Peak bone mass, bone loss and risk of fracture

Both peak bone mass and bone loss contribute to subsequent fracture risk. Other variables such as architectural abnormalities, microdamage, geometric properties, and trauma probably contribute as well. Until the contribution of these other potentially important risk factors can be quantified, it will be difficult to determine precisely the relative importance of peak bone mass and subsequent bone loss in the etiology of fractures.     

Normative Data for Multisite Quantitative Ultrasound: The Canadian Multicenter Osteoporosis Study

Multisite quantitative ultrasound (mQUS) machines are attractive tools for assessing fragility fracture risk as they are often portable, comparatively inexpensive, require little training for their use, and emit no ionizing radiation. The primary objective of this investigation was to generate an mQUS normative database of speed of sound (SOS, in m/s) measures from a large sample of randomly selected community-based individuals. mQUS (BeamMed Omnisense MultiSite Quantitative Ultrasound 7000 S) measurements were obtained and assessed at the distal radius, tibia, and phalanx. All analyses were made separately for men and women and for each anatomical site. Scatterplots (SOS vs age) identified 30–39 yr of age as periods of both maximal SOS and of relative stability for all 3 sites over the age span investigated (30–96 yr of age; 2948 women and 1176 men) and, thus, was used as the “reference” population. For cross-sectional comparison of trends over aging, a number of age groupings were created: 30–39, 40–49, 50–59, 60–69, 70–79, and 80+ yr. In general, there were decreases in SOS over increasing age groupings. The normative data generated can be used to compare a given patient's mQUS measurement with reference to a young, healthy population, assigning them a gender-appropriate T-score.     

Peak bone mass is increased in the hip in daughters of women with osteoarthritis.

The mechanism behind the inverse association between osteoporosis and osteoarthritis shown in large epidemiological studies remains unclear. Because both diseases often demonstrate a family history, the objective of the present study was to compare peak bone density in daughters categorized according to the presence or absence of hand osteoarthritis in their mothers. Radiographs of the hands were obtained in women aged 50-75 years from a well-defined community population group. X-rays were graded for hand osteoarthritis (OA) using the Kellgren and Lawrence criteria. In 60 daughters (mean age 33.6 years) of these women, bone mineral density (BMD) was measured at five regions of the hip and lumbar spine and quantitative ultrasound (QUS) at the calcaneus. Daughters whose mothers had hand OA (i.e., OA at either the carpometacarpal [CMC] or distal interphalageal [DIP] joints) had significantly higher mean BMD, when adjusted for body mass index (BMI) (5.1%-8.1%, p < 0.05), at all hip regions except the trochanter. However, differences in lumbar BMD and calcaneal QUS were not statistically significant. In multiple regression analysis, maternal hand OA status was found to be a significant predictor of daughters' hip BMD when daughters' BMI and mothers' BMD were included in the model. These findings suggest that the observation of higher BMD in older patients with OA may be due in part to achievement of a higher peak bone mass at some sites.     

High bone mass in a female Hutterite population.

We examined a Hutterite population (n = 243) to determine if their agriculturally diverse, self-sufficient communal lifestyle promotes optimal bone mass attainment because of adequate calcium intake and high physical activity levels during growth and young adulthood. We measured total body (TB) and lumbar bone mineral content (BMC) and bone mineral density (BMD) in 39 school-age (younger) females and 204 working (older) females. Forty-five percent of older females and 79% of younger females currently consumed > or = 3 servings (svg) of dairy per day. Older females had lumbar (0.6 +/- 1.3) and TB (1.1 +/- 1.1) BMD Z scores greater than 0 (both, p < 0.001). The lumbar BMD Z score of younger females was not different from 0 (-0.1 +/- 1.0; p = 0.5). Both lumbar (r = 0.46; p < 0.001) and TB (r = 0.20; p = 0.02) BMD Z scores increased with increasing age. In multiple regression analyses for older females, lumbar bone area (p < 0.001), weight (p < 0.001), current hours on feet per day (p = 0.01), colony workload (p < 0.01), and estrogen status (p = 0.06) predicted lumbar BMC. TB bone area (p < 0.001), current hours on feet per day (p < 0.001), and colony workload (p < 0.01) predicted TB BMC. For younger females, lumbar bone area (p < 0.001), weight (p < 0.01), years in present colony (p = 0.02), and menses (p < 0.001) predicted lumbar BMC. TB bone area (p < 0.001), height (p < 0.01), years in present colony (p = 0.03), and menses (p < 0.01) predicted TB BMC. The effect of colony workload could not be separated from other factors different by colony. A heritability estimate of 0.66 was calculated for lumbar BMD using mother and daughter Z scores. Adequate calcium intake during growth, high physical activity early in life, and genetic factors may be contributing to above normal BMD levels in adult female Hutterites.     

Epidemiology of hip fracture in Iran: results from the Iranian Multicenter Study on Accidental Injuries

Introduction The incidence of hip fracture varies substantially between countries. As a result of improving life expectancy, the number of elderly people susceptible to hip fractures is increasing rapidly in the developing world. Little is known, however, about the epidemiology of hip fractures in the Middle Eastern countries. In this study, our objective was to estimate the incidence of hip fracture in Iran and compare it with other populations.Methods The data used were obtained from the Iranian Multicenter Study on Accidental Injuries, a large-scale population-based study conducted in nine provinces across the country. All of the hospitals in these provinces, which provide services to about 9.5 million people, were prospectively surveyed for any incident injury resulting from accidental events occurring in the study period of 135 days (4.5 months). All patients aged ≥50 with radiographically confirmed proximal femur fractures were included in this study. A total of 555 new cases of hip fracture (284 male, 271 female) were recorded during the study period. The annual incidence of hip fracture per 100,000 person-years was 115.2 (95% CI: 107.2–123.7) in men and 115.6 (95% CI: 107.4–124.3) in women; of these,73.2 and 89.2%, respectively, were fall-related fractures. The female-to-male ratios for fall-induced and total hip fracture rates were 1.2 and 1.0, respectively.Results The incidence rates increased exponentially after the age of 60 years in both genders and nearly tripled with each successive decade. When these results are compared to those of other studies, the Iranian age-standardized incidence rates of 127.3 (men) and 164.6 (women) per 100,000 person-years are considerably lower than those of all Western countries when standardized to data on the U.S. population in 2000. When compared with incidence rates reported for other Asian countries, those of Iranian females are the lowest next to China.Conclusion The low incidence rate of hip fracture for older Iranian women may be the result of several potential factors related to genetic or lifestyle differences between Iranians and people of other countries. Further studies are required to investigate contributing factors in more detail.     

Peak spine and femoral neck bone mass in young women

Achievement of higher peak bone mass early in life may play a critical role against postmenopausal bone loss. Bone mineral density (BMD) of the spine, femoral neck, greater trochanter, Ward's triangle, and spine bone mineral content (BMC) and bone surface area (BSA) were assessed by dual energy x-ray absorptiometry in 300 healthy females (age 6-32 years). Bone measurements were described by using nonlinear models with age, weight, height, or dietary calcium intake as the explanatory variables. At the spine, femoral neck, greater trochanter, and Ward's triangle, the highest BMD level was observed at 23.0 +/- 1.4, 18.5 +/- 1.6, 14.2 +/- 2.0, and 15.8 +/- 2.1 years, respectively. The age of attaining peak spine BMC and BSA cannot be estimated, as significant increases in these two measures were observed through this age group. Age, weight, and height were all significant predictors of all these bone measurements. Weight was a stronger predictor than age for all sites. Dietary calcium intake was not a significant predictor for any of these bone measurements. We conclude that age of attaining peak bone mass at the hip is younger than at the spine, and BMC and BSA at the spine continue to increase through the early thirties in females.     

Reference database of biochemical markers of bone turnover for the Japanese female population. Japanese Population-based Osteoporosis (JPOS) Study

The present study was conducted as a part of the Japanese Population-based Osteoporosis (JPOS) Study to establish reference values on the biochemical markers of bone turnover in the general Japanese female population over an applicable age range. The study recruited 3250 women aged 15–79 years, randomly selected from five municipalities throughout Japan, and obtained measurements of serum osteocalcin (OC) and bone-specific alkaline phosphatase (BAP); free and total forms of immunoreactive deoxypyridinoline, free pyridinolines and type I collagen cross-linked C-terminal telopeptide (CTx) in urine; serum intact parathyroid hormone (PTH) and 1,25 dihydroxy vitamin D (1,25 (OH)₂D); and bone density at the spine, hip and distal forearm. After excluding subjects with apparent or suggested abnormalities affecting bone mass, 2535 (78%) subjects were further analyzed. The authors presented 5-year age-specific mean values of the markers and mean marker levels derived from women aged 30–44 years with normal bone density as a healthy young adult reference. Values of the markers decreased with increasing age before the age of 40, increased steeply among subjects in their 50s, and remained elevated in the elderly. Serum calcium, phosphorus, PTH and 1,25 (OH)₂D levels were higher in postmenopausal women than in premenopausal women. However, 1,25 (OH)₂D was lower among early postmenopausal subjects. The levels of OC, BAP, CTx, PTH and 1,25(OH)₂D were significantly greater for women with osteoporosis than for those without. The diagnostic value of the markers was limited as the sensitivity and specificity ranged from 55% to 60%. These findings will aid health professionals in the correct assessment of bone turnover status in Japanese women over a wide range of age.     

Two polymorphisms in the vitamin D receptor gene--association with bone mass and 5-year change in bone mass with or without hormone-replacement therapy in postmenopausal women: the Danish Osteoporosis Prevention Study.

The significance of an interrelation between nongenetic factors and genotype effects in the regulation of bone mass is not clear. In this prospective study of 429 healthy early postmenopausal Danish women, we investigated the association between bone mineral density (BMD) and the FokI and BsmI polymorphisms in the vitamin D receptor (VDR) gene. Participants were allocated to either hormone-replacement therapy (HRT) or no treatment by randomization or personal choice. After 5 years, 332 women with unchanged treatment status were available for analyses, 98 of these women were still on HRT. No association with initial BMD or 5-year change in BMD was found for either polymorphism. In women with body mass index (BMI) < 25 (n = 282), the f allele was associated with lower BMD of the hip (p < 0.001) and forearm (p = 0.001), and the b allele was associated with lower spine BMD (p = 0.02). Comparing thin/normal weight women with overweight/ obese women of the same genotype, FF women had similar BMD at all measured sites in contrast to Ff and ff women in whom BMD, as expected, was higher in the overweight/obese women. Similar results were found for the BsmI polymorphism with no difference in BMD between BMI groups in BB women. Segregation into groups according to dietary calcium intake did not reveal any genotype association with BMD. These results provide some evidence of a modifying effect of nongenetic factors, specifically BMI, on the association between VDR genotype and BMD. High BMI may protect against lower BMD seen in association with thef or b alleles. In some genotypes (FF and BB), BMI had relatively little effect on BMD.     

Peak bone mass after exposure to antenatal betamethasone and prematurity: follow-up of a randomized controlled trial.

Small birth size is associated with reduced adult bone mass. We determined if antenatal betamethasone exposure, birth weight, or prematurity affects peak bone mass in 174 adults. Antenatal betamethasone exposure did not. Lower birth weight and prematurity predicted reduced adult height. Slower fetal growth rather than prematurity predicted lower bone mass, but this lower bone mass was appropriate for reduced adult height. INTRODUCTION: Small size at birth is reported to be associated with lower bone mass in adulthood. However, previous studies have not distinguished the relative contributions of length of gestation and fetal growth to size at birth. Fetal exposure to excess glucocorticoids has been proposed as a core mechanism underlying the associations between birth size and later disease risk. Antenatal glucocorticoids are given to pregnant women at risk for preterm delivery for the prevention of neonatal respiratory distress syndrome in their infants. We determined the relationship of antenatal exposure to betamethasone, birth weight, and prematurity to peak bone mass and femoral geometry in the adult survivors of the first randomized trial of antenatal glucocorticoids. MATERIALS AND METHODS: We studied 174 young adults (mean age, 31 years) whose mothers participated in a randomized trial of antenatal betamethasone. Mothers received two doses of intramuscular betamethasone or placebo 24 h apart. Two thirds of participants were born preterm (<37 weeks gestation). We measured indices of bone mass and size and derived estimates of volumetric density and bone geometry from DXA assessments of the lumbar spine, femur, and total body. RESULTS: There were no differences between betamethasone-exposed and placebo-exposed groups in any of the lumbar spine, femur, or total body DXA measures. There was no effect of antenatal betamethasone on adult height, although leg length was increased relative to trunk length (p = 0.002). A lighter birth weight (p 相似文献   

Determinants of bone mass in the Chinese old-old population

One hundred and eighty-eight elderly men and women were included in a study of bone mass at the neck of femur and its related factors. The study subjects were a subsample of a Hong Kong wide study of the elderly population aged 70 years and above. The study variables included age, sex, body measurements of height, weight, body mass index, dietary calcium intake, grip strength, 16 feet (5 m) gait speed, smoking, drinking, and years since menopause among women. The neck of femur bone mineral density among elderly men was about 1 standard deviation higher than that of women. Subjects aged 85 years and above had about 20% lower bone mineral density at the neck of femur when compared with those in the age group 70–74 years. Mean dietary calcium intake ranged between 300 and 430 mg/day and was not associated with bone mass. Multiple regression analysis showed that body weight, 16 feet gait speed, sex and alcohol consumption explained 46% of the total variance of femoral neck bone mineral density. Body weight was the most significant predictor of bone mineral density, with a partial correlation coefficient of 0.5. The maintenance of body weight within the acceptable weight range and promotion of physical fitness may be important measures in reducing bone loss in the elderly population.     

The effect of proton pump inhibitors on fracture risk: report from the Canadian Multicenter Osteoporosis Study

Summary

A large Canadian cohort was studied over 10 years to see if proton pump inhibitor (PPI) use increased the risk of sustaining a fragility fracture. We found an increased risk of fracture in individuals who used PPIs. The risk remained after controlling for other known fracture risk factors.

Introduction

Multiple retrospective studies have linked proton pump inhibitor use with increased risk of fragility fracture. We prospectively studied the association between PPI use and fracture in a large cohort over a 10-year period while controlling for known fracture risk factors.

Methods

We studied 9,423 participants in the Canadian Multicenter Osteoporosis Study. The cohort was formed in 1995–1997 and followed for 10 years with monitoring for incident nontraumatic fracture and PPI use. Cox regression analyses were used to assess the association between PPI use and incident fracture risk.

Results

PPI use, coded as a time-dependent variable, was associated with a shorter time to first nontraumatic fracture, hazard ratio (HR)?=?1.75 (95 % confidence interval (CI) 1.41–2.17, p?<?0.001). After controlling for multiple risk factors, including femoral neck bone density, the association remained significant, HR?=?1.40 (95 % CI 1.11–1.77, p?=?0.004). Similar results were obtained after controlling for bisphosphonate use, using PPI “ever” use, or when the outcome was restricted to hip fracture.

Conclusions

In this large prospective population-based cohort study, we found an association between PPI use and increased risk of fragility fracture. Although the increased risk found was modest, this finding is important, given the high prevalence of PPI use and the excess morbidity and mortality associated with osteoporosis-related fractures.     

Opportunistic Screening Using Low-Dose CT and the Prevalence of Osteoporosis in China: A Nationwide,Multicenter Study

Opportunistic screening for osteoporosis can be performed using low-dose computed tomography (LDCT) imaging obtained for other clinical indications. In this study we explored the CT-derived bone mineral density (BMD) and prevalence of osteoporosis from thoracic LDCT in a large population cohort of Chinese men and women. A total of 69,095 adults (40,733 men and 28,362 women) received a thoracic LDCT scan for the purpose of lung cancer screening between 2018 and 2019, and data were obtained for analysis from the China Biobank Project, a prospective nationwide multicenter population study. Lumbar spine (L₁–L₂) trabecular volumetric bone mineral density (vBMD) was derived from these scans using quantitative computed tomography (QCT) software and the American College of Radiology QCT diagnostic criteria for osteoporosis were applied. Geographic regional differences in the prevalence of osteoporosis were assessed and the age-standardized, population prevalence of osteoporosis in Chinese men and women was estimated from the 2010 China census. The prevalence of osteoporosis by QCT for the Chinese population aged >50 years was 29.0% for women and 13.5% for men, equating to 49.0 million and 22.8 million, respectively. In women, this rate is comparable to estimates from dual-energy X-ray absorptiometry (DXA), but in men, the prevalence is double. Prevalence varied geographically across China, with higher rates in the southwest and lower rates in the northeast. Trabecular vBMD decreased with age in both men and women. Women had higher peak trabecular vBMD (185.4 mg/cm³) than men (176.6 mg/cm³) at age 30 to 34 years, but older women had lower trabecular vBMD (62.4 mg/cm³) than men (92.1 mg/cm³) at age 80 years. We show that LDCT-based opportunistic screening could identify large numbers of patients with low lumbar vBMD, and that future cohort studies are now required to evaluate the clinical utility of such screening in terms of fracture prevention and supporting national health economic analyses. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)..     

Biochemical markers can predict the response in bone mass during alendronate treatment in early postmenopausal women. Alendronate Osteoporosis Prevention Study Group

Data from the Danish cohort (n = 67) of a multicenter trial of oral alendronate in the prevention of postmenopausal osteoporosis were used to evaluate the capacity of the biochemical markers to predict changes in bone mineral density (BMD). A panel of markers were measured: serum N-terminal midfragment osteocalcin (N-MID OC); serum total osteocalcin (total OC); bone-specific alkaline phosphatase (BSAP); serum and urine C-telopeptides of type I collagen (sCL and uCL); urine N-telopeptide crosslinks of type I collagen (NTX); and deoxypyridinoline (dPyr). The correlation between change from baseline at months 3-12 in total OC, N-MID OC, sCL, uCL, and NTX and 2 year response in spine BMD ranged from r = -0.45 to r = -0.78 (p < 0.001), and from r = -0.38 to r = 0.10 (n.s. to p < 0.002) for BSAP and dPyr. Sensitivity and specificity were used to assess the accuracy of change from baseline at month 6 in the biochemical markers for predicting prevention of bone loss in the spine over 2 years. The cutpoints used were a 30% (N-MID OC) or 50% (all other markers) decrease from baseline. Sensitivity levels were 82% (N-MID OC), 98% (total OC), 78% (sCL and NTX), and 89% (uCL). Specificities were 91% (N-MID OC), 59% (total OC), 100% (sCL), 71% (uCL), and 84% (NTX). Positive predictive values were 95% (N-MID OC), 82% (total OC), 100% (sCL), 87% (uCL), and 90% (NTX). In comparison, the predictive capacities of change from baseline at year 2 in hip BMD in predicting prevention of bone loss at the spine were similar: sensitivity, 82%; specificity, 55%; and positive predictive value, 79%. In conclusion, short-term changes in biochemical markers were valid predictors of long-term changes in BMD. Short-term changes in the sensitive biochemical markers revealed a predictive capacity similar to bone densitometry at the hip measured over 2 years. The sensitive biochemical markers offered a fast and valid alternative to bone densitometry for monitoring of alendronate treatment.     

Risk factors for longitudinal bone loss in elderly men and women: the Framingham Osteoporosis Study.

Few studies have evaluated risk factors for bone loss in elderly women and men. Thus, we examined risk factors for 4-year longitudinal change in bone mineral density (BMD) at the hip, radius, and spine in elders. Eight hundred elderly women and men from the population-based Framingham Osteoporosis Study had BMD assessed in 1988-1989 and again in 1992-1993. BMD was measured at femoral neck, trochanter, Ward's area, radial shaft, ultradistal radius, and lumbar spine using Lunar densitometers. We examined the relation of the following factors at baseline to percent BMD loss: age, weight, change in weight, height, smoking, caffeine, alcohol use, physical activity, serum 25-OH vitamin D, calcium intake, and current estrogen replacement in women. Multivariate regression analyses were conducted with simultaneous adjustment for all variables. Mean age at baseline was 74 years +/-4.5 years (range, 67-90 years). Average 4-year BMD loss for women (range, 3.4-4.8%) was greater than the loss for men (range, 0.2-3.6%) at all sites; however, BMD fell with age in both elderly women and elderly men. For women, lower baseline weight, weight loss in interim, and greater alcohol use were associated with BMD loss. Women who gained weight during the interim gained BMD or had little change in BMD. For women, current estrogen users had less bone loss than nonusers; at the femoral neck, nonusers lost up to 2.7% more BMD. For men, lower baseline weight and weight loss also were associated with BMD loss. Men who smoked cigarettes at baseline lost more BMD at the trochanter site. Surprisingly, bone loss was not affected by caffeine, physical activity, serum 25-OH vitamin D, or calcium intake. Risk factors consistently associated with bone loss in elders include female sex, thinness, and weight loss, while weight gain appears to protect against bone loss for both men and women. This population-based study suggests that current estrogen use may help to maintain bone in women, whereas current smoking was associated with bone loss in men. Even in the elderly years, potentially modifiable risk factors, such as weight, estrogen use, and cigarette smoking are important components of bone health.     

Vertebral Fracture Definition from Population-Based Data: Preliminary Results from the Canadian Multicenter Osteoporosis Study (CaMos)

The Canadian Multicenter Osteoporosis Study is a large population-based prospective study of osteoporosis in the Canadian population. The study involves 9424 subjects, both male and female, from nine centers and seven regions of Canada. Each subject completed an extensive interview to obtain medical, demographic and lifestyle information, and was examined by dual-energy X-ray absorptiometry of the spine and hip, ultrasound of the heel and, for subjects over 50 years of age, lateral spine radiographs. Spinal morphometry of the initial radiographs was performed to determine the prevalence of vertebral deformity. A method is utilized to extract reference norms for vertebral shape from a subset of the population data, which is then used to categorize any deformity within the whole data set. Using 3 standard deviations (SD) as a limit of normality, the male prevalence of 21.5% was similar to the female prevalence of 23.5%. Using 4 SD this reduced to 7.3% and 9.3% respectively. The younger men (50–59 years) showed a higher prevalence of deformity than the women and a lower increase of prevalence with age. In the older age group (over 80 years) the female prevalence of 45% compared with 36% for the men using 3 SD (grade 1) to define the limit of normality. The female group presented with more severe deformities on average than the male group. This continuing study will provide longitudinal information regarding the development of osteoporosis and associated risk factors which will eventually be of use to develop public health policies. Received: 27 September 1999 / Accepted: 4 February 2000     

Peak bone mineral density and its determinants in an Asian Indian population

Data on peak bone mineral density (BMD) and its determinants in Asian Indians are limited. We studied the peak BMD and its determinants in Asian Indians. A total of 1137 young (age: 25--35yr) healthy volunteers of either sex (558 men and 579 women) were recruited for dietary evaluation, analyses of serum calcium, inorganic phosphorus, alkaline phosphatase, 25-hydroxyvitamin D [25(OH)D], and intact parathyroid hormone (iPTH) levels, and measurement of BMD with dual-energy X-ray absorptiometry. In men and women, peak bone mass (PBM) at the femoral neck, femoral trochanter, total femur, and lumbar spine was achieved between 25 and 30yr of age, whereas PBM at the femoral intertrochanter occurred between 30 and 35yr of age. Peak BMD was lower than that of Caucasians by 15.2--21.1% in men and 14.4--20.6% in women. On stepwise multiple regression, height and weight were the most consistent predictors of BMD at all sites in both groups. In men, 25(OH)D positively predicted BMD at the hip, whereas in women, serum iPTH negatively predicted BMD at the femoral trochanter and total femur. The study concluded that Asian Indians have significantly lower peak BMD than Caucasians and that weight and height are the most consistent predictors of BMD at all sites in both men and women.     

峰值骨量及影响因素在骨质疏松诊断中价值的探讨

为了对骨质疏松进行诊断，必须建立自己实验室的峰值骨量正常值，并应考虑到对峰值骨量的各种影响因素。本文采用ＳＰＡ和ＤＥＸＡ，测定了中国３６８７９人群的挠骨、尺骨中远１／３部位的骨矿密度（ＢＭＤ）及股骨近端（股骨颈、大转子，ＷＡＲＤ’Ｓ区）ＢＭＤ。通过其中所测１０９７５人群上述部位的结果建立了峰值骨量的正常值，峰值骨量的年龄段是在２０～３９岁。本文在讨论中与国内外不同作者进行了对比，并分析了影响峰值骨量的各种因素，以便在诊断骨质疏松时恰当使用峰值骨正常值。     

Beta-adrenergic blockers reduce the risk of fracture partly by increasing bone mineral density: Geelong Osteoporosis Study.

This population-based study documented beta-blocker use in 59/569 cases with incident fracture and 112/775 controls. OR for fracture associated with beta-blocker use was 0.68 (95%CI, 0.49-0.96). Beta-blockers were associated with higher BMD at the total hip (2.5%) and UD forearm (3.6%) after adjusting for age, anthropometry, and thiazide use. Beta-blocker use is associated with reduced fracture risk and higher BMD. INTRODUCTION: Animal data suggests that bone formation is under beta-adrenergic control and that beta-blockers stimulate bone formation and/or inhibit bone resorption. MATERIALS AND METHODS: We evaluated the association between beta-blocker use, bone mineral density (BMD), and fracture risk in a population-based study in Geelong, a southeastern Australian city with a single teaching hospital and two radiological centers providing complete fracture ascertainment for the region. Beta-blocker use was documented for 569 women with radiologically confirmed incident fractures and 775 controls without incident fracture. Medication use and lifestyle factors were documented by questionnaire. RESULTS: Odds ratio for fracture associated with beta-blocker use was 0.68 (95% CI, 0.49-0.96) for any fracture. Adjusting for age, weight, medications, and lifestyle factors had little effect on the odds ratio. Beta-blocker use was associated with a higher BMD at the total hip (2.5%, p = 0.03) and ultradistal forearm (3.6%, p = 0.04) after adjustment for age, anthropometry, and thiazide use. CONCLUSION: Beta-blockers are associated with a reduction in fracture risk and higher BMD.