dietary animal to vegetable protein increases the rate of bone loss and the risk of fracture in postmenopausal women. Study of Osteoporotic Fractures Research Group. More acidic dietary acid-base load is associated with reduced calcaneal broadband ultrasound attenuation in women but not in men: results from the EPIC-Norfolk cohort study. Long-term protein intake and dietary potential renal acid load are associated with bone modeling and remodeling at the proximal radius in healthy children. Fruit and vegetable intakes are an independent predictor of bone size in early pubertal children. Increased circulating concentrations of parathyroid hormone in healthy, young women consuming a protein-restricted diet. Fruit and vegetable intakes and bone mineral status: a cross sectional study in 5 age and sex cohorts. Meat and soy protein affect calcium homeostasis in healthy women. Protein intake: effects on bone mineral density and the rate of bone loss in elderly women. Calciuric effects of protein and potassium bicarbonate but not of sodium chloride or phosphate can be detected acutely in adult women and men. Controlled high meat diets do not affect calcium retention or indices of bone status in healthy postmenopausal women. Dietary protein and phosphorus do not affect calcium absorption. Fruit and vegetable consumption and bone mineral density: the Northern Ireland Young Hearts Project. Acid-base status affects renal magnesium losses in healthy, elderly persons. Treatment with potassium bicarbonate lowers calcium excretion and bone resorption in older men and women. Effects of potassium alkali and calcium supplementation on bone turnover in postmenopausal women. Quality of diet and potential renal acid load as risk factors for reduced bone density in elderly women. Dried plums improve indices of bone formation in postmenopausal women. Phosphate supplementation in young men: lack of effect on calcium homeostasis and bone turnover Neutralization of Western diet inhibits bone resorption independently of K intake and reduces cortisol secretion in humans. A dictionary of epidemiology Effects of a short course of oral phosphate treatment on serum parathyroid hormone (1–84) and biochemical markers of bone turnover: A dose-response study Effect of high vegetable protein diets on urinary calcium loss in middle-aged men and women Low urine pH and acid excretion do not predict bone fractures or the loss of bone mineral density: a prospective cohort study Controlled substitution of soy protein for meat protein: effects on calcium retention, bone, and cardiovascular health indices in postmenopausal women. Effect of fruit on net acid and urinary calcium excretion in an acute feeding trial of women. Proteins, dietary acid load, and calcium and risk of postmenopausal fractures in the E3N French women prospective study. Whole-body vibration can reduce calciuria induced by high protein intakes and may counteract bone resorption: A preliminary study Urinary Calcium Loss in Elderly Menon a Vegetable:Animal (1:1)High-Protein Diet The effects of a low-sodium base-producing diet including red meat compared with a high-carbohydrate, low-fat diet on bone turnover markers in women aged 45-75 years. The impact of dietary protein on calcium absorption and kinetic measures of bone turnover in women. Potassium bicarbonate, but not sodium bicarbonate, reduces urinary calcium excretion and improves calcium balance in healthy men. Long-term persistence of the urine calcium-lowering effect of potassium bicarbonate in postmenopausal women. Inorganic phosphorus reduces hypercalciuria during total parenteral nutrition by enhancing renal tubular calcium absorption. Comparative effects of potassium chloride and bicarbonate on thiazide-induced reduction in urinary calcium excretion. Protein sparing during treatment of obesity: ketogenic versus nonketogenic very low calorie diet. Phosphate deposition capacity of athletes during hypokinesia, phosphate loading, and ambulation Renal response to acute acid loadingAn organ physiological approach Effect of cranberry juice consumption on urinary stone risk factors. Effects of dietary nutrients and food groups on bone loss from the proximal femur in men and women in the 7th and 8th decades of age Increased sulfate as an etiological factor in the hypercalciuria associated with total parenteral nutrition. Fruits, vegetables and lung cancer: a pooled analysis of cohort studies. Potassium bicarbonate attenuates the urinary nitrogen excretion that accompanies an increase in dietary protein and may promote calcium absorption. Dietary protein intake and risk of osteoporotic hip fracture in elderly residents of Utah. Higher calcium urinary loss induced by a calcium sulphate-rich mineral water intake than by milk in young women. Partial neutralization of the acidogenic Western diet with potassium citrate increases bone mass in postmenopausal women with osteopenia. Contrasting effects of potassium citrate and sodium citrate therapies on urinary chemistries and crystallization of stone-forming salts. Effect of dietary protein supplements on calcium excretion in healthy older men and women. Acute effects of calcium sodium citrate supplementation of a test meal on mineral homeostasis, oxalate, and calcium oxalate crystallization in the urine of healthy humans--preliminary results in patients with idiopathic calcium urolithiasis. Paleolithic nutrition: twenty-five years later. Protein Supplements Increase Serum Insulin-Like Growth Factor-I Levels and Attenuate Proximal Femur Bone Loss in Patients with Recent Hip Fracture An acute intake of phosphate increases parathyroid hormone secretion and inhibits bone formation in young women. Potassium citrate prevents increased urine calcium excretion and bone resorption induced by a high sodium chloride diet. Elevated secretion and action of serum parathyroid hormone in young adults consuming high phosphorus, low calcium diets assembled from common foods. Ketosis, weight loss, uric acid, and nitrogen balance in obese women fed single nutrients at low caloric levels. Biological effects of drinking-water mineral composition on calcium balance and bone remodeling markers.
abstract: BACKGROUND The effect of meat protein on calcium retention at different calcium intakes is unresolved . OBJECTIVE The objective was to test the effect of dietary protein on calcium retention at low and high intakes of calcium . DESIGN In a r and omized controlled feeding study with a 2 x 2 factorial crossover design , healthy postmenopausal women ( n = 27 ) consumed either approximately 675 or approximately 1510 mg Ca/d , with both low and high protein ( providing 10 % and 20 % energy ) for 7 wk each , separated by a 3-wk washout period . After 3 wk , the entire diet was extrinsically labeled with (47)Ca , and isotope retention was monitored by whole-body scintillation counting . Clinical markers of calcium and bone metabolism were measured . RESULTS High compared with low dietary protein significantly increased calcium retention from the low-calcium ( 29.5 % compared with 26.0 % absorbed ) but not the high-calcium diet ( 18 % absorbed ) . For the low-calcium diet , this effect nearly balanced a protein-related 0.5-mmol/d greater urinary calcium excretion . Protein-related calciuretic effects were independent of dietary calcium . Testing at 1 , 2 , 3 , 5 , and 7 wk showed no long-term adaptation in urinary acidity or urinary calcium excretion . High compared with low dietary protein decreased urinary deoxypyridinoline and increased serum insulin-like growth factor I without affecting parathyroid hormone , osteocalcin , bone-specific alkaline phosphatase , or tartrate-resistant acid phosphatase . CONCLUSIONS In healthy postmenopausal women , a moderate increase in dietary protein , from 10 % to 20 % of energy , slightly improved calcium absorption from a low-calcium diet , nearly compensating for a slight increase in urinary calcium excretion . Under practical dietary conditions , increased dietary protein from animal sources was not detrimental to calcium balance or short-term indicators of bone health Many postmenopausal women have a calcium intake far below the recommended amount and , in addition to attempting to improve their diet , need a calcium supplement . The aim of the study was to assess the effects of the consumption of a high calcium mineral water ( HCaMW ) on biochemical indices of bone remodeling in postmenopausal women with low Ca intake . A 6-month r and omized double-blind placebo-controlled trial was design ed to assess the effects of a daily consumption of 1 liter of a HCaMW ( 596 mg Ca/l ) on serum parathyroid hormone ( PTH ) and biochemical markers of bone remodeling in postmenopausal women with a dietary Ca intake lower than 700 mg/day . The placebo group drank 1 liter of a mineral water with a low calcium content ( 10 mg/l ) . One hundred eighty healthy women were recruited ( mean age : 70.1±4.0 years ) ; 152 completed the 6-month trial . The changes from baseline of biochemical indices after 6 months consisted of a significant 14.1 % decrease of serum PTH , osteocalcin ( –8.6 % ) , bone alkaline phosphatase ( –11.5 % ) , serum ( –16.3 % ) and urine ( –13.0 % ) type-1 collagen C-telopeptide in the HCaMW group compared to the placebo group , where all biochemical indices increased after 6 months . The additive effect of a small vitamin D supplement ( 400 iu/day ) was also evaluated . In women receiving vitamin D in addition to HCaMW , the decrease in bone indices was not found to be greater than in women drinking only the HCaMW . A daily supplement of 596 mg of Ca through the consumption of 1 l of HCaMW was able to lower serum PTH and the indices of bone turnover in postmenopausal women with a low Ca intake . This could contribute to the repair of calcium deficiency and to the reduction of age-related bone loss in this population This paper describes and quantifies acute responses of the kidneys in correcting plasma volume , acid-base , and ion disturbances result ing from  NaHCO(3 ) and KHCO(3 )  ingestion . Renal excretion of ions and water was studied in five men after ingestion of 3.57 mmol/kg body mass of sodium bicarbonate ( NaHCO(3 ) ) and , in a separate trial , potassium bicarbonate ( KHCO(3 ) ) .  Subjects had a Foley catheter inserted into the bladder and indwelling catheters placed into an antecubital vein and a brachial artery . Blood and urine were sample d in the 30-min period before , the 60-min period during , and the 210-min period after ingestion of the solutions . NaHCO(3 ) ingestion result ed in a rapid , transient diuresis and natriuresis . Cumulative urine output was 44 + /- 11 % of ingested volume , result ing in a 555 + /- 119 ml increase in total body water at the end of the experiment . The cumulative increase ( above basal levels ) in renal Na(+ ) excretion accounted for 24 + /- 2 % of ingested Na(+ ) . In the KHCO(3 ) trial , arterial plasma K(+ ) concentration rapidly increased from 4.25 + /- 0.10 to a peak of 7.17 + /- 0.13 meq/l 140 min after the beginning of ingestion . This increase result ed in a pronounced , transient diuresis , with cumulative urine output at 270 min similar to the volume ingested , natriuresis , and a pronounced kaliuresis that was maintained until the end of the experiment . Cumulative ( above basal ) renal K(+ ) excretion at 270 min accounted for 26 + /- 5 % of ingested K(+ ) . The kidneys were important in mediating rapid corrections of substantial portions of the fluid and electrolyte disturbances result ing from ingestion of KHCO(3 ) and NaHCO(3 ) solutions Dietary protein increases urinary calcium losses and has been associated with higher rates of hip fracture in cross-cultural studies . However , the relation between protein and risk of  osteoporotic bone fractures among individuals has not been examined in detail . In this prospect i ve study , usual dietary intake was measured in 1980 in a cohort of 85,900 women , aged 35 - 59 years , who were participants in the Nurses ' Health Study . A mailed food frequency question naire was used and incident hip ( n = 234 ) and distal forearm ( n = 1,628 ) fractures were identified by self-report during the following 12 years . Information on other factors related to osteoporosis , including obesity , use of postmenopausal estrogen , smoking , and physical activity , was collected on biennial question naires . Dietary measures were up date d in 1984 and 1986 . Protein was associated with an increased risk of forearm fracture ( relative risk ( RR ) = 1.22 , 95 % confidence interval ( Cl ) 1.04 - 1.43 , p for trend = 0.01 ) for women who consumed more than 95 g per day compared with those who consumed less than 68 g per day . A similar increase in risk was observed for animal protein , but no association was found for consumption of vegetable protein . Women who consumed five or more servings of red meat per week also had a significantly increased risk of forearm fracture ( RR = 1.23 , 95 % Cl 1.01 - 1.50 ) compared with women who ate red meat less than once per week . Recall of teenage diet did not reveal any increased risk of forearm fracture for women with higher consumption of animal protein or red meat during this earlier period of life . No association was observed between  adult protein intake  and the incidence of hip fractures , though power to assess this association was low Objective : Assessment of the physiological effects of a diet rich in phosphorus in young women . Design : Control period I — commercial basic diet containing 1700 mg P and 1500 mg Ca/day for 4 weeks . Supplementation period — a 6 week high-phosphorus period of 3008 mg P and 1995 mg Ca/day . Control period II—4 weeks washout with basic diet as in period I. Setting : Institute of Nutritional Science , Friedrich Schiller University , Jena . Subjects : Ten healthy women , aged 20–30 y. Interventions : Orange juice and tablets , containing supplements of Ca5(PO4)3OH and NaH2PO4 , totalling 1436 mg elemental phosphorus per day . Results : There was an increase of 10.7±13.7 pg/ml in serum PTH , a decrease of 0.6±0.6 ng/ml in serum osteocalcin , an increase of 73.6±136.6 nmol/mmol creatinine in urinary pyridinoline and of 19.3±36.0 nmol/mmol creatinine in urinary deoxypyridinoline , and a decrease of 2.6±9.3 mg/l in urinary microalbumin . All changes were insignificant . There were no changes in serum levels of Ca , PO4 or Zn , in serum concentration of 1,25-(OH)2D3 , and in urinary β-2-microglobulin excretion  . Phosphorus supplementation  caused intestinal distress , soft stools or mild diarrhoea . Conclusions : In spite of a high phosphorus supplementation no significant changes in bone-related hormones , pyridinium crosslinks as markers of bone resorption and parameters of renal function in young women were found . European Journal of Clinical Nutrition ( 2001 ) 55 , BACKGROUND Intake of carbonated beverages has been associated with increased fracture risk in observational studies . The usual explanation given is that one or more of the beverage constituents increase urinary calcium . OBJECTIVE We assessed the short-term effects on urinary calcium excretion of carbonated beverages of various compositions . DESIGN An incomplete r and om block design was used to study 20 - 40-y-old women who customarily consumed > or = 680 mL carbonated beverages daily . Four carbonated beverages were tested : 2 with caffeine and 2 without . Two contained phosphoric acid as the acidulant and 2 contained citric acid . The study included one neutral control ( water ) and one positive control ( skim or chocolate milk ) . Serving size was 567 mL for the carbonated beverages and water and 340 mL for the milks . Beverages were consumed with a light breakfast after an overnight fast ; no other foods were ingested until urine collection was complete . pH , titratable and total acidity , sodium , creatinine , and calcium were measured in 2-h ( morning ) fasting and 5-h postbeverage urine specimens . RESULTS Relative to water , urinary calcium rose significantly only with the milks and the 2 caffeine-containing beverages . The excess calciuria was approximately 0.25 mmol , about the same as previously reported for caffeine alone . Phosphoric acid without caffeine produced no excess calciuria ; nor did it augment the calciuria of caffeine . CONCLUSIONS The excess calciuria associated with consumption of carbonated beverages is confined to caffeinated beverages . Acidulant type has no acute effect . Because the caffeine effect is known to be compensated for by reduced calciuria later in the day , we conclude that the net effect of carbonated beverage constituents on calcium economy is negligible . The skeletal effects of carbonated beverage consumption are likely due primarily to milk displacement This study was conducted to determine whether the markers of bone resorption , pyridinium cross-links of collagen , are sensitive to changes in dietary protein and calcium intake . Fifteen young healthy subjects ( 7 males and 8 females ) participated in three 5-d diet periods . Dietary intake during each dietary period consisted of : 1 ) low nitrogen and low calcium [ 0.49 + /- 0.11 g protein/ ( kg.d ) , 429 + /- 190 mg calcium/d ] ; 2 ) low nitrogen and high calcium [ 0.44 + /- 0.08 g protein/(kg.d ) , 1643 + /- 171 mg calcium/d ] ; and 3 ) a high nitrogen and high calcium [ 2.71 + /- 0.75 g protein/(kg.d ) , 1589 + /- 633 mg calcium/d ] diet , and this was compared with subjects ' baseline dietary intake [ 0.99 + /- 0.51 g protein/(kg.d ) , 589 + /- 152 mg calcium/d ] . The order of these diets was r and omly assigned . Twenty-four-hour and 3-h urine sample s were collected before and during each dietary period and were analyzed for pyridinium cross-links ( pyridinoline , deoxypyridinoline ) , nitrogen and creatinine . The rate of pyrdinium cross-link excretion did not vary with protein intake but was approximately 33 % lower ( P < 0.01 ) during periods of high compared with low calcium intake . These data indicate that a short-term increase in calcium intake is accompanied by a reduced rate of bone resorption and that this effect is independent of dietary protein intake It has been suggested that the sulfur amino acids in protein are responsible for the calciuria observed after protein ingestion . This hypothesis was tested by feeding meals containing either 15 g protein ( control ) , 45 g protein ( high protein ) , or 15 g protein plus sulfur amino acids equivalent to those in the high protein diet . Compared to the control , the high protein diet caused an increase in urinary calcium and sulfate and a decrease in the renal reabsorption of calcium . In contrast , the sulfur amino acid supplement had no effect on calcium excretion or reabsorption . Net acid excretion was unaffected by dietary treatment The effect of supplementing a basal diet containing 697 mg calcium daily ( 17.4 mmol/d ) with an additional 900 mg Ca daily from milk , Ca chloride , or a Ca carbonate preparation was examined in eight adult males during a 56-d metabolic balance study . The ingestion of the milk or Ca supplements had no overall effect on Ca retention by these subjects because the milk and supplements depressed apparent absorption of Ca in the gut and fractional tubular reabsorption of Ca in the kidneys . Supplementation of the diet with CaCl and to a lesser extent with milk significantly increased renal acid excretion whereas supplementation with CaCO3 depressed renal acid excretion . The three Ca supplements significantly altered magnesium and phosphorus absorption and urinary excretion in different manners but had no overall effect on retention of P or Mg . The responses of our subjects to these treatments may be different than those of subjects who are chronically in negative balance in regard to Ca We studied the effect of acute oral phosphate loading on parathyroid hormone ( PTH ) secretion and action .  Eighteen adults were studied before and after ingestion of 1 g elemental phosphorus as neutral sodium-potassium phosphate in grape juice or in water and 1.7 g NaCl in juice was used as a control .  Five subjects were studied after ingesting 1.5 g P in juice . Blood was drawn every 15 min from -45 to + 300 min for measurement of serum ionized calcium ( Ca++ ) , P , total Ca , creatinine , and immunoreactive PTH ( iPTH ) ; urine was collected hourly . Serum P declined after NaCl ingestion but rose significantly after ingestion of 1 g P in juice or in water . There were no significant changes in serum Ca++ , iPTH , or urinary cyclic AMP excretion . Acute ingestion of 1 - 1.5 g P , which exceeds the P content of a normal meal , does not decrease serum Ca++ or increase iPTH secretion or renal action in normal adults BACKGROUND Different sources of dietary protein may have different effects on bone metabolism . Animal foods provide predominantly acid precursors , whereas protein in vegetable foods is accompanied by base precursors not found in animal foods . Imbalance between dietary acid and base precursors leads to a chronic net dietary acid load that may have adverse consequences on bone . OBJECTIVE We wanted to test the hypothesis that a high dietary ratio of animal to vegetable foods , quantified by protein content , increases bone loss and the risk of fracture . DESIGN This was a prospect i ve cohort study with a mean ( + /-SD ) of 7.0+/-1.5 y of follow-up of 1035 community-dwelling white women aged > 65 y.  Protein intake  was measured by using a food-frequency question naire and  bone mineral density was measured by dual-energy X-ray absorptiometry . RESULTS Bone mineral density was not significantly associated with the ratio of animal to vegetable protein intake . Women with a high ratio had a higher rate of bone loss at the femoral neck than did those with a low ratio ( P = 0.02 ) and a greater risk of hip fracture ( relative risk = 3.7 , P = 0.04 ) . These associations were unaffected by adjustment for age , weight , estrogen use , tobacco use , exercise , total calcium intake , and total protein intake . CONCLUSIONS Elderly women with a high dietary ratio of animal to vegetable protein intake  have more rapid femoral neck bone loss and a greater risk of hip fracture than do those with a low ratio . This suggests that an increase in vegetable protein intake and a decrease in animal protein intake may decrease bone loss and the risk of hip fracture . This possibility should be confirmed in other prospect i ve studies and tested in a r and omized trial BACKGROUND Dietary patterns that promote mild metabolic acidosis may have a negative effect on  bone density .  OBJECTIVE We investigated the relation between a measure of  dietary acid-base load , potential renal acid load ( PRAL ) , and calcaneal broadb and ultrasound attenuation ( BUA ) after adjustment for confounders and also compared the results with different estimates of acid-base load . DESIGN A cross-sectional study was conducted in 14 563 men and women aged 42 - 82 y living in Norfolk , United Kingdom , in which measures of calcaneal BUA  and dietary PRAL were estimated by using the European Prospect i ve Investigation into Cancer and Nutrition Norfolk ( EPIC-Norfolk ) food-frequency question naire . RESULTS A more acidic dietary intake ( high PRAL ) was significantly associated with lower calcaneal BUA in women but not in men ; there was a difference of approximately 2 % in BUA between the highest and lowest quintiles of PRAL , independent of age , body mass index , smoking habit , physical activity , diagnosed osteoporosis , and history of fracture , and ( in women ) hormone replacement therapy . No relation was observed between history of fracture or incident fracture and PRAL . Those with the greatest PRAL had higher intakes of meat , fish , eggs , and cereal and cereal products and lower intakes of fruit and vegetables , tea , and coffee . CONCLUSION PRAL was inversely associated with bone ultrasound measures in women , but the magnitude of the association was relatively small compared with other known risk factors . Further longitudinal studies are required to establish whether , in the long term , these small effects are important in overall fracture risk in population BACKGROUND Protein and alkalizing minerals are increasingly described as playing a major role in influencing bone status , not only in the elderly but also in children and adolescents . OBJECTIVE We examined whether the long-term dietary protein intake and diet net acid load are associated with bone status in children . DESIGN In a prospect i ve study design in 229 healthy children and adolescents aged 6 - 18 y , long-term dietary intakes were calculated from 3-d weighed dietary records that were collected yearly over the 4-y period before a one-time bone analysis . Dietary acid load was characterized as potential renal acid load ( PRAL ) by using an algorithm including dietary protein , phosphorus , magnesium , and potassium . Proximal forearm bone variables were measured by peripheral quantitative computed tomography . RESULTS After adjustment for age , sex , and energy intake and control for forearm muscularity , BMI , growth velocity , and pubertal development , we observed that long-term  dietary protein intake  was significantly positively associated with periosteal circumference ( P < 0.01 ) , which reflected bone modeling , and with cortical area ( P < 0.001 ) , bone mineral content ( P < 0.01 ) , and polar strength strain index ( P < 0.0001 ) , which reflected a combination of modeling and remodeling . Children with a higher dietary PRAL had significantly less cortical area ( P < 0.05 ) and bone mineral content ( P < 0.01 ) . Long-term calcium intake had no significant effect on any bone variable . CONCLUSIONS Long-term dietary protein intake appears to act anabolically on diaphyseal bone strength during growth , and this may be negated , at least partly , if dietary PRAL is high , ie , if the intake of alkalizing minerals is low BACKGROUND Adequate intakes of fruit and vegetables are recommended for optimum health in children . OBJECTIVE The objective of this study was to determine whether consuming fruit and vegetables > 3 times per day is beneficial to bone mass in children . DESIGN Fifty-six white females ( Tanner stage 2 ) recorded dietary intake on 3 independent days . The numbers of servings of fruit and vegetables were recorded for each day and tallied , and the subjects were divided into 2 consumption groups for analysis ( low consumption : <3 servings/d , n = 22 ; high consumption : > or = 3 servings/d , n = 34 ) . Bone area and the bone mineral content of the whole body and radius were assessed by using dual-energy X-ray absorptiometry . Radioimmunoassays measured serum parathyroid hormone and 25-hydroxyvitamin D. Twenty-four-hour urine sample s were assessed for calcium , sodium , and creatinine . RESULTS After adjustment for age , body mass index , and physical activity , those children who reported consuming > or = 3 servings fruit and vegetables/d had more bone area of the whole body ( 6.0 % ; P = 0.03 ) and radius ( 8.3 % ; P = 0.03 ) , lower urinary calcium excretion ( 2.6 + /- 0.2 compared with 1.8 + /- 0.3 mg/kg ; P = 0.04 ) , and lower parathyroid hormone ( 19.6 + /- 1.9 compared with 25.0 + /- 1.6 pg/mL ; P = 0.01 ) than did those children who reported consuming <3 servings fruit and vegetables/d . CONCLUSIONS High fruit and vegetable intakes have beneficial effects on the bone area of the radius and whole body in early pubertal girls . The lower urinary calcium output associated with higher fruit and vegetable intakes may be a modulating factor Increasing dietary protein induces hypercalciuria and a negative calcium balance . Despite this , the influence of dietary protein on the parathyroid hormone ( PTH ) I-a-hydroxylase axis is not well understood . We therefore examined the effect of three amounts of dietary protein : low ( 0.7 g/kg ) , medium ( 1.0 g/kg ) , and high ( 2.1 g/kg ) on mineral metabolism and the PTH-1-alpha-hydroxylase axis in 16 healthy women aged 26.7 + /- 1.3 y. By day 4 , urinary calcium decreased significantly with the low-protein diet and increased significantly with the high-protein diet compared with the medium-protein diet ( control ) . Also by day 4 , there were striking elevations in serum PTH and calcitriol [ 1,25-dihydroxyvitamin D ] in subjects consuming the low-protein diet .  Serum PTH , by two different assays , was 1.5 - 2.4 times higher and by day 14 1.6 - 2.7 times higher during the low-protein diet compared with the medium-protein diet . This was accompanied by a significant increase in both nephrogenous cyclic adenosine monophosphate ( cAMP ) , a sensitive and specific indicator of PTH bioactivity , and serum calcitriol by day 14 . In comparison , there were relatively minor changes in the calcitropic hormones with the medium- and high-protein diets . The stimulus for the elevation in PTH induced by protein restriction is unclear , but probably does not involve a simple renal mechanism and could reflect either a decline in intestinal calcium absorption , a reduction of bone turn-over , or both . Our data indicate that dietary protein is a powerful regulator of calcium metabolism . Further study is needed to both clarify the mechanisms by which these changes are induced and to better define the amount of dietary protein that will optimize skeletal health in young women BACKGROUND Evidence is increasing for positive effects of fruit and vegetable intakes on bone health . However , most of the studies to date were conducted in adults , and few reports included adolescents . OBJECTIVE We explored the association between bone mineral status and fruit and vegetable intakes in adolescent boys and girls ( aged 16 - 18 y ) , young women ( aged 23 - 37 y ) , and older men and women ( aged 60 - 83 y ) . DESIGN Bone mineral measurements of the whole body , hip , and spine were made in all subjects by using dual-energy X-ray absorptiometry . Information on health and lifestyle and physical activity was obtained by question naire . Fruit , vegetable , and nutrient intakes were ascertained from 7-d food diaries . RESULTS In adolescent boys and girls and older women , significant positive associations were observed between spine size-adjusted bone mineral content ( SA- BMC ) and fruit intake . In boys only , femoral neck SA- BMC was also significantly and positively associated with the intakes of both fruit and dietary vitamin C. No significant associations were found in the young women or older men , or between bone measurements and intake of vegetables alone ( after adjustments ) in any of the groups . CONCLUSIONS Higher fruit and vegetable intakes may have positive effects on bone mineral status in both younger and older age groups , especially at the spine and femoral neck . The specific mechanisms remain to be ascertained , but vitamin C , other fruit-specific antioxidants , and lifestyle may play a role We showed that increasing dietary protein from omnivorous sources increases intestinal calcium absorption and urinary calcium , whereas a low-protein diet decreases calcium absorption and lowers urinary calcium . To assess the effect of soy protein on this relation , we substituted soy for meat in high- and low-protein diets fed to healthy women . The study consisted of a 2-wk adjustment period followed by a 4-d experimental period in which 20 healthy women consumed , in r and om order , the following 4 diets : high-protein soy-based , low-protein soy-based , high-protein meat-based , low-protein meat-based . Measures of calcium homeostasis were evaluated at baseline and after 4 d of the experimental period . At 24 h , net acid excretion was higher during the high- compared with the low-protein intervention ( P < 0.05 ) , and during the meat compared with the soy intervention ( P < 0.05 ) . The high-protein diets increased 24-h urinary calcium ( P < 0.001 ) , but urinary calcium did not differ due to the type of protein . Serum concentrations of parathyroid hormone and calcitriol , and urinary nephrogenous cAMP were higher during the low- compared with the high-protein intervention and during the soy compared with the meat protein ( P < 0.05 ) . In a subset of subjects , intestinal calcium absorption tended to be lower ( P = 0.1 ) when they consumed the soy diets rather than the meat diets . These data indicate that when soy protein is substituted for meat protein , there is an acute decline in dietary calcium bioavailability BACKGROUND The role of dietary protein in bone metabolism is controversial . OBJECTIVE We investigated the associations of dietary protein intake with baseline bone mineral density ( BMD ) and the rate of bone loss over 3 y in postmenopausal elderly women . DESIGN Women aged 65 - 77 y ( n = 489 ) were enrolled in an osteoporosis intervention trial . We studied the associations of protein intake as a percentage of energy with baseline BMD and the rate of bone loss in 96 women in the placebo group ( n = 96 ) . We also examined the effect of the interaction of dietary  calcium  intake with protein intake on BMD . RESULTS In the cross-sectional study , a higher intake of protein was associated with higher BMD . BMD was significantly higher ( P < 0.05 ) in the spine ( 7 % ) , midradius ( 6 % ) , and total body ( 5 % ) in subjects in the highest quartile of protein intake than in those in the lower 2 quartiles . This positive association was seen in women with calcium intakes > 408 mg/d . There was no significant effect of protein intake on hip BMD . In the longitudinal study of the placebo group , there was no association between protein intake and the rate of bone loss . CONCLUSIONS The highest quartile of protein intake (: 72 g/d ) was associated with higher BMD  in elderly women at baseline only when the calcium intake exceeded 408 mg/d . In the longitudinal study , no association was seen between protein intake and the rate of bone loss , perhaps because the sample size was too small or the follow-up period of 3 y was not long enough to detect changes An acute load test was used to test the influence of dietary factors on urinary calcium excretion . In study 1 , 10 fasting premenopausal women consumed test meals providing a moderate amount of protein ( MP ; 23 g ) , MP plus 23 mmol KHCO3 ( MP+K ) , MP plus 23 mmol NaCl ( MP+Na ) , and a high amount of protein ( HP ; 53 g ) , HP plus 70 mmol KHCO3 ( HP+K ) , and HP plus 70 mmol NaCl ( HP+Na ) . Protein was casein : lactalbumin ( 80:20 ) , except for the treatments with added sodium chloride , to which only casein was added . In study 2 , the effects of HP and HP plus 50 mmol KHCO3 ( HP+K ) were compared with those of MP or MP plus 7.5 mmol phosphate ( MP+Pi ) , equaling the additional phosphate of HP , in 10 adult men . Subjects completed all treatments in r and om order . In study 1 , the peak of calcium excretion was at 3 h for all treatments , except for HP+K , which indicated an acute hypocalciuric effect of potassium . Unexpectedly , there was no hypercalciuric effect of adding sodium chloride , nor was urine sodium increased . In study 2 , calcium excretion was significantly higher with HP than with MP+Pi but not with MP at 3 h , indicating an acute hypercalciuric effect of protein alone . A hypocalciuric effect of potassium ( HP+K compared with HP ) but not of phosphate ( MP compared with MP+Pi ) was seen . An acute load test measuring changes 3 h postload was appropriate for examining the calciuric effects of protein and potassium bicarbonate , but not those of sodium chloride or phosphate in adults Calcium balance is decreased by an increased intake of purified proteins , although the effects of common dietary sources of protein ( like meat ) on calcium economy remain controversial . We compared the effects of several weeks of controlled high and low meat diets on body calcium retention , using sensitive radiotracer and whole body scintillation counting methodology . Healthy postmenopausal women ( n = 15 ) consumed diets with similar calcium content ( approximately 600 mg ) , but either low or high in meat ( 12 vs. 20 % of energy as protein ) for 8 wk each , in a r and omized crossover design . After 4 wk of equilibration of each diet , calcium retention was measured by extrinsically labeling the 2-d menu with (47)Ca , followed by whole body scintillation counting for 28 d. Urinary and blood indicators of bone metabolism were also determined for each diet . Calcium retention was not different during the high and low meat dietary periods ( d 28 , mean + /- pooled SD : 17.1 and 15.6 % , + /-0.6 % , respectively ; P = 0.09 ) . An initially higher renal acid excretion in subjects consuming the high meat compared with the low meat diet decreased significantly with time . The diets did not affect urinary calcium loss or indicators of bone metabolism . In conclusion , under controlled conditions , a high meat compared with a low meat diet for 8 wk did not affect calcium retention or biomarkers of bone metabolism in healthy postmenopausal women .  Calcium retention is not reduced when subjects consume a high protein diet from common dietary sources such as meat BACKGROUND Variation in absorption efficiency explains more of the variability in calcium balance than does actual calcium intake . Several investigators have suggested that the relatively high phosphorus and protein intakes of the diets of industrialized nations reduce calcium absorption and thereby aggravate the problem of calcium deficiency . OBJECTIVE My objective was to test whether variation in phosphorus and protein intakes is associated with variation in calcium absorption . DESIGN One hundred ninety-one Roman Catholic nuns aged 48.7 + /- 7.0 y were studied approximately 3 times each over a > 20-y period with a full metabolic balance regimen ; controlled , chemically analyzed diets ; and double-tracer measurement of calcium absorption . RESULTS Although the expected associations with absorption were found for age , calcium intake , and estrogen status , no association was observed for intakes of either phosphorus or protein . CONCLUSION Phosphorus and protein intakes do not contribute to the wide variability in calcium absorption efficiency BACKGROUND Studies examining the relation between bone mineral density ( BMD ) and  fruit and vegetable consumption  during adolescence are rare . OBJECTIVE Our objective was to determine whether usual fruit and vegetable intakes reported by adolescents have any influence on BMD . DESIGN BMD was measured by dual-energy X-ray absorptiometry at the nondominant forearm and dominant heel in a r and om sample of 12-y-old boys ( n = 324 ) , 12-y-old girls ( n = 378 ) , 15-y-old boys ( n = 274 ) , and 15-y-old girls ( n = 369 ) .  Usual fruit and vegetable consumption  was assessed by an interviewer-administered diet history method . Relations between BMD and fruit and vegetable intake were assessed by using regression modeling . RESULTS Using multiple linear regression to adjust for the potential confounding influence of physical and lifestyle factors , we observed that 12-y-old girls consuming high amounts of fruit had significantly higher heel BMD ( beta = 0.037 ; 95 % CI : 0.017 , 0.056 ) than did the moderate fruit consumers . No other associations were observed . CONCLUSION High intakes of fruit may be important for bone health in girls . It is possible that fruit 's alkaline-forming properties mediate the body 's acid-base balance . However , intervention studies are required to confirm the findings of this observational study Magnesium and calcium deficiency in humans is related to a number of pathological phenomena such as arrhythmia , osteoporosis , migraine , and fatal myocardial infa rct ion . Clinical ly established metabolic acidosis induces renal losses of calcium . In normal subjects , even moderate increases in net endogenous acid production ( NEAP ) impair renal calcium reabsorption but no information is available whether this also influences renal magnesium h and ling . The aim of the study was to examine the relation between NEAP and renal magnesium excretion in healthy , free-living , elderly subjects . The subjects ( age 64 + /- 4.7 y , n = 85 ) were r and omly selected from the population register in Gothenburg ( Sweden ) .  Magnesium , calcium , and potassium  were measured in 24-h urine sample s and NEAP was quantified as renal net acid excretion ( NAE ) . NAE was positively correlated with excretions of magnesium ( R(2 ) = 0.27 , P < 0.0001 ) and calcium ( R(2 ) = 0.30 , P < 0.0001 ) but not potassium . When 24-h urinary magnesium excretion was adjusted for 24-h urinary potassium excretion , a biomarker for dietary potassium intake , the association between magnesium excretion and NAE remained significant ( R(2 ) = 0.21 , P < 0.0001 ) . The significant association between potassium-adjusted magnesiuria and NAE suggests that the acid-base status affects renal magnesium losses , irrespectively of magnesium intake . Magnesium deficiency could thus , apart from an insufficient intake , partly be caused by the acid load in the body CONTEXT Bicarbonate has been implicated in bone health in older subjects on acid-producing diets in short-term studies . OBJECTIVE The objective of this study was to determine the effects of potassium bicarbonate and its components on changes in bone resorption and calcium excretion over 3 months in older men and women . DESIGN , PARTICIPANTS , AND INTERVENTION In this double-blind , controlled trial , 171 men and women age 50 and older were r and omized to receive placebo or 67.5 mmol/d of potassium bicarbonate , sodium bicarbonate , or potassium chloride for 3 months . All subjects received calcium ( 600 mg of calcium as triphosphate ) and 525 IU of vitamin D(3 ) daily . MAIN OUTCOME MEASURES Twenty-four-hour urinary N-telopeptide and calcium were measured at entry and after 3 months . Changes in these measures were compared across treatment groups in the 162 participants included in the analyses . RESULTS Bicarbonate affected the study outcomes , whereas potassium did not ; the two bicarbonate groups and the two no bicarbonate groups were therefore combined . Subjects taking bicarbonate had significant reductions in urinary N-telopeptide and calcium excretion , when compared with subjects taking no bicarbonate ( both before and after adjustment for baseline laboratory value , sex , and changes in urinary sodium and potassium ; P = 0.001 for both , adjusted ) . Potassium supplementation did not significantly affect N-telopeptide or calcium excretion . CONCLUSIONS Bicarbonate , but not potassium , had a favorable effect on bone resorption and calcium excretion . This suggests that increasing the alkali content of the diet may attenuate bone loss in healthy older adults Potassium citrate may improve calcium balance by conferring an alkali load . Calcium supplementation slows postmenopausal bone loss by inhibiting PTH secretion . This study explores whether combined treatment with potassium citrate and calcium citrate is more effective than either agent alone in inhibiting bone loss . In a crossover study involving 18 postmenopausal women , the following treatments were compared : potassium citrate ( 4.3 g or 40 mmol/d ) , calcium citrate ( 800 mg or 20 mmol/d ) , combined treatment , and placebo . During the last 2 d of each 2-wk phase , serum and 24-h urine were collected for assessment of calcium metabolism , alkali load , and bone turnover markers . Compared with placebo , potassium citrate provided an alkali load and significantly decreased urinary calcium without changing serum PTH ( sPTH ) or bone turnover markers .  Calcium citrate significantly increased absorbed calcium , marginally decreased sPTH , and significantly reduced bone resorption markers . Combined treatment retained key features of potassium citrate and calcium citrate . However , more alkali was delivered than with potassium citrate alone , and absorbed calcium did not differ from calcium citrate alone . Compared with placebo , combined treatment increased urinary calcium , marginally reduced sPTH , provided a clear alkali load , and reduced the bone resorption markers serum type I collagen C-telopeptide and urinary N-telopeptide by 20.4 % ( P < 0.0001 ) and 18.2 % ( P = 0.005 ) , respectively . A significant trend was noted for the decrease in bone resorption markers as treatment changed from placebo to potassium citrate to calcium citrate to combined treatment . In postmenopausal women , combined treatment with potassium citrate and calcium citrate inhibits bone resorption by providing an alkali load and increasing absorbed calcium BACKGROUND Bone mineral density ( BMD ) may be influenced by the general dietary pattern and the potential renal acid load ( PRAL ) . METHODS We compared the dietary intake ( estimated using the European Prospect i ve Investigation into Cancer and nutrition question naire ) of 497 community-living women ( 60 years of age and older ) grouped according to tertiles of baseline total , trabecular and cortical BMD estimated using tibial peripheral quantitative computed tomography ( pQCT ) , and of BMD variation over 6 years . RESULTS None of the nutrients taken into account nor PRAL was associated with total BMD , with the exception that the intake of polyunsaturated fatty acids ( PUFA ) was slightly higher among women with the highest total BMD . Similar results were found for trabecular BMD . Cortical BMD was associated with serum 25-OH vitamin D ( 38.8 , 43.2 , and 49.5 nmol/L in the first , second , and third tertiles , respectively ; P=0.042 ) . In the longitudinal analysis , a lower BMI was associated with greater loss of total BMD , while lower serum 25-OH vitamin D at baseline was associated with smaller loss of cortical BMD . CONCLUSIONS We found no relationship between dietary acid load and BMD . We also confirmed the role of well-recognized risk factor for osteoporosis Menopause drastically increases the risk of osteoporosis . Aside from drug therapy , lifestyle and nutritional factors play an important role in the maintenance of skeletal health . Our recent findings suggest that dried plums , a rich source of phenolic and flavonoid compounds , are highly effective in modulating bone mass in an ovarian hormone-deficient rat model of osteoporosis . The objective of this study was to examine whether the addition of dried plums to the diets of postmenopausal women positively influences markers of bone turnover .  Fifty-eight postmenopausal women not on hormone replacement therapy ( HRT )  were r and omly assigned to consume either 100 g dried plums or 75 g dried apples daily for 3 months . Both dried fruit regimens provided similar amount of calories , fat , carbohydrate , and fiber . Serum and urinary biochemical markers of bone status were assessed before and after treatment . In comparison with corresponding baseline values , only dried plums significantly increased serum levels of insulin-like growth factor-I ( IGF-I ) and bone-specific alkaline phosphatase ( BSAP ) activity . Higher levels of both serum IGF-I and BSAP are associated with greater rates of bone formation . Serum and urinary markers of bone resorption , however , were not affected by either dietary regimen . The results of this study suggest that dried plums may exert positive effects on bone  in postmenopausal women . Longer duration studies are needed to confirm the beneficial effects of dried plum on bone mineral density ( BMD ) and the skeletal health  of postmenopausal women Objective : To examine the effect of phosphate supplements on calcium homeostasis and bone turnover in young men . Design : Study 1 was a r and omised , controlled , cross-over trial of 1000 mg elemental phosphate given for one week , with a st and ard diet of 800 mg/d each of calcium and phosphorus . Study 2 was an escalating dose study of 0 , 1000 , 1500 and 2000 mg/d elemental phosphate , each given for one week , with a st and ard diet of 1000 mg/d each of calcium and phosphate . Setting : Northern General Hospital , Sheffield . Subjects : Study 1 , 10 healthy men ages 19–32 y. Study 2 , 12 healthy men ages 19–38 y. Interventions : Sodium acid phosphate tablets each containing 500 mg elemental phosphorus ( 16.1 mmol/d ) , given with meals . Results : Study 1 , administration of 32.2 mmol/d phosphorus result ed in a mean increase of 13.2 mmol/d urinary phosphorus , a mean decrease of 1.1 mmol/d urinary calcium , and a mean increase of 7 ng/mL in serum intact PTH . There were no changes in serum phosphate , osteocalcin or urinary N-telopeptide excretion . Study 2 , administration of 64.4 mmol/d phosphorus result ed in a mean increase of 27.2 mmol/d urinary phosphorus , a mean decrease of 2.4 mmol/d urinary calcium , with no change in serum phosphate , PTH or urinary deoxypyridinoline . Conclusions : Phosphate supplementation of the diet does not affect bone turnover in young men . Sponsorship : Arthritis and Rheumatism Council Programme Grant A  Western-type diet  is associated with osteoporosis and calcium nephrolithiasis . On the basis of observations that calcium retention and inhibition of bone resorption result from alkali administration , it is assumed that the acid load inherent in this diet is responsible for increased bone resorption and calcium loss from bone . However , it is not known whether the dietary acid load acts directly or indirectly ( i.e. , via endocrine changes ) on bone metabolism . It is also unclear whether alkali administration affects bone resorption/calcium balance directly or whether alkali-induced calcium retention is dependent on the cation ( i.e. , potassium ) supplied with administered base . The effects of neutralization of dietary acid load ( equimolar amounts of NaHCO(3 ) and KHCO(3 ) substituted for NaCl and KCl ) in nine healthy subjects ( 6 men , 3 women ) under metabolic balance conditions on calcium balance , bone markers , and endocrine systems relevant to bone [ glucocorticoid secretion , IGF-1 , parathyroid hormone (PTH)/1,25(OH)(2 ) vitamin D and thyroid hormones ] were studied . Neutralization for 7 days induced a significant cumulative calcium retention ( 10.7 + /- 0.4 mmol ) and significantly reduced the urinary excretion of deoxypyridinoline , pyridinoline , and n-telopeptide . Mean daily plasma cortisol decreased from 264 + /- 45 to 232 + /- 43 nmol/l ( P = 0.032 ) , and urinary excretion of tetrahydrocortisol ( THF ) decreased from 2,410 + /- 210 to 2,098 + /- 190 microg/24 h ( P = 0.027 ) . No significant effect was found on free IGF-1 , PTH/1,25(OH)(2 ) vitamin D , or thyroid hormones . An acidogenic Western diet results in mild metabolic acidosis in association with a state of cortisol excess , altered divalent ion metabolism , and increased bone resorptive indices . Acidosis-induced increases in cortisol secretion and plasma concentration may play a role in mild acidosis-induced alterations in bone metabolism and possibly in osteoporosis associated with an acidogenic Western diet When the first edition of A Dictionary of Epidemiology was launched in 1983 , its principal aim was to facilitate communication among health professionals . The field was relatively young and comprised complex interdisciplinary relations ranging from the biomedical sciences to statistics and the social sciences . The International Epidemiological Association ( IEA ) co-sponsored the project with the aim of developing certain st and ards for teaching , research reports and communication of epidemiological findings to the public . This is a well-known history : John M Last , the emeritus professor of epidemiology and community medicine from the University of Ottawa , Canada , was appointed as the editor of A Dictionary ... , and kept ahead of the task during the subsequent decades . The original slim pocket book grew substantially with each re-edit , keeping pace with the remarkable developments in the discipline . When the fourth edition was launched in 2001 , John Last told me with a smile that he would die soon , supposedly to increase the value of the signature he had just h and written in my book . Fortunately , he did not , and his love for dictionary-making allowed him to produce his A Dictionary of Public Health , and to collaborate in the recently launched fifth edition of A Dictionary ... , now edited by Miquel Porta , professor of preventive medicine and public health from the Universitat Autònoma de Barcelona , senior scientist of the Institut Municipal d’Investigació Mèdica in Barcelona , Spain , and collaborator in the previous editions . If he had to limit his professional bookcase to a single volume , Professor Charles du V Florey , the former president of the IEA , would choose to keep A Dictionary .... I argue that anybody among us — epidemiologists and would-be epidemiologists ( hopefully with a larger shelf)—should also have a copy of this book at h and for frequent consultation . The collective effort gathered in its making is impressive . Miquel Porta has built over the previously crafted editions , and has relied on the support of a wide network of professionals to up date each entry and to exp and the selection of subjects . The Journal of Epidemiology and Community Health joined the initiative by publishing a call for su bmi ssions . Items already selected from the previous edition have been revised and up date d ; several new items have been added . As a result , the fifth edition of A Dictionary ... performs normative and informative functions : you will be informed on important matters and instructed on how to proceed in the epidemiological field . Readers with different needs and anxieties with knowledge will find straightforward writing , authoritative definitions and pertinent bibliographical references . How to differentiate a rate from a ratio , incidence from prevalence , confounding from intervening variables , type I from type II error ? How to appraise emerging themes in the epidemiological literature such as genetic polymorphisms and Bayesian statistics ? Key method ological issues such as meta- analysis , multilevel analysis and regression models : the list solely enrols a small sample of possible search es . The selection of issues was broad in scope ; intelligent and synthetic writing contemplated from the easier to the more intricate subjects . You may want to up date conceptual and method ological issues relevant to your teaching and research activities , to resolve doubts or to confirm an impression . You may want to check on terminology , fulfil curiosities or learn about topics unrelated to your preferential themes . You may be a professional applied to other health specialities , an undergraduate or a high school student . Several users will meet their needs by consulting A Dictionary ... ; even those who aim lessly scan the text may find some valuable insight . While it will not resolve all your needs in the epidemiological field , it surely provides enough substance to build on — a very good start or ammunition for more comprehensive search es . Miquel Porta dealt with the challenge of preparing reader-friendly texts on a wide range of subjects , which will satisfy both a beginner and an experienced epidemiologist . He seems to have transposed Occam ’s razor ( see the correspondent entry : ‘ ‘ the philosophical principle of parsimony ... assumptions to explain a phenomenon must not be multiplied beyond necessity ... ’ ’ ) to the writing of the book . If I may indulge in selftestimony , I found my teenage daughter consulting the book and it motivated a conversation on subjects so dear to me .... Arousing the interest of the young for a speciality admittedly perceived as difficult by adolescents ; as goes the popular saying , this is priceless ! ‘ ‘ Epidemiology is the study of the occurrence and distribution of healthrelated states or events in specified population s , including the study of the determinants influencing such states , and the application of this knowledge to control the health problems ’ ’ . The definition has matured over the years and presents slight modifications from its previous formulation in the fourth edition . The entry for ‘ ‘ Epidemiology ’ ’ exp and s the conceptualisation of terms comprised in the definition and includes historical aspects . In subsequent years , this definition will be the benchmark of the discipline , until Miquel Porta and his collaborators eventually prepare a further edition to meet the new needs that the future may bring forth . I dare to guess that the prospect i ve sixth edition of A Dictionary ... will have an online dynamic interface interacting with the hard copy . I also dare to guess that it will include a new entry for A Dictionary of Epidemiology , whose importance to the professional field will surely have earned it Summary To investigate the possible use of oral phosphate as an activator of bone remodeling in coherence treatment of osteoporosis , 82 postmenopausal females , aged 50–75 years , were r and omized to treatment with oral phosphate ( 750 , 1500 , or 2550 mg/day ) or placebo for 7 days and followed for 4 months thereafter . All patients had sustained at least one previous fracture of the distal forearm and had a bone mineral content of the contralateral forearm or bone mineral density of the lumbar spine lower than normal mean for age . Urinary phosphate/creatinine ratio increased in a dose-dependent fashion during treatment ( P<0.001 ) , whereas no significant changes were seen in serum phosphate or serum calcium . Serum parathyroid hormone ( PTH ) rose significantly ( P<0.05 ) during treatment to a maximum of 36 and 33 % in the groups receiving 1500 and 2250 mg/day , respectively , whereas serum 1,25-dihydroxycholecalciferol remained unchanged . In the group receiving 1500 mg/day , mean serum osteocalcin was increased in the period from day 1 to day 28 ( P<0.05 ) , but no significant changes were observed in urinary hydroxyproline/creatinine ratio , or serum bone alkaline phosphatase . We conclude that a short course of oral phosphate treatment increases serum PTH considerably . Furthermore , 1500 mg/day but not 2250 mg/day increases serum osteocalcin . No clear biochemical evidence , however , of increased activation of bone remodeling could be demonstrated in either group Objective : To determine the effect of high-protein diets , which have recently been promoted for their health benefits , on urinary calcium losses and bone turnover in older subjects . Design : R and omized controlled cross-over study . Setting : Teaching hospital and university . Subjects : Twenty hyperlipidemic men and postmenopausal women ( age 56±2 y ) completed the study . Interventions : One-month test and control phases during which subjects consumed equi-energy metabolic diets high in calcium ( 1578 and 1593 mg/day , respectively ) . On the test diet 11 % of total dietary energy from starch in the control bread was replaced by protein ( wheat gluten ) , result ing in 27 % of energy from protein on the test diet vs 16 % on the control diet . Main outcome measure : Urinary calcium excretion . Results : Compared with the control diet , at week 4 , the test diet increased mean ( ±s.e.m . ) 24 h urinary output of calcium ( 139±15 vs 227±21 mg , P=0.004 ) . The treatment difference in urinary calcium loss correlated with the serum anion gap as a marker of metabolic acid production ( r=0.57 , P=0.011 ) . Serum calcium levels were marginally lower 2.41±0.02 vs 2.38±0.02 mmol/l ( P=0.075 ) , but there was no significant treatment difference in calcium balance , possibly related to the high background calcium intake on both diets . Conclusions : In the presence of high dietary calcium intakes the vegetable protein gluten does not appear to have a negative effect on calcium balance despite increased urinary calcium loss . Sponsorship : The University-Industry Research Partnership Program of the Natural Sciences and Engineering Research Council of Canada , Loblaw Br and s Limited , Toronto , ON , and Kraft Canada Inc. Don Mills , ON . DJAJ is funded as a Canada Research Chair in Metabolism and Nutrition at the University of Toronto by the Federal Government of Canada , Ottawa Background The acid-ash hypothesis , the alkaline diet , and related products are marketed to the general public . Websites , lay literature , and direct mail marketing encourage people to measure their urine pH to assess their health status and their risk of osteoporosis . The objectives of this study were to determine whether 1 ) low urine pH , or 2 ) acid excretion in urine [ sulfate + chloride + 1.8x phosphate + organic acids ] minus [ sodium + potassium + 2x calcium + 2x magnesium mEq ] in fasting morning urine predict : a ) fragility fractures ; and b ) five-year change of bone mineral density ( BMD ) in adults . Methods Design : Cohort study : the prospect i ve population -based Canadian Multicentre Osteoporosis Study .  Multiple logistic regression was used to examine associations between acid excretion ( urine pH and urine acid excretion ) in fasting morning with the incidence of fractures ( 6804 person years ) . Multiple linear regression was used to examine associations between acid excretion with changes in BMD over 5-years at three sites : lumbar spine , femoral neck , and total hip ( n = 651 ) . Potential confounders controlled included : age , gender , family history of osteoporosis , physical activity , smoking , calcium intake , vitamin D status , estrogen status , medications , renal function , urine creatinine , body mass index , and change of body mass index . Results There were no associations between either urine pH or acid excretion and either the incidence of fractures or change of BMD after adjustment for confounders . Conclusion Urine pH and urine acid excretion do not predict osteoporosis risk In a controlled feeding study , the effects of substituting 25 g soy protein for meat on calcium retention and bone biomarkers were determined . Postmenopausal women ( n = 13 ) ate two diets that were similar , except that , in one diet , 25 g high-isoflavone soy protein ( SOY ) was substituted for an equivalent amount of meat protein ( control diet ) , for 7 wk each in a r and omized crossover design . After 3 wk of equilibration , calcium retention was measured by labeling the 2-d menu with (47)Ca , followed by whole-body counting for 28 d. Urinary calcium and renal acid excretion were measured at wk 3 , 5 , and 7 . Biomarkers of bone and cardiovascular health were measured at the beginning and end of each diet . Calcium was similarly retained during the control and SOY diets ( d 28 , percent dose , mean + /- pooled sd : 14.1 and 14.0 + /- 1.6 , respectively ) . Despite a 15 - 20 % lower renal acid excretion during the SOY diet , urinary calcium loss was unaffected by diet . Diet also did not affect any of the indicators of bone or cardiovascular health . Substitution of 25 g high isoflavone soy protein for meat , in the presence of typical calcium intakes , did not improve or impair calcium retention or indicators of bone and cardiovascular health in postmenopausal women OBJECTIVE Consumption of fruits and vegetables has been implicated in lowering net acid excretion ( NAE ) , but few studies have directly examined NAE and urinary calcium effects . Further , there is no evidence that only fresh fruits and vegetables must be consumed for a beneficial effect on bone . METHODS A crossover , acute-load study was design ed to investigate whether processed fruit was as effective as fresh fruit in reducing NAE and protein-induced hypercalciuria .  Fifteen women completed three dietary treatments on three different mornings . A fasting urine sample was collected before consuming one of the following three isocaloric high-protein treatments : control , fresh apples , and processed applesauce . The serving size for the applesauce treatment was 2.5 times that for fresh apples . Urine was collected at baseline ( 0 h ) and at 1.5 , 3.0 , and 4.5 h. RESULTS Compared with baseline , NAE increased after control treatment but decreased after fresh or processed apple treatment ( P = 0.041 ) . Calcium excretion increased with all treatments by 3 h ; however , the increase was less for fresh apple and applesauce ( P = 0.024 ) . CONCLUSIONS In an acute feeding model , fruit intake reduced NAE and urinary calcium excretion . Processed fruit appears to be effective , although a larger serving size was needed than with fresh fruit Excess dietary proteins and " acid ash " diets have been suspected to increase the risk of osteoporosis , but experimental and epidemiological evidence is mixed . We aim ed to determine whether the association between protein intake and the overall acid-base equilibrium of the diet ( as renal net acid excretion [ RNAE ] estimate ) and fracture risk vary according to calcium intake . During an average of 8.37 + /- 1.73 yr of follow-up , 2408 women reported a fracture ( excluding high-impact trauma ) among 36,217 postmenopausal women from the E3N prospect i ve study . We used Cox regression models to study the interaction between calcium and , respectively , proteins and RNAE , from the 1993 dietary question naire for fracture risk determination , adjusting for potential confounders . There was no overall association between fracture risk and total protein or RNAE . However , in the lowest quartile of calcium ( < 400 mg/1000 kcal ) , high protein intake was associated with a significant increased fracture risk ( RR = 1.51 for highest versus lowest quartile ; 95 % CI , 1.17 - 1.94 ) . An increasing fracture risk with increasing animal protein intake was also observed ( trend , p < 0.0001 ) . A similar pattern of interaction for fracture risk was observed between RNAE and calcium . In this Western population of postmenopausal women with normal to high protein intake and fairly high calcium intake , there was no overall association between total protein or RNAE and fracture risk . However , there was some evidence that high protein-high acid ash diets were associated with an increased risk of fracture when calcium intake was low ( < 400 mg/1000 kcal ) Abstract Excess protein intake can adversely affect the bone via an increase in calcium excretion , while suitable mechanical loading promotes osteogenesis . We therefore investigated whether vibration exposure could alleviate the bone mineral losses associated with a metabolic acidosis . Ten healthy individuals aged 22 – 29 years ( median = 25 ) underwent three 5-day study periods while monitoring their dietary intake . The study consisted of recording the participants ' usual dietary intake for 5 consecutive days . Participants were then r and omly divided into two groups , one of which received a protein supplement ( 2 g · kg−1 body mass · day−1 ; n = 5 ) and the other whole-body low-magnitude ( 3.5 g ) , low-frequency ( 30 Hz ) mechanical vibration ( WBV ) delivered through a specially design ed vibrating plate for 10 min each day ( n = 5 ) . Finally , for the third treatment period , all participants consumed the protein supplement added to their normal diet and were exposed to WBV exercise for 10 min per day . Daily urine sample s were collected throughout the experimental periods to determine the excretion of calcium , phosphate , titratable acid , urea , and C-telopeptide . As expected , when the participants underwent the high protein intake , there was an increase in urinary excretion rates of calcium ( P < 0.001 ) , phosphate ( P < 0.003 ) , urea ( P < 0.001 ) , titratable acid ( P < 0.001 ) , and C-telopeptide ( P < 0.05 ) compared with baseline values . However , high protein intake coupled with vibration stimulation result ed in a significant reduction in urinary calcium ( P = 0.006 ) , phosphate excretion ( P = 0.021 ) , and C-telopeptide ( P < 0.05 ) compared with protein intake alone , but did not affect titratable acid and urea output . The participants showed no effect of WBV exercise alone on urinary excretion of calcium , phosphate , urea , titratable acid , or C-telopeptide . The results indicate that vibration stimulation can moderate the increase in bone resorption and reduction in bone formation caused by a metabolic acidosis Background : A high purified protein intake has been shown to induce urinary calcium loss . However , these findings could not be reproduced with a high-protein meat diet . Also , most studies have been carried out in young subjects and the applicability of their results to the elderly population on a mixed vegetable : animal diet  remains unclear . Objectives : To study whether a mixed vegetable : animal high-protein intake increases urinary calcium loss in elderly volunteers , as has been shown for younger subjects on a purified high-protein intake . Methods : Eight male volunteers , with ages ranging from 66 to 88 years , recruited from the University Hospital Geriatric Medicine Out patients Clinic , were studied . 24-hour urinary calcium , phosphorus , and creatinine were measured during a period of usual protein intake ( approximately 0.6 g/kg/day ) and during 7 days of vegetable : animal ( 1:1 ) high-protein intake ( 2 g/kg/day ) . Calcium and phosphorus intake were adjusted to be kept constant ( 1 g/day of each ) during the whole study . Results : Mean calcium urinary levels did not change significantly during the study ( 1.89 and 1.83 mmol/24 h during the usual and high-protein diet , respectively ) . Urinary phosphorus and creatinine levels also remained stable throughout the entire study . Conclusions : This study has not detected any increased calcium urinary excretion in male elderly volunteers su bmi tted to the mixed vegetable : animal high-protein diet . Therefore , it does not support the suggestion that a high-protein intake is a risk factor for urinary calcium loss in elderly men A r and omised , parallel- design dietary intervention study was conducted in women ( aged 45 - 75 years ) with prehypertension or stage 1 hypertension . The aim was to compare the effects on bone turnover of a low-Na base-producing ( LNAB ) Dietary Approaches to Stop Hypertension (DASH)-type diet ( including six serves lean red meat/week ) with a high-carbohydrate low-fat ( HCLF ) diet with a higher acid load ( both > 800 mg dietary Ca/d ) . Fasting serum bone markers ( baseline and week 14 ) and 24 h urinary electrolyte excretion ( baseline , weeks 4 , 8 , 12 and 14 ) were measured . After the intervention period , the LNAB group ( n 46 ) had a fall of 26 ( sem 6 ) % ( P < 0.0001 ) in urinary Na , an increase in K excretion ( 6.8 ( sem 3.6 ) mmol/d ; P = 0.07 ) and , compared with the HCLF group ( n 49 ) , a greater reduction in urinary Ca excretion by 0.7 ( sem 0.3 ) mmol/d . Serum 25-hydroxyvitamin D , intact parathyroid hormone and osteocalcin did not change , and both groups had a similar increase of 23 ( sem 5 ) % ( P < 0.0001 ) in C-terminal telopeptide of type I collagen . The HCLF group had an 11 ( sem 4 ) % increase ( P = 0.003 ) in N-terminal propeptide , type I procollagen , which could indicate an increased rate of bone turnover . The fall in urinary Ca with the lower-Na lower-acid load diet is likely to have long-term beneficial effects on bone . As bone resorption was not different between the two dietary patterns with relatively high Ca intake , the effect on bone health of a dietary pattern with a lower acid load warrants further study on a lower Ca intake Although high-protein diets induce hypercalciuria in humans , the source of the additional urinary calcium remains unclear . One hypothesis is that the high endogenous acid load of a high-protein diet is partially buffered by bone , leading to increased skeletal resorption and hypercalciuria . We used dual stable calcium isotopes to quantify the effect of a high-protein diet on calcium kinetics in women . The study consisted of 2 wk of a lead-in , well-balanced diet followed by 10 d of an experimental diet containing either moderate ( 1.0 g/kg ) or high ( 2.1 g/kg ) protein .  Thirteen healthy women received both levels of protein in r and om order . Intestinal calcium absorption increased during the high-protein diet in comparison with the moderate ( 26.2 + /- 1.9 % vs. 18.5 + /- 1.6 % , P < 0.0001 , mean + /- sem ) as did urinary calcium ( 5.23 + /- 0.37 vs. 3.57 + /- 0.35 mmol/d , P < 0.0001 , mean + /- sem ) . The high-protein diet caused a significant reduction in the fraction of urinary calcium of bone origin and a nonsignificant trend toward a reduction in the rate of bone turnover . There were no protein-induced effects on net bone balance . These data directly demonstrate that , at least in the short term , high-protein diets are not detrimental to bone Previous studies demonstrated that the administration of NaHCO3 or sodium citrate had either only a small effect to reduce urinary Ca excretion or no effect , but that potassium citrate significantly reduced urinary Ca excretion . In order to further evaluate and compare the effects of NaHCO3 and of KHCO3 , we performed ten metabolic balances in healthy men during 18 control days , 12 days of NaHCO3 , 60 mmol/day and 12 days of KHCO3 , 60 mmol/day . Six subjects were fed a low Ca diet ( 5.2 + /- 0.7 SD mmol/day ) and three of these were also given calcitriol ( 0.5 microgram 6-hourly ) . Four subjects ate a normal Ca diet ( 19.5 + /- 1.3 mmol/day ) . For all 10 subjects , KHCO3 administration reduced urinary Ca excretion from control by -0.9 + /- 0.7 mmol/day , P less than 0.001 . Net intestinal Ca absorption did not change detectably so that Ca balances became less negative by a + 0.9 + /- 0.9 mmol/day ; P = 0.01 . KHCO3 administration was also accompanied by more positive PO4 and Mg balances .  NaHCO3 administration had no significant effect on urinary Ca excretion or Ca balance .  NaHCO3 and KHCO3 administration were accompanied by equivalently more positive Na or K balances , respectively and equivalently more negative acid balances ( HCO3 retention ) . Neither NaHCO3 or KHCO3 altered fasting serum HCO3 concentrations , blood pH , serum 1,25-(OH)2-D or PTH concentrations . We conclude that KHCO3 promotes more positive Ca balances by either enhancing renal Ca retention or skeletal Ca retention or both Potassium bicarbonate ( KBC ) potently reduces urine calcium excretion in adult humans , including patients with hypertension or calcium urolithiasis , and postmenopausal women . In the latter , who have substantial risk of calcium deficiency , it remains unknown whether the observed short-term urine calcium-lowering effect of KBC persists over years . We studied 170 postmenopausal women r and omized to KBC 30 , 60 , or 90 mmol/d ( KBC treatment ) , or placebo , for up to 36 months . Each received a multivitamin with 400 IU vitamin D , and calcium carbonate as needed to produce a total dietary calcium intake of at least 30 mmol daily . Daily urine calcium excretion ( UCaV ) did not differ among groups at baseline ( all-groups mean + /- SD , 155 + /- 83 mg/d ) . From 1 - 36 months of KBC treatment , adjusting UCaV for creatinine ( Cr ) excretion , each dose of KBC reduced UCaV ( P < 0.01 ) with a dose-dependent trend ( P = 0.05 ) . The reduced UCaV/Cr persisted throughout the KBC treatment period ( up to 36 months ) in all KBC , and the greatest reductions occurred in the subjects with greatest baseline UCaV/Cr ( Delta UCaV/Cr vs. baseline UCaV/Cr ; P < 0.001 ) . Twenty-eight percent of the subjects had high baseline calciuria ( UCaV/Cr > 200 mg Ca/1000 mg Cr ) . With baseline UCaV/Cr of 250 mg/1000 mg Cr , KBC 60 mmol decreased UCaV/Cr by 55.8 mg/1000 mg Cr , a potential daily calcium retention that over a 36-month period would accumulate up to 55,845 mg of calcium , nearly 5 % of bone calcium content . KBC treatment induced a dose-dependent decrease in UCaV/Cr that persisted up to 36 months , with the greatest decreases occurring in those women with the greatest baseline UCaV , nearly a third of whom had high baseline calciuria . Thus , one can preselect postmenopausal women most likely to have the urine calcium-lowering effect of KBC and predict their potential bone calcium increase BACKGROUND Increasing the inorganic phosphorus content of total parenteral nutrition ( TPN ) formulas has been shown to decrease TPN-induced hypercalciuria in experimental animals and humans . The mechanism of this effect , however , has been uncertain . METHODS By using a r and omized cross-over design , seven patients on cyclic TPN  were given otherwise identical formulas providing either 15 or 45 mmol/d of inorganic phosphorus .  Urinary calcium excretion , serum ultrafilterable calcium , filtered calcium load , fractional calcium excretion , urinary cyclic adenosine 5'-monophosphate ( cAMP ) , and serum levels of ionized calcium , parathyroid hormone ( PTH ) , and vitamin D metabolites were determined at the end of each study period . RESULTS Urinary calcium excretion was significantly lower when the patients received the higher inorganic phosphorus formula . Increasing the inorganic phosphorus in the TPN formula did not change ultrafilterable calcium or filtered calcium load , but significantly reduced fractional calcium excretion . No differences in serum levels of ionized calcium , PTH , 25-hydroxyvitamin D , 1,25-dihydroxyvitamin D , or urinary cAMP were observed between treatments . CONCLUSIONS These results demonstrate that increasing the inorganic phosphorus content of the TPN formula decreases urinary calcium excretion by increasing renal tubular calcium resorption . This effect is not due to alterations in the PTH-1,25-dihydroxyvitamin D axis , but likely reflects a direct action of inorganic phosphorus on the renal tubules BACKGROUND The chronic low- grade metabolic acidosis that occurs in various renal disorders and in normal people , and that is related both to dietary net acid load and age-related renal functional decline , may contribute to osteoporosis by increasing urine calcium excretion . Administration of potassium ( K ) alkali salts neutralizes acid and lowers urine calcium excretion . Urine calcium excretion also can be reduced by the administration of thiazide diuretics , which are often given with supplemental K to avoid hypokalemia . We determined whether the K alkali salt potassium bicarbonate ( KHCO3 ) and the thiazide diuretic hydrochlorothiazide ( HCTZ ) combined is more effective in reducing urinary calcium than KHCO3 alone or HCTZ combined with the conventionally coadministered nonalkalinizing K salt potassium chloride ( KCl ) . METHODS Thirty-one healthy men and women aged 50 or greater were recruited for a four-week , double-blind , r and omized study . After a baseline period of 10 days with three 24-hour urine and arterialized blood collection s , subjects were r and omized to receive either HCTZ ( 50 mg ) plus potassium ( 60 mmol daily ) as either the chloride or bicarbonate salt . Another 19 women received potassium bicarbonate ( 60 mmol ) alone . After two weeks , triplicate collection s of 24-hour urines and arterialized bloods were repeated . RESULTS Urinary calcium excretion decreased significantly in all groups . KHCO3 alone and HCTZ + KCl induced similar decreases ( -0.70 + /- 0.60 vs. -0.80 + /- 1 . 0 mmol/day , respectively ) . Compared with those treatments , the combination of HCTZ + KHCO3 induced more than a twofold greater decrease in urinary calcium excretion ( -1.8 + /- 1.2 mmol/day , P < 0 . 05 ) . Both HCTZ + KHCO3 and KHCO3 alone reduced net acid excretion significantly ( P < 0.05 ) to values of less than zero . CONCLUSIONS KHCO3 was superior to KCl as an adjunct to HCTZ , inducing a twofold greater reduction in urine calcium excretion , and completely neutralizing endogenous acid production so as to correct the pre-existing mild metabolic acidosis that an acid-producing diet usually induces in older people . Accordingly , for reducing urine calcium excretion in stone disease and osteoporosis , the combination of HCTZ + KHCO3 may be preferable to that of HCTZ + KCl Although it is generally agreed that both ketogenic and nonketogenic very low calorie diets promote weight reduction , there is no consensus on a preference of one diet over the other in regard to protein sparing . In the present study , we compared the effects of isocaloric ( 600 kcal/d ) and isonitrogenous ( 8 g nitrogen/d ) ketogenic ( low carbohydrate ) and nonketogenic diets on parameters of protein and amino acid metabolism , in 16 morbidly obese women maintained on these diets for 4 weeks while confined to a metabolic ward .  Cumulative urinary nitrogen excretion ( g/4 wk ) was significantly ( P less than .01 ) greater ( 248 + /- 6 v 207 + /- 12 , mean + /- SEM , n = 8) , and cumulative nitrogen balance significantly ( P less than .02 ) more negative ( -50.4 + /- 4.4 v -18.8 + /- 5.7 ) , during treatment with the ketogenic than with the nonketogenic diet . Plasma leucine concentration ( mumol/L ) was significantly higher ( P less than .05 ) during treatment with the ketogenic than with the nonketogenic diet at day 14 ( 210 + /- 17 v 150 + /- 8) , but not at day 28 ( 174 + /- 9 v 148 + /- 8) . Whole-body rates of leucine oxidation ( mmol/h ) were significantly higher ( P less than .05 ) during treatment with the ketogenic than with the nonketogenic diet at day 14 ( 1.29 + /- 0.20 v 0.92 + /- 0.10 ) and at day 28 ( 1.00 + /- 0.16 v 0.75 + /- 0.10 ) . Conversely , proteolysis , as measured by leucine turnover rate and urinary excretion of 3-methylhistidine , was not significantly different between the diets . ( ABSTRACT TRUNCATED AT 250 WORDS Hypokinesia ( diminished movement ) induces significant phosphate ( P ) excretion ; however , little is known about the P deposition ability of the body during hypokinesia ( HK ) . Using P loads , the aim of this study was to establish the deposition ability of the body to retain P during prolonged HK . Studies were done during a 30-d period of pre-HK and a 364-d period of HK . Forty male trained athletes aged 24.7 ± 8.0 yr were chosen as subjects . They were equally divided into four groups : unloaded ambulatory control subjects ( UACS ) , unloaded hypokinetic subjects ( UHKS ) , loaded ambulatory control subjects ( LACS ) , and loaded hypokinetic subjects ( LHKS ) . All hypokinetic subjects were limited to an average walking distance of 0.7 km/d . Loading tests with 85.0 mg of calcium phosphate/kg body weight were performed on the LACS and LHKS.Fecal P loss , urinary calcium ( Ca ) and P loss , serum P , Ca , and the ionized calcium ( CaI ) levels increased significantly ( p≤0.05 ) in the LHKS and UHKS groups when compared with the LACS and UACS groups , respectively . Serum intact parathyroid hormone ( iPTH ) and the 1,25-dihydroxyvitamin D3 [ 1,25-(OH)2 D3 ] levels decreased significantly ( p≤0.05 ) in the LHKS and UHKS groups when compared with the LACS and UACS groups , respectively . After the P load , significant ( p≤0.05 ) differences were observed between LHKS and UHKS groups regarding serum , urinary , and fecal P changes . Thus , the deposition capacity of P decreased significantly ( p≤0.05 ) more in the LHKS group than in the UHKS group . The deposition of P , fecal P , urinary P and Ca , serum CaI , P , Ca , 1,25-(OH)2 D3 , and iPTH changed insignificantly ( p>0.05 ) in control groups when compared with their baseline values . It was shown that after the P load , significant differences were observed between the loaded and unloaded hypokinetic subjects regarding serum , urinary , and fecal P values and P retention . The oral P load intensified P loss from the body . It was concluded that the higher the P intake increased the greater P loss and the lower P deposition and thus the less likely it is for the P load to benefit hypokinetic subjects Objective : In previous studies of the renal response to acute NH 4 Cl acidosis no correlation was found between systemic acid – base status and the traditionally used quantity , renal net acid excretion ( NAE ) . If NAE is to be considered a physiologically meaningful quantity then this is surprising , as the extracellular acid – base status would be expected to be the key physiological trigger for renal NAE . The object of this study was to investigate the renal response to acute non‐carbonic acid loading using a quantitative organ physiological approach . Material and Methods : Five‐h NH 4 Cl loading studies were performed in 10 healthy men using a r and omized , placebo‐controlled , crossover design . Arterialized capillary blood , serum and urine were collected hourly during the loading studies for the measurement of electrolytes and acid – base status . Concentrations of non‐metabolizable base ( NB ) and acid ( NA ) were calculated from measured concentrations of non‐metabolizable ions according to Kildeberg . Results : In the steady state ( placebo ) the rate of renal excretion of NA ( = −NB ) was close to zero , indicating that the net extrarenal input of NA ( endogeneous production , gastrointestinal absorption , skeletal release , etc . ) was likewise about zero . An inverse correlation was found between blood pH and the rate of renal excretion of NA . Only a small amount of the acid load ( ≈8 % ) was excreted during the 5‐h study period and this was accompanied by massive calciuria , indicating that mobilization of NB from bone contributed substantially to the current net extrarenal NA input . Conclusion : From a physiological point of view , NB can be regarded as the actual substrate for renal acid – base control , and measurement of renal turnover of NB may give a more precise description of renal acid – base metabolism during acid loading than previously described methods PURPOSE We evaluated the effect of cranberry juice on urinary stone risk factors . MATERIAL S AND METHODS A total of 12 normal subjects and 12 calcium oxalate stone formers underwent 2 , 7-day phases of study in r and om order while on a controlled metabolic diet . Subjects ingested 1 l of cranberry juice ( CBJ ) daily in 1 phase and 1 l of deionized water in the other phase . On the last 2 days of each phase 2 , 24-hour urine collection s and blood sample s were obtained for stone risk factors and serum chemistries . RESULTS No significant differences were found between normal subjects and stone formers in response to CBJ and , therefore , the groups were combined . CBJ significantly increased urinary calcium ( from 154 to 177 mg per day , p = 0.0008 ) and urinary oxalate ( from 26.4 to 29.2 mg per day , p = 0.04 ) , thereby increasing urinary saturation of calcium oxalate by 18 % . Urinary citrate was unchanged and urinary magnesium increased slightly . Urinary pH decreased ( from 5.97 to 5.67 , p = 0.0005 ) , and urinary ammonium , titratable acidity and net acid excretion increased during CBJ ingestion . Urinary uric acid decreased ( from 544 to 442 mg per day , p < 0.0001 ) as did serum uric acid . Thus , the urinary saturation of brushite and monosodium urate was reduced by CBJ but the amount of undissociated uric acid increased . CONCLUSIONS CBJ exerts a mixed effect on urinary stone forming propensity . It reduces urinary pH likely by providing an acid load and decreases urinary uric acid perhaps by retarding urate synthesis . Overall CBJ increases the risk of calcium oxalate and uric acid stone formation but decreases the risk of brushite stones We measured the impact of diet , anthropometry , physical activity and lifestyle variables on rates of hip bone mineral density ( BMD ) loss  in 470 white men and 474 white women aged 67–79 years at recruitment dwelling in the community . The subjects were recruited from a prospect i ve population -based diet and cancer study ( EPIC-Norfolk ) in Eastern Engl and .  Dietary intake was measured at baseline using 7-day food diaries and used to calculate intakes of some 31 nutrients and 22 food groups . St and ardised question naires were used to collect data on anthropometry , physical activity and lifestyle variables . BMD loss ( percent per annum ; % p.a . ) was measured using dual-energy X-ray absorptiometry performed on two occasions an average of 3 years apart ( range 2–5 years ) . The mean rate of BMD change at the total hip region was −0.17 % p.a . ( SD 1.3 % p.a . ) in men and −0.41 % p.a . ( SD 1.2 % p.a . ) in women . In both men and women , weight gain protected against ( and weight loss promoted ) BMD loss ( P<0.0001 ) . Markers of current physical activity were protective . In men , an increase of 1 l/s in FEV1 was associated with an increase in BMD at an average rate of 0.25 % p.a . ( P=0.013 ) . In women , for every ten trips made per day climbing a flight of stairs , BMD increased at a rate of 0.22 % p.a . ( P=0.005 ) and additionally a 10 % increase in activities of daily living score was associated with BMD increasing at a rate of 0.12 % p.a . ( P=0.011 ) in women . Nutritional variation appeared to have less impact on BMD loss . In men there was no evidence of an effect of any of the nutrients evaluated . However , in women , low intake of vitamin C was associated with faster rate of BMD loss . Women in the lowest tertile ( 7–57 mg/day ) of vitamin C  intake lost BMD at an average rate of −0.65 % p.a . , which was significantly faster compared to loss rates in the middle ( 58–98 mg/day ) and upper ( 99–363 mg/day ) tertiles of intake , which were −0.31 % p.a . and −0.30 % p.a . , respectively ( P=0.016 ) . There was no effect of fruits and vegetables , combined or separately , on rate of BMD loss . The results confirm that weight maintenance ( or gain ) and commonly practice d forms of physical activity appear to protect against BMD loss in this age group . Measures such as ensuring good general nutrition to guard against weight loss in the non-overweight elderly and maintenance of physical fitness could be valuable in protecting against BMD loss . The protective effect of vitamin C in women needs to be further investigated in other prospect i ve cohort or intervention studies Hypercalciuria and osteopenic bone disease have been identified in many of the patients maintained on long-term total parenteral nutrition ( TPN )  , but the causes ofthe disturbance in calcium balance have not yet been determined . We suggest that the increased sulfate burden experienced when TPN is instituted may be one of those causes . We found substantially increased sulfur amino acid and inorganic sulfate ( 42 to 54 moh/l00 ml of total sulfur ) contents in a commercially available amino acid solution . Administration of TPN to a group of premature newborns result ed in elevated serum sulfate Ifrom 408 ± 54 � amol/l ( mean ± SE , n = 7 ) to 731 ± 99 amol/l ( n = 4 ) ) and increased calcium excretion ( from 26 ± 17 to 86 ± 13 amoh/kg body weight per day ) . Supplemental cysteine ( 0.5 mmol/kg/day ) provoked a further increase in serum sulfate ( 1182 ± 168 � amol/l , n = 9 ) and urinary calcium excretion ( 158 ± 64 � amol/kg/day).In a group of eight infants receiving both TPN and TPN + cysteine , sulfate excretion increased from 1113 ± 106 to 1584 ± 75 � amol/kg/day , while calcium loss increased from 149 ± 40 to 252 ± 26 � amol/kg/day . The possible association of hypersulfatemia , hypercalciuria , and TPN-associated bone disease merits further attention . Am J Clin Nutr l983;37:l08-l13 Inverse associations between fruit and vegetable consumption and  lung cancer risk have been consistently reported . However , identifying the specific fruits and vegetables associated with lung cancer is difficult because the food groups and foods evaluated have varied across studies . We analyzed fruit and vegetable groups using st and ardized exposure and covariate definitions in 8 prospect i ve studies . We combined study -specific relative risks ( RRs ) using a r and om effects model . In the pooled data base , 3,206 incident lung cancer cases occurred among 430,281 women and men followed for up to 6 - 16 years across studies . Controlling for smoking habits and other lung cancer risk factors , a 16 - 23 % reduction in lung cancer risk was observed for quintiles 2 through 5 vs. the lowest quintile of consumption for total fruits ( RR = 0.77 ; 95 % CI = 0.67 - 0.87 for quintile 5 ; p-value , test for trend < 0.001 ) and for total fruits and vegetables ( RR = 0.79 ; 95 % CI = 0.69 - 0.90 ; p-value , test for trend = 0.001 ) . For the same comparison , the association was weaker for  total vegetable consumption  ( RR = 0.88 ; 95 % CI = 0.78 - 1.00 ; p-value , test for trend = 0.12 ) . Associations were similar between never , past , and current smokers . These results suggest that elevated fruit and vegetable consumption is associated with a modest reduction in lung cancer risk , which is mostly attributable to fruit , not vegetable , intake . However , we can not rule out the possibility that our results are due to residual confounding by smoking . The primary focus for reducing lung cancer incidence should continue to be smoking prevention and cessation CONTEXT Protein is an essential component of muscle and bone . However , the acidic byproducts of protein metabolism may have a negative impact on the musculoskeletal system , particularly in older individuals with declining renal function . OBJECTIVE We sought to determine whether adding an alkaline salt , potassium bicarbonate ( KHCO3 ) , allows protein to have a more favorable net impact on intermediary indices of muscle and bone conservation than it does in the usual acidic environment . DESIGN We conducted a 41-d r and omized , placebo-controlled , double-blind study of KHCO3 or placebo with a 16-d phase-in and two successive 10-d metabolic diets containing low ( 0.5 g/kg ) or high ( 1.5 g/kg ) protein in r and om order with a 5-d washout between diets . SETTING The study was conducted in a metabolic research unit . PARTICIPANTS Nineteen healthy subjects ages 54 - 82 yr participated . INTERVENTION KHCO3 ( up to 90 mmol/d ) or placebo was administered for 41 d. MAIN OUTCOME MEASURES We measured 24-h urinary nitrogen excretion , IGF-I , 24-h urinary calcium excretion , and fractional calcium absorption . RESULTS KHCO3 reduced the rise in urinary nitrogen excretion that accompanied an increase in protein intake ( P = 0.015 ) and was associated with higher IGF-I levels on the low-protein diet ( P = 0.027 ) with a similar trend on the high-protein diet ( P = 0.050 ) . KHCO3 was also associated with higher fractional calcium absorption on the low-protein diet ( P = 0.041 ) with a similar trend on the high-protein diet ( P = 0.064 ) . CONCLUSIONS In older adults , KHCO3 attenuates the protein-induced rise in urinary nitrogen excretion , and this may be mediated by IGF-I. KHCO3 may also promote calcium absorption independent of the dietary protein content UNLABELLED The role of protein intake in osteoporosis is unclear . In a case-control study in Utah ( n = 2501 ) , increasing level of protein intake was associated with a decreased risk of hip fracture in men and women 50 - 69 years of age but not in those 70 - 89 years of age . Protein intake may be important for optimal bone health . INTRODUCTION Protein is an important component of bone , but the role of dietary protein intake in osteoporosis and fracture risk remains controversial . MATERIAL AND METHODS The role of dietary protein intake in osteoporotic hip fracture was evaluated in a statewide case-control study in Utah . Patients , 50 - 89 years of age , with hip fracture ( cases ) were ascertained through surveillance of 18 Utah hospitals during 1997 - 2001 . Age- and gender-matched controls were r and omly selected . Participants were interviewed in their place of residence , and diet was assessed using a picture-sort food frequency question naire previously reported to give a useful measure of usual dietary intake in the elderly Utah population . The association between  protein intake  and risk of hip fracture was examined across quartiles of protein intake and stratified by age group for 1167 cases ( 831 women , 336 men ) and 1334 controls ( 885 women , 449 men ) . RESULTS In logistic regression analyses that controlled for gender , body mass index , smoking status , alcohol use , calcium , vitamin D , potassium , physical activity , and estrogen use in women , the odds ratios ( OR ) of hip fracture decreased across increasing quartiles of total protein intake for participants 50 - 69 years of age ( OR : 1.0 [ reference ] ; 0.51 [ 95 % CI : 0.30 - 0.87 ] ; 0.53 [ 0.31 - 0.89 ] ; 0.35 [ 0.21 - 0.59 ] ; p < 0.001 ) . No similar associations were observed among participants 70 - 89 years of age . Results from analyses stratified by low and high calcium and potassium intake did not differ appreciably from the results presented above . CONCLUSION Higher total protein intake was associated with a reduced risk of hip fracture in men and women 50 - 69 years of age but not in men and women 70 - 89 years of age . The association between  dietary protein intake  and risk of hip fracture may be modified by age . Our study supports the hypothesis that adequate dietary protein is important for optimal bone health in the elderly 50 - 69 years of age It is well known that the intestinal availability of Ca from Ca-rich mineral waters is equivalent to that of milk Ca . However , the effect of associated anions on Ca urinary loss needs to be addressed . The aim of the current study was to compare , under ordinary conditions of consumption , milk and a SO4-rich mineral water as the Ca provider in a large number of subjects consuming the same quantity of Ca from the two sources in a crossover study lasting for an extended period . Thirty-seven healthy women completed a 12-week protocol , divided into four periods of 3 weeks ( W ) . In the first ( W1 - 3 ) and third ( W6 - 9 ) periods , dietary Ca intake was restricted to 600 mg/d . In the second ( W4 - 6 ) and final ( W10 - 12 ) periods , either 400 ml/d medium-fat milk or 1 litre of a Ca- and SO4-rich mineral water , each providing about 480 mg Ca/d , was added to the diet in a r and om manner . Dietary evaluation , blood and urinary measures were performed during the last week ( W6 and W12 ) of each Ca supplementation period . The urinary excretion of Ca was higher ( 0.5 mmol/d more ) with water than with milk ( P<0.001 ) . An examination of all the dietary factors known to influence calciuria suggested that the acidogenic action of SO4 was responsible for this increased calciuria . Thus , despite an equal Ca intake and assuming an unchanged intestinal absorption , these results suggest that Ca balance is better with milk consumption than with CaSO4-rich water Chronic acid loads are an obligate consequence of the high animal/grain protein content of the Western diet . The effect of this diet-induced metabolic acidosis on bone mass is controversial . In a r and omized , prospect i ve , controlled , double-blind trial , 161 postmenopausal women ( age 58.6 + /- 4.8 yr ) with low bone mass ( T score -1 to -4 ) were r and omly assigned to 30 mEq of oral potassium ( K ) citrate ( Kcitrate ) or 30 mEq of K chloride ( KCl ) daily . The primary end point was the intergroup difference in mean percentage change in bone mineral density ( BMD ) at lumbar spine ( L2 through L4 ) after 12 mo . Compared with the women who received KCl , women who received Kcitrate exhibited an intergroup increase in BMD ( + /-SE ) of 1.87 + /- 0.50 % at L2 through L4 ( P < 0.001 ) , of 1.39 + /- 0.48 % ( P < 0.001 ) at femoral neck , and of 1.98 + /- 0.51 % ( P < 0.001 ) at total hip . Significant secondary end point intragroup changes also were found : Kcitrate increased L2 through L4 BMD significantly from baseline at months 3 , 9 , and 12 and reached a month 12 increase of 0.89 + /- 0.30 % ( P < 0.05 ) , whereas the KCl arm showed a decreased L2 through L4 BMD by -0.98 + /- 0.38 % ( P < 0.05 ) , significant only at month 12 . Intergroup differences for distal radius and total body were NS . The Kcitrate-treated group demonstrated a sustained and significant reduction in urinary calcium excretion and a significant increase in urinary citrate excretion , with increased citrate excretion indicative of sustained systemic alkalization . Urinary bone resorption marker excretion rates were significantly reduced by Kcitrate , and for deoxypyridinoline , the intergroup difference was significant . Urinary net acid excretion correlated inversely and significantly with the change in BMD in a subset of patients . Large and significant reductions in BP were observed for both K supplements during the entire 12 mo . Bone mass can be increased significantly in postmenopausal women with osteopenia by increasing their daily alkali intake as citrate , and the effect is independent of reported skeletal effects of Effects of potassium citrate therapy ( 60 mEq/day ) on urinary chemistries and crystallization were compared to those of sodium citrate treatment in five patients with uric acid lithiasis . Both alkali treatments significantly increased urinary pH ( P less than 0.001 ) , from 5.35 + /- 0.18 SD to 6.68 + /- 0.14 for potassium citrate and 6.73 + /- 0.20 for sodium citrate . During potassium citrate therapy , urinary calcium significantly declined from 154 + /- 47 mg/day to 99 + /- 23 mg/day ( P less than 0.01 ) and urinary citrate rose from 398 + /- 119 mg/day to 856 + /- 103 mg/day ( P less than 0.001 ) . The urinary saturation ( activity product ratio ) of calcium oxalate decreased from 3.21-fold to 1.69-fold saturation ( P less than 0.01 ) , and the inhibitor activity against calcium oxalate precipitation ( formation product ratio ) significantly increased . However , sodium citrate therapy did not significantly decrease urinary calcium ( to 139 + /- 24 mg/day ) , although it increased urinary citrate substantially ( to 799 + /- 89 mg/day , P less than 0.01 ) . Urinary environment became supersaturated with respect to brushite ( calcium phosphate ) and monosodium urate . The inhibitor activity against calcium oxalate precipitation was not significantly altered for the whole group ; in two patients , it decreased by more than 30 % . The results indicate that ( 1 ) both alkali therapies are equally effective in preventing uric acid stone formation because of their ability to increase urinary pH , and ( 2 ) potassium citrate may prevent the complication of calcium nephrolithiasis in patients with uric acid stones , whereas sodium citrate may not Currently there is no consensus on the impact of dietary protein on calcium and bone metabolism . This study was conducted to examine the effect of increasing protein intake on urinary calcium excretion and to compare circulating levels of IGF-I and biochemical markers of bone turnover in healthy older men and women who consumed either a high or a low protein food supplement for 9 wk . Thirty-two subjects with usual protein intakes of less than 0.85 g/kg.d were r and omly assigned to daily high ( 0.75 g/kg ) or low ( 0.04 g/kg ) protein supplement groups . Isocaloric diets were maintained by advising subjects to reduce their intake of carbohydrates . Selected biochemical measurements were made at baseline and on d 35 and either d 49 or 63 . Changes in urinary calcium excretion in the two groups did not differ significantly over the course of the study . The high protein group had significantly higher levels of serum IGF-I ( P = 0.008 ) and lower levels of urinary N-telopeptide ( P = 0.038 ) over the period of d 35 - 49 or 63 . We conclude that increasing protein intake from 0.78 to 1.55 g/kg.d with meat supplements in combination with reducing carbohydrate intake did not alter urine calcium excretion , but was associated with higher circulating levels of IGF-I , a bone growth factor , and lowered levels of urinary N-telopeptide , a marker of bone resorption . In contrast to the widely held belief that increased protein intake results in calcium wasting , meat supplements , when exchanged isocalorically for carbohydrates , may have a favorable impact on the skeleton in healthy older men and women Calcium , in the form of regular food supplementation , can improve bone metabolism , but it can also increase the risk for renal calcium stones , and may aggravate pre-existing calcium urolithiasis . To study the first of these two aspects , ten healthy volunteers were given a conventional test meal ( breakfast ; calcium content 28 mg ) with or without two dosages of calcium ( as calcium-sodium citrate , CSC 1 , 680 mg ; CSC 2 1,360 mg ) , taken after an overnight 12 h fast . To study the latter aspect , patients with idiopathic recurrent calcium urolithiasis ( ICU ) received a balanced test meal of fixed composition , containing 1,000 mg calcium either as CSC ( Meal + CSC3 ; n = 6 ) or as calcium gluconate ( Mcal ; n = 8) . In normals , CSC induced a dose-dependent increasing intestinal absorption of calcium , and a decrease in oxalate absorption ; in serum , CSC  increased calcitonin and suppressed parathyroid hormone , but left unchanged the markers of bone turnover , serum osteocalcin and bone alkaline phosphatase . In urine ,  CSC decreased bone resorption markers ( collagen crosslinks ) and phosphaturia increased citrate , created signs of metabolic alkalosis , and inhibited several parameters of CaOx crystallization . In ICU , the CSC3 load failed to promote the crystallization of CaOx and calcium phosphate . It was concluded that CSC supplementation of a meal : ( 1 ) is well tolerated by healthy subjects and ICU patients , renders calcium highly available to bone , and prevents post-pr and ial oxaluria from rising ; and , ( 2 ) is followed by the inhibition of crystallization of renal stone forming calcium-containing substances . Long-term studies aim ed at evaluating the usefulness of CSC in preserving healthy bone , and in the metaphylaxis of renal stones would appear justified A quarter century has passed since the first publication of the evolutionary discordance hypothesis , according to which departures from the nutrition and activity patterns of our hunter-gatherer ancestors have contributed greatly and in specifically definable ways to the endemic chronic diseases of modern civilization . Refinements of the model have changed it in some respects , but anthropological evidence continues to indicate that ancestral human diets prevalent during our evolution were characterized by much lower levels of refined carbohydrates and sodium , much higher levels of fiber and protein , and comparable levels of fat ( primarily unsaturated fat ) and cholesterol . Physical activity levels were also much higher than current levels , result ing in higher energy throughput . We said at the outset that such evidence could only suggest testable hypotheses and that recommendations must ultimately rest on more conventional epidemiological , clinical , and laboratory studies . Such studies have multiplied and have supported many aspects of our model , to the extent that in some respects , official recommendations today have targets closer to those prevalent among hunter-gatherers than did comparable recommendations 25 years ago . Furthermore , doubts have been raised about the necessity for very low levels of protein , fat , and cholesterol intake common in official recommendations . Most impressively , r and omized controlled trials have begun to confirm the value of  hunter-gatherer diets  in some high-risk groups , even as compared with routinely recommended diets . Much more research needs to be done , but the past quarter century has proven the interest and heuristic value , if not yet the ultimate validity , of the model Fracture of the proximal femur is the most dramatic clinical sequela of osteoporosis [ 1 , 2 ] . It is associated with a high mortality rate , need for long-term medical care , and prolonged disability [ 3 - 5 ] . Protein malnutrition is often seen in elderly persons and is more severe in patients with hip fracture [ 6 - 11 ] . Protein deficiency may contribute to the occurrence of hip fracture by reducing muscle strength , impairing movement coordination , and diminishing the protective layer of soft tissue padding [ 9 , 10 , 12 - 14 ] It may also be associated with lower bone mineral density at the proximal femur [ 15 ] . Furthermore , malnutrition in general and protein deficiency in particular at admission and during recovery may adversely influence clinical outcome after hip fracture [ 7 , 9 , 10 , 16 - 18 ] . Protein restriction has been shown to reduce plasma levels of insulin-like growth factor-I ( IGF-I ) by inducing resistance to the action of growth hormone in the liver and increasing the metabolic clearance rate of the growth factor [ 19 - 23 ] . Furthermore , evidence shows that protein depletion may blunt the effect of IGF-I on target organs [ 20 ] . Thus , low protein intake in elderly persons may be detrimental to skeletal integrity , muscle strength , and immune response [ 11 , 24 - 27 ] because of decreased production and action of IGF-I , which favorably influences these systems [ 28 - 33 ] . Previous studies [ 16 , 17 ] have shown that a 5-week course of protein supplements can reduce the medical complication rate and duration of hospital stay in patients with recent hip fracture . These findings were independent of energy , calcium , and vitamin D intake [ 17 ] . Whether these observations were related to the restoration of decreased IGF-I levels and whether bone may benefit from long-term protein supplementation are not known . We investigated whether protein supplements in vitamin D-replete patients with a recent hip fracture who were receiving calcium supplements could increase circulating IGF-I levels and favorably influence bone mineral density . Methods Patients Patients were recruited in the orthopedic ward of Geneva University Hospital , the referral center that receives 94.6 % of all patients with hip fracture from an area with a population of approximately 400 000 persons [ 5 ] . The protocol was approved by the ethical committee of the Geneva University Hospital Department of Surgery . Inclusion criteria were age greater than 60 years ; recent hip fracture ( within 2 weeks ) attributable to osteoporosis ( that is , a fracture after a minor trauma , such as a fall from st and ing height ) ; and the ability to give written , informed consent . Exclusion criteria were pathologic fracture ; fracture caused by severe trauma ; history of contralateral hip fracture ; severe mental impairment ; active metabolic bone disease ; renal failure ( plasma creatinine concentration 200 mol/L ) ; acute illness that could interfere with the study protocol ; severe malnutrition ( serum albumin level < 15 g/L ) ; consumption of drugs known to alter bone metabolism , such as calcitonin , fluoride , sex hormones , corticosteroids , or bisphosphonates ; and life expectancy of less than 1 year . Using a r and om number table , we assigned patients to receive an oral protein supplement composed of 90 % milk proteins or a placebo made isocaloric by the addition of maltodextrins . Patients took the assigned intervention 5 days a week for 6 months in addition to their regular diet . All patients received one oral dose of vitamin D3 , 200 000 IU ( vitamine D3B.O.N. , Doms-Adrian , Courbevoie , France ) , to correct any possible vitamin D deficiency [ 34 ] . The daily protein supplement ( Meritene , S and oz Nutrition Ltd. , Berne , Switzerl and ) provided 1050 kJ ( 250 kcal ) of energy in the form of 20 g of proteins , 3.1 g of lipids , and 35.7 g of carbohydrates ( 54.4 g in placebo ) . The other constituents of the 65 g powder supplement were vitamin A ( 1000 IU ) , vitamin K1 ( 30 g ) , vitamin C ( 20 mg ) , calcium ( 550 mg ) , magnesium ( 91 mg ) , phosphorus ( 429 mg ) , and sodium ( 228 mg ) . The supplement is design ed to normalize but not overcompensate for the insufficient dietary intake of protein of elderly persons with a recent fracture of the proximal femur [ 16 ] . Compliance was verified by weekly phone calls and by counting the remaining nutritional supplement bags , which were forwarded monthly by mail . Clinical Data Medical history , clinical characteristics , anthropometric data , and performance status according to an Activities of Daily Living score [ 35 ] were evaluated . Dietary intakes were recorded by using a food-frequency question naire [ 36 ] about the week before the fracture . Food intakes were analyzed by using a nutrient software system ( Fruitdor , Astra-Calve , Paris , France ) . Dietary intake of calcium , phosphorus , and protein was calculated from intake of dairy products , meat , fish , and vegetables . Because many patients were unable to st and a few days after hip fracture , their height was determined with a fathom measure while they were recumbent . Body weight was determined with a scale that correlated highly with that provided by measurement of whole body bone , fat , and lean mass as assessed by dual x-ray absorptiometry [ 37 ] . Mid-arm circumference was measured with a tape measure ( coefficient of variation , 2 % ) . Isometric muscle strength of the biceps of the dominant arm was evaluated with a dynamometer ( Lido , Lidoactive Isokinetic System , Loredan Biomedical Inc. , West Sacramento , California ) , which measures the peak torque ( coefficient of variation < 5 % ) . The grip strength of the same arm was measured with a dynamometer ( Vigorimeter , Martin Medizin-Technik , Tuttlingen , Germany ) [ 38 ] . The mean of three measurements was used for calculation . Biochemical Data Within 120 hours after surgery , we used st and ard methods to analyze venous blood sample s for protein-corrected plasma levels of calcium , phosphate , creatinine , total proteins , albumin , and prealbumin . We also measured levels of IGF-I ( Nichols Institute , San Juan Capistrano , California ) after acid-ethanol extraction and cryoprecipitation [ 39 ] , intact parathyroid hormone ( Immulite , Diagnostic Products , Los Angeles , California ) , calcitriol , calcidiol ( Incstar , Stillwater , Minnesota ) , and osteocalcin ( CIS-BIO International , Gif-sur-Yvette , France ) . Biochemical measurements were repeated 6 and 12 months after the fracture . Serum IGF-I binding proteins were measured by Western lig and blot analysis [ 40 ] . Briefly , 3 L of serum was boiled and separated onto 15 % sodium dodecylsulfate polyacrilamide gel electrophoresis under nonreducing conditions . Proteins were electrically blotted onto a nitrocellulose membrane , and IGF-I binding proteins were detected after incubating the membranes with radioiodinated IGF-I at 4C for 24 hours . Insulin-like growth factor binding proteins were quantified by phosphorimaging ( Molecular Dynamics , Sunnyvale , California ) . The intensity of the b and s corresponding to the appropriate molecular weights [ 40 ] was expressed as the percentage of total bound radioactive IGF-I. Measurements of calcium , phosphate , and creatinine were obtained from the second fasting morning urine . The ratio of hydroxyproline to creatinine in the same sample was taken as a reflection of bone resorption . Markers of bone resorption ( pyridinoline and deoxypyridinoline ) in the first morning spot urine were measured by detecting fluorescence emission after acid hydrolysis and separation with isocratic reverse-phase high-performance liquid chromatography ( BioRad System , Munich , Germany ) , and the values were adjusted to the creatinine concentration . Immunologic Data Concentrations of IgA , IgG , IgM , and isohemagglutinins were measured by using st and ard methods . Cell-mediated immunity was assessed by using a skin-test antigens for cellular hypersensitivity system ( STACH , Institut Merieux , Lyon , France ) , which evaluates the size of the skin reaction to various antigens injected intradermally [ 41 ] . Bone Mass Assessment We measured areal bone mineral density at the lumbar spine ( anteroposterior and lateral views ) , the contralateral proximal femur ( femoral neck and trochanter ) , and the contralateral mid-femoral shaft . We also measured whole-body bone mineral content , fat , and lean mass by using dual x-ray absorptiometry ( Hologic QDR-2000 , Waltham , Massachusetts ) . The coefficients of variation of these measurements are reported elsewhere [ 37 , 42 ] . Vertebral Deformity Two series of lateral radiography of the thoracic and lumbar spine were taken at the start of the study and at 12 months . The films were examined by a single investigator ( who was unaware of treatment group assignment ) according to a 6-point analysis procedure for each vertebral body from T4 to L4 [ 43 , 44 ] ( intra-observer coefficient of variation , 1.8 % to 3.1 % ) . At baseline , fracture was defined by a decrease of 20 % in the ratio of anterior or middle height to posterior height . Patients were considered to have a new vertebral deformity if the anterior , middle , or posterior height decreased by more than 20 % between the two examinations . Statistical Analysis All values are given as the mean SD for baseline measurement and the mean SE for comparisons of outcome results . All analyses were performed by using the SAS procedure ( Cary , North Carolina ) . One-way analysis of variance was used . A two-tailed P value less than 0.05 was considered significant . Role of the Funding Sources This study was supported by grants from S and oz Nutrition Ltd. , Berne , Switzerl and , and the Swiss National Research Science Foundation . The skin-test antigens for cellular hypersensitivity system was supplied by Rhone-Poulenc , Thalwil , Switzerl and . No organization influenced the design , conduct , or reporting of the study . Results Of 842 patients evaluated from April 1992 to February 1994 , 82 were recruited into the r and omized , double-blind , placebo-controlled trial . This low enrollment rate was due to patients ' poor medical or cognitive conditions and reluctance to give informed consent . We studied the effects of a single oral phosphate ( Pi ) dose as well as those of three consecutive oral phosphate doses on calcium and bone metabolism . In the first part of the study ( P1 study ) 10 female volunteers were given orally 1500 mg of Pi in water , as a single dose , or plain water in r and omized order at two different sessions . In the second part of the study ( P3 study ) , 10 female volunteers were given orally 1500 mg of Pi , as three separate 500 mg doses in water , or plain water in r and omized order . Calcium and bone metabolism was monitored for 24 h by measuring the concentrations of serum ionized calcium ( S-iCa ) , urinary calcium , serum phosphate ( S-P ) , urinary P , serum intact parathyroid hormone ( PTH ) , serum carboxy-terminal propeptide of type I collagen ( PICP ) , serum osteocalcin ( BGP ) , serum carboxy-terminal telopeptide of type I collagen ( ICTP ) , urine deoxypyridinoline ( DPD ) and bone-specific alkaline phosphatase activity ( B-ALP ) . The S-P increased ( p = 0.00005 and p = 0.0005 , in the P1 and P3 studies , respectively ) , the S-iCa concentration declined significantly only in the P1 study ( p = 0.0014 ) , the urinary calcium excretion decreased ( p = 0.02 and 0.013 , in the P1 and P3 studies , respectively ) , and the PTH concentration rose ( p = 0.0083 and p = 0.014 , in the P1 and P3 studies , respectively ) during the phosphate experiment as compared with the control session . Of the three markers of bone formation studied , PICP declined in the P1 study ( p = 0.04 ) , and B-ALP declined in both parts of the study ( p = 0.027 , p = 0.026 , in the P1 and P3 studies , respectively ) after phosphate administration , whereas there was no significant change in BGP in either of the studies . The markers of bone resorption , ICTP and DPD , were unaffected by the phosphate load in both studies . In conclusion , acute ingestion of phosphate leads to an increase in S-P , a decrease in S-iCa , and an increase in intact PTH secretion . Our results indicate that these events may lead to an acute inactivation of the early phases of bone formation . In this setting , there was no indication of enhanced bone resorption despite the increase in PTH secretion , which could be due to the combined effect of phosphate and PTH on bone resorption The amount of sodium chloride in the diet of industrialized nations far exceeds physiological requirements . The impact of abundant dietary salt on skeletal health has yet to be established , but is potentially detrimental through increased urinary calcium losses . We examined the effect of increased dietary sodium chloride on urine calcium excretion and bone turnover markers in postmenopausal women and , further , whether potassium citrate attenuates the effects of increased dietary salt . Postmenopausal women ( n = 60 ) were adapted to a low-salt ( 87 mmol/d sodium ) diet for 3 wk , then r and omized to a high-salt ( 225 mmol/d sodium ) diet plus potassium citrate ( 90 mmol/d ) or a high-salt diet plus placebo for 4 wk . Urine calcium , urine N-telopeptide , urine cAMP , serum osteocalcin , and fasting serum PTH were measured at the end of the low- and high-salt diets . On the high salt plus placebo diet , urine calcium increased 42 + /- 12 mg/d ( mean + /- SEM ) , but decreased 8 + /- 14 mg/d in the high salt plus potassium citrate group ( P = 0.008 , potassium citrate vs. placebo , unpaired t test ) . N-telopeptide increased 6.4 + /- 1.4 nanomoles bone collagen equivalents per millimole creatinine in the high salt plus placebo group and 2.0 + /- 1.7 nanomoles bone collagen equivalents per millimole creatinine in the high salt plus potassium citrate group ( P < 0.05 , potassium citrate vs. placebo , unpaired t test ) . Osteocalcin , PTH , and cAMP were not significantly altered . The addition of oral potassium citrate to a high-salt diet prevented the increased excretion of urine calcium and the bone resorption marker caused by a high salt intake . Increased intake of dietary sources of potassium alkaline salts , namely fruit and vegetables , may be beneficial for postmenopausal women at risk for osteoporosis , particularly those consuming a diet generous in sodium chloride We sought to determine if the high phosphorus , moderately low calcium intake typical of U.S. teenagers and young adults alters parathyroid function as it does in experimental animals . Because those animals ultimately developed osteopenia , it has been suggested that low dietary calcium to phosphorus ratios may reduce peak bone mass and increase susceptibility to osteoporotic fracture later in life . However , it is not known whether PTH secretion or action increases in response to commonly consumed phosphorus-rich , calcium-poor foods . We studied the 24-h mineral and hormonal responses of eight men and eight women , aged 18 - 25 yr , after 8 days of ingesting a control diet that had calcium ( 820 mg ) and phosphorus ( 930 mg ) contents near the recommended daily intakes , and a test diet with calcium and phosphorus contents ( 1660 mg phosphorus , 420 mg calcium ) typical of current intakes . Both diets were made from common grocery store foods . The 24-h mean serum immunoreactive PTH levels increased in men ( 11 % ; P less than 0.006 ) and women ( 22 % ; P less than 0.003 ) during the test diet . In both sexes , the test diet significantly increased serum phosphorus , plasma 1,25-dihydroxyvitamin D , and urinary hydroxyproline and cAMP excretion ; in women only it decreased serum ionized and total calcium levels . Thus , short term ingestion of a diet typifying current levels of calcium and phosphorus intake result ed in elevated serum iPTH levels and indexes of PTH action in young adults Abstract Five obese women were fed for six successive 5-day periods 400 kcal from single energy sources and 800 kcal combinations of these . At 400 kcal/day , ketosis was least with carbohydrate and greatest with fat as the diet . Four hundred kcal exogenous protein per day , without any other dietary energy source , was found to reduce the degree of ketosis . The addition of 400 kcal exogenous carbohydrate to 400 kcal protein was found effectively to prevent the development of ketosis in the obese , but addition of 400 kcal as fat was not beneficial . As has been previously observed , serum uric acid was found to rise and urinary uric acid to fall in obese subjects on lowcalorie , high-fat diets . A low-calorie , high-carbohydrate diet had the reverse effect . Loss of weight , sodium , and potassium was much greater with diets based on fat than on carbohydrate . Four hundred kcal carbohydrate per day had a greater protein-sparing effect than 400 kcal fat per day in obese women . There appeared to be adaptation to continued low-calorie intake , evidence d by progressively less negative nitrogen balances in successive periods . In the last period , one subject maintained positive balance with only 400 kcal , as protein . We conclude that carbohydrate is necessary in the diet to prevent ketosis and loss of cations , to spare tissue protein and to promote adequate clearance of uric acid , when endogenous fat is the chief source of energy . Exogenous protein can fulfill part of this function , but it is less effective than carbohydrate at equivalently low calorie intakes OBJECTIVE To compare the effects of 2 drinking waters containing similar calcium ( Ca ) concentration in order to analyze the role of ions other than Ca on bone metabolism . These mineral drinking-waters differed by their mineral composition primarily concerning the concentration of bicarbonate ( HCO3- ) , high in the HB , and sulfate , high in HS water . DESIGN Of 60 included women , 39 completed the study . Patients were r and omly assigned to an intake of 1 liter per day of mineral water HB or HS for 28 d , followed by cross-over to the alternative drinking-water for a further 28 d. At baseline and after each period of one month , Ca metabolism parameters , acid-base status , and bone remodeling markers were measured . RESULTS Changes in Ca metabolism were significant in the HB group where the ionized Ca increased and the PTH decreased . Serum pH showed a similar increase whatever the used drinking water compared to baseline . In the HB group , significant increase in urine pH , and significant decrease in AT-HCO3- and NH4 + were observed . Bone resorption markers , urinary CTx/Cr , Pyr/Cr , and D-Pyr/Cr , significantly decreased in the HB group compared to baseline , and were not significantly modified in the HS group . CONCLUSIONS These results showed a beneficial effect of the bicarbonaterich HB water on bone metabolism . This may account for a better bioavailability of the Ca , a greater alkalinization , and a larger decrease in PTH level secondary to a higher ionized Ca level . The higher content of silica in HB water may have also participated to the positive action on bone balance that was observed . In this short term study , these data underlined the potential role of the mineral drinking water composition on bone metabolism
target: Urine calcium excretion rates were consistent with osteoporosis development ; however calcium balance studies did not demonstrate loss of whole body calcium with higher net acid excretion .
  No study revealed a biologic mechanism functioning at physiological pH. Finally , r and omized studies did not provide evidence for an adverse role of phosphate , milk , and grain foods in osteoporosis .
  Conclusions A causal association between dietary acid load and osteoporotic bone disease is not supported by evidence and there is no evidence that an alkaline diet is protective of bone health
background: Background Modern diets have been suggested to increase systemic acid load and net acid excretion .
  In response , alkaline diets and products are marketed to avoid or counteract this acid , help the body regulate its pH to prevent and cure disease .
  The objective of this systematic review was to evaluate causal relationships between dietary acid load and osteoporosis using Hill 's criteria .