title: Combined Calcium and Vitamin D3 Supplementation in Elderly Women: Confirmation of Reversal of Secondary Hyperparathyroidism and Hip Fracture Risk: The Decalyos II Study Spinal bone loss in postmenopausal women supplemented with calcium and trace minerals. Bone mineral density and bone markers in patients with a recent low-energy fracture: effect of 1 y of treatment with calcium and vitamin D. Effect of calcium supplementation on forearm bone mineral content in postmenopausal women: a prospective, sequential controlled trial. The Effect of Calcium and Vitamin D3 Supplementation on the Healing of the Proximal Humerus Fracture: A Randomized Placebo-Controlled Study Peripheral computed tomography (pQCT) detected short-term effect of AAACa (heated oyster shell with heated algal ingredient HAI): A double-blind comparison with CaCO3 and placebo Acute and 3-month effects of microcrystalline hydroxyapatite, calcium citrate and calcium carbonate on serum calcium and markers of bone turnover: a randomised controlled trial in postmenopausal women. Inhibition of bone turnover by milk intake in postmenopausal women. Does calcium supplementation prevent postmenopausal bone loss? A double-blind, controlled clinical study. Prophylaxis of osteoporosis with calcium, estrogens and/or eelcatonin: comparative longitudinal study of bone mass. Calcium Supplementation with and without Hormone Replacement Therapy To Prevent Postmenopausal Bone Loss The effect of calcium citrate on bone density in the early and mid-postmenopausal period: a randomized placebo-controlled study. Effects of calcium and vitamin D supplementation on hip bone mineral density and calcium-related analytes in elderly ambulatory Australian women: a five-year randomized controlled trial. Bone mineral content in women with Colles' fracture: effect of calcium supplementation. Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial. The effects of calcium supplementation and exercise on bone density in elderly Chinese women Effect of low-dose calcium supplements on bone loss in perimenopausal and postmenopausal Asian women: a randomized controlled trial. Bone mineral density in postmenopausal Chinese women treated with calcium fortification in soymilk and cow's milk Preventing postmenopausal bone loss with ossein-hydroxyapatite compounds. Results of a two-year, prospective trial. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Principal results from the Women's Health Initiative randomized controlled trial Increase of bone mineral density by calcium supplement with oyster shell electrolysate. Two-year randomized controlled trial of vitamin K1 (phylloquinone) and vitamin D3 plus calcium on the bone health of older women. Calcium- and vitamin D3-fortified milk reduces bone loss at clinically relevant skeletal sites in older men: a 2-year randomized controlled trial. Supplementation with oral vitamin D3 and calcium during winter prevents seasonal bone loss: a randomized controlled open-label prospective trial. Effect of calcium or 25OH vitamin D3 dietary supplementation on bone loss at the hip in men and women over the age of 60. Effects of a multi-component exercise program and calcium–vitamin-D3-fortified milk on bone mineral density in older men: a randomised controlled trial Calcium supplementation reduces vertebral bone loss in perimenopausal women: a controlled trial in 248 women between 46 and 55 years of age. Correcting calcium nutritional deficiency prevents spine fractures in elderly women. Overweight postmenopausal women lose bone with moderate weight reduction and 1 g/day calcium intake. The effects of calcium supplementation (milk powder or tablets) and exercise on bone density in postmenopausal women. The effect of milk supplementation on bone mineral density in postmenopausal Chinese women in Malaysia Calcium plus vitamin D supplementation and the risk of fractures. Calcium and Vitamin D Supplementation Increases Spinal BMD in Healthy, Postmenopausal Women
   Calcium supplementation suppresses bone turnover during weight reduction in postmenopausal women. Calcium supplementation prevents seasonal bone loss and changes in biochemical markers of bone turnover in elderly New England women: a randomized placebo-controlled trial. Vascular events in healthy older women receiving calcium supplementation: randomised controlled trial An open, crossover trial of calcium-fortified milk in prevention of early postmenopausal bone loss. Effects of calcium supplements on femoral bone mineral density and vertebral fracture rate in vitamin-D-replete elderly patients Effect of calcium supplementation on bone loss in postmenopausal women. Prevention of bone loss with alendronate in postmenopausal women under 60 years of age. Early Postmenopausal Intervention Cohort Study Group. The efficacy of calcium supplementation alone in elderly Thai women over a 2-year period: a randomized controlled trial Effects of calcium supplementation on clinical fracture and bone structure: results of a 5-year, double-blind, placebo-controlled trial in elderly women. A controlled trial of the effect of calcium supplementation on bone density in postmenopausal women. The effect of fluoride and calcium on spinal bone mineral content: A controlled, prospective (3 years) study Long-term effects of calcium supplementation on serum parathyroid hormone level, bone turnover, and bone loss in elderly women. Milk supplementation of the diet of postmenopausal Chinese women on a low calcium intake retards bone loss. Effect of estrogens and calcium carbonate on bone loss in postmenopausal women. The rate of bone mineral loss in normal men and the effects of calcium and cholecalciferol supplementation. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial. A 1-y walking program and increased dietary calcium in postmenopausal women: effects on bone. A randomised, controlled comparison of different calcium and vitamin D supplementation regimens in elderly women after hip fracture: The Nottingham Neck of Femur (NONOF) Study. Heated oyster shell-seaweed calcium (AAA Ca) on osteoporosis Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older. Treatment with alendronate plus calcium, alendronate alone, or calcium alone for postmenopausal low bone mineral density Clodronate reduces the incidence of fractures in community-dwelling elderly women unselected for osteoporosis: results of a double-blind, placebo-controlled randomized study. Does daily vitamin D 800 IU and calcium 1000 mg supplementation decrease the risk of falling in ambulatory women aged 65-71 years? A 3-year randomized population-based trial (OSTPRE-FPS). Effects on bone mineral density of calcium and vitamin D supplementation in elderly women with vitamin D deficiency. Calcium supplementation and bone loss in middle-aged women. Randomized controlled trial of calcium in healthy older women. Randomized controlled trial of calcium supplementation in healthy, nonosteoporotic, older men.
abstract: Vitamin D insufficiency and low calcium intake contribute to increase parathyroid function and bone fragility in elderly people .  Calcium and vitamin D supplements can reverse secondary hyperparathyroidism thus preventing hip fractures , as proved by Decalyos I. Decalyos II is a 2-year , multicenter , r and omized , double-masked , placebo-controlled confirmatory study . The intention-to-treat population consisted of 583 ambulatory institutionalized women ( mean age 85.2 years , SD = 7.1 ) r and omized to the  calcium – vitamin D3  fixed combination group ( n= 199 ) ; the calcium plus vitamin D3 separate combination group ( n= 190 ) and the placebo group ( n= 194 ) . Fixed and separate combination groups received the same daily amount of calcium ( 1200 mg ) and vitamin D3 ( 800 IU ) , which had similar pharmacodynamic effects . Both types of calcium-vitamin D3 regimens increased serum 25-hydroxyvitamin D and decreased serum intact parathyroid hormone to a similar extent , with levels returning within the normal range after 6 months . In a subgroup of 114 patients  , femoral neck bone mineral density ( BMD ) decreased in the placebo group ( mean = –2.36 % per year , SD = 4.92 ) , while remaining unchanged in women treated with calcium-vitamin D3 ( mean = 0.29 % per year , SD = 8.63 ) . The difference between the two groups was 2.65 % ( 95 % CI = –0.44 , 5.75 % ) with a trend in favor of the active treatment group . No significant difference between groups was found for changes in distal radius BMD and quantitative ultrasonic parameters at the os calcis . The relative risk ( RR ) of HF in the placebo group compared with the active treatment group was 1.69 ( 95 % CI = 0.96 , 3.0 ) , which is similar to that found in Decalyos I ( RR = 1.7 ; 95 % CI = 1.0 , 2.8 ) . Thus , these data are in agreement with those of Decalyos I and indicate that calcium and vitamin D3 in combination reverse senile secondary hyperparathyroidism and reduce both hip bone loss and the risk of hip fracture  in elderly institutionalized women The effects of calcium supplementation ( as calcium citrate malate , 1000 mg elemental Ca/d ) with and without the addition of zinc ( 15.0 mg/d ) , manganese ( 5.0 mg/d ) and copper ( 2.5 mg/d ) on spinal bone loss ( L2-L4 vertebrae ) was evaluated in healthy older postmenopausal women ( n = 59 , mean age 66 y ) in a 2-y , double-blind , placebo-controlled trial . Changes ( mean + /- SEM ) in bone density were -3.53 + /- 1.24 % ( placebo ) , -1.89 + /- 1.40 % ( trace minerals only ) , -1.25 + /- 1.46 % ( calcium only ) and 1.48 + /- 1.40 % ( calcium plus trace minerals ) . Bone loss relative to base-line value was significant ( P = 0.0061 ) in the placebo group but not in the groups receiving trace minerals alone , calcium alone , or calcium plus trace minerals . The only significant group difference occurred between the placebo group and the group receiving calcium plus trace minerals ( P = 0.0099 ) . These data suggest that bone loss in calcium-supplemented , older postmenopausal women can be further arrested by concomitant increases in trace mineral intake BACKGROUND Low-energy fractures of the hip , forearm , shoulder , and spine are known consequences of osteoporosis . OBJECTIVE We evaluated the effect of 1 y of treatment with calcium and vitamin D on bone mineral density ( BMD ) and bone markers in patients with a recent low-energy fracture . DESIGN In a double-blinded design , patients with fracture of the hip ( lower-extremity fracture , or LEF ) or upper extremity ( UEF ) were r and omly assigned to receive 3000 mg calcium carbonate + 1400 IU cholecalciferol or placebo ( 200 IU cholecalciferol ) . BMD of the hip ( HBMD ) and lumbar spine ( LBMD ) were evaluated by dual-energy X-ray absorptiometry , and physical performance was assessed by the timed Up & Go test . Serum concentrations of 25-hydroxycholecalciferol , parathyroid hormone ( PTH ) , telepeptide of type I collagen ( ICTP ) , osteocalcin , and N-terminal propeptide of collagen type I were measured . RESULTS A total of 122 patients were included ( 84 % women ; x + /- SD age : 70 + /- 11 y ) ; 68 % completed the study . In an intention-to-treat analysis , LBMD increased in the intervention group and decreased in the placebo group , and the difference between the groups was significant after 12 mo : 0.931 + /- 0.211 compared with 0.848 + /- 0.194 ( P<0.05 ) . No significant change was shown for HBMD . The effect of treatment was more pronounced in patients aged < 70 y. The intervention decreased bone turnover . PTH was significantly lower in the intervention group ( P<0.01 ) for the LEF patients . ICTP and change in LBMD were significantly related to physical performance . CONCLUSIONS A 1-y intervention with calcium and vitamin D reduced bone turnover , significantly increased BMD in patients younger than 70 y , and decreased bone loss  in older patients . The effect of treatment was related to physical performance Three hundred ten normal postmenopausal volunteers were invited to enter a controlled trial of the effects of calcium supplementation on forearm mineral content ( FMC ) ; 269 entered the study and 210 completed it . Of those who completed the study , 158 were allocated to one of three calcium-supplemented treatment regimes and 52 were allocated to a control group . Twenty-two of the subjects allocated to the treatment group were unable to take supplementary calcium but agreed to remain in the study as additional controls . There were therefore 136 treated subjects , 52 strict controls and 74 controls altogether . During the initial observation period of 9 mo , there was a highly significant loss of bone in all groups ( P less than 0.001 ) . During the 9-mo period of treatment , there was a highly significant reduction in the rate of bone loss in the treated subjects ( P less than 0.001 ) , a just significant reduction in the strict controls ( P less than 0.05 ) and a nonsignificant reduction in the rate of loss in all controls . The difference between the treated and strict controls in the second period was not significant but the difference between the treated and all controls in the second period was significant ( P less than 0.025 ) . When the analysis was applied only to women within 10 yr of menopause , the difference between the treated and strict control groups in period 2 was significant ( P less than 0.025 ) and the difference between the treated and all controls was highly significant ( P less than 0.001 ) The purpose of this study was to ( 1 ) quantify the healing process of the human osteoporotic proximal humerus fracture ( PHF ) expressed in terms of callus formation over the fracture region using BMD scanning , and ( 2 ) quantify the impact of medical intervention with vitamin D3 and calcium on the healing process of the human osteoporotic fracture . The conservatively treated PHF was chosen in order to follow the genuine fracture healing without influence of osteosynthetic material s or casts . Thirty women ( mean age = 78 years ; range = 58–88 ) with a PHF , osteoporosis or osteopenia ( based on a hip scan , WHO criteria ) , and not taking any drugs related to bone formation , including calcium or vitamin D supplementation  , were r and omly assigned to either oral 800 IU vitamin D3 plus 1 g calcium or placebo , in a double-blind prospect i ve study . We measured biochemical , radiographic , and bone mineral density effect parameters to evaluate the impact on the healing process . Scanning procedures of the fractured shoulder included use of a fixation device to obtain the highest possible precision . Double scans of the fractured shoulder revealed a coefficient of variation ( CV ) on BMD measurements that improved from 2.8 % immediately after fracture occurrence to 1.7 % at 12 weeks ( P = 0.003 ) approaching the 1.2 % levels observed over the healthy shoulder . BMD was similar in the two groups at baseline ( active 0.534 g/cm2 vs. placebo 0.518 g/cm2 ) , and both increased over the 12-week observation period , with peak levels in week 6 . By week 6 BMD levels were higher in the active group ( 0.623 g/cm2 ) compared with the placebo group ( 0.570 g/cm2 , P = 0.006 ) . Thirty seven percent of the patients presented with vitamin D levels below 30 nmol/l , indicative of mild vitamin D insufficiency . In conclusion , we have demonstrated that it is possible to quantify callus formation of the PHF with sufficiently high precision to demonstrate the positive influence of vitamin D3 and calcium over the first 6 weeks after fracture . Whether this results in more stable fractures , extends to other fracture types , or applies to other osteogenic bone agents such as bisphosphonates remains to be examined Abstract : Trabecular bone density at the distal radius and cortical bone density at the midradius were measured in four r and omized groups of women before and after 4 months administration of AAACa , oyster shell heated under reduced pressure with addition of heated algal ingredient ( HAI ) ( group A ) ; AACa , the same preparation without HAI ( group B ) ; CaCO3 ( group C ) ; and placebo ( group D ) in a double-blind system using peripheral quantitative computed tomography ( pQCT ) with lumbar spine density measurement by dual-energy X-ray absorptiometry ( DXA ) . Groups A , B , and C received 900 mg/day elemental calcium and D received none . In subjects of group A , but not B , C , and D , radial trabecular bone density increased significantly , to 106.2 % ± 2.1 % of the initial value ( mean ± SEM ) . The increase of trabecular bone density was significantly different from the placebo group ( D ) only in AAACa ( group A ) and not in AACa ( group B ) and the calcium carbonate ( group C ) . Cortical bone density increase was also greater in group A ( but not in B and C ) than in D. Lumbar spine density did not change significantly . AAACa was apparently more effective , increasing trabecular bone density more than AACa and CaCO3 containing the same amount of elemental calcium Ca supplements are used for bone health ; however , they have been associated with increased cardiovascular risk , which may relate to their acute effects on serum Ca concentrations . Microcrystalline hydroxyapatite ( MCH ) could affect serum Ca concentrations less than conventional Ca supplements , but its effects on bone turnover are unclear . In the present study , we compared the acute and 3-month effects of MCH with conventional Ca supplements on concentrations of serum Ca , phosphate , parathyroid hormone and bone turnover markers . We r and omised 100 women ( mean age 71 years ) to 1 g/d of Ca as citrate or carbonate ( citrate-carbonate ) , one of two MCH preparations , or a placebo . Blood was sample d for 8 h after the first dose , and after 3 months of daily supplementation . To determine whether the acute effects changed over time , eight participants assigned to the citrate dose repeated 8 h of blood sampling at 3 months . There were no differences between the citrate and carbonate groups , or between the two MCH groups , so their results were pooled . The citrate-carbonate dose increased ionised and total Ca concentrations for up to 8 h , and this was not diminished after 3 months . MCH increased ionised Ca concentrations less than the citrate-carbonate dose ; however , it raised the concentrations of phosphate and the Ca-phosphate product . The citrate-carbonate and MCH doses produced comparable decreases in bone resorption ( measured as serum C-telopeptide ( CTX ) ) over 8 h and bone turnover ( CTX and procollagen type-I N-terminal propeptide ) at 3 months . These findings suggest that Ca preparations , in general , produce repeated sustained increases in serum Ca concentrations after ingestion of each dose and that Ca supplements with smaller effects on serum Ca concentrations may have equivalent efficacy in suppressing bone turnover Increased postmenopausal bone turnover leads to bone loss and fragility fracture risk . In the absence of osteoporosis , risk preventive measures , particularly those modifying nutritional lifestyle , are appropriate . We tested the hypothesis that milk supplementation affects bone turnover related to biochemical markers in a direction that , in the long term , may be expected to reduce  postmenopausal bone loss .  Thirty healthy postmenopausal women aged 59.3 ( SD 3.3 ) years were enrolled in a prospect i ve crossover trial of 16 weeks . After a 4-week period of adaptation with diet providing 600 mg calcium plus 300 mg ingested as 250 ml semi-skimmed milk , participants were maintained during 6 weeks under the same 600 mg calcium diet and r and omized to receive either 500 ml semi-skimmed milk , thus providing a total of 1200 mg calcium , or no milk supplement . In the next 6 weeks they were switched to the alternative regimen . At the end of the each period , i.e. after 4 , 10 and 16 weeks , blood and urinary sample s were collected . The changes in blood variables between the periods of 6 weeks without and with milk supplementation were : for parathyroid hormone , -3.2 pg/ml ( P=0.0054 ) ; for crosslinked telopeptide of type I collagen , -624 pg/ml ( P<0.0001 ) ; for propeptide of type I procollagen , -5.5 ng/ml ( P=0.0092 ) ; for osteocalcin , -2.8 ng/ml ( P=0.0014 ) . In conclusion , a 6-week period of milk supplementation induced a decrease in several biochemical variables compatible with diminished bone turnover mediated by reduction in parathyroid hormone secretion . This nutritional approach to postmenopausal alteration in bone metabolism may be a valuable measure in the primary prevention of osteoporosis During a two-year study , we examined the effect of calcium supplementation on postmenopausal bone loss in 43 women in the early postmenopausal period who were assigned to one of three treatment groups : percutaneous 17 beta-estradiol ( combined with progesterone during the second year ) , oral calcium ( 2000 mg daily ) , and placebo . All participants were examined every three months . Bone mineral content in the forearm ( measured by single-photon absorptiometry ) and in the entire body and spine ( measured by dual-photon absorptiometry ) remained constant in the estrogen-treated group but decreased significantly in the groups receiving calcium and placebo . In the calcium-treated group , we observed a tendency toward a slowed loss of compact bone ( in the proximal forearm and total skeleton ) as compared with the placebo group , while the rate of loss of trabecular bone ( the distal forearm and spine ) was the same as in the placebo group . Our preliminary data suggest that calcium supplementation in the dosage we used is not as effective as estrogen therapy for the prevention of early postmenopausal bone loss .  Calcium supplementation may have had a minor effect on the loss of cortical bone , but it had no effect on the trabecular bone OBJECTIVE To evaluate three different therapeutic regimens for the prevention of osteoporosis  in natural and surgical postmenopausal women who had been found to have rapid bone loss in analytical studies . METHODS A total of 104 naturally or surgically postmenopausal women were studied , and subsequently followed-up during 1 year for avoidance of the influence of seasonal variation on bone mass , a factor overlooked in several studies . They were r and omized into four groups of 26 patients each : the  untreated control group ( mean age 50 + /- 5 years ) ; the  hormonal replacement treatment ( HRT ) group ( mean age 48 + /- 6 years ) , which was treated for 24 days each month with transdermal 17 beta-estradiol , 50 mg/day , together with medroxiprogesterone , 10 mg during 12 days ; the  calcium group ( mean age 50 + /- 4 years ) , which was treated with elemental calcium , 1 g/day ; and the  calcitonin group ( mean age 50 + /- 5 years ) , which was treated for 10 days each month with eel calcitonin , 40 IU/day and with elemental calcium , 500 mg/day . Full-body bone densitometry , for measuring total body bone mineral content ( TB BMC ) , was carried out in all the women at baseline and 1 year . TB BMC was corrected for body weight by dividing its value by body weight ( TB BMC /W ) . RESULTS After 1 year TB BMC /W was lower in every group : -2.14 % ( P < 0.001 ) in the control group ; -0.14 % ( P = NS ) in the HRT group ( P < 0.05 vs. controls ) ; -0.18 % ( P = NS ) in the calcium group ( P < 0.05 vs. controls ) ; and -0.06 % ( P = NS ) in the calcitonin group ( P < 0.01 vs. controls ; P < 0.05 vs. calcium and HRT ) . CONCLUSIONS These findings show that all three treatments are effective in the prevention of postmenopausal loss of bone mass Postmenopausal bone loss is a major factor in the increasing prevalence of osteoporotic fractures . Evidence is abundant that hormonal replacement therapy prevents the bone loss that follows natural or surgical menopause and reduces the prevalence of osteoporotic fractures in later life [ 1 - 4 ] . However , only about 10 % of American women elect to receive replacement therapy because of attitudes of physicians and patients , the undesirability of menstrual bleeding , and unresolved questions about the relation of the use of estrogen to breast cancer [ 5 ] . Moreover , the duration of hormonal therapy may need to be prolonged because bone loss recurs when therapy is discontinued , yet the incidence of some adverse effects increases with the duration of estrogen use . Safer alternatives to estrogen use have been sought . Epidemiologic and cross-sectional studies have suggested that increasing calcium intake might prevent postmenopausal bone loss , and prospect i ve studies have yielded conflicting results [ 6 - 17 ] . Moreover , some investigators have suggested that effects differ on the various skeletal sites used to determine the rate of bone loss [ 18 ] . We compared the efficacy of calcium augmentation in early postmenopause with calcium augmentation plus hormonal replacement therapy and with placebo . The study had a three-arm , r and omized , parallel design . The patients receiving hormonal replacement therapy were obviously not blinded nor were their physicians , whereas the placebo and calcium groups were double blinded . Methods Healthy , white women between 6 months and 6 years after a natural menopause were recruited to participate in the study . The protocol was approved by the Human Investigation Review Committees of Winthrop-University Hospital and Brookhaven National Laboratory ; written informed consent was obtained from each participant . Participants were recruited by announcements in the local press and in hospital and university publications and through a direct mail campaign . All participants had a history and physical examination . Exclusion characteristics included any disorder known to affect bone metabolism such as glucocorticoid use , gastrointestinal disease , or any chronic illness . Previous or current malignancy was an exclusion characteristic as were absolute contraindications to estrogen replacement or calcium supplements . Absolute contraindications to estrogen replacement therapy included estrogen-dependent neoplasm ( breast or uterus ) , undiagnosed vaginal bleeding , thrombophlebitis or thromboembolism , and acute liver disease .  Women with the following problems considered by some investigators to be relative contraindications to estrogen therapy were also excluded : gallbladder disease , history of liver disease , first-degree relatives with breast cancer , and hypertension . Calcium urolithiasis was also an exclusion factor . Women with known osteoporosis or with a vertebral compression fracture were not eligible for the study . One hundred eighteen women entered the study . The women were r and omly assigned to three groups : 1 ) hormonal replacement [ estrogen-progesterone-calcium carbonate ] , 2 ) calcium carbonate , or 3 ) placebo . Assignment to the groups was based on computer-generated r and om numbers provided by the statistician , with stratification for years postmenopause . The women in the hormonal replacement group took conjugated equine estrogens ( Premarin , Wyeth-Ayerst Laboratories , Inc. ; Philadelphia , Pennsylvania ) , 0.625 mg daily for 25 days of the month along with medroxyprogesterone ( Provera , Upjohn ; Kalamazoo , Michigan ) , 10 mg from days 16 to 25 . All women received 400 IU of vitamin D daily in the form of a multivitamin , and calcium supplementation ( as Caltrate , Lederle ; Clifton , New Jersey ) was provided to the two treatment groups . The duration of the study was 2.9 1.1 years ( mean SD ) . A 7-day dietary history was review ed with a nutritionist every 2 months ; calcium was provided as calcium carbonate , 600 mg ( Caltrate ) , and used to supplement the diet to approximate a total daily intake of 1700 mg of elemental calcium ( the mean + 2 SD found by Heaney and colleagues [ 7 ] to result in zero calcium balance in estrogen-deprived women ) . The calcium supplements were taken with meals in divided doses . The placebo appeared identical to the calcium carbonate tablets . No patients took antacids or histamine-2 blockers . All women had a baseline mammogram . Measurements Routine laboratory studies included a complete blood count , urinalysis , and serum fasting calcium , phosphorus , urea nitrogen , creatinine , alkaline phosphatase , cholesterol , and aminotransferase measurements [ 19 , 20 ] . In addition , follicle-stimulating hormone , estradiol , parathyroid hormone , osteocalcin , free thyroxine , and bone alkaline phosphatase were measured , and a urine specimen was collected after an overnight fast for hydroxyproline , calcium , and creatinine determinations , following a 3-day low-hydroxyproline diet [ 21 - 23 ] . Total body calcium was measured annually in the participants , using the delayed neutron activation method at Brookhaven National Laboratory [ 24 , 25 ] . This method uses a whole-body counter to measure the characteristic rays emitted from the neutron capture of Calcium-48 ( natural abundance of 0.187 % ) in the body . The Brookhaven National Laboratory whole-body counter was up grade d in 1987 to use 32 NaI ( T1 ) detectors of 10 cm 10 cm 46 cm positioned symmetrically above and below the patient [ 25 ] . The activated isotope , Calcium-49 , decays with a half-life of 8.72 minutes , emitting a 3.08 MeV characteristic line . More than 99.5 % of the body calcium is contained in the bone [ 26 ] . The method provides total body calcium with a coefficient of variation of about 1.5 % when no substantial change in the body weight occurs during the period of repeated studies . The measurements were made annually . The bone mineral density of the distal radius site was measured using a Lunar Radiation ( Madison , Wisconsin ) single-photon absorptiometer ( SP2 ) .  Bone mineral density of the spine ( L2-L4 ) and femur ( neck , trochanter , and Ward triangle ) was measured using a Lunar Radiation DP4 dual-photon absorptiometer . The software version used for the analysis of scans was DP4 Lunar Corporation Version 1.1 . All scans were analyzed using the same software version , which corrects for source decay . Instruments were calibrated daily , and the radioactive source was changed annually . Each measurement was done every 6 months . The coefficient of variation of these measurements was 2 % , except for the Ward triangle ( 2.5 % ) . Activity was measured using  activity monitors  ( large-scale integrated monitors ) , which were worn about the waist [ 27 ] . The average of 2 weekdays and 1 weekend day was used as an activity score . Activity was measured at baseline and at one other point during the study to ensure that differences among the groups were not due to varied levels of exercise . Statistical Analysis Total body calcium was selected as the primary criterion for efficacy for the following reasons : It measures mass rather than density per unit area ; it measures calcium balance precisely and accurately in the free living state and may be better related to previous studies using the balance technique ; it is more precise than the other measurements ; and it avoids sampling error by measuring the entire skeleton rather than a specific region of the appendicular or axial skeleton . The rate of change in bone mineral was calculated for each woman at each of the sites used in the study . St and ard linear regression procedures were used to estimate the rate of bone mineral change for each woman , and the regression intercept was used as the best estimate of the baseline value . Because some women terminated their participation in the study before others , the rate-of-change data were weighted by the inverse variance to reflect the fit of the regression line for each woman [ 28 ] . Analyses of covariance were done using body mass index , activity scores , cigarette smoking , calcium intake , age , and years postmenopause as covariates . The data reported in this article are based on all women who provided at least three observations for a particular skeletal site . We considered other criteria , such as using data only from women who had participated in the study for at least 2 years , and all data analyses were done for this subgroup as well . The results of these analyses were invariably similar to those reported here and therefore are not presented separately . The mean rates of change in bone mineral for each condition at each site were characterized in terms of both raw units and percentages ; separate analyses were carried out for each . The two indices were similar . Evidence from recent research is substantial that estrogen replacement therapy is effective , whereas the efficacy of calcium supplements is question able . Our expectation was that our data would confirm the efficacy of estrogen-progesterone-calcium therapy , and the critical question was whether or not a beneficial effect of calcium supplements given alone could be shown . A separate one-way analysis of covariance was done for each of the bone mineral measurements to compare the mean rates of change in bone mineral for each of the three conditions . We used two a priori contrasts : the first contrasting women taking estrogen with those receiving calcium and the second comparing women receiving calcium supplements with those on placebo . All P values reported are two-tailed . Results Baseline data for historical data and bone mineral measurements and chemical studies are given in Table 1 . Analysis of variance showed no significant differences in the baseline variables . The initial and final activity scores did not differ significantly . Table 1 . Baseline Values for Patient Characteristics , Bone Mineral Measurements , and Chemical Variables The range of initial daily calcium intake in the overall study group was 150 to 1263 mg ; in the calcium augmentation group , it was 222 to This placebo-controlled r and omized trial was conducted to ascertain the value of calcium citrate supplementation in averting bone loss in 63 postmenopausal women , 57 of whom were early postmenopausal ( five years after menopause ) and six of whom were mid-postmenopausal ( five to ten years after menopause ) .  Bone density data were available for 25 women who took 800 mg of calcium citrate daily and 31 women who received placebo for one to two years . The two groups were similar in baseline age , years postmenopause ( 3.3 in the calcium citrate group vs 2.7 in the placebo group ) , height , weight , calcium intake , and L2-L4 bone density . L2-L4 bone density did not change during calcium citrate treatment ( + 1.03 % after two years ) , whereas it declined significantly by -2.38 % after two years on placebo ( P < .001 ) . Femoral neck bone density did not change in either group . Radial shaft bone density did not change in the calcium citrate group ( -0.02 % after two years ) , but it declined significantly in the placebo group ( -1.79 % after one year and -3.03 % after two years , P < .01 ) . The difference in bone density of the L2-L4 vertebrae and radial shaft after two years of treatment was significant between the two groups . An analysis of covariance disclosed no significant effect of calcium citrate on L2-L4 bone density during the first three years after menopause , but a protective effect after three years . Although serum PTH did not change , serum and urinary calcium increased and serum calcitriol and urinary phosphorus decreased in the calcium citrate group , indicative of parathyroid suppression . Serum bone-specific alkaline phosphatase and osteocalcin , and urinary hydroxyproline and N-telopeptide decreased during some calcium citrate treatment periods , indicative of a reduction in bone turnover . Thus , calcium citrate supplementation ( 400 mg of calcium twice daily ) averted bone loss and stabilized bone density in the spine , femoral neck , and radial shaft in women relatively soon after menopause . This bone-sparing action was probably due to the inhibition of bone resorption from parathyroid suppression CONTEXT Effects of long-term calcium , with or without vitamin D , on  hip bone mineral density ( BMD ) and bone turnover in sunny climates have not been reported . OBJECTIVE The aim was to evaluate the effect of vitamin D added to calcium supplementation on hip dual-energy x-ray absorptiometry BMD and calcium-related analytes . DESIGN , SETTING , AND PARTICIPANTS The study was a 5-yr r and omized , controlled , double-blind trial of 120 community-dwelling women aged 70 - 80 yr . INTERVENTIONS The interventions were 1200 mg/d calcium with placebo vitamin D ( Ca group ) or with 1000 IU/d vitamin D2 ( CaD group ) , or double placebo ( control ) . MAIN OUTCOME MEASURES Hip BMD , plasma 25-hydroxyvitamin D , biomarkers of bone turnover , PTH , and intestinal calcium absorption were measured . RESULTS Hip BMD was preserved in CaD ( -0.17 % ) and Ca ( 0.19 % ) groups but not controls ( -1.27 % ) at yr 1 and maintained in the CaD group only at yr 3 and 5 . The beneficial effects were mainly in those with baseline 25-hydroxyvitamin D levels below the median ( 68 nmol/liter ) . At yr 1 , compared with controls , the Ca and CaD groups had 6.8 and 11.3 % lower plasma alkaline phosphatase , respectively ( P < or=0.02 ) , and 28.7 and 34.5 % lower urinary deoxypyridinoline to creatinine ratio , respectively ( P < or=0.05 ) . At 5 yr , this suppression was maintained only in the CaD group . CaD reduced PTH at 3 and 5 yr cf . controls ( 27.8 and 31.3 % , P < or=0.005 ) in those with baseline PTH levels above the median ( 3.6 pmol/liter ) . Therapy did not affect intestinal calcium absorption at high carrier loads . CONCLUSIONS Addition of vitamin D to calcium has long-term beneficial effects on bone density in elderly women living in a sunny climate , probably mediated by a long-term reduction in bone turnover rate The effect of dietary calcium supplementation on bone mineral content was studied in 40 postmenopausal women with Colles ' fracture . The participants were divided into two groups which were given either placebo or 1 g of calcium per day . The bone mineral content of the femur was determined before and after 1 year of medication . Women with Colles ' fracture were found to have the same mineral content in the femur as age-matched controls without fractures . Calcium supplementation had no significant effect on the bone mineral content CONTEXT Alendronate sodium reduces fracture risk in postmenopausal women who have vertebral fractures , but its effects on fracture risk have not been studied for women without vertebral fractures . OBJECTIVE To test the hypothesis that 4 years of alendronate would decrease the risk of clinical and vertebral fractures in women who have low bone mineral density ( BMD ) but no vertebral fractures . DESIGN R and omized , blinded , placebo-controlled trial . SETTING Eleven community-based clinical research centers . SUBJECTS Women aged 54 to 81 years with a femoral neck BMD of 0.68 g/cm2 or less ( Hologic Inc , Waltham , Mass ) but no vertebral fracture ; 4432 were r and omized to alendronate or placebo and 4272 ( 96 % ) completed outcome measurements at the final visit ( an average of 4.2 years later ) . INTERVENTION All participants reporting calcium intakes of 1000 mg/d or less received a supplement containing 500 mg of calcium and 250 IU of cholecalciferol . Subjects were r and omly assigned to either placebo or 5 mg/d of alendronate sodium for 2 years followed by 10 mg/d for the remainder of the trial . MAIN OUTCOME MEASURES Clinical fractures confirmed by x-ray reports , new vertebral deformities detected by morphometric measurements on radiographs , and BMD measured by dual x-ray absorptiometry . RESULTS Alendronate increased BMD at all sites studied ( P<.001 ) and reduced clinical fractures from 312 in the placebo group to 272 in the intervention group , but not significantly so ( 14 % reduction ; relative hazard [ RH ] , 0.86 ; 95 % confidence interval [ CI ] , 0.73 - 1.01 ) . Alendronate reduced clinical fractures by 36 % in women with baseline osteoporosis at the femoral neck ( > 2.5 SDs below the normal young adult mean ; RH , 0.64 ; 95 % CI , 0.50 - 0.82 ; treatment-control difference , 6.5 % ; number needed to treat [ NNT ] , 15 ) , but there was no significant reduction among those with higher BMD ( RH , 1.08 ; 95 % CI , 0.87 - 1.35 ) . Alendronate decreased the risk of radiographic vertebral fractures by 44 % overall ( relative risk , 0.56 ; 95 % CI , 0.39 - 0.80 ; treatment-control difference , 1.7 % ; NNT , 60 ) . Alendronate did not increase the risk of gastrointestinal or other adverse effects . CONCLUSIONS In women with low BMD but without vertebral fractures , 4 years of alendronate safely increased BMD and decreased the risk of first vertebral deformity .  Alendronate significantly reduced the risk of clinical fractures among women with osteoporosis but not among women with higher BMD A r and omized controlled trial was carried out to determine whether calcium supplementation and load-bearing exercise can increase or maintain bone mass in the elderly . Fifty Chinese women , aged 62–92 years , living in a hostel for the elderly in Hong Kong were r and omized to enter one of four treatment groups : ( I ) calcium supplementation of 800 mg ( as calcium lactate gluconate ) daily ; ( II ) load-bearing exercise four times a week plus a daily placebo tablet ; ( III ) calcium supplementation daily and load-bearing exercise four times a week ; ( IV ) a placebo tablet daily . The interventions went on for 10 months . The bone mineral density ( BMD ) was measured at three sites in the hip ( femoral neck , Ward 's triangle and intertrochanteric area ) and the L2–4 level of the spine . The percentage change in BMD in 10 months was used as the main outcome measurement . The parathyroid hormone level and indices of bone metabolism were also measured before and after 10 months of intervention . The BMD at Ward 's triangle and the intertrochanteric area increased significantly in subjects on calcium supplement ( p<0.05 ) , but there was no significant change at the spine and femoral neck . Exercise had no effect on bone loss at any site . However , the results of two-way analysis of variance showed a significant joint effect of calcium supplements and exercise  at the femoral neck ( p<0.05 ) , but not at the other sites . The parathyroid hormone levels fell significantly in subjects on calcium supplements (p<0.01).Calcium supplement in the form of calcium lactate gluconate was adequately absorbed in elderly Chinese women with a calcium intake of less than 300 mg per day . It was effective in reducing bone loss at the hip , and there may be interaction effects with exercise in maintaining bone density Current st and ard-dose calcium supplements ( eg , 1000 mg/d ) may increase the risk for cardiovascular events . Effectiveness of lower-dose supplements in preventing bone loss should thus be considered . This study aim ed to assess whether calcium supplements of 500 or 250 mg/d effectively prevent bone loss in perimenopausal and postmenopausal Japanese women . We recruited 450 Japanese women between 50 and 75 years of age . They were r and omly assigned to receive 500 mg of calcium ( as calcium carbonate ) , 250 mg of calcium , or placebo daily . Medical examinations conducted three times over a 2-year follow-up period assessed bone mineral density ( BMD ) of the lumbar spine and femoral neck . One-factor repeated measures ANOVA was used for statistical tests . Subgroup analyses were also conducted . Average  total daily calcium intake at baseline for the 418 subjects who underwent follow-up examinations was 493 mg/d . Intention-to-treat analysis showed less dramatic decreases in spinal BMD for the 500-mg/d calcium supplement group compared to the placebo group ( 1.2 % difference over 2 years , p = 0.027 ) . Per- protocol analysis ( ≥80 % compliance ) revealed that spinal BMD for the 500-mg/d and 250-mg/d calcium supplement groups decreased less than the placebo group ( 1.6 % , p = 0.010 and 1.0 % , p = 0.078 , respectively ) , and that femoral neck BMD for the 500-mg/d calcium supplement group decreased less relative to the placebo group ( 1.0 % , p = 0.077 ) . A low-dose calcium supplement of 500 mg/d can effectively slow lumbar spine bone loss  in perimenopausal and postmenopausal women with habitually low calcium intake , but its effect on the femoral neck is less certain . Calcium supplementation dosage should thus be reassessed . ( Clinical Trials Registry number : UMIN000001176 ) Summary Eighteen months of daily consumption of milk containing 250 mg calcium prevented bone mineral density ( BMD ) loss at the hip and the femoral neck in postmenopausal Chinese women aged 45 to 65 . Introduction Estrogen-related bone loss in postmenopausal women can be prevented by the consumption of milk with high doses of calcium and soymilk with high doses of isoflavones . However , high doses of calcium and isoflavones may not be necessary to attain a beneficial effect of milk and soymilk on BMD . We hypothesized that BMD will increase in postmenopausal Chinese women who consume daily 250 mg calcium in milk or soymilk . Milk prevented bone loss at the hip and the femoral neck in postmenopausal Chinese women . Methods A total of 141 eligible Chinese women without osteoporosis , aged 45–65 , and postmenopausal for more than 2 years were r and omized into groups receiving for 18 months ( A ) milk with 250 mg calcium daily , ( B ) soymilk with 250 mg calcium daily , or ( C ) neither milk nor soymilk . Dual-energy X-ray absorptiometry measured the BMD of the spine and hip at 0 , 6 , 12 , and 18 months . Results The BMD in the hip ( 2.52 % ) and the femoral neck ( 2.82 % ) of the women consuming milk was significantly higher ( hip , P = 0.01 ; femoral neck , P < 0.0000001 ) . The women in the control group experienced a reduction in BMD at all sites ; the reduction in BMD was only significant at the hip during 12 months ( P = 0.008 ) and at the femoral neck during 18 months ( P = 0.005 ) . Conclusions Daily consumption of milk containing 250 mg calcium over 18 months prevents BMD loss at the hip and the femoral neck in postmenopausal Chinese women OBJECTIVE To evaluate , in postmenopausal women who refuse hormone replacement therapy ( HRT ) , whether continuous administration of an osseinhydroxyapatite compound ( OHC ) reduces bone loss and protects from osteoporosis . STUDY DESIGN Sixty postmenopausal women were included in an open study and were allocated to three groups . The first group ( n = 19 ) received treatment consisting in 3.32 g/d of OHC per day , the second group ( n = 21 ) received 2.5 g of calcium carbonate per day , and the third group ( n = 20 ) was a treatment-free control group .  Bone mineral density ( BMD ) , assessed by dual x-ray absorptiometry , was measured prior to and at 12 and 24 months of treatment . RESULTS Subjects on OHC therapy did not show significant changes related to baseline on bone mass across the study , whereas a significant decrease was detected in the calcium carbonate group during the second year ( -3.7 % , P < .05 ) and in the control group at the first and second BMD measurement ( -3.5 % , P < .05 ; -5.6 % , P < .01 ) . CONCLUSION Continuous administration of OHC prevents bone loss  in postmenopausal women , suggesting that this drug may be useful in the management of postmenopausal bone loss CONTEXT Despite decades of accumulated observational evidence , the balance of risks and benefits for hormone use in healthy postmenopausal women remains uncertain . OBJECTIVE To assess the major health benefits and risks of the most commonly used combined hormone preparation in the United States . DESIGN Estrogen plus progestin component of the Women 's Health Initiative , a r and omized controlled primary prevention trial ( planned duration , 8.5 years ) in which 16608 postmenopausal women aged 50 - 79 years with an intact uterus at baseline were recruited by 40 US clinical centers in 1993 - 1998 . INTERVENTIONS Participants received conjugated equine estrogens , 0.625 mg/d , plus medroxyprogesterone acetate , 2.5 mg/d , in 1 tablet ( n = 8506 ) or placebo ( n = 8102 ) . MAIN OUTCOMES MEASURES The primary outcome was coronary heart disease ( CHD ) ( nonfatal myocardial infa rct ion and CHD death ) , with invasive breast cancer as the primary adverse outcome . A global index summarizing the balance of risks and benefits included the 2 primary outcomes plus stroke , pulmonary embolism ( PE ) , endometrial cancer , colorectal cancer , hip fracture , and death due to other causes . RESULTS On May 31 , 2002 , after a mean of 5.2 years of follow-up , the data and safety monitoring board recommended stopping the trial of estrogen plus progestin vs placebo because the test statistic for invasive breast cancer exceeded the stopping boundary for this adverse effect and the global index statistic supported risks exceeding benefits . This report includes data on the major clinical outcomes through April 30 , 2002 . Estimated hazard ratios ( HRs ) ( nominal 95 % confidence intervals [ CIs ] ) were as follows : CHD , 1.29 ( 1.02 - 1.63 ) with 286 cases ; breast cancer , 1.26 ( 1.00 - 1.59 ) with 290 cases ; stroke , 1.41 ( 1.07 - 1.85 ) with 212 cases ; PE , 2.13 ( 1.39 - 3.25 ) with 101 cases ; colorectal cancer , 0.63 ( 0.43 - 0.92 ) with 112 cases ; endometrial cancer , 0.83 ( 0.47 - 1.47 ) with 47 cases ; hip fracture , 0.66 ( 0.45 - 0.98 ) with 106 cases ; and death due to other causes , 0.92 ( 0.74 - 1.14 ) with 331 cases . Corresponding HRs ( nominal 95 % CIs ) for composite outcomes were 1.22 ( 1.09 - 1.36 ) for total cardiovascular disease ( arterial and venous disease ) , 1.03 ( 0.90 - 1.17 ) for total cancer , 0.76 ( 0.69 - 0.85 ) for combined fractures , 0.98 ( 0.82 - 1.18 ) for total mortality , and 1.15 ( 1.03 - 1.28 ) for the global index . Absolute excess risks per 10 000 person-years attributable to estrogen plus progestin were 7 more CHD events , 8 more strokes , 8 more PEs , and 8 more invasive breast cancers , while absolute risk reductions per 10 000 person-years were 6 fewer colorectal cancers and 5 fewer hip fractures . The absolute excess risk of events included in the global index was 19 per 10 000 person-years . CONCLUSIONS Overall health risks exceeded benefits from use of combined estrogen plus progestin for an average 5.2-year follow-up among healthy postmenopausal US women .  All-cause mortality was not affected during the trial . The risk-benefit profile found in this trial is not consistent with the requirements for a viable intervention for primary prevention of chronic diseases , and the results indicate that this regimen should not be initiated or continued for primary prevention of CHD The effect of calcium supplementation , in patients with osteoporosis is still a matter of controversy . Oyster shell electrolysate ( OSE ) was reported to raise serum calcium and increase urinary calcium excretion in vitamin D-deficient states more readily than calcium carbonate . Since the effect of calcium salts on osteoporosis depends heavily on its bioavailability , the effect of 900 mg/day calcium as OSE was tested in 12 elderly osteoporotic females , using radial bone mineral density measured by single photon absorptiometry and spinal trabecular bone density measured by quantitative computed tomography ( QCT ) as indicated , in comparison with 21 untreated controls in the same geriatric hospital .  Radial bone mineral density significantly increased from the pre-test value after 12 and 24 months in subjects given OSE by paired t-test , whereas it fell significantly in the controls . The spinal QCT value on OSE  did not change significantly in either the subjects under treatment with OSE , or the controls . Thus OSE may favorably influence osteoporosis by providing a readily available source of calcium UNLABELLED Dietary supplementation with vitamin K(1 ) , with vitamin D(3 ) and calcium or their combination , was examined in healthy older women during a 2-year , double-blind , placebo-controlled trial . Combined vitamin K with vitamin D plus calcium was associated with a modest but significant increase in BMC at the ultradistal radius but not at other sites in the hip or radius . INTRODUCTION The putative beneficial role of high dietary vitamin K(1 ) ( phylloquinone ) on BMD and the possibility of interactive benefits with vitamin D were studied in a 2-year double-blind , placebo-controlled trial in healthy Scottish women > or = 60 years of age . MATERIAL S AND METHODS Healthy , nonosteoporotic women ( n = 244 ) were r and omized to receive either ( 1 ) placebo , ( 2 ) 200 microg/day vitamin K(1 ) , ( 3 ) 10 microg ( 400 IU ) vitamin D(3 ) plus 1000 mg calcium/day , or ( 4 ) combined vitamins K(1 ) and D(3 ) plus calcium . Baseline and 6-month measurements included DXA bone mineral scans of the hip and wrist , markers of bone turnover , and vitamin status . Supplementation effects were tested using multivariate general linear modeling , with full adjustment for baseline and potential confounding variables . RESULTS Significant bone mineral loss was seen only at the mid-distal radius but with no significant difference between groups . However , women who took combined vitamin K and vitamin D plus calcium showed a significant and sustained increase in both BMD and BMC at the site of the ultradistal radius . Serum status indicators responded significantly to respective supplementation with vitamins K and D. Over 2 years , serum vitamin K(1 ) increased by 157 % ( p < 0.001 ) , the percentage of undercarboxylated osteocalcin ( % GluOC ) decreased by 51 % ( p < 0.001 ) , serum 25-hydroxyvitamin D [ 25(OH)D ] increased by 17 % ( p < 0.001 ) , and PTH decreased by 11 % ( p = 0.049 ) . CONCLUSIONS These results provide evidence of a modest synergy in healthy older women from nutritionally relevant intakes of vitamin K(1 ) together with supplements of calcium plus moderate vitamin D(3 ) to enhance BMC at the ultradistal radius , a site consisting of principally trabecular bone . The substantial increase in gamma-carboxylation of osteocalcin by vitamin K may have long-term benefits and is potentially achievable by increased dietary intakes of vitamin K rather than by supplementation UNLABELLED In this 2-year r and omized controlled study of 167 men > 50 years of age , supplementation with calcium-vitamin D3-fortified milk providing an additional 1000 mg of calcium and 800 IU of vitamin D3 per day was effective for suppressing PTH and stopping or slowing bone loss at several clinical ly important skeletal sites at risk for fracture . INTRODUCTION Low dietary calcium and inadequate vitamin D stores have long been implicated in age-related bone loss and osteoporosis . The aim of this study was to assess the effects of calcium and vitamin D3 fortified milk on BMD in community living men > 50 years of age . MATERIAL S AND METHODS This was a 2-year r and omized controlled study in which 167 men ( mean age + /- SD , 61.9 + /- 7.7 years ) were assigned to receive either 400 ml/day of reduced fat ( approximately 1 % ) ultra-high temperature ( UHT ) milk containing 1000 mg of calcium plus 800 IU of vitamin D3 or to a control group receiving no additional milk . Primary endpoints were changes in BMD , serum 25(OH)D , and PTH . RESULTS One hundred forty-nine men completed the study . Baseline characteristics between the groups were not different ; mean dietary calcium and serum 25(OH)D levels were 941 + /- 387 mg/day and 77 + /- 23 nM , respectively . After 2 years , the mean percent change in BMD was 0.9 - 1.6 % less in the milk supplementation compared with control group at the femoral neck , total hip , and ultradistal radius ( range , p < 0.08 to p < 0.001 after adjusting for covariates ) . There was a greater increase in lumbar spine BMD in the milk supplementation group after 12 and 18 months ( 0.8 - 1.0 % , p < or = 0.05 ) , but the between-group difference was not significant after 2 years ( 0.7 % ; 95 % CI , -0.3 , 1.7 ) . Serum 25(OH)D increased and PTH decreased in the milk supplementation relative to control group after the first year ( 31 % and -18 % , respectively ; both p < 0.001 ) , and these differences remained after 2 years . Body weight remained unchanged in both groups at the completion of the study . CONCLUSIONS Supplementing the diet of men > 50 years of age with reduced-fat calcium- and vitamin D3-enriched milk may represent a simple , nutritionally sound and cost-effective strategy to reduce  age-related bone loss  at several skeletal sites at risk for fracture in the elderly UNLABELLED Bone metabolism follows a seasonal pattern with high bone turnover and bone loss during the winter . In a r and omized , open-label 2-year sequential follow-up study of 55 healthy adults , we found that supplementation with oral vitamin D3 and calcium during winter abolished seasonal changes in calciotropic hormones and markers of bone turnover and led to an increase in BMD . Supplementation with oral vitamin D3 and calcium during the winter months seems to counteract the effects of seasonal changes in vitamin D and thus may be beneficial as a primary prevention strategy for age-related bone loss . INTRODUCTION Bone metabolism follows a seasonal pattern characterized by high bone turnover and bone loss during winter . We investigated whether wintertime supplementation with oral vitamin D3 and calcium had beneficial effects on the circannual changes in bone turnover and bone mass . MATERIAL S AND METHODS This prospect i ve study comprised an initial observation period of 12 months ( " year 1 " ) , followed by an intervention during parts of year 2 . Fifty-five healthy subjects living in southwestern Germany ( latitude , 49.5 degrees N ) were r and omized into two groups : 30 subjects were assigned to the treatment group and received oral cholecalciferol ( 500 IU/day ) and calcium ( 500 mg/day ) during the winter months of year 2 ( October-April ) , while 25 subjects assigned to the control group obtained no supplements . Primary endpoints were changes in calciotropic hormones [ serum 25(OH)D , 1,25(OH)2D , and parathyroid hormone ] , markers of bone formation ( serum bone-specific alkaline phosphatase ) and of bone resorption ( urinary pyridinoline and deoxypyridinoline ) , and changes in lumbar spine and femoral neck BMD . RESULTS Forty-three subjects completed the study . During year 1 , calciotropic hormones , markers of bone turnover , and BMD varied by season in both groups . During the winter months of year 1 , bone turnover was significantly accelerated , and lumbar spine and femoral BMD declined by 0.3 - 0.9 % . In year 2 , seasonal changes in calciotropic hormones and markers of bone turnover were either reversed or abolished in the intervention group while unchanged in the control cohort . In the subjects receiving oral vitamin D3 and calcium , lumbar and femoral BMD increased significantly ( lumbar spine : + 0.8 % , p = 0.04 versus year 1 ; femoral neck : + 0.1 % , p = 0.05 versus year 1 ) , whereas controls continued to lose bone ( intervention group versus control group : lumbar spine , p = 0.03 ; femoral neck , p = 0.05 ) . CONCLUSIONS Supplementation with oral vitamin D3 and calcium during winter prevents seasonal changes in bone turnover and bone loss in healthy adults . It seems conceivable that annually recurring cycles of low vitamin D and mild secondary hyperparathyroidism during the winter months contributes , at least in part and over many years , to age-related bone loss . Supplementation with low-dose oral vitamin D3 and calcium during winter may be an efficient and inexpensive strategy for the primary prevention of bone loss in northern latitudes Dietary supplements that prevent bone loss at the hip and that can be applied safely in the elderly are likely to reduce hip fractures . A daily dietary supplement of 750 mg calcium or 15 microg 25OH vitamin D3 on bone loss at the hip and other sites , bone turnover and calcium-regulating hormones were studied over 4 yr in elderly volunteers using a r and omized , double-blind , placebo-controlled trial . Bone mineral density ( BMD ) was measured by dual x-ray absorptiometry and bone structure by radiographs . Calcium biochemistry and bone turnover markers were measured in blood and urine . The 316 women entering the trial had a mean age of 73.7 yr and the 122 men of 75.9 yr . Baseline median calcium intake was 546 mg/day , and median serum 25OH vitamin D3 was 59 nmol/L. On placebo , loss of BMD at total hip was 2 % and femoral medulla expansion was 3 % over 4 yr . Calcium reduced bone loss , secondary hyperparathyroidism , and bone turnover . 25OH vitamin D3 was intermediate between placebo and calcium . Fracture rates and drop-out rates were similar among groups , and there were no serious adverse events with either supplement . A calcium supplement of 750 mg/day prevents loss of BMD , reduces femoral medullary expansion , secondary hyperparathyroidism , and high bone turnover . A supplement of 15 microg/day 25OH vitamin D3 is less effective , and because its effects are seen only at low calcium intakes , suggests that its beneficial effect is to reverse calcium insufficiency Summary We examined the independent and combined effects of a multi-component exercise program and calcium – vitamin-D3-fortified milk on bone mineral density ( BMD ) in older men .  Exercise result ed in a 1.8 % net gain in femoral neck BMD , but additional calcium – vitamin D3 did not enhance the response in this group of older well-nourished men . Introduction This 12-month r and omised controlled trial assessed whether calcium – vitamin-D3-fortified milk could enhance the effects of a multi-component exercise program on BMD in older men . Methods Men ( n = 180 ) aged 50–79 years were r and omised into : ( 1 )  exercise + fortified milk ; ( 2 ) exercise ; ( 3 ) fortified milk ; or ( 4 ) controls . Exercise consisted of high intensity progressive resistance training with weight-bearing impact exercise . Men assigned to fortified milk consumed 400 mL/day of low fat milk providing an additional 1,000 mg/day calcium and 800 IU/day vitamin D3 . Femoral neck ( FN ) , total hip , lumbar spine and trochanter BMD and body composition ( DXA ) , muscle strength 25-hydroxyvitamin D and parathyroid hormone ( PTH ) were assessed . Results There were no exercise-by-fortified milk interactions at any skeletal site . Exercise result ed in a 1.8 % net gain in FN BMD relative to no-exercise ( p < 0.001 ) ; lean mass ( 0.6 kg , p < 0.05 ) and muscle strength ( 20–52 % , p < 0.001 ) also increased in response to exercise . For lumbar spine BMD , there was a net 1.4–1.5 % increase in all treatment groups relative to controls ( all p < 0.01 ) . There were no main effects of fortified milk at any skeletal site . Conclusion A multi-component community-based exercise program was effective for increasing FN BMD in older men , but additional calcium – vitamin D3 did not enhance the osteogenic response To study the effect of calcium supplementation on  perimenopausal bone loss , 295 women were r and omized into a control group and 2 supplementation groups receiving , respectively , 1000 and 2000 mg elemental calcium/day for a period of 2 yr . We observed a significant decrease in lumbar bone loss in relation to the calcium supplementation ( mean loss after 2 yr of 3.5 % in the control group vs. 1.3 % and 0.7 % in the 1000 and 2000 mg groups , respectively ) , a significant increase in urinary calcium excretion , and a significant decrease in the urinary hydroxyproline/creatine ratio , serum alkaline phosphatase , osteocalcin , and 1,25-dihydroxyvitamin D. The effect of calcium supplementation on lumbar bone loss was significant in the first year of supplementation , but not in the second . However , the urinary hydroxyproline/creatinine ratio and the serum alkaline phosphatase level remained significantly decreased in the treatment groups at the end of the study ; this was not the case for serum osteocalcin . Calcium supplementation did not have a significant effect on metacarpal cortical bone loss . The difference in biochemical parameters between the 2 supplementation groups was small . No significant interaction was observed between the menopausal status of the subjects and the effect of calcium supplementation . We conclude that calcium supplementation retards lumbar bone loss in the first year of calcium supplementation by reducing bone turnover . However , the effect on lumbar bone loss over a longer time span is still uncertain We tested the spine antifracture and bone sparing efficacy of 1.2 g/day of oral calcium as carbonate in two groups of elderly women , one with prevalent fractures ( PF , n = 94 ) on entry and the other without ( NPF , n = 103 ) . It was a prospect i ve r and omized , double-blind , placebo-controlled trial in mostly rural communities in women over age 60 who were living independently and were consuming < 1 g/day of calcium .  We obtained annual lateral spine radiographs  and semiannual forearm bone density  over 4.3 + /- 1.1 years and determined vertebral fractures by radiographic morphometry augmented by physician assessment . In the PF group , 15 of 53 subjects on calcium had incident fractures , compared with 21 of 41 on placebo ( p = 0.023 , chi2 ) . Calcium did not reduce the rate of incident fractures in the NPF group . Those with a prevalent fracture on entry and not treated with calcium were 2.8 times more likely to experience an incident fracture than all others . Change in the forearm bone mass on placebo in the PF group was -1.24 + /- 2.41%/year compared with + 0.31 + /- 1.80%/year on calcium ( p < 0.001 ) . In the NPF group , the difference was less : -0.39 + /- 2.08%/year versus 0.00 + /- 1.64%/year ( p = 0.2 ) . We conclude that in elderly postmenopausal women with spine fractures and selfselected calcium intakes of < 1 g/day , a calcium supplement of 1.2 g/day reduces the incidence of spine fractures and halts measurable bone loss UNLABELLED Overweight postmenopausal women may be more susceptible to bone loss with weight reduction than previously studied obese women . The influence of energy restriction and Ca intake on BMD was assessed in 66 individuals .  Weight reduction result ed in bone loss at several sites in women consuming 1 g Ca/day and was mitigated with higher calcium intake at 1.7 g/day . INTRODUCTION Bone loss is associated with weight loss in obese postmenopausal women and can be prevented with calcium ( Ca ) supplementation . However , because bone loss caused by weight loss may be greater in overweight than obese women , it is not clear whether Ca supplementation is also beneficial in overweight women . MATERIAL S AND METHODS We assessed the influence of caloric restriction at two levels of Ca intake on BMD and BMC in 66 overweight postmenopausal women ( age , 61 + /- 6 years ; body mass index , 27.0 + /- 1.8 kg/m2 ) . Subjects completed either a 6-month energy-restricted diet ( WL , n = 47 ) and lost 9.3 + /- 3.9 % weight or maintained weight ( WM ; 1 g Ca/day , n = 19 ) . Participants in the WL group were r and omly assigned to either normal ( 1 g/day ; WL NL-Ca ) or high ( 1.7 g/day ; WL Hi-Ca ) Ca intake .  Regional BMD and BMC were measured at baseline and after 6 months . RESULTS During normal Ca intake , trochanter BMD and BMC and total spine BMD were decreased more in WL than WM women ( p < 0.05 ) . The WL NL-Ca group lost more trochanter BMD ( -4.2 + /- 4.1 % ) and BMC ( -4.8 + /- 7.1 % ) than the WL Hi-Ca group ( -1.4 + /- 5.6 % and -1.1 + /- 8.1 % , respectively ; p < 0.05 ) . There were no significant changes in BMD or BMC at the femoral neck in any group . Weight loss correlated with trochanter BMD loss ( r = 0.687 , p < 0.001 ) in the WL NL-Ca group . CONCLUSION Despite an intake of 1 g Ca/day , bone loss occurred at some sites because of weight loss . Calcium intake of 1.7 g/day will minimize bone loss during weight loss in postmenopausal overweight women The etiology of age-related bone loss is unclear but both lack of exercise and dietary calcium deficiency have been implicated in its causation . This 2-year r and omized placebo-controlled study was design ed to examine the effects of increased dietary calcium and exercise in 168 women who were more than 10 years postmenopausal . The subjects were r and omized into one of 4 groups : placebo , milk powder containing 1 g of calcium , calcium tablets 1 g/night , and calcium tablets 1 g/night and an exercise regimen . The exercise group aim ed to undertake 4 h of extra weight-bearing exercise per week and were undertaking 10 % more activity than other groups at 2 years . Bone mineral density at the lumbar spine , three hip sites , and two sites of the tibia close to the ankle joint were measured at 6 month intervals .  Dietary intake  was evaluated by a weighed food record ,  exercise  was evaluated by an exercise diary , and blood and urine sample s were obtained to examine effects on calcium homeostasis . Individual data points were compared using repeated measures ANOVA and least squares regression . Calcium supplementation by either the calcium tablets or the milk powder result ed in cessation of bone loss at the intertrochanteric hip site ( placebo , calcium tablets , calcium and exercise , milk powder -0.81 , + 0.17 , + 0.23 , and + 0.07 % per year , respectively ; p < 0.05 for all supplementation groups compared with placebo ) with similar results at the trochanteric hip site . The calcium and exercise group had less bone loss at the femoral neck site when compared with calcium supplementation alone ( placebo , calcium tablets , calcium and exercise , milk powder -0.67 , -0.18 , + 0.28 , and -0.18 % per year , respectively ; p < 0.05 for calcium and exercise compared with calcium alone ) . There was a significant reduction in the rate of bone loss at the ultradistal site of the tibia ( placebo , calcium tablets , calcium and exercise , milk powder -2.5 , -1.6 , -1.0 , and -1.5 % per year , respectively ; p < 0.05 for all supplementation groups compared with placebo ) . There was no significant bone loss at the spine site in any group . ( ABSTRACT TRUNCATED AT 250 WORDS Dietary studies often report low calcium intake amongst post-menopausal Malaysian women and calcium deficiency has been implicated as part of the etiology of age-related bone loss leading to osteoporosis . Therefore , the objective of this study was to examine the effectiveness of high calcium skimmed milk ( Anlene Gold ™ , New Zeal and Milk , Wellington , New Zeal and ) to reduce bone loss in Chinese postmenopausal women . Two hundred subjects aged 55–65 years and who were more than 5 years postmenopausal were r and omized to a milk group and control group . The milk group consumed 50 g of high calcium skimmed milk powder daily , which contained 1200 mg calcium ( taken as two glasses of milk a day ) . The control group continued with their usual diet . Using repeated measures ANCOVA , the milk supplement was found to significantly reduce the percentage of bone loss at the total body compared to the control group at 24 months ( control −1.04 % , milk −0.13 % ; P<0.001 ) . At the lumbar spine , the percentage of bone loss in the control group was significantly higher ( −0.90 % ) when compared to the milk ( −0.13 % ) supplemented group at 24 months ( P<0.05 ) . Similarly , milk supplementation reduced the percentage of bone loss at the femoral neck ( control −1.21 % , milk 0.51 % ) ( P<0.01 ) and total hip ( control −2.17 % , milk −0.50 % ) ( P<0.01 ) . The supplemented group did not experience any significant weight gain over the 24 months . The serum 25-hydroxy vitamin D level improved significantly ( P<0.01 ) from 69.1±16.1 nmol/l at baseline to 86.4±22.0 nmol/l at 24 months in the milk group . In conclusion , ingestion of high calcium skimmed milk was effective in reducing the rate of bone loss at clinical ly important lumbar spine and hip sites in postmenopausal Chinese women in Malaysia . Supplementing with milk had additional benefits of improving the serum 25-hydroxy vitamin D status of the subjects BACKGROUND The efficacy of calcium with vitamin D supplementation for preventing hip and other fractures in healthy postmenopausal women remains equivocal . METHODS We recruited 36,282 postmenopausal women , 50 to 79 years of age , who were already enrolled in a Women 's Health Initiative ( WHI ) clinical trial . We r and omly assigned participants to receive 1000 mg of elemental [ corrected ] calcium as calcium carbonate with 400 IU of vitamin D3 daily or placebo .  Fractures were ascertained for an average follow-up period of 7.0 years . Bone density was measured at three WHI centers . RESULTS Hip bone density was 1.06 percent higher in the calcium plus vitamin D group than in the placebo group ( P<0.01 ) . Intention-to-treat analysis indicated that participants receiving calcium plus vitamin D supplementation had a hazard ratio of 0.88 for hip fracture ( 95 percent confidence interval , 0.72 to 1.08 ) , 0.90 for clinical spine fracture ( 0.74 to 1.10 ) , and 0.96 for total fractures ( 0.91 to 1.02 ) . The risk of renal calculi increased with calcium plus vitamin D ( hazard ratio , 1.17 ; 95 percent confidence interval , 1.02 to 1.34 ) . Censoring data from women when they ceased to adhere to the study medication reduced the hazard ratio for hip fracture to 0.71 ( 95 percent confidence interval , 0.52 to 0.97 ) . Effects did not vary significantly according to prer and omization serum vitamin D levels . CONCLUSIONS Among healthy postmenopausal women , calcium with vitamin D supplementation result ed in a small but significant improvement in hip bone density , did not significantly reduce hip fracture , and increased the risk of kidney stones . ( Clinical Trials.gov number , NCT00000611 . ) Abstract : We undertook a double-masked , r and omized , placebo-controlled trial to evaluate the effect of a calcium and vitamin D supplement and a calcium supplement plus multivitamins on bone loss at the hip , spine and forearm . The study was performed in 240 healthy women , 58–67 years of age . Duration of treatment was 2 years . Bone mineral density ( BMD ) was measured at the lumbar spine , hip and forearm . A dietary question naire was administered twice during the study and revealed a fairly good calcium and vitamin D intake ( 919 mg calcium/day ; 3.8 mg vitamin D/day ) . An increase in lumbar spine BMD of 1.6 % was observed in the treatment group after 2 years ( p50.002 ) . In the placebo group no significant changes were observed during the 2 years . Lumbar spine BMD was significantly higher in the treatment group at both 1 ( p50.01 ) and 2 years ( p50.05 ) compared with the placebo group . Though not significant , the same trend was seen at the hip . No significant changes from baseline values were observed at the distal forearm in either the treatment or the placebo group . In conclusion , we found a significant increase in urinary calcium excretion in the treatment group compared with the placebo group . Together with significant changes in serum calcium and serum parathyroid hormone , this indicates that a long-term calcium and vitamin supplement of 1 g elementary calcium ( calcium carbonate ) and 14 mg vitamin D3 increases intestinal calcium absorption . A positive effect on BMD was demonstrated , even in a group of early postmenopausal age , with a fairly good initial calcium and vitamin D status Bone mobilization , lowering of bone mineral density ( BMD ) , and osteoporotic fractures are recognized in postmenopausal women with weight loss . Because a high-calcium intake suppresses bone loss in peri- and postmenopausal women , the present r and omized , double-blind , placebo-controlled study was design ed to test the hypothesis that calcium supplementation prevents net bone mobilization and consequent bone mineral loss during voluntary weight reduction in obese postmenopausal women . Subjects were placed on a moderate energy-restricted diet and either calcium supplementation ( 1 g/day ) or placebo for 6 months . Body weight , bone turnover markers ( pyridinium cross-links ) , osteocalcin , and parathyroid hormone ( PTH ) were measured at treatment weeks 1 - 5 , 7 , 10 , 13 , 16 , 20 , and 25 . Total body BMD , insulin-like growth factor , 25-hydroxyvitamin D , and sex hormone binding globulin ( SHBG ) were measured at baseline and week 25 . The calcium supplemented ( n = 15 ; age 60.9 + /- 9.4 years , body mass index [ BMI ] 33.2 + /- 4.6 kg/m2 ) and placebo ( n = 16 ; age 55.8 + /- 8.3 years , BMI 32.9 + /- 4.5 kg/m2 ) groups lost similar amounts of weight over the study interval ( 10.2 + /- 5.3 % vs. 10.0 + /- 5.2 % ) and both groups increased SHBG ( p < 0.001 ) . There was a statistical effect of calcium supplementation during weight loss to suppress pyridinium cross-links , osteocalcin , and PTH ( p < 0.05 , < 0.01 , and < 0.05 , respectively ) . Loss of BMD tended to be greater in the placebo group by 1.4 % ( p < 0.08 ) after weight loss . One gram per day calcium supplementation normalizes the increased calcium-PTH axis activity and the elevated bone turnover rate observed during moderate voluntary energy restriction in postmenopausal women Elderly women are at increased risk for bone loss and fractures . In previous cross-sectional and longitudinal studies of women residing in northern latitudes , bone loss was most pronounced during winter months and in those consuming less than 1 g calcium per day . In this study we sought to test the hypothesis that calcium supplementation by either calcium carbonate or dietary means would prevent seasonal bone loss and preserve bone mass . Sixty older postmenopausal women without osteoporosis were r and omized to one of three treatment arms : Dietary milk supplementation ( D-4 glasses of milk/day ) , Calcium carbonate ( CaCO3 - 1000 mg/day in two divided doses ) , or placebo ( P ) . After 2 yr , placebo-treated women consumed a mean of 683 mg/day of calcium and lost 3.0 % of their greater trochanteric ( GT ) bone mineral density ( BMD ) ( P < 0.03 vs. baseline ) ; Dietary supplemented women averaged a calcium intake of 1028 mg/day and sustained minimal loss from the GT ( -1.5 % ; P = 0.30 ) , whereas CaCO3-treated women ( total Ca intake , 1633 mg/day ) suffered no bone loss from the GT and showed a significant increase in spinal and femoral neck BMD ( P < 0.05 ) . Femoral bone loss occurred exclusively during the two winters of the study ( i.e. total loss , -3.2 % ; P < 0.02 in placebo-treated women ) with virtually no change in GT BMD during summer . Serum 25-OH vitamin D declined by more than 20 % ( P < 0.001 ) in all groups during the winter months but returned to baseline in summer ; PTH levels rose approximately 20 % ( P < 0.001 ) during winter but did not return to baseline during the summers . Urine N-telopeptide and osteocalcin levels increased significantly but only in the P-treated women and only during winter . Serum insulin growth factor binding protein 4 , an inhibitory insulin growth factor binding protein , rose 15 % ( P < 0.03 ) from summer to winter , but this increase was significant only in those women consuming < 1000 mg/day of calcium . By multivariate analysis , total calcium intake was the strongest predictor of bone loss from the hip . Urinary N-telopeptide also closely correlated with GT BMD but only during winter ( P = 0.003 ) . We conclude that calcium supplementation prevents bone loss  in elderly women by suppressing bone turnover during the winter when serum 25-OH vitamin D declines and serum PTH increases . The precise amount of calcium necessary to preserve BMD in elderly women requires further studies , although in this study , at least 1000 mg/day of supplemental calcium was adequate prophylaxis against femoral bone loss Objective To determine the effect of calcium supplementation on myocardial infa rct ion , stroke , and sudden death in healthy postmenopausal women . Design R and omised , placebo controlled trial . Setting Academic medical centre in an urban setting in New Zeal and . Participants 1471 postmenopausal women ( mean age 74 ) : 732 were r and omised to calcium supplementation and 739 to placebo .  Main outcome measures Adverse cardiovascular events over five years : death , sudden death , myocardial infa rct ion , angina , other chest pain , stroke , transient ischaemic attack , and a composite end point of myocardial infa rct ion , stroke , or sudden death . Results Myocardial infa rct ion was more commonly reported in the calcium group than in the placebo group ( 45 events in 31 women v 19 events in 14 women , P=0.01 ) . The composite end point of myocardial infa rct ion , stroke , or sudden death was also more common in the calcium group ( 101 events in 69 women v 54 events in 42 women , P=0.008 ) . After adjudication myocardial infa rct ion remained more common in the calcium group ( 24 events in 21 women v 10 events in 10 women , relative risk 2.12 , 95 % confidence interval 1.01 to 4.47 ) . For the composite end point 61 events were verified in 51 women in the calcium group and 36 events in 35 women in the placebo group ( relative risk 1.47 , 0.97 to 2.23 ) . When unreported events were added from the national data base of hospital admissions in New Zeal and the relative risk of myocardial infa rct ion was 1.49 ( 0.86 to 2.57 ) and that of the composite end point was 1.21 ( 0.84 to 1.74 ) . The respective rate ratios were 1.67 ( 95 % confidence intervals 0.98 to 2.87 ) and 1.43 ( 1.01 to 2.04 ) ; event rates : placebo 16.3/1000 person years , calcium 23.3/1000 person years . For stroke ( including unreported events ) the relative risk was 1.37 ( 0.83 to 2.28 ) and the rate ratio was 1.45 ( 0.88 to 2.49 ) . Conclusion Calcium  supplementation in healthy postmenopausal women is associated with upward trends in cardiovascular event rates . This potentially detrimental effect should be balanced against the likely benefits of calcium on bone . Trial registration Australian Clinical Trials Registry ACTRN 012605000242628 OBJECTIVE To establish whether calcium-enriched milk reduces bone loss in women who are within five years of the menopause and have a basal calcium intake < or = 1,250 mg . DESIGN Two-year open , crossover study . SETTING A community-based study carried out in Adelaide , South Australia , between September 1997 and June 2000 . PARTICIPANTS 115 women recruited by newspaper advertisement , who were less than five years postmenopausal , were not taking hormone or other therapy that could affect bone and had a usual calcium intake < or = 1,250 mg daily . INTERVENTION Participants were r and omly allocated to Group 1 ( who received a supplement of 3 L of calcium-fortified milk weekly in the first year ) or Group 2 ( who followed their usual diets in the first year ) . In the second year , Group 1 reverted to their usual diets , and Group 2 received the milk supplement . MAIN OUTCOME MEASURES Difference in loss of bone mineral density ( BMD ) at the spine and forearm in the same individuals on and off the milk supplement ;  urinary excretion of bone resorption markers in a subset of 72 participants in the first year . RESULTS With each woman serving as her own control , the rate of bone loss from the spine was 1.76 percentage points less when the women were taking the milk supplement than when they were on their usual diet ( 95 % CI , 0.54%-2.98 % ; P=0.006 ) . However , there was no significant difference in bone loss in the forearm . Fasting urine levels of two markers of bone resorption ( hydroxyproline and deoxypyridinoline ) were significantly lower in 36 women in the milk group than in 36 women in the usual-diet group ( P=0.03 for both markers ) . CONCLUSION Supplementing the diet with calcium-fortified milk early in the postmenopausal period delays bone loss at the spine but not at the forearm , and reduces the excretion of bone resorption markers The efficacy of calcium ( Ca ) in reducing bone loss is debated . In a r and omized placebo-controlled double-masked study , we investigated the effects of oral Ca supplements on femoral shaft ( FS ) , femoral neck ( FN ) and lumbar spine ( LS ) bone mineral density ( BMD ) , and on the incidence of vertebral fracture in vitamin-D-replete elderly . Ninety-three healthy subjects ( 72.1±0.6 years ) were r and omly allocated to three groups receiving 800 mg/day Ca in two different forms or a placebo for 18 months . Sixty-three patients ( 78.4±1.0 years ) with a recent hip fracture were allocated to two groups receiving the two forms of Ca without placebo . FS BMD changes in Ca-supplemented non-fractured women were significantly different from those in the placebo group ( + 0.6±0.5 % v −1.2±0.7%,p<0.05 ) . There was no difference in effect between the two forms of Ca . The changes of + 0.7±0.8 % v −1.7±1.6 % in FN BMD of Ca-supplemented women and the placebo group did not reach statistical significance . In fractured patients , FS , FN and LS BMD changes were −1.3±0.8 , + 0.3±1.6 and + 3.1±1.2 % ( p<0.05 for the last ) . The rate of new vertebral fractures was 74.3 and 106.2 fractures per 1000 patient-years in Ca-supplemented non-fractured subjects and in the placebo group , respectively , and 144.0 in Ca-supplemented fractured patients . Thus , oral Ca supplements prevented a femoral BMD decrease and lowered vertebral fracture rate in the elderly BACKGROUND The use of calcium supplements slows bone loss in the forearm and has a beneficial effect on the axial bone density of women in late menopause whose calcium intake is less than 400 mg per day . However , the effect of a calcium supplement of 1000 mg per day on the axial bone density of postmenopausal women with higher calcium intakes is not known . METHODS We studied 122 normal women at least three years after they had reached menopause who had a mean dietary calcium intake of 750 mg per day . The women were r and omly assigned to treatment with either calcium ( 1000 mg per day ) or placebo for two years . The bone mineral density of the total body , lumbar spine , and proximal femur was measured every six months by dual-energy x-ray absorptiometry .  Serum and urine indexes of calcium metabolism were measured at base line and after 3 , 12 , and 24 months . RESULTS The mean ( + /- SE ) rate of loss of total-body bone mineral density was reduced by 43 percent in the calcium group ( -0.0055 + /- 0.0010 g per square centimeter per year ) as compared with the placebo group ( -0.0097 + /- 0.0010 g per square centimeter per year , P = 0.005 ) . The rate of loss of bone mineral density was reduced by 35 percent in the legs ( P = 0.02 ) , and loss was eliminated in the trunk ( P = 0.04 ) . Calcium use was of significant benefit in the lumbar spine ( P = 0.04 ) , and in Ward 's triangle the rate of loss was reduced by 67 percent ( P = 0.04 ) . Calcium supplementation had a similar effect whether dietary calcium intake was above or below the mean value for the group . Serum parathyroid hormone concentrations tended to be lower in the calcium group , as were urinary hydroxyproline excretion and serum alkaline phosphatase concentrations . CONCLUSIONS Calcium supplementation significantly slowed axial and appendicular bone loss in normal post-menopausal women BACKGROUND Estrogen-replacement therapy prevents osteoporosis in postmenopausal women by inhibiting bone resorption , but the balance between its long-term risks and benefits remains unclear . Whether other antiresorptive therapies can prevent osteoporosis in these women is also not clear . METHODS We studied the effect of 2.5 mg or 5 mg of alendronate per day or placebo on bone mineral density in 1174 postmenopausal women under 60 years of age . An additional 435 women who were prepared to receive a combination of estrogen and progestin  were r and omly assigned to one of the above treatments or open-label estrogen-progestin . The main outcome measure was the change in bone mineral density of the lumbar spine , hip , distal forearm , and total body measured annually for two years by dual-energy x-ray absorptiometry . RESULTS The women who received placebo lost bone mineral density at all measured sites , whereas the women treated with 5 mg of alendronate daily had a mean ( + /-SE ) increase in bone mineral density of 3.5+/-0.2 percent at the lumbar spine , 1.9+/-0.1 percent at the hip , and 0.7+/-0.1 percent for the total body ( all P<0.001 ) . Women treated with 2.5 mg of alendronate daily had smaller increases in bone mineral density .  Alendronate did not increase bone mineral density of the forearm , but it slowed the loss . The responses to estrogen-progestin were 1 to 2 percentage points greater than those to the 5-mg dose of alendronate . Alendronate was well tolerated , with a safety profile similar to that of placebo or estrogen-progestin . CONCLUSIONS Alendronate prevents bone loss in postmenopausal women under 60 years of age to nearly the same extent as estrogen-progestin Summary Supplementation with elemental calcium 500 mg/day alone for 2 years is able to decrease bone turnover and is effective in retarding bone loss at lumbar spine and slowing bone loss at femoral neck in elderly Thai women who had low dietary calcium intake . Introduction Most elderly Thais have a total dietary calcium intake of less than the recommended amount . The aim of the study was to investigate the effect of calcium supplementation on bone mineral density and biochemical indices of bone remodeling in Thai postmenopausal women . Methods Four hundred and four healthy postmenopausal women 60 years old or older without osteoporosis were recruited and conducted in a r and omized , double-blinded , placebo-controlled trial . They were r and omly given elementary calcium 500 mg/day or placebo for 2 years . Dietary calcium intake was calculated from the nutrient compositional analysis of the 3-day food records . Serum 25 hydroxyvitamin D was measured by radioimmunoassay and bone turnover markers were determined by electrochemiluminescence immunoassay . Results The age of the subjects was 65.8 ± 4.4 years . All baseline characteristics of the subjects in the calcium-supplemented group and the placebo group were not statistically different . At the end of the study , significant decreases in serum C-terminal telopeptide of type I collagen and serum total procollagen type I amino terminal propeptide in the calcium-supplemented group were observed , while there was no change in the placebo group . In addition , plasma parathyroid hormone decreased , although not significantly , only in the calcium-supplemented group . Percent changes from baseline of lumbar spine ( L2–L4 ) bone mineral density increased 2.76 % in the calcium-supplemented group and 0.87 % in the placebo group , whereas the percent changes from baseline of femoral neck decreased 0.21 % in the calcium-supplemented group and 0.90 % in the placebo group . Conclusions Calcium supplementation is necessary for the decrease of bone turnover and prevention of bone loss in Thai elderly women BACKGROUND Increased dietary calcium intake has been proposed as a population -based public health intervention to prevent osteoporotic fractures . We have examined whether calcium supplementation decreases clinical fracture risk in elderly women and its mechanism of action . METHODS Five-year , double-blind , placebo-controlled study of 1460 women recruited from the population and older than 70 years ( mean age , 75 years ) who were r and omized to receive calcium carbonate , 600 mg twice per day , or identical placebo .  The primary end points included clinical incident osteoporotic fractures , vertebral deformity , and adverse events ascertained in 5 years . Bone structure was also measured using dual x-ray absorptiometry of the hip and whole body , quantitative ultrasonography of the heel , and peripheral quantitative computed tomography of the distal radius . RESULTS Among our patients , 16.1 % sustained 1 or more clinical osteoporotic fractures . In the intention-to-treat analysis , calcium supplementation did not significantly reduce fracture risk ( hazard ratio , 0.87 ; 95 % confidence interval , 0.67 - 1.12 ) . However , 830 patients ( 56.8 % ) who took 80 % or more of their tablets ( calcium or placebo ) per year had reduced fracture incidence in the calcium compared with the placebo groups ( 10.2 % vs 15.4 % ; hazard ratio , 0.66 ; 95 % confidence interval , 0.45 - 0.97 ) . Calcium-treated patients had improved quantitative ultrasonography findings of the heel , femoral neck and whole-body dual x-ray absorptiometry data , and bone strength compared with placebo-treated patients . Of the 92 000 adverse events recorded , constipation was the only event increased by the treatment ( calcium group , 13.4 % ; placebo group , 9.1 % ) . CONCLUSION Supplementation with calcium carbonate tablets supplying 1200 mg/d is ineffective as a public health intervention in preventing clinical fractures in the ambulatory elderly population owing to poor long-term compliance , but it is effective in those patients who are compliant Background . The effectiveness of calcium in retarding bone loss in older postmenopausal women is unclear . Earlier work suggested that the women who were most likely to benefit from calcium supplementation were those with low calcium intakes . Methods . We undertook a double-blind , placebo-controlled , r and omized trial to determine the effect of calcium on bone loss from the spine , femoral neck , and radius in 301 healthy postmenopausal women , half of whom had a calcium intake lower than 400 mg per day and half an intake of 400 to 650 mg per day . The women received placebo or either calcium carbonate or calcium citrate malate ( 500 mg of calcium per day ) for two years . Results . In women who had undergone menopause five or fewer years earlier , bone loss from the spine was rapid and was not affected by supplementation with calcium . Among the women who had been postmenopausal for six years or more and who were given placebo , bone loss was less rapid in the group with the higher dietary calcium intake . In those with the lower calcium intake , calcium citrate malate prevented bone loss during the two years of the study ; its effect was significantly different from that of placebo ( P less than 0.05 ) at the femoral neck ( mean change in bone density [ + /- SE ] , 0.87 + /- 1.01 percent vs. -2.11 + /- 0.93 percent ) , radius ( 1.05 + /- 0.75 percent vs. -2.33 + /- 0.72 percent ) , and spine ( -0.38 + /- 0.82 percent vs. -2.85 + /- 0.77 percent ) . Calcium carbonate maintained bone density at the femoral neck ( mean change in bone density , 0.08 + /- 0.98 percent ) and radius ( 0.24 + /- 0.70 percent ) but not the spine ( -2.54 + /- 0.85 percent ) . Among the women who had been postmenopausal for six years or more and who had the higher calcium intake , those in all three treatment groups maintained bone density at the hip and radius and lost bone from the spine . Conclusions . Healthy older postmenopausal women with a daily calcium intake of less than 400 mg can significantly reduce bone loss by increasing their calcium intake to 800 mg per day . At the dose we tested , supplementation with calcium citrate malate was more effective than supplementation with calcium carbonate Summary Daily treatment with 30 mg of sodium fluoride ( NaF ) and 1 g of calcium over a 3-year period increased the bone mineral content ( BMC ) in the spines of women ( n=25 ) with osteoporosis . Determination of the BMC was followed with dual photon absorptiometry ( 137Cs-241Am ) in the third lumbar vertebra . No increase in BMC was found with only 10 mg sodium fluoride in combination with calcium ( n=25 ) , with calcium alone ( n=25 ) , or with placebo ( n=25 ) . No serious side effects were registered . There was , however , minor gastrointestinal distress in one-fifth of the patients taking 30 mg NaF daily We report a 4-year r and omized , double-blind , placebo-controlled clinical trial in 236 normal postmenopausal women ( mean age + /- SE , 66.3+/-0.2 years ) who were r and omized to a calcium ( 1600 mg/day as the citrate ) or placebo group .  The women were seen every 6 months ; 177 completed the trial . Net percentage changes in each group are given relative to baseline . The differences in net percentage changes ( calcium group minus placebo group ) in medians were : for lumbar spine bone density , 2.0 % ( p < 0.001 ) at year 1 and 0.3 % ( not significant ) at year 4 ; for proximal femur bone density , 1.3 % ( p = 0.003 ) at year 1 and 1.3 % ( p = 0.015 ) at year 4 ; and for total body bone mineral , 0.4 % ( p = 0.002 ) at year 1 and 0.9 % ( p = 0.017 ) at year 4 . Similar differences at year 4 were : -18.9 % ( p = 0.002 ) for parathyroid hormone ( PTH ) , -11.9 % ( p = 0.026 ) for serum osteocalcin , and -32.2 % ( p = 0.003 ) for urine free pyridinoline . We conclude that long-term administration of calcium supplements  to elderly women partially reverses age-related increases in serum PTH level and bone resorption and decreases bone loss . However , the effects on bone loss were weaker than those reported for estrogen , bisphosphonates , or calcitonin therapy , indicating that calcium supplements alone can not substitute for these in treating established osteoporosis . Nonetheless , because of their safety , high tolerance , and low expense , calcium supplements may be a useful preventive measure for elderly postmenopausal women whose bone mineral density values are normal for their age The Chinese diet is low in calcium ( less than 500 mg/day on average ) , and previous observational studies have suggested an association between a low calcium intake and risk of hip and vertebral fracture . In this study , we r and omly assigned 200 postmenopausal Chinese women ( age range , 55 - 59 years ) to receive 50 g of milk powder containing 800 mg of calcium per day or to a control group . The following are the mean percentage changes ( and SEs ) in height and bone mineral density ( BMD ) over 24 months : for height , -0.1 + /- 0.2 cm in the milk supplementation group and -0.2 + /- 0.1 cm in the control group ; for BMD at the total hip , -0.06 + /- 0.22 % in the milk supplementation group and -0.88 + /- 0.26 % in the control group ; for BMD at the spine ( L1-L4 ) , -0.56 + /- 0.29 % in the milk supplementation group and -1.5 + /- 0.29 % in the control group ; for total body BMD , -0.32 + /- 0.16 % in the milk supplementation group and -1.2 + /- 0.19 % in the control group ( p < 0.05 by analysis of covariance [ ANCOVA ] for repeated measures for height and BMD at all sites ) . The milk supplementation group had less loss in terms of both height and BMD than the control group ( p < 0.05 by ANCOVA for repeated measures ) . Serum parathyroid hormone ( PTH ) concentration was lower and serum 25-hyroxyvitamin D [ 25(OH)D ] level was higher in the milk supplementation group than the control group at 12 months ( p < 0.05 by paired t-test ) . We conclude that supplementing the diet of postmenopausal Chinese women with high calcium milk powder retards bone loss Sixty postmenopausal women were placed in three groups -- control , sex hormone-treated , and CaCO3-treated-- and followed for 2 years . Skeletal mass decreased by 1.18%/year in the control group , 0.15%/year in the hormone group , and 0.22%/year in the CaCO3 group by radiogrammetry ; and 2.88%/year in the control group , 0.73%/year in the hormone group , and 1.83%/year in the CaCO3 group by photon absorptiometry . The treatment groups differed significantly from the control group except for photon absorptiometry in the CaCO3 group . Bone accretion and resorption decreased in the treatment groups as measured by calcium tracer kinetics , resorption more so than accretion . We conclude that [ 1 ] these techniques are sufficiently sensitive to detect age-related bone loss ; [ 2 ] postmenopausal sex-hormone replacement measurably decreases age-related bone loss by suppressing bone turnover , resorption more than accretion ; and [ 3 ] calcium supplements produce the same effect but at the dose we used were slightly less effective OBJECTIVE To determine the rate of bone loss in normal men , and to examine the effects of dietary calcium and cholecalciferol supplementation on bone loss in men . DESIGN Double-blinded , placebo-controlled 3-year trial of supplementation with calcium ( 1000 mg/d ) and cholecalciferol ( 25 micrograms/d ) . SETTING Clinical research center at a university medical facility . SUBJECTS Normal men 30 to 87 years old , recruited from the Portl and community . MEASUREMENTS AND MAIN RESULTS Radial bone mineral content ( assessed by single-photon absorptiometry ) fell by 1.0%/y ( 95 % CI , -1.3 % to 0.7 % ) at a proximal radial site and 1.0%/y ( 95 % CI , -1.4 % to -0.6 % ) at a distal radial site . Vertebral bone mineral content ( assessed by dual-energy quantitative computed tomography ) declined by 2.3%/y ( 95 % CI , -2.8 % to -1.8 % ) . In these healthy men with a high basal dietary calcium intake ( 1159 mg/d ) , calcium and cholecalciferol supplementation did not affect bone loss at any site . CONCLUSIONS Normal men experience a substantial bone loss at both axial and appendicular sites that is not prevented by calcium and vitamin D supplementation in a well-nourished population CONTEXT Despite decades of use and considerable research , the role of estrogen alone in preventing chronic diseases in postmenopausal women remains uncertain . OBJECTIVE To assess the effects on major disease incidence rates of the most commonly used postmenopausal hormone therapy in the United States . DESIGN , SETTING , AND PARTICIPANTS A r and omized , double-blind , placebo-controlled disease prevention trial ( the estrogen-alone component of the Women 's Health Initiative [ WHI ] ) conducted in 40 US clinical centers beginning in 1993 . Enrolled were 10 739 postmenopausal women , aged 50 - 79 years , with prior hysterectomy , including 23 % of minority race/ethnicity . INTERVENTION Women were r and omly assigned to receive either 0.625 mg/d of conjugated equine estrogen ( CEE ) or placebo . MAIN OUTCOME MEASURES The primary outcome was coronary heart disease ( CHD ) incidence ( nonfatal myocardial infa rct ion or CHD death ) . Invasive breast cancer incidence was the primary safety outcome . A global index of risks and benefits , including these primary outcomes plus stroke , pulmonary embolism ( PE ) , colorectal cancer , hip fracture , and deaths from other causes , was used for summarizing overall effects . RESULTS In February 2004 , after review ing data through November 30 , 2003 , the National Institutes of Health ( NIH ) decided to end the intervention phase of the trial early . Estimated hazard ratios ( HRs ) ( 95 % confidence intervals [ CIs ] ) for CEE vs placebo for the major clinical outcomes available through February 29 , 2004 ( average follow-up 6.8 years ) , were : CHD , 0.91 ( 0.75 - 1.12 ) with 376 cases ; breast cancer , 0.77 ( 0.59 - 1.01 ) with 218 cases ; stroke , 1.39 ( 1.10 - 1.77 ) with 276 cases ; PE , 1.34 ( 0.87 - 2.06 ) with 85 cases ; colorectal cancer , 1.08 ( 0.75 - 1.55 ) with 119 cases ; and hip fracture , 0.61 ( 0.41 - 0.91 ) with 102 cases . Corresponding results for composite outcomes were : total cardiovascular disease , 1.12 ( 1.01 - 1.24 ) ; total cancer , 0.93 ( 0.81 - 1.07 ) ; total fractures , 0.70 ( 0.63 - 0.79 ) ; total mortality , 1.04 ( 0.88 - 1.22 ) , and the global index , 1.01 ( 0.91 - 1.12 ) . For the outcomes significantly affected by CEE , there was an absolute excess risk of 12 additional strokes per 10 000 person-years and an absolute risk reduction of 6 fewer hip fractures per 10 000 person-years . The estimated excess risk for all monitored events in the global index was a nonsignificant 2 events per 10 000 person-years . CONCLUSIONS The use of CEE increases the risk of stroke , decreases the risk of hip fracture , and does not affect CHD incidence in postmenopausal women with prior hysterectomy over an average of 6.8 years . A possible reduction in breast cancer risk requires further investigation . The burden of incident disease events was equivalent in the CEE and placebo groups , indicating no overall benefit . Thus , CEE should not be recommended for chronic disease prevention in postmenopausal women The effects of a supervised 1-y walking program and increased dietary calcium ( milk supplement , 831 mg/d , vs placebo drink , 41 mg/d ) on bones were examined in 36 postmenopausal women ( 60.2 + /- 6.5 y ) .  Trabecular bone-mineral density ( BMD ) of the lumbar spine ( L1-L3 ) , measured by computed tomography , increased by 0.5 % in exercising women ( n = 18 ) and decreased by 7.0 % in sedentary women ( n = 18 ; P = 0.02 ) . Femoral-neck BMD measured by dual-photon absorptiometry ( DPA ) increased by 2.0 % in women consuming high dietary calcium ( n = 18 ) and decreased by 1.1 % in those on moderate calcium intake ( n = 18 ; P = 0.001 ) . Neither exercise nor  dietary calcium  had an effect on lumbar spine ( L2-L4 ) measured by DPA , distal radius measured by single-photon absorptiometry , or total body calcium measured by in vivo neutron activation . The varying proportions and rates of turnover of trabecular and cortical bone from one site to another suggest that exercise and high dietary calcium may preferentially alter bone density at different skeletal sites BACKGROUND survivors of hip fracture are at 5- to 10-fold risk of a second hip fracture . There is little consensus about secondary prevention . Many are given calcium and vitamin D , but the evidence supporting this is circumstantial . OBJECTIVE to compare the effects of different calcium and vitamin D supplementation regimens on bone biochemical markers , bone mineral density and rate of falls in elderly women post-hip fracture . DESIGN r and omised controlled trial . SETTING orthogeriatric rehabilitation ward . METHODS 150 previously independent elderly women , recruited following surgery for hip fracture , were assigned to receive a single injection of 300,000 units of vitamin D(2 ) , injected vitamin D(2 ) plus 1 g/day oral calcium , 800 units/day oral vitamin D(3 ) plus 1 g/day calcium , or no treatment . Follow-up was one year , with measurement of 25-hydroxyvitamin D , parathyroid hormone , bone mineral density , and falls . RESULTS mean 25-hydroxyvitamin D increased and mean parathyroid hormone was suppressed in all the actively treated groups , more so in the group receiving combined oral vitamin D and calcium . Twenty per cent of participants injected with vitamin D were deficient in 25-hydroxyvitamin D a year later . Bone mineral density showed small but statistically significant differences of up to 4.6 % between actively treated groups and placebo . Relative risk of falling in the groups supplemented with vitamin D was 0.48 ( 95 % CI 0.26 - 0.90 ) compared with controls . CONCLUSION Vitamin D supplementation , either orally or with injected vitamin D , suppresses parathyroid hormone , increases bone mineral density and reduces falls . Effects may be more marked with calcium co-supplementation . The 300,000 units of injected vitamin D may not last a whole year A r and omized , prospect i ve , double-blind test was carried out to compare the effects of heated oyster shell-seaweed calcium ( AAA Ca ) , calcium carbonate , and placebo in 58 elderly , hospitalized women with the mean age of 80 divided into three groups . Group A received 900 mg/day Ca as AAA Ca , Group B 900 mg/day Ca as CaCO3 , and Group C placebo besides regular hospital diet containing approximately 600 mg Ca/day for 24 months . From the 25th to the 30th month , all groups were given AAA Ca .  Lumbar spine and radial bone mineral density ( BMD ) were measured at 3-month intervals . Urinary Ca/Cr and serum alkaline phosphatase , intact and midportion serum parathyroid hormone ( PTH ) , and calcitonin were also measured at intervals . From the 6th to the 24th month of the study , the ratio of lumbar spine BMD ( L2–L4 by DPX , Lunar ) to the basal pretest value was consistently and significantly higher in Group A than Group C but not higher in Group B than in Group C. PTH , measured 12 months after the beginning of the study , was lower in Group A than in Group C , but no significant difference was found between Groups B and C. At 3 months after the placebo was switched to AAA Ca in Group C , serum PTH was significantly decreased from the level during placebo supplement . Morning urine Ca/Cr decreased in Groups A after 18 months and in B after 12 months , but not in C. Serum alkaline phosphatase decreased in Group A significantly compared with Group C , but not in Group B. AAA Ca appears to be effective for increasing BMD in elderly subjects BACKGROUND Inadequate dietary intake of calcium and vitamin D may contribute to the high prevalence of osteoporosis among older persons . METHODS We studied the effects of three years of dietary supplementation with calcium and vitamin D on bone mineral density , biochemical measures of bone metabolism , and the incidence of nonvertebral fractures in 176 men and 213 women 65 years of age or older who were living at home . They received either 500 mg of calcium plus 700 IU of vitamin D3 ( cholecalciferol ) per day or placebo .  Bone mineral density was measured by dual-energy x-ray absorptiometry , blood and urine were analyzed every six months , and cases of nonvertebral fracture were ascertained by means of interviews and verified with use of hospital records . RESULTS The mean ( + /-SD ) changes in bone mineral density in the calcium-vitamin D and placebo groups were as follows : femoral neck , + 0.50+/-4.80 and -0.70+/-5.03 percent , respectively ( P=0.02 ) ; spine,+2.12+/-4.06 and + 1.22+/-4.25 percent ( P=0.04 ) ; and total body , + 0.06+/-1.83 and -1.09+/-1.71 percent ( P<0.001 ) . The difference between the calcium-vitamin D and placebo groups was significant at all skeletal sites after one year , but it was significant only for total-body bone mineral density in the second and third years . Of 37 subjects who had nonvertebral fractures , 26 were in the placebo group and 11 were in the calcium-vitamin D group ( P=0.02 ) . CONCLUSIONS In men and women 65 years of age or older who are living in the community , dietary supplementation with calcium and vitamin D moderately reduced bone loss measured in the femoral neck , spine , and total body over the three-year study period and reduced the incidence of nonvertebral fractures ABSTRACT Objective : Bisphosphonates such as alendronate are widely used for postmenopausal osteoporosis . Supplemental calcium is also generally recommended . This trial directly compares alendronate to supplemental calcium and examines the effect of calcium supplementation on alendronate treatment . Methods : This 2-year , r and omized , double-blind , multicenter trial enrolled healthy , postmenopausal women with low bone mineral density ( BMD ) . Patients with a dietary calcium intake ≥ 800 mg/day received daily vitamin D 400 IU and alendronate 10 mg/calcium-placebo , alendronate 10 mg/elemental calcium 1000 mg , or alendronate-placebo/calcium 1000 mg ( 2:2:1 ) . Endpoints included BMD , bone turnover markers ( BTMs ) , and adverse events . Results : R and omized patients ( N = 701 ) were an average of 20.4 years postmenopausal . After 24 months , increases in lumbar spine BMD differed significantly between patients receiving calcium alone ( 0.8 % ) and either alendronate alone ( 5.6 % ) or alendronate + calcium ( 6.0 % ) ( p < 0.001 ) . Significant differences were also seen at the trochanter and femoral neck ( p < 0.001 ) . BTMs were significantly lower with alendronate-containing treatments than calcium alone ( p < 0.001 ) . Addition of calcium supplementation to alendronate did not significantly increase BMD  compared to alendronate alone ( p = 0.29 to 0.97 ) , but did result in a statistically significant , though small , additional reduction in urinary NTx . Adverse events were similar among treatment groups . Limitations include no assessment of vitamin D levels and a discontinuation rate of approximately 30 % , although discontinuation rates were similar among treatment groups . Conclusions : In postmenopausal women with a daily intake of ≥ 800 mg calcium and 400 IU vitamin D , 24-month treatment with alendronate 10 mg daily with or without calcium 1000 mg result ed in significantly greater increases in BMD and reduction of bone turnover than supplemental calcium alone . Addition of supplemental calcium to alendronate treatment had no effect on BMD and result ed in a small , though statistically significant , additional reduction in NTx UNLABELLED A 3-year prospect i ve , r and omized , placebo-controlled trial of oral clodronate 800 mg showed that the incidence of clinical fractures was decreased by 20 % in 5596 elderly women unselected for osteoporosis . The effect occurred in the absence of systematic calcium and vitamin D supplementation and was observed across a wide range of BMDs . INTRODUCTION To date , most studies with bisphosphonates have reported on their use in individuals selected to be at high risk for fracture usually by the presence of low BMD or a prior fragility fracture , usually of the spine . We wished to determine the effect of the bisphosphonate , clodronate , on the rate of fractures in women > or = 75 years of age living in the community . MATERIAL S AND METHODS Women > or = 75 years of age living in the general community in South Yorkshire and North Derbyshire , identified from general practice registers , were recruited by letter of invitation to a r and omized , double-blind , controlled trial of 800 mg oral clodronate ( Bonefos ) or matching placebo daily over 3 years . The main outcomes were the incidences of hip and any clinical fracture . RESULTS Of the 5579 elderly women included in the intention-to-treat analysis of efficacy , 114 had a new hip fracture during the 3-year treatment phase : 56 ( 2.0 % ) women in the clodronate group and 58 ( 2.1 % ) women in the placebo group ( hazard ration [ HR ] , 1.02 ; 95 % CI , 0.71 - 1.47 ) . Clodronate did , however , decrease the incidence of any clinical fracture by 20 % ( 264 women [ 9.5 % ] versus 337 [ 12.1 % ] in the placebo group ; HR , 0.80 ; 95 % CI , 0.68 - 0.94 ) . The incidence of osteoporosis-associated nonhip fractures was also significantly decreased by 29 % ( 5.2 % versus 7.4 % ; HR , 0.71 ; 95 % CI , 0.57 - 0.87 ) . The ability of clodronate to reduce the risk of osteoporotic fracture was independent of baseline BMD , but the number needed-to-treat was lower in the presence of osteoporosis . CONCLUSIONS Oral daily clodronate can prevent fractures without significant adverse effects in elderly women living in the general community . The effect on hip fracture risk is not significant , but an effect similar to that at other nonvertebral sites can not be excluded . This study suggests that antiresorptive therapies can reduce fracture incidence in high-risk individuals even in the presence of a normal or osteopenic BMD OBJECTIVE The hypothesis was that the calcium and vitamin D supplementation prevents falls at the population level . STUDY DESIGN The OSTPRE-FPS was a r and omized population -based open-trial with 3-year follow-up . The supplementation group ( n=1566 ) received daily cholecalciferol 800IU+calcium carbonate 1000 mg , while the  control group ( n=1573 ) received no supplementation or placebo .  A r and omly selected sub sample of 593 subjects underwent a detailed measurement program including serum 25(OH)D measurements . MAIN OUTCOME MEASURE The occurrence of falls was the primary outcome of the study . The participants in the sub sample were telephoned at 4 months intervals and the rest of the trial population was interviewed by phone once a year . RESULTS In the entire trial population ( ETP ) , there were 812 women with 1832 falls in the intervention group and 833 women with 1944 falls in the control group ( risk ratio was 0.98 , 95 % CI 0.92 - 1.05 , P=0.160 ) . The supplementation was not associated with single or multiple falls in the ETP . However , in the sub sample , multiple fall incidence decreased by 30 % ( odds ratio ( OR ) 0.70 , 95 % CI 0.50 - 0.97 , P=0.034 ) in the supplementation group . Further , the supplementation decreased the incidence of multiple falls requiring medical attention ( OR 0.72 , 95 % CI 0.53 - 0.97 , P=0.031 ) in the ETP . The mean compliance in the entire trial population was 78 % and in the sub sample 79 % . DISCUSSION Overall , the primary analysis showed no association between calcium and vitamin D supplementation and risk of falls . However , the results of a post hoc analysis suggested that there was a decreased risk of multiple falls requiring medical attention : this finding requires confirmation OBJECTIVE Calcium and vitamin D deficiency is common in older individuals , particularly those who live in nursing homes , and increases the risk of osteoporosis and fractures . METHODS We conducted a r and omized double-blind placebo-controlled study of combined supplementation with 500 mg of elemental calcium , as carbonate , and 400 IU of vitamin D bid for 12 months in women older than 65 years of age with vitamin D deficiency , defined as serum 25(OH)D concentrations < /=12 ng/ml . RESULTS Mean patient age was 75 + /- 7 years , and median daily dietary intakes of calcium and vitamin D were 697 mg and 66.8 IU in the supplemented group ( n = 95 ) and 671 mg and 61.8 IU in the placebo group ( n = 97 ) . The median serum 25(OH)D level was 7.0 ng/ml in both groups , and the medial intact parathyroid hormone ( PTHi ) levels were 49 and 48 pg/ml in the supplemented and placebo groups , respectively . The median increase in serum 25(OH)D was 22.0 ng/ml in the supplemented group and 4 ng/ml in the placebo group ( P < 0.0001 ) , and the median PTHi decrease was 17 and 5 pg/ml , respectively ( P < 0.0001 ) . The median bone mineral density increase was significantly greater in the supplemented group than in the placebo group : + 2.98 % vs. -0.21 % at L2-L4 ( P = 0.0009 ) , + 1.19 % and -0.83 % at the femoral neck ( P = 0.015 ) , + 0.86 % and -0.56 % at the trochanter ( P = 0.015 ) , and + 0.99 % and + 0.11 % for the whole body ( P = 0.01 ) . Similarly , the median decrease in the main bone markers was significantly greater in the treated group than in the placebo group : -1.35 microg/l vs. + 0.50 microg/l for bone alkaline phosphatase ( P = 0.008 ) , -16.6 nmol/mmol creatinine vs. -2.3 nmol/mmol creatinine for urinary type I amino-terminal telopeptide ( P = 0.001 ) , and -896 pmol/l vs. -201 pmol/l for serum type I carboxy-terminal telopeptide ( P = 0.003 ) . We found no significant differences between the two groups for serum calcium , although urinary calcium excretion changed more in the supplemented group than in the placebo group . In conclusion , bone mass in older women with vitamin D deficiency increases significantly at the lumbar spine , femur , trochanter , and whole body after calcium and vitamin D supplementation for 1 year , and concomitantly bone markers improved as vitamin D levels returned to normal This 4-y study investigated the effects of a calcium carbonate supplement on  bone loss in 169 women aged 35 - 65 y , r and omly assigned to placebo and treatment ( 1500 mg Ca/d ) groups in a double-blind design . Bone mineral content ( BMC ) and width ( W ) were measured bilaterally on the radius , ulna , and humerus . BMC and BMC /W loss rates were consistently lower in treatment than in control subjects . Loss was significantly reduced in the left and right humerus and the right radius . In premenopausal subjects , only left humerus BMC loss was significantly reduced by Ca supplementation . In postmenopausal treatment subjects , BMC and BMC /W bone loss was reduced in all 12 ( bilateral radius , ulna , and humerus ) of the bone variables measured , 5 at p less than 0.01 and 2 at p less than 0.05 . Ca supplementation counteracted a large portion of the additional bone loss attributable to menopause in this population PURPOSE Calcium has been shown to have positive effects on bone mineral density in postmenopausal women . However , these effects are small , it is unknown whether they are sustained with long-term use , they have not been shown with intention-to-treat analyses , and the evidence for fracture prevention with calcium monotherapy is inconsistent . METHODS A r and omized controlled trial of calcium ( 1 g/day as the citrate ) in 1471 healthy postmenopausal women ( aged 74+/-4 years ) was performed to assess the effects on  bone density and fracture incidence over 5 years . RESULTS Follow-up was complete in 90 % of subjects , and average medication compliance was 55 % to 58 % . Calcium had a significant beneficial effect on bone density ( intention-to-treat analysis ) , with between-groups differences at 5 years of 1.8 % ( spine ) , 1.6 % ( total hip ) , and 1.2 % ( total body ) . Effects were greater in a per- protocol analysis ( 5-year differences of 2.3 % , 2.8 % , and 1.8 % , respectively ) . A total of 425 fractures occurred in 281 women .  Hazard ratios , based on time to first fracture , were 0.90 ( 95 % confidence interval [ CI ] , 0.71 - 1.16 ) for any symptomatic fracture , 0.72 ( 95 % CI , 0.44 - 1.18 ) for vertebral , 3.55 ( 95 % CI , 1.31 - 9.63 ) for hip , and 0.65 ( 95 % CI , 0.41 - 1.04 ) for forearm fracture . Per- protocol analysis found respective hazard ratios of 0.86 ( 95 % CI , 0.64 - 1.17 ) , 0.62 ( 95 % CI , 0.33 - 1.16 ) , 3.24 ( 95 % CI , 0.65 - 16.1 ) , and 0.45 ( 95 % CI , 0.24 - 0.87 ) . Height loss was reduced by calcium in the per- protocol population ( P=.03 ) . Serum alkaline phosphatase and procollagen type-I N-terminal propeptide were lower in the calcium group at 5 years , but constipation was more common . CONCLUSIONS Calcium results in a sustained reduction in bone loss and turnover , but its effect on fracture remains uncertain . Poor long-term compliance limits its effectiveness BACKGROUND There is no consistent evidence , to our knowledge , that calcium supplementation affects  bone mineral density ( BMD ) in men , despite male osteoporosis being a common clinical problem . METHODS To determine the effects of calcium supplementation ( 600 mg/d , 1200 mg/d , or placebo ) on BMD in men , we conducted a double-blind , r and omized controlled trial for a 2-year period at an academic clinical research center . A total of 323 healthy men at least 40 years old ( mean age , 57 years ) were recruited by newspaper advertisement . Complete follow-up was achieved in 96 % of subjects . RESULTS The BMD increased at all sites in the group receiving calcium , 1200 mg/d , by 1 % to 1.5 % more than those receiving placebo . The results for the group receiving calcium , 600 mg/d , were not different from the placebo group at any BMD site . There was no interaction between the BMD treatment effect and either age or dietary calcium intake . There were dosage-related , sustained decreases in serum parathyroid hormone ( P < .001 ) , total alkaline phosphatase activity ( P = .01 ) , and procollagen type 1 N-terminal propeptide ( P < .001 ) amounting to 25 % , 8 % , and 20 % , respectively , in the group receiving calcium , 1200 mg/d , at 2 years . Tooth loss , constipation , and cramps were unaffected by calcium supplementation , falls tended to be less frequent in the group receiving calcium , 1200 mg/d , but vascular events tended to be more common in the groups receiving calcium vs the group receiving placebo . CONCLUSION Calcium , 1200 mg/d , has effects on BMD in men comparable with those found in postmenopausal women but a dosage of 600 mg/d is ineffective for treating BMD . TRIAL REGISTRATION actr.org.au Identifier : 012605000274673
target: Calcium supplements  increased BMD by 0.7 - 1.8 % at all five skeletal sites at one , two , and over two and a half years , but the size of the increase in BMD at later time points was similar to the increase at one year .
  Increasing calcium intake from dietary sources or by taking calcium supplements produces small non-progressive increases in BMD , which are unlikely to lead to a clinical ly significant reduction in risk of fracture
background: OBJECTIVE To determine whether increasing calcium intake from dietary sources affects  bone mineral density ( BMD ) and , if so , whether the effects are similar to those of calcium supplements .