Comparative Assessment of Bone Mineral Measurements Using Dual X-ray Absorptiometry and Peripheral Quantitative Computed Tomography The Women's Health Initiative calcium-vitamin D trial: overview and baseline characteristics of participants. A comparison of the effects of alfacalcidol treatment and vitamin D2 supplementation on calcium absorption in elderly women with vertebral fractures Use of Calcium Supplements, Vitamin D Supplements and Specific Osteoporosis Drugs Among French Women Aged 75–85 Years: Patterns of Use and Associated Factors Effect of withdrawal of calcium and vitamin D supplements on bone mass in elderly men and women. Rationale and design of the B-PROOF study, a randomized controlled trial on the effect of supplemental intake of vitamin B12 and folic acid on fracture incidence Effect of calcium and vitamin D supplementation on bone mineral density in women aged 65–71 years: a 3-year randomized population-based trial (OSTPRE-FPS) Early identification of children predisposed to low peak bone mass and osteoporosis later in life. Prevention of hip fractures by correcting calcium and vitamin D insufficiencies in elderly people. Increase of axial and appendicular trabecular and cortical bone density in established osteoporosis with intermittent nasal salmon calcitonin therapy. Treatment of Low Bone Density or Osteoporosis to Prevent Fractures in Men and Women: A Clinical Practice Guideline Update From the American College of Physicians. Associations of vitamin D status with bone mineral density, bone turnover, bone loss and fracture risk in healthy postmenopausal women. The OFELY study. Weekly clodronate treatment prevents bone loss and vertebral fractures in women with subclinical Cushing’s syndrome Long-term effects of calcium-vitamin-D3-fortified milk on bone geometry and strength in older men. Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older. Pharmacologic Treatment of Low Bone Density or Osteoporosis to Prevent Fractures: A Clinical Practice Guideline from the American College of Physicians Risedronate and ergocalciferol prevent hip fracture in elderly men with Parkinson disease [RETRACTED] Alendronate in combination with calcium and vitamin D prevents bone loss after orthotopic liver transplantation: a prospective single-center study. Low acceptance of treatment in the elderly for the secondary prevention of osteoporotic fracture in the acute rehabilitation setting Alendronate Prevents Postmenopausal Bone Loss in Women without Osteoporosis: A Double-Blind, Randomized, Controlled Trial Vitamin A intake and the risk of hip fracture in postmenopausal women: the Iowa Women’s Health Study Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial Vitamin D3 and calcium to prevent hip fractures in elderly women.
Abstract : A measurement of bone mass is the single most important determinant of future fracture . However , controversy exists as to which technique ( dual X-ray absorptiometry ( DXA ) or peripheral quanitative computed tomography ( pQCT ) ) , and which site of skeletal measurement ( axial vs appendicular ) provides the best prediction of fracture risk . The aims of this study were : ( 1 ) to determine the ability of pQCT to predict bone mass of the lumbar spine , proximal femur , and distal forearm measured using DXA , and ( 2 ) to compare the ability of DXA and pQCT to discriminate prevalent fractures in women with established osteoporosis . One hundred and sixty-five women were studied , including 47 with established osteoporosis ( vertebral , hip or Colles ' fractures ) as well as 118 who had bone mass measurements to assess osteoporosis risk . Each subject had bone mass measured by DXA at the lumbar spine and femoral neck , and at the distal radius by both DXA and pQCT . In women with fractures , bone mass , when expressed as a st and ardized score , was in general lower using DXA compared with the appendicular skeleton measured using pQCT .  Bone mass determinations at all sites were significantly correlated with each other . The highest correlation coefficients were observed within the axial skeleton . In women with fractures , the highest odds ratios were observed at skeletal regions measured using DXA . Likewise , the areas under the receiver-operating characteristic ( ROC ) curves were comparable at all skeletal regions measured using DXA ; and were significantly greater than the areas under the ROC curves for pQCT measurements . In summary , the strongest discriminators of prevalent fractures were measurements using DXA . Measurements of bone mass at the appendicular skeleton , using either DXA or pQCT , were poorly associated with axial bone mass .  PQCT has the poorer ability to discriminate persons with fractures , and appears to be less sensitive than measurements using DXA 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 Although vitamin D supplementation in the frail elderly improves calcium absorption , suppresses parathyroid hormone , decreases bone loss and reduces the risk of fractures , such treatment may be ineffective in patients with vertebral osteoporosis , because of impaired vitamin D metabolism or resistance to the action of vitamin D metabolites on the bowel . We have therefore performed a r and omized , single masked study comparing the effects of alfacalcidol treatment ( 0.25 µg twice daily ) and vitamin D2 supplementation ( 500 - 1000 units daily ) on calcium absorption and bone turnover in 46 elderly women ( median age 69 years , range 64–79 years ) with radiological evidence of vertebral fractures .  Serum 25-hydroxyvitamin D increased significantly after 3 and 6 months of treatment with vitamin D2 ( p<0.001 ) , but was unchanged in the group receiving alfacalcidol  . Serum 1,25-dihydroxyvitamin D did not change significantly in either group over the study period . Fractional45Ca absorption increased after 3 months of treatment with alfacalcidol ( p<0.05 ) , but was unchanged with vitamin D2 . There was also a reduction in plasma intact parathyroid hormone and serum alkaline phosphatase after 6 months of treatment with alfacalcidol ( p<0.05 ) which was not seen in the group receiving vitamin D2 . Our study shows that vitamin D2 supplementation is ineffective in stimulating calcium absorption in elderly women with vertebral osteoporosis . By increasing calcium absorption in such patients , alfacalcidol may prove more effective than vitamin D in the management of vertebral osteoporosis 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 BACKGROUND Supplementation with calcium and vitamin D reduces bone loss and prevents fractures in elderly people , but it is not known whether any lasting benefit remains if the supplements are discontinued . OBJECTIVE The objective was to determine whether gains in bone mineral density ( BMD ) induced by calcium and vitamin D supplementation persist after supplement withdrawal . DESIGN Two-hundred ninety-five healthy , elderly men and women ( aged > /=68 y ) who had completed a 3-y r and omized , placebo-controlled trial of calcium and vitamin D supplementation were followed for an additional 2 y during which no study supplements were given .  BMD was measured by dual-energy X-ray absorptiometry , and biochemical variables related to calcium metabolism and bone turnover were measured . RESULTS In the 128 men , supplement-induced increases in spinal and femoral neck BMD were lost within 2 y of supplement discontinuation , but small benefits in total-body BMD remained . In the 167 women , there were no lasting benefits in total-body BMD or at any bone site . Consistent with the observations on BMD , the bone turnover rates in both men and women ( as measured by serum osteocalcin concentrations ) returned to their original higher concentrations within the same 2-y period . CONCLUSION Discontinued calcium and vitamin D supplementation has limited cumulative effect on bone mass in men and women aged > /=68 Background Osteoporosis is a major health problem , and the economic burden is expected to rise due to an increase in life expectancy throughout the world . Current observational evidence suggests that an elevated homocysteine concentration and poor vitamin B12 and folate status are associated with an increased fracture risk . As vitamin B12 and folate intake and status play a large role in homocysteine metabolism , it is hypothesized that supplementation with these B-vitamins will reduce fracture incidence in elderly people with an elevated homocysteine concentration . Methods / Design The B-PROOF ( B-Vitamins for the PRevention Of Osteoporotic Fractures ) study is a r and omized double-blind placebo-controlled trial . The intervention comprises a period of two years , and includes 2919 subjects , aged 65 years and older , independently living or institutionalized , with an elevated homocysteine concentration ( ≥ 12 μmol/L ) . One group receives daily a tablet with 500 μg vitamin B12 and 400 μg folic acid and the other group receives a placebo tablet . In both tablets 15 μg ( 600 IU ) vitamin D is included . The primary outcome of the study is osteoporotic fractures . Measurements are performed at baseline and after two years and cover bone health i.e. bone mineral density and bone turnover markers , physical performance and physical activity including falls , nutritional intake and status , cognitive function , depression , genetics and quality of life . This large multi-center project is carried out by a consortium from the Erasmus MC ( Rotterdam , the Netherl and s ) , VUmc ( Amsterdam , the Netherl and s ) and Wageningen University , ( Wageningen , the Netherl and s ) , the latter acting as coordinator . Discussion To our best knowledge , the B-PROOF study is the first intervention study in which the effect of vitamin B12 and folic acid supplementation on osteoporotic fractures is studied in a general elderly population . We expect the first longitudinal results of the B-PROOF intervention in the second semester of 2013 . The results of this intervention will provide evidence on the efficacy of vitamin B12 and folate supplementation in the prevention of osteoporotic fractures . Trial Registration The B-PROOF study is registered with the Netherl and s Trial ( NTR NTR1333 ) and with Clinical Trials.gov ( NCT00696514 ) Summary The Osteoporosis Risk Factor and Prevention-Fracture Prevention Study ( OSTPRE-FPS ) was a r and omized population -based open trial ( n = 593 ) . The supplementation group ( n = 287 ) received daily cholecalciferol 800 IU + calcium 1,000 mg for 3 years while the control group ( n = 306 ) received neither supplementation nor placebo . Daily vitamin D and calcium supplementation have a positive effect on the skeleton in ambulatory postmenopausal women . Introduction Vitamin D deficiency is common in the elderly , and vitamin D levels are associated with low bone mineral density ( BMD ) . The working hypothesis was that vitamin D and calcium supplementation could prevent bone loss in ambulatory postmenopausal women . Methods The OSTPRE-FPS was a r and omized population -based open trial with a 3-year follow-up in 3,432 women ( aged 66 to 71 years ) . A r and omly selected sub sample of 593 subjects underwent BMD measurements . The supplementation group ( n = 287 ) received daily cholecalciferol 800 IU + calcium 1,000 mg for 3 years while the control group ( n = 306 ) received neither supplementation nor placebo . Results In the intention-to-treat analysis , total body BMD ( n = 362 ) increased significantly more in the intervention group than in the control group ( 0.84 % vs. 0.19 % , p = 0.011 ) . The BMD change differences at the lumbar spine ( p = 0.372 ) , femoral neck ( p = 0.188 ) , trochanter ( p = 0.085 ) , and total proximal femur ( p = 0.070 ) were statistically nonsignificant . Analyses in compliant women ( ≥80 % of use ) result ed in stronger and statistically significant effects at the total body and femoral regions . Conclusion Daily vitamin D and calcium supplementation have a positive effect on the skeleton in ambulatory postmenopausal women with adequate nutritional calcium intake The amount of bone that is gained during adolescence is the main contributor to peak bone mass , which , in turn , is a major determinant of osteoporosis and fracture risk in the elderly . We examined whether computed tomography measurements for the density and the volume of bone in the axial and the appendicular skeletons could be tracked through puberty in 40 healthy white children ( 20 girls and 20 boys ) . Longitudinal measurements of the cross-sectional area and cancellous bone density of the vertebral bodies and the cross-sectional and cortical bone areas of the femurs at the beginning of puberty accounted for 62 - 92 % of the variations seen at sexual maturity ; on average , 3 yr later . When baseline values for these bone traits were divided into quartiles , a linear relation across Tanner stages of sexual development was observed for each quartile in both girls and boys . The regression lines differed among quartiles for each trait , paralleled each other , and did not overlap . Thus , we are now in a position to identify those children who are genetically prone to develop low values for peak bone mass and toward whom osteoporosis prevention trials should be geared For a 50-year old caucasian woman today , the risk of a hip fracture over her remaining lifetime is about 17 % . Tomorrow the situation will clearly be worse because the continual increase in life expectancy will cause a 3-fold rise in worldwide fracture incidence over the next 60 years , particularly in women , but also in men . In addition , a secular increase in the incidence of hip fractures in individuals of the same age has been noted in both sexes by several investigators , and the cost of hip fractures is expected to dramatically increase in the next decades . Consequently , preventive strategies are urgently required . A great deal has been learned in recent years about the risk factors for hip fracture , the pathophysiology of this fracture , and the prediction of fracture risk , particularly through bone mass measurements on the hip and biochemical evaluations of parathyroid and vitamin D status . The two main determinants of hip fractures are falls and bone loss leading to an intrinsic femoral fragility . A substantial femoral bone loss continues throughout the old age , with a continuous and exponential increase in the risk of hip fracture , and any reduction or arrest of this loss will induce an important reduction in the incidence of hip fractures . A preventive effect on the risk of hip fracture may be partly achieved by using long term estrogen replacement therapy after menopause , but also by using vitamin D and calcium supplements for a late prevention in elderly people .  Vitamin D insufficiency and deficit in calcium intake are very common in elderly people living either in institutions or at home , particularly in Europe where dairy products are not fortified with vitamin D. The cumulative response to this deficit in calcium intake and low vitamin D status is a negative calcium balance which stimulates parathyroid hormone secretion . In 300 residents of nursing homes , we recently found a significant negative correlation between serum 25 OHD and log serum PTH after age-adjustment . In addition , in 446 elderly women living at home in 5 French cities and selected from the voting lists , we also found an age-adjusted relationship between serum 25 OHD and PTH concentrations . This senile secondary hyperparathyroidism is one of the determinants of femoral bone loss and can be reversed by calcium and vitamin D supplements . We have shown in a 3-year controlled prospect i ve study that the daily use of these supplements ( 1.2 g of calcium and 800 IU of vitamin D3 ) given in a large population of 3270 elderly ambulatory women living in nursing homes reduced of 23 % ( intention-to-treat analysis ) the number of hip fractures and other non vertebral fractures . In parallel , serum perathyroid hormone concentration was reduced of 28 % and low serum 25-hydroxyvitamin D concentration returned to normal values . After 18 months of treatment the bone density of the total proximal femoral region had increased 2.7 % the vitamin D3-calcium group and decreased 4.6 % in the placebo group ( p < 0.001 ) . This prevention is safe and can be recommended in people living in institutions . It could be also useful in other elderly subjects particularly at risk because of a low calcium intake , an absence of solar exposure and a previous history of falls . From the data of our study we assessed the economic consequences in terms of medical cost of this prevention . In case of treatment of all women living in nursing homes in France , this would saved FF 150000000 per year , the economic balance of prevention becoming positive as soon as the age of the beginning of the prevention reaches 73.5 years . It is now possible to partly stop bone loss in elderly people and it is never too late to prevent hip fractures with calcium and vitamin D supplements The aim of this study was to examine the effect of intranasal administration of salmon calcitonin to a group of 24 postmenopausal women with severe , established osteoporosis ( t score < -2.5 SD ) and more than one vertebral fracture . The patients were treated with 200 IU of nasal salmon calcitonin daily for 2 months with a subsequent pause of 2 months ( 3 cycles ) and 500 mg calcium daily over a total of 12 months in an open r and omized study . The patients were compared with an age matched control group of 18 women of a similar clinical status who were treated with calcium and vitamin D only . In the nasal calcitonin treatment group an increase in the trabecular axial bone density of 2.8 % was achieved , as well as increase in trabecular appendicular ( forearm ) bone density of 1.6 % , together with a cortical bone density increase of 1.8 % axial and 1 % appendicular . Initially , elevated values of urinary deoxypyridinoline were found in 12 women in the nasal calcitonin treatment group ; these levels returned to normal under salmon calcitonin nasal therapy and documented the inhibition of increased osteoclastic activity .  Cyclic intermittent calcitonin nasal therapy led to a general increase in trabecular and cortical axial and appendicular bone density , marked alleviation of the subjective sensation of pain , and a reduction in the daily dose of accompanying nonsteroidal anti-inflammatory drugs by 50 % Description This guideline up date s the 2008 American College of Physicians ( ACP ) recommendations on treatment of low bone density and osteoporosis to prevent fractures in men and women . This guideline is endorsed by the American Academy of Family Physicians . Methods The ACP Clinical Guidelines Committee based these recommendations on a systematic review of r and omized controlled trials ; systematic review s ; large observational studies ( for adverse events ) ; and case reports ( for rare events ) that were published between 2 January 2005 and 3 June 2011 . The review was up date d to July 2016 by using a machine-learning method , and a limited up date to October 2016 was done . Clinical outcomes evaluated were fractures and adverse events . This guideline focuses on the comparative benefits and risks of short- and long-term pharmacologic treatments for low bone density , including pharmaceutical prescriptions , calcium , vitamin D , and estrogen . Evidence was grade d according to the GRADE ( Grading of Recommendations Assessment , Development and Evaluation ) system . Target Audience and Patient Population The target audience for this guideline includes all clinicians . The target patient population includes men and women with low bone density and osteoporosis . Recommendation 1 ACP recommends that clinicians offer pharmacologic treatment with alendronate , risedronate , zoledronic acid , or denosumab to reduce the risk for hip and vertebral fractures in women who have known osteoporosis . ( Grade : strong recommendation ; high- quality evidence ) . Recommendation 2 ACP recommends that clinicians treat osteoporotic women with pharmacologic therapy for 5 years . ( Grade : weak recommendation ; low- quality evidence ) . Recommendation 3 ACP recommends that clinicians offer pharmacologic treatment with bisphosphonates to reduce the risk for vertebral fracture in men who have clinical ly recognized osteoporosis . ( Grade : weak recommendation ; low- quality evidence ) . Recommendation 4 ACP recommends against bone density monitoring during the 5-year pharmacologic treatment period for osteoporosis in women . ( Grade : weak recommendation ; low- quality evidence ) . Recommendation 5 ACP recommends against using menopausal estrogen therapy or menopausal estrogen plus progestogen therapy or raloxifene for the treatment of osteoporosis in women . ( Grade : strong recommendation ; moderate- quality evidence ) . Recommendation 6 ACP recommends that clinicians should make the decision whether to treat osteopenic women 65 years of age or older who are at a high risk for fracture based on a discussion of patient preferences , fracture risk profile , and benefits , harms , and costs of medications . ( Grade : weak recommendation ; low- quality evidence ) INTRODUCTION Vitamin D status is considered as an important determinant of bone health but supplementation trials with vitamin D(3 ) have yielded conflicting results . The aim of this study was to investigate the associations between serum 25-hydroxyvitamin D ( 25-OH D ) , bone turnover markers , bone mineral density ( BMD ) , radius bone loss and incidence of fracture in postmenopausal women . METHODS 669 postmenopausal women ( mean age : 62.2 years ) belonging to a population -based cohort were followed prospect ively for a median of 11.2 years . At baseline , 25-OH D levels , BMD , bone turnover markers and clinical risk factors of osteoporosis were assessed . BMD loss at the radius was estimated by annual measurements of BMD and all incident fractures which occurred in 134 women were confirmed by radiographs . RESULTS 73 % and 35 % of women had serum 25-OH D levels below 75 and 50 nmol/l which correspond respectively to the median and lowest optimal values recently proposed for fracture prevention . 11 % of women had levels below 30 nmol/l . Serum 25-OH D correlated modestly with intact PTH ( r(2)=0.023 , p<0.0001 ) , but not with bone turnover markers or BMD at the hip and radius after adjustment for age . When levels of 25-OH D were considered as a continuous variable , there was no significant association between 25-OH D levels and radius BMD loss or fracture risk . After adjustment for age , there was no significant difference in incidence of fracture , BMD , radius BMD loss , bone turnover markers , grip strength and the percentage of fallers in the previous year between women with 25-OH D levels below or above 75 , 50 or 30 nmol/l . CONCLUSIONS In a population of home-dwelling healthy postmenopausal women with few of them with severe vitamin D deficiency , vitamin D status may not be an important determinant of bone health Introduction : Chronic mild endogenous glucocorticoid excess has been shown to cause bone loss and to increase fracture risk in both post-menopausal and premenopausal women . Currently , it is unclear if patients with sub clinical Cushing ’s syndrome ( SCS ) with osteoporosis or osteopenia may benefit from antiresorptive treatment and the type of therapy to be given . Objective : This pilot r and omized study was aim ed at evaluating the effects of 12-month i m administration of clodronate ( 100 mg every week ) on vertebral and femoral bone mineral density ( BMD ) , bone turnover markers and on subjective pain in premenopausal women with SCS due to adrenal incidentalomas . Methods : Forty-six women ( age , 43.1 ±7.7 yr ) with SCS due to adrenal incidentaloma and osteoporosis/osteopenia were r and omized to receive clodronate plus supplement of Calcium ( 500 mg daily ) and Vitamin D3 ( 800 mg daily ) ( group 1 , no.=23 ) or supplements only ( group 2 , no.=23 ) . Both groups were similar in terms of age , body mass index , cortisol levels , BMD values , and bone turnover markers . All of the women were re-evaluated after 12 months . Results : After 12 months of treatment , in group 1 , a significant increase in lumbar BMD occurred ( p=0.04 ) , while bone turnover markers decreased by about one third ( p<0.05 ) . In group 2 , bone turnover markers did not change and BMD values slightly decreased ( p = ns ) . The differences in bone turnover markers and in lumbar BMD between the two groups were significant ( p<0.05 , all ) . No new vertebral fracture occurred in group 1 , while in group 2 the spine radiographies revealed 2 new fractures and a worsening of two pre-existent fractures . An improvement in subjective back pain , assessed by visual analogue scale pain score was observed in group 1 ( from 4.3±2.7 to 2.9±2.0 ; p<0.05 ) but not in group 2 ( from 4.4±3.1 to 4.2±3.4 ; p = ns ) . No significant changes occurred in cortisol secretion or clinical picture of the SCS during the study . Conclusions : Intramuscular administration of clodronate effectively increased lumbar BMD values , preserved bone mass at the femoral neck , stabilized vertebral fracture index , and decreased subjective back pain in pre-menopausal women with SCS . Since the untreated group continued to lose bone , antiresorptive treatment should be considered in patients with SCS , according to the prevision of surgical treatment , prevalent fractures , BMD values , age , concomitant morbidities , and desire for pregnancy The long-term effects of calcium and vitamin D supplementation on bone material and structural properties in older men are not known . The aim of this study was to examine the effects of high calcium ( 1000 mg/day)- and vitamin-D(3 ) ( 800 IU/day)-fortified milk on cortical and trabecular volumetric BMD ( vBMD ) and bone geometry at the axial and appendicular skeleton in men aged over 50 years . One hundred and eleven men who were part of a larger 2-year r and omized controlled trial had QCT scans  of the mid-femur and lumbar spine ( L(1)-L(3 ) ) to assess vBMD , bone geometry and indices of bone strength [ polar moment of inertia ( I(polar ) ) ] . After 2 years , there were no significant differences between the milk supplementation and control group for the change in any mid-femur or L(1)-L(3 ) bone parameters for all men aged over 50 years . However , the mid-femur skeletal responses to the fortified milk varied according to age , with a split of < or=62 versus > 62 years being the most significant for discriminating the changes between the two groups . Subsequent analysis revealed that , in the older men ( > 62 years ) , the expansion in mid-femur medullary area was 2.8 % ( P < 0.01 ) less in the milk supplementation compared to control group , which helped to preserve cortical area in the milk supplementation group ( between group difference 1.1 % , P < 0.01 ) . Similarly , for mid-femur cortical vBMD and I(polar ) , the net loss was 2.3 and 2.8 % less in the milk supplementation compared to control group ( P < 0.01 and < 0.001 , respectively ) . In conclusion , calcium-vitamin-D(3)-fortified milk may represent an effective strategy to maintain bone strength by preventing endocortical bone loss and slowing the loss in cortical vBMD in elderly men 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 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 ) BACKGROUND There is a high incidence of hip fractures in patients with Parkinson disease ( PD ) .  Bone mineral density ( BMD ) is decreased in patients with PD , correlating with the immobilization-induced bone resorption and hypovitaminosis D with compensatory hyperparathyroidism . OBJECTIVE To evaluate the effectiveness of risedronate , an inhibitor of bone resorption , on osteoporosis and the risk of hip fractures in elderly men with PD . METHODS This was a 2-year , r and omized , double-blind , placebo-controlled trial . In a prospect i ve study of patients with PD , 121 patients received a daily dose of 2.5 mg risedronate and vitamin D2 1,000 IU for 2 years , and the remaining 121 received placebo and vitamin D2  1,000 IU . Incidence of hip fractures was compared between the two groups . RESULTS Nine patients sustained hip fractures in the placebo group , and three hip fractures occurred in the risedronate group . The relative risk of a hip fracture in the risedronate group vs the placebo group was 0.33 ( 95 % CI , 0.09 to 1.20 ) . BMD increased by 2.2 % in the risedronate group and decreased by 2.9 % in the placebo group ( p < 0.0001 ) . Urinary deoxypyridinoline , a bone resorption marker , decreased by 46.7 % in the risedronate group and by 33.0 % in the placebo group . CONCLUSION Treatment with risedronate and vitamin D2 increases bone mineral density in elderly men with Parkinson disease and reduces the risk of hip fractures Bone loss is a common complication in patients before and after liver transplantation ( LT ) . The aim of this study was to investigate the efficacy of prophylactic treatment with bisphosphonates after LT in preventing progressive bone loss in LT patients . We included 136 patients with end-stage liver diseases awaiting LT .  Bone mineral density ( BMD ) ( by dual X-ray absorptiometry ) and markers of bone metabolism were determined before , and 4 , 12 , 24 , 36 , and 48 months after LT . All patients received vitamin D and calcium supplementation before and after LT , those with osteopenia or osteoporosis prior to LT were additionally treated with alendronate following LT . Decreased BMD was seen in a high percentage of patients undergoing LT ( osteopenia 48.5 % , osteoporosis 23.5 % ) . Reduced BMD before LT was not related to gender , underlying liver disease , or Child-Turcotte-Pugh classification . Body mass index ( BMI ) prior to LT , however , correlated significantly with the fracture risk . Alendronate prevented the ubiquitously observed bone loss after LT in patients with osteoporosis and osteopenia and , in addition , led to an increase in BMD in patients with osteoporosis within 24 months after LT . In conclusion , our study suggests that alendronate is efficacious in preventing the natural course of bone loss associated with LT Background and aims : Given the high risk of subsequent fracture among elderly persons with fracture , it is important to initiate secondary treatment for osteoporosis . Acute rehabilitation centers may offer a unique opportunity to introduce treatment . Therefore , we evaluated willingness-to-participate and compliance with evidence -based interventions for the secondary prevention of  osteoporotic fracture in a non-r and omized study conducted in the acute rehabilitation setting . We also described differences in baseline characteristics between study participants and non- participants . Methods : All consecutive , community-dwelling admissions to an acute rehabilitation unit ( Boston , MA ) with the diagnosis of fracture were screened for enrollment . Eligible subjects were offered a free , 6-month supply of alendronate/cholecalciferol ( 70 mg/2800 IU weekly ) , calcium and vitamin D supplements , and fall prevention strategies . Six-month compliance ( ≥75 % consumption of medication or supplement ) with the interventions was determined at a home visit . Results : Among 62 eligible subjects , 25 agreed to participate . Non- participants were older than participants ( 86 vs 80 yrs , p<0.01 ) . There was no significant difference between other characteristics of participants and non- participants including sex , weight , type of fracture , cognitive status , and functional status . The most common reason for non-participation was reluctance to take another medication . Among participants , only 52 % were compliant with alendronate and 58 % were compliant with calcium and vitamin D supplementation at 6 months . Conclusions : Willingness-to-participate and compliance with secondary prevention strategies for osteoporosis was low in the acute rehabilitation setting , even when medications were provided free of cost . Educating individuals with fracture and their families on the consequences and treatment of osteoporosis may help to decrease the risk of sustaining a second fracture by accepting secondary preventive measures Osteoporosis is characterized by low bone mass and architectural changes in bone that render the skeleton brittle and susceptible to fracture [ 1 ] . As the elderly population grows , the worldwide annual incidence of hip fractures is projected to increase from 1.7 million in 1990 to 6.3 million by 2050 , placing great economic strain on health care systems [ 2 ] . Currently , a 50-year-old woman is estimated to have a risk as high as 40 % for sustaining a fracture related to osteoporosis at some point in the future [ 3 ] . The age-adjusted risk for fracture seems to be increasing , and this risk may be an underestimate for the future [ 4 ] . Bone loss after menopause , which results in low bone density , is an important determinant of risk for fracture , although other factors ( such as advanced age , hip geometry , and falls and injuries ) also contribute [ 5 , 6 ] . Bone loss is most rapid during the first few years after menopause , but evidence suggests that the rate of loss also becomes accelerated in advanced old age [ 7 , 8 ] . One strategy to reduce the number of fractures in postmenopausal women is to begin treatment for osteoporosis only in patients who are at high risk for fracture , including those with osteoporosis or previous fragility fractures .  Pharmacologic therapy in women with osteoporosis with or without fractures reduces the incidence of fracture by about 50 % [ 9 , 10 ] . However , half of women who would have sustained fractures without treatment still do so with treatment . Thus , preventing rather than treating osteoporosis is a more appealing clinical objective because it can avoid the increased risk for fracture . There may also be an advantage in terms of preserving the normal microarchitecture of bone . Preventing bone loss associated with menopause and aging and maintaining normal microarchitecture provide important opportunities for the prevention of osteoporosis and fractures . Estrogen is effective in preventing bone loss in early and late postmenopausal women , but it must be taken over the long term to decrease the incidence of vertebral and hip fractures [ 11 ] . Estrogen also relieves menopausal symptoms and , in epidemiologic cohort studies , seemed to protect against cardiovascular disease . However , most women who begin estrogen therapy do not continue it for more than a year , in part because of such side effects as breast tenderness , headache , fluid retention , and withdrawal bleeding [ 12 , 13 ] . Although the benefits of estrogen therapy outweigh the risks in most women , concern about risk for breast cancer is sufficiently great that many women avoid estrogen therapy [ 14 , 15 ] . Alendronate sodium ( monosodium 4-amino , 1-hydroxybutylidene-1 , 1-bisphosphonate ) is a potent and selective inhibitor of osteoclast-mediated bone resorption . Studies in animals with low bone mineral density have shown that alendronate therapy is associated with increased bone mass of normal quality and increased bone strength [ 16 ] . Alendronate treatment of osteoporosis in postmenopausal women induces progressive increases in bone density and a reduction in the incidence of new fractures of the vertebrae , hip , and forearm in osteoporotic women [ 9 , 10 ] . We performed a 3-year r and omized , double-blind , placebo-controlled , dose-ranging study to evaluate the efficacy of alendronate therapy in preventing bone loss in healthy women who had recently experienced menopause . Methods Study Participants Healthy women aged 40 to 59 years who had experienced menopause 6 to 36 months before enrollment were eligible to participate in this study . Women were excluded if their spine bone mineral density was more than 2 SDs above or below normal peak bone mineral density or if they had a history of nontraumatic spine or hip fracture . Women with disorders of bone and mineral metabolism were also excluded , as were those with recent ( within 1 year of study entry ) major upper gastrointestinal diseases ( such as peptic ulcer , esophageal disease , and malabsorption ) . Other exclusion criteria were previous treatment with bisphosphonates or fluoride ( > 1 mg/d ) or treatment within the 12 months before enrollment with estrogen , progestin , calcitonin , glucocorticoids , anticonvulsant agents , phosphate-binding antacids , or excessive vitamin A or vitamin D. Women who regularly used ( > four times per week ) any medication that had the potential to cause gastrointestinal irritation ( such as aspirin ) , who smoked more than 20 cigarettes per day , or who drank three or more alcoholic beverages per day were also excluded . Four hundred forty-seven women met the inclusion criteria and were enrolled at 15 centers throughout the world . The target sample size of 250 women completing the study was selected to detect a difference in bone density of 2.4 % between an individual alendronate dosage and placebo at a P value of 0.05 or less , with 95 % power using an SD of 3.3 % that was obtained from 1-year bone density data in placebo recipients [ 17 ] . All centers conducted the study with appropriate approval from the institutional review boards , and all participants gave informed consent . Treatment Participants were r and omly assigned ( in allocation blocks of five ) to one of five regimens : placebo for 3 years ; alendronate at 1 , 5 , or 10 mg/d for 3 years ; or alendronate at 20 mg/d for 2 years followed by placebo for 1 year ( 20/0 mg/d ) . In all groups , double-blinding was maintained for all 3 years . Alendronate and placebo tablets were identical in size , shape , and color . The women were instructed to take the study drug daily at least 1 hour before breakfast or , as a less desirable alternative , at least 2 hours after a meal and 1 hour before the next meal . All participants also received a daily supplement of calcium carbonate ( Os-Cal 500 , Smith-Kline Beecham Consumer Br and s , LP , Pittsburgh , Pennsylvania , or the equivalent ) unless dietary calcium intake exceeded 1000 mg/d . This supplement was usually taken with the evening meal . After beginning therapy , each participant was seen at months 1 and 3 and every 3 months thereafter . Eight participants ( four in the placebo group and four in the 1-mg/d group ) lost more than 6 % of their spine bone density at 24 months relative to their baseline measurements and were therefore design ated fast bone losers . Seven of these participants completed the study ; from month 24 to the end of the study , they received 5 mg of open-label alendronate per day . The other patient discontinued therapy at month 24 . Bone Mineral Density Bone mineral density of the spine , proximal femur , total body , and forearm was measured every 6 months by dual-energy x-ray absorptiometry with a Hologic QDR-1000 , 1000/W , or 2000 densitometer ( Waltham , Massachusetts ) or a Lunar DPX-L densitometer ( Madison , Wisconsin ) . One bone density quality assurance center ( Oregon Osteoporosis Center ) that remained blinded to treatment allocation was responsible for the quality control of all participant and phantom calibration scans [ 18 ] . Factors to correct for machine calibration drift were applied as necessary . The primary end point was bone mineral density of the lumbar spine ; the other most important end points were bone mineral density of the femoral neck , trochanter , and total body . Bone mineral density of the total body , total hip , and forearm was measured at the centers that had densitometers capable of performing these measurements ( 11 centers measured bone mineral density of the total body ; 10 centers measured bone mineral density of the total hip and forearm ) . Biochemical Markers and Indices of Mineral Metabolism Fasting serum and urine sample s ( second morning void ) were obtained at all clinic visits except those in months 27 and 33 . The resorption markers included urine deoxypyridinoline , measured by high-pressure liquid chromatography , and ( in a subgroup of 268 participants ) urine N-telopeptide cross-links of type I collagen ( Ostex , Seattle , Washington ) . Each of these markers was expressed as a ratio to urine creatinine . Serum osteocalcin levels , measured by radioimmunoassay ( INCSTAR , Stillwater , Nebraska ) , and serum bone-specific alkaline phosphatase levels were used to assess the rate of bone formation . Levels of serum calcium , phosphorus , intact parathyroid hormone ( measured by immunoradiometric assay ) , and 1,25 dihydroxyvitamin D ( measured by competitive binding assay ) were also determined to assess the effects of treatment on mineral metabolism .  N-telopeptide  levels were measured by Medical Research Laboratories ( Highl and Heights , Kentucky ) . All other assays were done at Corning-Nichols Institute ( San Juan Capistrano , California ) . Safety Evaluations At each visit , vital signs were measured and any new or worsening symptoms were recorded . Physical examinations were performed at the baseline , month 3 , and yearly visits . St and ard laboratory safety evaluations ( including evaluations of hematologic , renal , and liver function ) were performed at every visit . Investigators reported any unfavorable or unintended clinical or laboratory events as adverse experiences . After 3 years of therapy , biopsy specimens of transiliac bone were obtained for histologic and histomorphometric assessment from 55 women who provided specific informed consent for this procedure . These analyses were performed , as previously described , by a single investigator who was blinded to treatment groups [ 19 ] . Statistical Analysis The Tukey trend test [ 20 ] was used to assess the trend in response with increasing alendronate dosages . The 20/0-mg/d group was excluded from this test because of the change in dosage . This test uses the minimum P value , adjusted for multiplicity [ 21 ] , that was obtained from tests of the regression sloped on three dosage scalings . The test is done in a stepwise manner , with the highest dosage eliminated , until the minimum P value exceeds 0.05 . Dose-response relations were examined for the responses of the percentage change in bone density variables , natural logarithm ( fraction of the baseline value ) for biochemical Excessive intake of vitamin A is postulated to have a detrimental effect on bone by inducing osteoporosis . This may lead to an increased risk of fracture , particularly in persons who are already at risk of osteoporosis . However , few studies have specifically examined the association of vitamin A intake through diet and supplement use , with fractures in a cohort of older , community-dwelling women . We prospect ively followed a cohort of 34,703 postmenopausal women from the Iowa Women ’s Health Study to determine if high levels of vitamin A and retinol intake through food and supplement use were associated with an increased risk of hip or all fractures . A semiquantitative food frequency question naire was used to obtain the participants ’ baseline vitamin A and retinol intake . Participants were followed for a mean duration of 9.5 years for incident self-reported hip and nonhip fractures . After multivariate adjustment , it was revealed that users of supplements containing vitamin A had a 1.18-fold increased risk of incident hip fracture ( n=525 ) compared with nonusers ( 95 % CI , 0.99 to 1.41 ) , but there was no evidence of an increased risk of all fractures ( n=6,502 ) among supplement users . There was also no evidence of a dose-response relationship in hip fracture risk with increasing amounts of vitamin A or retinol from supplements . Furthermore , our results showed no association between vitamin A or retinol intake from food and supplements , or food only , and the risk of hip or all fractures . In conclusion , we found little evidence of an increased risk of hip or all fractures with higher intakes of vitamin A or retinol among a cohort of older , postmenopausal women Abstract Objective : To determine the effect of four monthly vitamin D supplementation on the rate of fractures in men and women aged 65 years and over living in the community . Design : R and omised double blind controlled trial of 100 000 IU oral vitamin D3 ( cholecalciferol ) supplementation or matching placebo every four months over five years . Setting and participants : 2686 people ( 2037 men and 649 women ) aged 65 - 85 years living in the general community , recruited from the British doctors register and a general practice register in Suffolk . Main outcome measures : Fracture incidence and total mortality by cause . Results : After five years 268 men and women had incident fractures , of whom 147 had fractures in common osteoporotic sites ( hip , wrist or forearm , or vertebrae ) . Relative risks in the vitamin D group compared with the placebo group were 0.78 ( 95 % confidence interval 0.61 to 0.99 , P=0.04 ) for any first fracture and 0.67 ( 0.48 to 0.93 , P=0.02 ) for first hip , wrist or forearm , or vertebral fracture . 471 participants died . The relative risk for total mortality in the vitamin D group compared with the placebo group was 0.88 ( 0.74 to 1.06 , P=0.18 ) . Findings were consistent in men and women and in doctors and the general practice population . Conclusion : Four monthly supplementation with 100 000 IU oral vitamin D may prevent fractures without adverse effects in men and women living in the general community . What is already known in this topic Vitamin D and calcium supplements are effective in preventing fractures in elderly women Whether isolated vitamin D supplementation prevents fractures is not clear What this paper adds Four monthly oral supplementation with 100 000 IU vitamin D reduces fractures in men and women aged over 65 living in the general community  Total fracture incidence was reduced by 22 % and fractures in major osteoporotic sites by 33 BACKGROUND Hypovitaminosis D and a low calcium intake contribute to increased parathyroid function in elderly persons .  Calcium and vitamin D supplements reduce this secondary hyperparathyroidism , but whether such supplements reduce the risk of hip fractures among elderly people is not known . METHODS We studied the effects of supplementation with vitamin D3 ( cholecalciferol ) and calcium on the frequency of hip fractures and other nonvertebral fractures , identified radiologically , in 3270 healthy ambulatory women ( mean [ + /- SD ] age , 84 + /- 6 years ) . Each day for 18 months , 1634 women received tricalcium phosphate ( containing 1.2 g of elemental calcium ) and 20 micrograms ( 800 IU ) of vitamin D3 , and 1636 women received a double placebo . We measured serial serum parathyroid hormone and 25-hydroxyvitamin D ( 25(OH)D ) concentrations in 142 women and determined the femoral bone mineral density at base line and after 18 months in 56 women . RESULTS Among the women who completed the 18-month study , the number of hip fractures was 43 percent lower ( P = 0.043 ) and the total number of nonvertebral fractures was 32 percent lower ( P = 0.015 ) among the women treated with vitamin D3 and calcium than among those who received placebo . The results of analyses according to active treatment and according to intention to treat were similar . In the vitamin D3-calcium group , the mean serum parathyroid hormone concentration had decreased by 44 percent from the base-line value at 18 months ( P < 0.001 ) and the serum 25(OH)D concentration had increased by 162 percent over the base-line value ( P < 0.001 ) . The bone density of the proximal femur increased 2.7 percent in the vitamin D3-calcium group and decreased 4.6 percent in the placebo group ( P < 0.001 ) . CONCLUSIONS Supplementation with vitamin D3 and calcium reduces the risk of hip fractures and other nonvertebral fractures among elderly women
Two regimens , each represented by one large trial , which showed limited evidence of efficacy in reducing the incidence of hip or other appendicular skeleton fractures were : 1 ) Oral Vitamin D when accompanied by calcium supplementation .
2 ) 1,25 dihydroxy Vitamin D ( calcitriol ) .
This appeared more effective than calcium in a direct comparison .
Hypercalcaemia and gastro-intestinal symptoms , reported in less than 5 % of participants , were slightly more common when Vitamin D analogues were taken .
However , the risk of death was marginally less .
REVIEW ER 'S CONCLUSIONS Uncertainty remains about the efficacy of regimens which include Vitamin D or its analogues in fracture prevention .
Particularly if co-supplementation of calcium is required , significant cost differences are likely to exist between regimens .
BACKGROUND Due to their known effects on bone metabolism , Vitamin D and related compounds have been proposed for the prevention of osteoporosis and fractures .
OBJECTIVES To determine the effects of supplementation with Vitamin D or a Vitamin D analogue in the prevention of fractures of the axial and appendicular skeleton in elderly men or women with involutional or post-menopausal osteoporosis .