title: Spinal bone loss in postmenopausal women supplemented with calcium and trace minerals. Effect of calcium supplementation on forearm bone mineral content in postmenopausal women: a prospective, sequential controlled trial. Does calcium supplementation prevent postmenopausal bone loss? A double-blind, controlled clinical study. Calcium Supplementation with and without Hormone Replacement Therapy To Prevent Postmenopausal Bone Loss Bone mineral content in women with Colles' fracture: effect of calcium supplementation. Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators. The effects of calcium supplementation and exercise on bone density in elderly Chinese women Fluoride Salts are no Better at Preventing New Vertebral Fractures than Calcium-Vitamin D in Postmenopausal Osteoporosis: The FAVOStudy 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. The effects of calcium supplementation (milk powder or tablets) and exercise on bone density in postmenopausal women. Osteoporosis clinical trials endpoints: candidate variables and clinimetric properties. Effect of calcium supplementation on bone loss in postmenopausal women. Long-term effects of calcium supplementation on serum parathyroid hormone level, bone turnover, and bone loss in elderly women. 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. Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older. Calcium supplementation and bone loss in middle-aged women.
abstract: 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 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 ) 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 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 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 Raloxifene hydrochloride , a selective estrogen receptor modulator , prevents bone loss in postmenopausal women , but whether it reduces fracture risk in these women is not known . OBJECTIVE To determine the effect of raloxifene therapy on risk of vertebral and nonvertebral fractures . DESIGN The Multiple Outcomes of Raloxifene Evaluation ( MORE ) study , a multicenter , r and omized , blinded , placebo-controlled trial . SETTING AND PARTICIPANTS A total of 7705 women aged 31 to 80 years in 25 countries who had been postmenopausal for at least 2 years and who met World Health Organization criteria for having osteoporosis . The study began in 1994 and had up to 36 months of follow-up for primary efficacy measurements and nonserious adverse events and up to 40 months of follow-up for serious adverse events . INTERVENTIONS Participants were r and omized to 60 mg/d or 120 mg/d of raloxifene or to identically appearing placebo pills ; in addition , all women received supplemental calcium and cholecalciferol . MAIN OUTCOME MEASURES Incident vertebral fracture was determined radiographically at baseline and at scheduled 24- and 36-month visits . Nonvertebral fracture was ascertained by interview at 6-month-interim visits . Bone mineral density was determined annually by dual-energy x-ray absorptiometry . RESULTS At 36 months of the evaluable radiographs in 6828 women , 503 ( 7.4 % ) had at least 1 new vertebral fracture , including 10.1 % of women receiving placebo , 6.6 % of those receiving 60 mg/d of raloxifene , and 5.4 % of those receiving 120 mg/d of raloxifene .  Risk of vertebral fracture was reduced in both study groups receiving raloxifene ( for 60-mg/d group : relative risk [ RR ] , 0.7 ; 95 % confidence interval [ CI ] , 0.5 - 0.8 ; for 120-mg/d group : RR , 0.5 ; 95 % CI , 0.4 - 0.7 ) . Frequency of vertebral fracture was reduced both in women who did and did not have prevalent fracture . Risk of nonvertebral fracture for raloxifene vs placebo did not differ significantly ( RR , 0.9 ; 95 % CI , 0.8 - 1.1 for both raloxifene groups combined ) . Compared with placebo , raloxifene increased bone mineral density in the femoral neck by 2.1 % ( 60 mg ) and 2.4 % ( 120 mg ) and in the spine by 2.6 % ( 60 mg ) and 2.7 % ( 120 mg ) P<0.001 for all comparisons ) . Women receiving raloxifene had increased risk of venous thromboembolus vs placebo ( RR , 3.1 ; 95 % CI , 1.5 - 6.2 ) . Raloxifene did not cause vaginal bleeding or breast pain and was associated with a lower incidence of breast cancer . CONCLUSIONS In postmenopausal women with osteoporosis , raloxifene increases bone mineral density in the spine and femoral neck and reduces risk of vertebral fracture 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 Abstract . Although fluoride salts have been shown to be capable of linearly increasing spinal bone mineral density ( BMD ) in postmenopausal osteoporosis , the effects of this gain in density on the vertebral fracture rate remain controversial . We conducted a 2-year multicenter , prospect i ve , r and omized , double-masked clinical trial in 354 osteoporotic women with vertebral fractures ( mean age 65.7 years ) . They received either fluoride ( 208 patients ) , given as sodium fluoride ( 50 mg/day ) or as monofluorophosphate ( 200 mg/day or 150 mg/day ) , or a placebo ( 146 patients ) . All patients received daily supplements of 1 g of calcium ( Ca ) and 800 IU of vitamin D2 ( D ) . A 1-year open follow-up on Ca-D was obtained in 124 patients . After 2 years the fluoride group and the Ca-D group had increased their lumbar BMD by 10.8 % and 2.4 % respectively ( p = 0.0001 ) . However , the rate of patients with at least one new vertebral fracture , defined by semiquantitative assessment and evaluable on an intention-to-treat basis in 89 % of patients , was similar in the fluoride groups and the Ca-D group . No difference between the three fluoride regimens was found . The percentage of patients with nonvertebral fractures was not different in the fluoride and Ca-D groups ( 1.9 % and 1.4 % respectively for hip fractures ) . A lower limb pain syndrome occurred more frequently in the fluoride groups . In the 124 patients followed for 1 year after cessation of fluoride therapy , the percentage of patients with at least one new vertebral fracture after 36 months was identical to the percentages in the previous fluoride group and the Ca-D group . We conclude that flouride-Ca-D regimen was no more effective that Ca-D supplements for the prevention of new vertebral fractures in women with postmenopausal osteoporosis 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 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 We review ed evidence on endpoints used in osteoporosis clinical trials to assist in the development of a set of endpoints to be included in all trials . A MEDLINE search was conducted using the Cochrane Collaboration strategy for each endpoint . Additional published literature was obtained from content experts . A proposed list of endpoints was developed after consultation with experts in the field . Each endpoint was evaluated with respect to validity , reproducibility , redundancy , and feasibility . We classified the endpoints into 2 major categories : clinical health status outcomes and intermediate endpoints , and for each endpoint we present current evidence from the literature as pertains to defined method ologic criteria . Multiple endpoints have been used in osteoporosis clinical trials , and an agreement on a core set of measures needs to be evidence based with an emphasis on validity , reproducibility , and feasibility and to satisfy clinical credibility 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 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 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 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 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
target: Calcium was more effective than placebo in reducing rates of bone loss after two or more years of treatment .
  REVIEW ER 'S CONCLUSIONS Calcium supplementation alone has a small positive effect on bone density .
  The data show a trend toward reduction in vertebral fractures , but it is unclear if calcium reduces the incidence of non vertebral fractures
background: BACKGROUND Although calcium is one the simplest and least expensive strategies for preventing osteoporotic fractures calcium supplementation is nevertheless not without controversy ( Kanis 1989 ; Nordin 1990 ) .
  The Food and Drug Administration in the US has permitted a bone health cl aim for calcium-rich foods , and the NIH in its Consensus Development Process approved a statement that high calcium intake reduces the risk of osteoporosis .
  OBJECTIVES To assess the effects of calcium on bone density and fractures in postmenopausal women .