Calcium, vitamin D, milk consumption, and hip fractures: a prospective study among postmenopausal women. The Women's Health Initiative calcium-vitamin D trial: overview and baseline characteristics of participants. [Optimization of calcium intake for the prevention of osteoporosis and osteoporotic fractures: a review of the evidence]. Pharmacologic Treatment of Low Bone Density or Osteoporosis to Prevent Fractures: A Clinical Practice Guideline from the American College of Physicians Milk, dietary calcium, and bone fractures in women: a 12-year prospective study. Guidance for the management of breast cancer treatment-induced bone loss: a consensus position statement from a UK Expert Group. The effects of a high calcium dairy food on bone health in pre-pubertal children in New Zealand. Long-term effects of nutrient intervention on markers of bone remodeling and calciotropic hormones in late-postmenopausal women. The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis. Effects of calcitriol or calcium on bone mineral density, bone turnover, and fractures in men with primary osteoporosis: a two-year randomized, double blind, double placebo study. Effect of Recombinant Human Parathyroid Hormone (1-84) on Vertebral Fracture and Bone Mineral Density in Postmenopausal Women with Osteoporosis Use of Calcium Supplements, Vitamin D Supplements and Specific Osteoporosis Drugs Among French Women Aged 75–85 Years: Patterns of Use and Associated Factors Fluoride Salts are no Better at Preventing New Vertebral Fractures than Calcium-Vitamin D in Postmenopausal Osteoporosis: The FAVOStudy Dietary calcium and vitamin D intake in relation to osteoporotic fracture risk. Nutritional factors that influence change in bone density and stress fracture risk among young female cross-country runners.
BACKGROUND Short trials of calcium supplementation show that it reduces loss of bone density in postmenopausal women ; longer observational studies do not generally find a lower risk of hip fracture with higher-calcium diets . Fewer studies have focused on vitamin D in preventing postmenopausal osteoporosis or fractures . OBJECTIVE We assessed relations between postmenopausal hip fracture risk and calcium , vitamin D , and milk consumption . DESIGN In an 18-y prospect i ve analysis in 72 337 postmenopausal women , dietary intake and nutritional supplement use were assessed at baseline in 1980 and up date d several times during follow-up . We identified 603 incident hip fractures result ing from low or moderate trauma .  Relative risks ( RRs ) from proportional hazards models were controlled for other dietary and nondietary factors . RESULTS Women consuming > or = 12.5 microg vitamin D/d from food plus supplements had a 37 % lower risk of hip fracture ( RR = 0.63 ; 95 % CI : 0.42 , 0.94 ) than did women consuming < 3.5 microg/d . Total calcium intake was not associated with hip fracture risk ( RR = 0.96 ; 95 % CI : 0.68 , 1.34 for > or = 1200 compared with < 600 mg/d ) . Milk consumption was also not associated with a lower risk of hip fracture ( P for trend = 0.21 ) . CONCLUSIONS An adequate vitamin D intake is associated with a lower risk of osteoporotic hip fractures in postmenopausal women . Neither milk nor a high-calcium diet appears to reduce risk . Because women commonly consume less than the recommended intake of vitamin D , supplement use or dark fish consumption may be prudent Osteoporosis is a major public health issue leading to significant morbidity , loss of independence and excess loss of life . It has been estimated that 13 to 17 million postmenopausal women have low bone mass or osteoporosis ( 1 , 2 ) . This is associated with almost 1.5 million fractures annually , including 300,000 hip fractures ( 2 , 3 ) . A review of the evidence by Cumming in 1990 ( 4 ) and subsequently published r and omized clinical trials have shown that calcium and /or vitamin D supplements may play a role in the prevention and treatment of osteoporosis by slowing the rates of bone loss in postmenopausal and elderly women ( 5–9 ) . However , there are a limited number of calcium and /or vitamin D trials ( 10–13 ) and observational studies [ review of evidence by Cumming and Nevitt ( 14 ) and Kanis ( 15 ) ] , to support a role for calcium and vitamin D supplementation in the reduction of hip and other fractures . It has also been suggested that calcium and vitamin D supplementation may play a role in the reduction of colorectal cancer incidence ( 16–21 ) . To address these major health concerns of postmenopausal women , the Calcium-Vitamin D ( CaD ) trial of the Women ’s Health Initiative ( WHI ) was design ed to test the primary hypothesis that women who are r and omized to receive calcium and vitamin D supplementation will have a lower risk of hip fracture and secondarily , a lower risk of all fractures and colorectal cancer than women receiving corresponding placebo . The objective of this paper is One of the main focuses of lifestyle modification for the prevention of osteoporosis and osteoporotic fractures  in Japan is improvement in dietary calcium intake . However , virtually no r and omized controlled trial to assess the preventive effects of administration of calcium on the risk of fractures has been conducted in Japan . In this study , we review ed all the scientific papers currently available from medical literature data bases to propose evidence -based recommendations on the preventive procedures for osteoporosis . The result of the present systematic review gives the evidence showing that calcium supplementation or optimal dietary calcium intake increases bone density in childhood and adolescence and reduces the risk of fracture due to osteoporosis in the elderly people regardless of the gender . The evidence also supports the current health policy guiding the elderly to increase their dietary calcium intake in daily life The National Institutes of Health 's consensus conference ( 1 ) defined osteoporosis as a skeletal disorder characterized by compromised bone strength predisposing to an increased risk for fracture . Bone strength reflects the integration of two main features : bone density and bone quality .Bone quality refers to architecture , turnover , damage accumulation ( e.g. , microfractures ) , and mineralization . Although osteoporosis can affect any bone , the hip , spine , and wrist are most likely to be affected . Osteoporosis affects an estimated 44 million Americans or 55 % of people 50 years of age or older . Another 34 million Americans are estimated to have low bone mass , meaning that they are at an increased risk for osteoporosis . Osteoporosis can be diagnosed by the occurrence of fragility fracture . In patients without fragility fracture , osteoporosis is often diagnosed by low bone density .  Dual x-ray absorptiometry ( DXA ) is the current gold st and ard test for diagnosing osteoporosis in people without an osteoporotic fracture .  Dual x-ray absorptiometry results are scored as st and ard deviations ( SDs ) from a young healthy norm ( usually female ) and reported as T-scores . For example , a T-score of 2 indicates a bone mineral density that is 2 SDs below the comparative norm . The international reference st and ard for the description of osteoporosis in postmenopausal women and in men age 50 years or older is a femoral neck bone mineral density of 2.5 SD or more below the young female adult mean ( 2 ) . Low bone density , as measured by DXA , is an imperfect predictor of fracture risk , identifying fewer than half the people who go on to have an osteoporotic fracture . Screening guidelines for women are well established ( 3 ) , and the American College of Physicians ( ACP ) recently published guidelines on screening for men ( 4 ) . This guideline presents the available evidence on various pharmacologic treatments to prevent fractures in men and women with low bone density or osteoporosis . Medications used to treat osteoporosis may affect different parts of the skeletal system differently , and efficacy for vertebral fractures does not necessarily imply efficacy for nonvertebral fractures . The target audience for this guideline is all clinicians and the target patient population is all adult men and women with low bone density or osteoporosis . These recommendations are based on the systematic evidence review by MacLean and colleagues ( 5 ) and the Agency for Healthcare Research and Quality sponsored Southern California Evidence -Based Practice Center evidence report ( 6 ) . The drugs currently approved for prevention of osteoporosis include alendronate , ib and ronate , risedronate , zoledronic acid , estrogen , and raloxifene . The drugs currently approved for treatment of osteoporosis include alendronate , ib and ronate , risedronate , calcitonin , teriparatide , zoledronic acid ( in postmenopausal women ) , and raloxifene . Testosterone , pamidronate , and etidronate are not approved by the U.S. Food and Drug Administration for the treatment or prevention of osteoporosis . Methods The literature search done by MacLean and colleagues for the systematic review ( 5 ) included studies from MEDLINE ( 1966 to December 2006 ) , the ACP Journal Club data base , the Cochrane Central Register of Controlled Trials ( no date limits ) , the Cochrane Data base of Systematic Review s ( no date limits ) , Web sites of the United Kingdom National Institute of Health and Clinical Excellence ( no date limits ) , and the United Kingdom Health Technology Assessment Program ( January 1998 to December 2006 ) . The review ers limited their search to English- language publications and human studies . They derived evidence for comparative benefits of various treatments exclusively from r and omized , controlled trials , whereas they included evidence from other types of studies for short- and long-term harms . Two physicians independently abstract ed data about study population s , interventions , follow-up , and outcome ascertainment by using a structured form . For each group within a r and omized trial , a statistician extracted the sample size and number of persons reporting fractures . Two review ers , under the supervision of the statistician , independently abstract ed information about adverse events . The statistician or the principal investigator resolved disagreements . This guideline is based on an evaluation of 76 r and omized , controlled trials , 4 of which were identified in the up date d search , and 24 meta-analyses that were included in the efficacy analyses . The analyses of adverse events included 491 articles , representing 417 r and omized trials , 25 other controlled clinical trials , 11 open-label trials , 31 large observational studies , and 9 case reports of osteonecrosis among bisphosphonate users . MacLean and colleagues ' background article ( 5 ) includes details about the methods used for the systematic evidence review . The ACP rates the evidence and recommendations by using the Grading of Recommendations , Assessment , Development , and Evaluation ( GRADE ) system with minor modifications ( Table 1 ) . In addition , the evidence review ers used predefined criteria to assess the quality of systematic review s and r and omized trials , based on internal and external validity assessment s detailed in the Quality of Reporting of Meta-Analyses ( QUOROM ) statement ( 7 ) . Table 1 . The American College of Physicians ' Guideline Grading System The objective of this guideline is to synthesize the evidence for the following questions : What are the comparative benefits in fracture reduction among and also within the following treatments for low bone density :  bisphosphonates , specifically alendronate , risedronate , etidronate , ib and ronate , pamidronate , and zoledronic acid ; calcitonin ; estrogen for women ; teriparatide ; selective estrogen receptor modulators ( SERMs ) , specifically raloxifene and tamoxifen ; testosterone for men ; vitamins and minerals , specifically vitamin D and calcium ; and the combination of calcium plus vitamin D ? How does fracture reduction result ing from treatments vary among individuals with different risks for fracture as determined by bone mineral density ( borderline , low , or severe ) , previous fractures ( prevention vs. treatment ) , age , sex , glucocorticoid use , and other factors ( such as community-dwelling vs. institutionalized or vitamin Ddeficient vs. not ) ? What are the short- and long-term harms ( adverse effects ) of these therapies , and do these vary by specific sub population s ? Comparative Benefits of Drugs versus Placebo in Fracture Reduction Evidence from 24 meta-analyses ( 830 ) and 35 additional r and omized trials published after the meta-analyses ( 3165 ) described the effect of 9 of the 14 agents ( alendronate , etidronate , risedronate , calcitonin , estrogen , teriparatide , raloxifene , calcium , and vitamin D ) on fracture incidence . For 4 agents ( ib and ronate , pamidronate , zoledronic acid , and tamoxifen ) , the review ers found no meta-analyses and instead gathered the evidence from 14 r and omized trials ( 6679 ) . No studies were found that reported fracture rates for testosterone . Three r and omized trials ( 35 , 80 , 81 ) and 1 meta- analysis ( 82 ) evaluated the combination of calcium plus vitamin D  on fractures .  Bisphosphonates Good- quality evidence showed that alendronate , etidronate , ib and ronate , and risedronate prevent vertebral fractures . In addition , evidence from good- quality studies demonstrated that both alendronate and risedronate prevent nonvertebral and hip fractures . Two large r and omized trials showed that zoledronic acid prevents vertebral and nonvertebral fractures in high-risk population s and reduces the risk for hip fracture ( 67 , 74 ) . Ib and ronate has not been shown to reduce nonvertebral fractures ( 68 ) . Of the 6 fairly small trials that looked at vertebral fractures , 1 demonstrated a statistically significant reduction in fractures with pamidronate relative to placebo ( 0.14 [ 95 % CI , 0.03 to 0.72 ] ) ( 73 ) . However , after these data were pooled , the pooled risk estimate for fractures for pamidronate relative to placebo was not significant ( 0.52 [ CI , 0.21 to 1.24 ] ) ( 6 ) . Calcitonin Fair- quality evidence shows that calcitonin reduces vertebral fractures ( 83 , 84 ) . Good- quality evidence indicates that calcitonin does not reduce nonvertebral fractures ( 13 , 16 ) . Estrogen Good- quality evidence shows that estrogen reduces the incidence of vertebral ( 29 , 85 ) , nonvertebral ( 86 ) , and hip fractures ( 85 ) . Teriparatide Good- quality evidence shows that teriparatide prevents vertebral fractures . The evidence related to teriparatide preventing nonvertebral fractures is mixed ; 1 large r and omized trial showed a reduction in nonvertebral fractures ( 34 ) but 2 small trials did not ( 87 , 88 ) . SERMs Good- quality evidence shows that raloxifene prevents vertebral fractures , but that tamoxifen has no effect on vertebral fractures ( 8991 ) . In addition , both raloxifene and tamoxifen had no effect on hip fractures ( 91 ) . Tamoxifen is not approved by the U.S. Food and Drug Administration for the treatment or prevention of osteoporosis . Testosterone No studies reported fracture rates for testosterone . Calcium and Vitamin D In the studies evaluated by MacLean and colleagues ( 5 ) , the evidence for the effect of calcium alone on reduction of fractures is complex . Most studies of pharmacologic agents for osteoporosis include calcium and vitamin D as part of the treatment regimen . Evidence from 1 meta- analysis ( 27 ) and several r and omized trials ( 35 , 48 , 51 , 92 ) showed no significant difference between calcium and placebo in preventing vertebral , nonvertebral , and hip fractures in postmenopausal women . However , nonadherence to therapy may influence this result , and 1 trial with a prespecified analysis of adherent patients found a reduction in fracture risk ( 48 ) . A recent meta- analysis ( 82 ) concluded that the relative risk ( RR ) for fracture with calcium alone was 0.90 ( CI , 0.80 to 1.00 ) , but it did not include a modestly large trial with negative results ( 35 ) . MacLean and colleagues ( 5 ) OBJECTIVES This study examined whether higher intakes of milk and other calcium-rich foods during adult years can reduce the risk of  osteoporotic fractures .  METHODS This was a 12-year prospect i ve study among 77761 women , aged 34 through 59 years in 1980 , who had never used calcium supplements .  Dietary intake was assessed with a food-frequency question naire in 1980 , 1984 , and 1986 . Fractures of the proximal femur ( n = 133 ) and distal radius ( n = 1046 ) from low or moderate trauma were self-reported on biennial question naires . RESULTS We found no evidence that higher intakes of milk or calcium from food sources reduce fracture incidence . Women who drank two or more glasses of milk per day had relative risks of 1.45 for hip fracture ( 95 % confidence interval [ CI ] = 0.87 , 2.43 ) and 1.05 for forearm fracture ( 95 % CI = 0.88 , 1.25 ) when compared with women consuming one glass or less per week . Likewise , higher intakes of total  dietary calcium or calcium from dairy foods were not associated with decreased risk of hip or forearm fracture . CONCLUSIONS These data do not support the hypothesis that higher consumption of milk or other food sources of calcium  by adult women protects against hip or forearm fractures In postmenopausal women , the use of aromatase inhibitors increases bone turnover and induces bone loss at sites rich in trabecular bone at an average rate of 1 - 3 % per year leading to an increase in fracture incidence compared to that seen during tamoxifen use . The bone loss is much more marked in young women with treatment-induced ovarian suppression followed by aromatase inhibitor therapy ( average 7 - 8 % per annum ) . Pre-treatment with tamoxifen for 2 - 5 years may reduce the clinical significance of the adverse bone effects associated with aromatase inhibitors , particularly if this leads to a shortening in the duration of exposure to an aromatase inhibitor . However , skeletal status should still be assessed at the commencement of aromatase inhibitor therapy . The rate of bone loss in women who experience a premature menopause before the age of 45 or are receiving ovarian suppression therapy is accelerated by the concomitant use of aromatase inhibitors . These patients are considered to be at high risk of clinical ly important bone loss and should have a baseline dual energy X-ray absorptiometry ( DXA ) assessment of bone mineral density ( BMD ) . R and omised clinical trials in postmenopausal women indicate that bisphosphonates prevent the bone loss and accelerated bone turnover associated with aromatase inhibitor therapy and are a promising strategy for the prevention and treatment of osteoporosis in this setting . Treatment initiation recommendations are based on a combination of risk factors for osteoporotic fracture and BMD levels .  Bisphosphonates , along with a healthy lifestyle and adequate intake of calcium and vitamin D are the treatments of choice to prevent bone loss . Due to the rate of bone loss associated with breast cancer treatments , and uncertainties about the interaction between aromatase inhibitor use and BMD for fracture risk , the threshold for intervention has been set at a higher level than that generally recommended for postmenopausal osteoporosis . Management recommendations have been summarised in two algorithms , one for women experiencing a premature menopause and the other for postmenopausal women requiring adjuvant aromatase inhibitor therapy Childhood and adolescence is the period of most rapid skeletal growth in an individual 's lifetime . A greater peak bone mass achieved in the first 2 - 3 decades of life , may protect against the risk of osteoporotic fracture in later life . The aim of this r and omized , controlled study was to assess in pre-pubertal boys and girls ( aged 8 - 10 years ) the effect of 18 months of a calcium enriched , cocoa flavoured product on bone density , bone growth and bone size in New Zeal and children . One hundred and fifty four pre-pubertal boys and girls ( aged 8 - 10 years ) were r and omized to receive a high calcium dairy drink or a control drink reconstituted with water for 18 months . They were assessed at baseline and then every 6 months for the first 18 months , while they were having the supplement ; they were then followed up 12 months after supplementation had finished . Bone mineral density and bone mineral content were assessed at the total body , hip and spine . Indicators of bone size ( vertebral width and height ) were also measured at the spine . Anthropometric data was collected , medical history question naires were administered ( including the Tanner or pubertal stage question naire ) , dietary calcium intake was assessed with a calcium food frequency question naire and calcium supplement compliance was determined . There was no significant difference between the 2 groups for bone mineral density or bone mineral content at any time point . There was no difference in vertebral height or width at any stage of the study , indicating no additional influence on bone size at the lumbar vertebrae . There were no significant differences between height , weight , lean mass or fat mass at any time point . Both groups had higher habitual calcium intakes than recommended for this age group going into the study and throughout the study . In this 2(1/2 ) year study ( 18 months supplementation , 1 year follow-up ) we did not observe a difference in bone mineral density in pre-pubertal children . This was probably due to their high habitual dietary calcium intake whereby minimal addition of calcium to the diet reached the threshold level where no further benefit was seen . There were no significant differences between the two groups in body composition . Growth and the mean height and weight remained between the 50th and 75th percentile for their age . We have shown calcium supplementation in children with high habitual dietary calcium intake appears not to have additional effects on bone mass . Calcium supplementation needs to be targeted in those children with low habitual dietary calcium intake BACKGROUND Adequate intakes of calcium and vitamin D reduce bone loss and fracture risk in the elderly . Other nutrients also affect bone health , and adequate intakes may influence bone turnover and balance . OBJECTIVE We compared the long-term effects on bone turnover markers and calciotropic hormones of a multinutrient supplement , a calcium and vitamin D supplement , and dietary instruction aim ed at increasing calcium intake through foods . DESIGN Ninety-nine healthy postmenopausal women participated in a 3-y , r and omized trial , receiving either 1 ) supplemental calcium ( 1450 mg/d ) and vitamin D [ 10 microg ( 400 IU)/d ] , 2 ) calcium , vitamin D , and other nutrients ( multinutrient supplement ) , or 3 ) dietary instruction ( dietary control group ) . Data are from 83 subjects who completed the trial . RESULTS Increases over baseline in calcium intakes and serum 25-hydroxyvitamin D concentrations were sustained over 3 y in all treatment groups . Circulating parathyroid hormone concentrations were reduced at year 1 in all treatment groups but trended toward baseline thereafter . Bone turnover markers followed a similar pattern , and none of the changes in biochemical concentrations differed significantly between groups . CONCLUSIONS All 3 interventions offer long-term feasibility for increasing calcium intake and serum 25-hydroxyvitamin D concentrations . The dietary addition of micronutrients implicated in skeletal physiology confers no obvious bone-sparing effect in healthy postmenopausal women beyond that of calcium and vitamin D alone . The attenuation over time in suppression of parathyroid hormone and bone turnover might help explain why nutrient intervention tends to have less of a bone-sparing effect than do skeletally active medications such as estrogen or bisphosphonates BACKGROUND Osteoporotic structural damage and bone fragility result from reduced bone formation and increased bone resorption . In a phase 2 clinical trial , strontium ranelate , an orally active drug that dissociates bone remodeling by increasing bone formation and decreasing bone resorption , has been shown to reduce the risk of vertebral fractures and to increase bone mineral density . METHODS To evaluate the efficacy of strontium ranelate in preventing vertebral fractures in a phase 3 trial , we r and omly assigned 1649 postmenopausal women with osteoporosis ( low bone mineral density ) and at least one vertebral fracture to receive 2 g of oral strontium ranelate per day or placebo for three years . We gave calcium and vitamin D supplements to both groups before and during the study . Vertebral radiographs were obtained annually , and measurements of bone mineral density were performed every six months . RESULTS New vertebral fractures occurred in fewer patients in the strontium ranelate group than in the placebo group , with a risk reduction of 49 percent in the first year of treatment and 41 percent during the three-year study period ( relative risk , 0.59 ; 95 percent confidence interval , 0.48 to 0.73 ) . Strontium ranelate increased bone mineral density at month 36 by 14.4 percent at the lumbar spine and 8.3 percent at the femoral neck ( P<0.001 for both comparisons ) . There were no significant differences between the groups in the incidence of serious adverse events . CONCLUSIONS Treatment of postmenopausal osteoporosis with strontium ranelate leads to early and sustained reductions in the risk of vertebral fractures Osteoporosis in men is an emerging public health problem . As calcitriol reduces the rate of vertebral fractures in osteoporotic postmenopausal women , we conducted a prospect i ve study of this treatment in men with primary osteoporosis . Our study was a 2-yr , r and omized , double masked , double placebo-controlled trial of calcitriol ( 0.25 microg twice daily ) or calcium ( 500 mg twice daily ) in 41 men with primary osteoporosis and at least 1 baseline fragility fracture . Thirty-three men ( 85 % ) completed the study . There were no differences in baseline characteristics . Spinal and femoral neck bone mineral densities at 2 yr were unchanged in both groups . Serum osteocalcin decreased in both groups by 30 % ( P < 0.05 ) , whereas urine N-telopeptide cross-links decreased only in the calcium group by 30 % ( P < 0.05 ) . After 2 yr , fractional calcium absorption increased by 34 % ( P < 0.01 ) in the calcitriol group . Nineteen incident fragility fractures occurred ( 14 vertebral and 5 nonvertebral ) in 7 men . Over 2 yr , the number of men with vertebral fractures ( 6 vs. 1 ; P = 0.097 ) was similar in both groups . In conclusion , the efficacy of calcitriol remains unproven as a single agent for the treatment of osteoporosis in men Context Research ers have not previously reported the efficacy and safety of parathyroid hormone ( 1 - 84 ) ( PTH ) for the primary prevention of osteoporotic fractures .  Contributions Among 2532 postmenopausal women with osteoporosis r and omly assigned to receive PTH or placebo , PTH decreased new vertebral fractures . The magnitude of the effect depended on assumptions about fractures in the one third of patients who withdrew from the trial prematurely . Adverse effects included hypercalciuria , hypercalcemia , and nausea . Caution Endogenous PTH and vitamin D levels could affect patients response to the drug but were not assessed in the study . Implication s Parathyroid hormone ( 1 - 84 ) effectively prevented new vertebral fractures but also increased hypercalciuria , hypercalcemia , and nausea . The Editors Osteoporosis is a skeletal disorder characterized by compromised bone strength predisposing patients to an increased risk for fracture ( 1 ) . Optimal treatment for osteoporosis should improve the amount , density , and quality of bone , thereby reducing skeletal fragility and fractures .  Antiresorptive agents , such as bisphosphonates , are commonly used for treating postmenopausal osteoporosis . Although these agents preserve bone architecture , they do not stimulate new bone formation or improve bone architecture . Anabolic or bone-forming agents are an alternative approach to the treatment of osteoporosis . Research ers have shown that parathyroid hormone ( PTH ) and certain peptide fragments of PTH increase bone mass and improve bone quality ( 2 , 3 ) . Teriparatide , a fragment of human PTH composed of its N-terminal 34 amino acids , has been approved for the treatment of postmenopausal women with osteoporosis who are at high risk for bone fracture . However , research ers have studied this agent only in women with prevalent vertebral fractures ( 4 ) , and data demonstrating prevention of the first vertebral fracture are lacking . We conducted the Treatment of Osteoporosis with Parathyroid Hormone ( TOP ) Study to examine the efficacy and safety of PTH ( 1 - 84 ) versus placebo for treating postmenopausal women with osteoporosis . We design ed the study to examine the change in incidence of all vertebral fractures between the treatment groups . We also design ed the study to examine the efficacy of this new bone-forming agent in preventing a first vertebral fracture in women without a vertebral fracture . Methods Study Participants We included postmenopausal women 45 to 54 years of age if bone mineral density ( BMD ) was 3.0 SDs or more ( T-score 3.0 ) below the mean peak bone mass of young adult women at the lumbar spine , femoral neck , or total hip with no prevalent vertebral fracture or if BMD T-score was2.5 and they had 1 to 4 vertebral fractures before enrollment . We included postmenopausal women 55 years of age or older if BMD T-score was2.5 and they had no vertebral fractures or if BMD T-score was2.0 and they had 1 to 4 vertebral fractures . We excluded women if baseline serum calcium level was greater than 2.66 mmol/L ( > 10.7 mg/dL ) or if urinary calciumcreatinine ratio was 1.0 or more . We included women with mild hypercalcemia ( serum calcium , 2.55 to 2.66 mmol/L [ 10.2 to 10.7 mg/dL ] ) and mild hypercalciuria ( 24-hour urine calcium7.6 mmol [ 302 mg ] ) at baseline . We did not measure baseline levels of serum PTH and vitamin D. We excluded women if they had taken bisphosphonates for a total of more than 12 months or for more than 90 days in the 12 months before enrollment . We allowed  previous estrogen therapy  if it had been discontinued for at least 4 weeks before the screening visit . We excluded women who had received PTH ( or a peptide fragment or analogue ) , PTH-related protein , fluoride , or strontium and those who had a history of metabolic bone disease ( other than osteoporosis ) , nephrolithiasis , or clinical ly significant hepatic or renal disorders . We also excluded women who were taking medications known to affect bone mineral metabolism . The ethics review committee for each center approved the study . All women provided written informed consent . An independent data and safety monitoring board review ed the progress and safety of the study . Study Design We conducted a r and omized , double-blind , placebo-controlled , parallel-group study in 168 centers in 9 countries . We r and omly assigned the study drug to blocks of 4 patients by using a computer-generated algorithm and shipped it in blocks of 4 to each study site . Women at each site were sequentially assigned the uniquely numbered , r and omly assigned study drug treatment kits by telephone . Women were stabilized for at least 2 weeks with supplemental calcium , 700 mg/d citrate salt , and vitamin D3 , 400 U/d , and then received 100 g of recombinant human PTH or placebo daily by subcutaneous injection for 18 months with continued calcium and vitamin D3 supplementation . Patients were instructed to administer the injection in the morning in the thigh or abdomen by using an injector pen . Study Conduct and Outcome Measures The primary end point was the occurrence of new or worsened vertebral fractures ( in all women and in women with and without a prevalent fracture ) identified by radiography at baseline , month 18 , or the final study visit . Radiologists assessed vertebral fractures in a blinded manner at a central reading organization by using a semiquantitative 4-point grading scale ( 5 ) . An incident vertebral fracture ( new or worsened ) was identified by a change in grade of 1 or more from baseline . Secondary outcomes included changes in BMD at lumbar spine , hip , whole body , and forearm ( distal one-third radius ) that we measured by using dual-energy x-ray absorptiometry with Hologic ( Hologic Inc. , Bedford , Massachusetts ) or Lunar ( GE Medical Systems , Madison , Wisconsin ) densitometers ( reported as percentage change from baseline to st and ardize instrumental differences in determining absolute BMD ) and stadiometric measurements of height . We measured whole body and forearm BMD only in a subset of approximately 300 women from selected sites with appropriate software . We reported nonvertebral clinical fractures and bone loss ( > 7 % at lumbar spine or > 9 % at total hip or femoral neck ) as adverse events . We did not distinguish between traumatic and fragility nonvertebral fractures . We used quantitative computed tomography ( 6 , 7 ) to evaluate the effects of PTH treatment at month 18 on volumetric cortical and trabecular BMD at lumbar vertebra ( L3 ) and the hip in 122 consenting women from a single center at which the technique was available . We assessed bone turnover markers ( serum bone-specific alkaline phosphatase and urinary N-telopeptides of type I collagen ) in the first 600 r and omly assigned women in the study . We measured bone-specific alkaline phosphatase by using the T and em R-Ostase immunoradiometric assay ( interassay coefficient of variation , 8 % ) ( Hybritech , San Diego , California ) . We measured N-telopeptides of type I collagen by using Osteomark enzyme-linked immunoabsorbent assay kits ( interassay coefficient of variation , 4.0 % ) ( Wampole Laboratories , Princeton , New Jersey ) normalized to urine creatinine concentrations . We made safety assessment s at months 1 , 3 , 6 , 9 , 12 , 15 , and 18 that included physical examinations , vital signs , electrocardiography ( months 1 , 12 , and 18 ) , adverse-event monitoring and central clinical laboratory assessment s consisting of chemistry ( including serum total calcium and creatinine ) , hematology , and urinalysis ( including 24-hour urine collection s and fasting , morning urinary calciumcreatinine ratios ) . Adverse events were reported spontaneously by patients , captured in a patients diary , or reported by a patient in response to an open-ended question from clinical study personnel . We used a central laboratory normal range for serum total calcium level of 2.15 to 2.55 mmol/L ( 8.6 to 10.2 mg/dL ) . We performed an analysis for antibodies to PTH with a vali date d electrochemiluminescent immunoassay by using biotinylated recombinant human PTH ( range , 26.3 to 2632.5 pmol/L ; intra-assay coefficient of variation , 8 % to 16 % ) ( Igen International , Inc. , Gaithersburg , Maryl and ) . We obtained iliac crest bone biopsy specimens at month 12 or 18 from a subset of 40 consenting women after tetracycline double-labeling ( 8) that we examined for abnormal bone structure . We anticipated that women might need to discontinue calcium supplementation and reduce the dosing frequency of the study drug to prevent excessive increases in serum calcium level , urinary calcium level , or both . We conservatively predefined hypercalcemia as a single , unconfirmed , predose serum total calcium value greater than 2.66 mmol/L ( > 10.7 mg/dL ) and hypercalciuria as a 24-hour urinary calcium value of 7.6 mmol or more ( 302 mg ) ( increased to > 9.0 mmol [ > 360 mg ] during the study ) or a fasting urinary calciumcreatinine ratio of 1.0 or more . If a woman developed hypercalcemia or hypercalciuria , we discontinued the daily calcium supplementation ; if either condition continued , we reduced the dosing frequency of the study drug . Statistical Analysis We estimated the sample size for our study by assuming that 67 % of the patients would not have a prevalent fracture ; that the 18-month vertebral fracture incidence for patients with and without a prevalent fracture who received placebo would be 10 % and 2.5 % , respectively ; and that 20 % of the patients in each group would discontinue the study early without a new or worsened fracture .  We expected a sample of 2600 patients ( 1300 per treatment group ) to provide at least 90 % power to detect a significant 60 % or greater reduction in vertebral fracture incidence in the PTH treatment group compared with the placebo group ( 2-sided level of 0.05 ) . We analyzed data by using SAS software , version 8.0 ( SAS Institute , Inc. , Cary , North Carolina ) . We used descriptive statistics to summarize demographic and other baseline variables . We assessed comparability of the treatment groups at baseline by using t-tests for continuous Background Despite the availability of effective preventive and curative medications for osteoporosis , and guidelines for its diagnosis and management , few individuals are treated for osteoporosis , even among those who have already had a fracture . Objectives Our objective was to describe the patterns of use of medication for osteoporosis , i.e. , calcium supplements , vitamin D supplements , and specific anti-osteoporotic drugs , such as bisphosphonates , in a large sample of French older women living at home , and to identify individual factors associated with use of these medications overall and in two specific clinical situations . Methods Cross-sectional analysis of data from 4,221 women aged 75–85 years who participated in a balance and mobility examination as part of the screening procedure for the Ossébo study , a r and omized controlled trial testing the effectiveness of exercise for the prevention of fall-related injuries .  Electoral rolls  were used to invite women in 16 towns to participate ( participation rate 10.3 % ) . Information collected through question naires included current medication use and , in particular , use of osteoporosis medications ( specific osteoporosis drugs , calcium and vitamin D supplementation ) in the past 6 months , and history of fracture since the age of 50 , including fracture locations . Fractures were categorized in three groups : no fracture , major osteoporotic fracture ( hip , humerus , wrist , pelvis , and vertebra ) , and other fracture . Results Nearly 48 % of the participants reported they did not take calcium or vitamin D supplements or any specific  osteoporosis drugs  . Of the 2,133 women who reported using osteoporosis medication , 85 % used  vitamin D supplements ( 25 % as the sole medication against this disease ) , 59 % calcium supplements , and 42 % a specific anti-osteoporotic drug ( 75 % of them combining it with vitamin D supplementation ) . The use of any osteoporosis medication was significantly associated ( p < 0.001 ) with a history of a major osteoporotic fracture , lower weight , dual-energy X-ray absorptiometry ( DXA ) bone-density measurement in the past 5 years , a cancer-screening examination in the past 5 years , and a positive attitude toward medication use in general . Living alone was associated with a lower likelihood of using a specific anti-osteoporotic drug  , and a higher education level was associated with a higher likelihood of vitamin D supplementation . Of the 1,553 women who had already had a major osteoporotic fracture , one-third ( 34.8 % ) were not taking any osteoporosis medication . In this subgroup , use of this medication was associated with the same factors as in the overall study population . In particular , neither older age nor a history of falls in the previous 12 months was associated with a higher likelihood of using osteoporosis medication . Among the 909 women who reported using a specific osteoporosis drug , vitamin D use was associated with a higher educational level and a more frequent preventive attitude . Conclusion In France , as in other western countries , women aged 75 years and over are not managed according to guidelines . Further studies should address the barriers encountered in improving quality of care in osteoporosis management 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 The etiologic role of dietary calcium and vitamin D intake in primary prevention of  osteoporotic fractures is uncertain , despite considerable research efforts . With the aim to examine these associations with an improved precision , we used data from a large population -based prospect i ve cohort study in central Sweden . We estimated nutrient intake from a self-administered food-frequency question naire filled in by 60,689 women , aged 40 - 74 years at baseline during 1987 - 1990 . During follow-up , we observed 3986 women with a fracture at any site and 1535 with a hip fracture .  Rate ratio of fractures ( RR ) and 95 % CI were estimated using Cox proportional hazards models . We found no dose-response association between dietary calcium intake and fracture risk . The age-adjusted RR of hip fracture was 1.01 ( 95 % CI 0.96 - 1.06 ) per 300 mg calcium/day and the corresponding risk of any osteoporotic fracture was 0.99 ( 95 % CI 0.96 - 1.03 ) . Furthermore , women with an estimated calcium intake below 400 mg/day and those with a calcium intake higher than 1200 mg/day both had a similar age-adjusted hip fracture risk as those with intermediate calcium intakes : RR 1.07 ( 95 % CI 0.92 - 1.24 ) and RR 1.00 ( 95 % CI 0.79 - 1.27 ) , respectively . Vitamin D intake was not associated with fracture risk . Furthermore , women in the highest quintiles compared to the lowest quintiles of both calcium and vitamin D intake had an age-adjusted RR of 1.02 for all fractures ( 95 % CI 0.88 - 1.17 ) . Dietary calcium or vitamin D intakes estimated at middle and older age do not seem to be of major importance for the primary prevention of osteoporotic fractures in women OBJECTIVE To identify nutrients , foods , and dietary patterns associated with stress fracture risk and changes in bone density among young female distance runners . DESIGN AND SETTING Two-year , prospect i ve cohort study . Observational data were collected in the course of a multicenter r and omized trial of the effect of oral contraceptives on bone health . PARTICIPANTS One hundred and twenty-five female competitive distance runners ages 18 - 26 years . ASSESSMENT OF RISK FACTORS Dietary variables were assessed with a food frequency question naire . MAIN OUTCOME MEASUREMENTS Bone mineral density and content ( BMD/ BMC ) of the spine , hip , and total body were measured annually by dual x-ray absorptiometry ( DEXA ) .  Stress fractures were recorded on monthly calendars , and had to be confirmed by radiograph , bone scan , or magnetic resonance imaging . RESULTS Seventeen participants had at least one stress fracture during follow-up . Higher intakes of calcium , skim milk , and dairy products were associated with lower rates of stress fracture . Each additional cup of skim milk consumed per day was associated with a 62 % reduction in stress fracture incidence ( P < .05 ) ; and a dietary pattern of high dairy and low fat intake was associated with a 68 % reduction ( P < .05 ) . Higher intakes of skim milk , dairy foods , calcium , animal protein , and potassium were associated with significant ( P < .05 ) gains in whole-body BMD and BMC . Higher intakes of calcium , vitamin D , skim milk , dairy foods , potassium , and a dietary pattern of high dairy and low fat were associated with significant gains in hip BMD . CONCLUSIONS In young female runners , low-fat dairy products and the major nutrients in milk ( calcium , vitamin D , and protein ) were associated with greater bone gains and a lower stress fracture rate . Potassium intake was also associated with greater gains in hip and whole-body BMD
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 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 .