Association between fat-mass-and-obesity-associated (FTO) gene and hip fracture susceptibility.

OBJECTIVE: Common variants in the fat-mass-and-obesity-associated (FTO) gene are related to body mass index (BMI), which is a predictor of hip fracture risk. This study sought to examine the association between variants in the FTO gene and hip fracture risk. DESIGN AND PARTICIPANTS: This is a prospective study including 934 postmenopausal women aged 60 years and above living in Dubbo, Australia (Dubbo Osteoporosis Epidemiology Study), followed up between 1989 and 2007. MEASUREMENTS: Six single nucleotide polymorphisms (SNPs) (rs1421085, rs1558902, rs1121980, rs17817449, rs9939609 and rs9930506) of the FTO gene were genotyped using Taqman assay. Bone mineral density at the lumbar spine and femoral neck was measured by DXA (GE-Lunar) at baseline. Incidence of hip fractures during the follow-up was ascertained by reviewing X-ray reports. We used Cox's models to estimate the association between the genetic variants and hip fracture risk. We also utilized Bayes factor to evaluate the association. RESULTS: One hundred and two women (11%) had sustained a hip fracture. The incidence of hip fracture was greater in women homozygous for the minor allele of all SNPs. Women homozygous for the minor allele (AA) of rs1121980 had significantly higher risk of hip fracture (hazard ratio, 2.06; 95% CI 1.17-3.62) than women homozygous for the major allele (TT). The observed data favoured the hypothesis of FTO gene and fracture association over the hypothesis of nonassociation by a factor of nine. CONCLUSION: Common variations in the FTO gene are associated with hip fracture risk in women and that FTO gene may help improve the predictive value of hip fracture risk.

Serum level of under-carboxylated osteocalcin and bone mineral density in early menopausal Norwegian women.

PURPOSE: Serum level of under-carboxylated osteocalcin (ucOC) is considered a sensitive measure of vitamin K status, and ucOC levels are associated with bone mineral density (BMD) and fracture risk in elderly persons. The aim of this study was to assess the relationship between ucOC and BMD in early menopausal women. METHODS: The data reported here come from the enrollment in a double-blinded placebo-controlled randomized trial comprising 334 healthy Norwegian women between 50 and 60 years, 1-5 years after menopause, not using warfarin or medication known to affect bone metabolism. Total hip, femoral neck, lumbar spine, and total body BMD and serum level of ucOC and total osteocalcin were measured, and information of lifestyle was collected through questionnaires. The association between ucOC and BMD at all measurement sites was assessed by multiple regression analyses adjusting for possible confounding variables. RESULTS: The absolute serum level of ucOC was significantly and negatively associated with BMD at all measurements sites, both in univariate analyses (p < 0.01) and in multivariate analyses adjusting for years since menopause, smoking status and weight (p < 0.01). However, serum ucOC, expressed as percentage of the total osteocalcin level, was not associated with BMD at any site. CONCLUSIONS: Achievement of adequate vitamin K nutritional intake is important, but ucOC expressed as percentage of total osteocalcin levels as reflection of vitamin K status does not seem to play a central role in determining BMD levels in early menopausal women.

Quantification of the relative contribution of estrogen to bone mineral density in men and women.

BACKGROUND: The study quantified the relative contributions of estrogen (E2) and total testosterone (TT) to variation in bone mineral density in men and women. METHODS: This was a cross-sectional study which involved 200 men and 415 women aged 18 to 89 years. BMD at the lumbar spine (LS) and femoral neck (FN) was measured by DXA. Serum levels of E2 and TT were measured by electrochemiluminescence immunoassays. The association between E2, TT, and BMD was analyzed by the multiple linear regression model, adjusting for age and BMI. The contribution of each hormone to the variation in BMD was quantified by the bootstrap method. RESULTS: In women, higher serum levels of E2, but not TT, were significantly associated with greater BMD at the FN (P = 0.001) and LS (P < 0.0001). In men, higher serum levels of E2 were independently associated with greater FNBMD (P = 0.008) and LSBMD (P = 0.086). In the multiple linear regression model, age, body weight and E2 accounted for 50-55% variance in FNBMD, and 25% (in men) and 48% (in women) variance in LSBMD. Variation in E2 accounted for 2.5% (95% CI 0.4-7.8%) and 11.3% (95% CI 8.1-15.3%) variation in FNBMD in men and women, respectively. Moreover, E2 contributed 1.2% (95% CI 0.1-5.8%) and 11.7% (95% CI 8.5-15.9%) variation in LSBMD in men and women, respectively. CONCLUSIONS: Estrogen is more important than testosterone in the determination of age-related bone mineral density men and women of Vietnamese background. However, the relative contributions of estrogen to bone mineral density in men are likely modest.

Absolute fracture-risk prediction by a combination of calcaneal quantitative ultrasound and bone mineral density.

Quantitative ultrasound measurement (QUS) and bone mineral density (BMD) have each been shown to predict fracture risk in women. The present study examined whether a combination of QUS and BMD could improve the predictive accuracy of fracture risk. This is a population-based prospective study which involved 454 women and 445 men aged 62-89 years. Femoral neck BMD (FNBMD) was measured by DXA and calcaneal QUS was measured as broadband ultrasound attenuation (BUA) by a CUBA sonometer. Fragility fracture was ascertained by X-ray reports during the follow-up period, which took place between mid-1989 and 2009. During the follow-up period (median 13 years, range 11-15), 75 men and 154 women sustained a fragility fracture. In women, the model with FNBMD and BUA had a higher AUC compared to that without BUA (0.73 vs. 0.71 for any fracture, 0.81 vs. 0.77 for hip fracture, and 0.72 vs. 0.70 for vertebral fracture). Reclassification analysis yielded a total net reclassification improvement of 7.3%, 11.1%, and 5.2% for any, hip, and vertebral fractures, respectively. For men, the addition of BUA to FNBMD did not improve the predictive power for any, hip, or vertebral fracture. These results suggest that calcaneal QUS is an independent predictor of fracture risk and that a combination of QUS and BMD measurement could improve the predictive accuracy of fracture risk in elderly women.

Important risk factors and attributable risk of vertebral fractures in the population-based Tromsø study.

BACKGROUND: Vertebral fractures, the most common type of osteoporotic fractures, are associated with increased risk of subsequent fracture, morbidity, and mortality. The aim of this study was to examine the contribution of important risk factors to the variability in vertebral fracture risk. METHODS: Vertebral fracture was ascertained by VFA method (DXA, GE Lunar Prodigy) in 2887 men and women, aged between 38 and 87 years, in the population-based Tromsø Study 2007/2008. Bone mineral density (BMD; g/cm2) at the hip was measured by DXA. Lifestyle information was collected by questionnaires. Multivariable logistic regression model, with anthropometric and lifestyle factors included, was used to assess the association between each or combined risk factors and vertebral fracture risk. Population attributable risk was estimated for combined risk factors in the final multivariable model. RESULTS: In both sexes, age (odds ratio [OR] per 5 year increase: 1.32; 95% CI 1.19-1.45 in women and 1.21; 95% CI 1.10-1.33 in men) and BMD (OR per SD decrease: 1.60; 95% CI 1.34-1.90 in women and1.40; 95% CI 1.18-1.67 in men) were independent risk factors for vertebral fracture. At BMD levels higher than 0.85 g/cm2, men had a greater risk of fracture than women (OR 1.52; 95% CI 1.14-2.04), after adjusting for age. In women and men, respectively, approximately 46% and 33% of vertebral fracture risk was attributable to advancing age (more than 70 years) and low BMD (less than 0.85 g/cm2), with the latter having a greater effect than the former. CONCLUSIONS: These data confirm that age and BMD are major risk factors for vertebral fracture risk. However, in both sexes the two factors accounted for less than half of fracture risk. The identification of individuals with vertebral fracture is still a challenge.

Prevalence of vertebral fractures in women and men in the population-based Tromsø Study.

BACKGROUND: Osteoporotic vertebral fractures are, as the hip fractures, associated with increased morbidity and mortality. Norway has one of the highest reported incidences of hip fractures in the world. Because of methodological challenges, vertebral fractures are not extensively studied. The aim of this population based study was to describe, for the first time, the age- and sex specific occurrence of osteoporotic vertebral fractures in Norway. METHODS: Data was collected in the Tromso Study, 2007/8 survey. By the use of dual x-ray absorptiometry (GE Lunar Prodigy) vertebral fracture assessments were performed in 2887 women and men aged from 38 to 87 years, in addition to measurements of bone mineral density at the femoral sites. Information on lifestyle was collected through questionnaires. Comparisons between fractures and non-fractures were done sex stratified, by univariate analyses, adjusting for age when relevant. RESULTS: The prevalence of vertebral fractures varied from about 3% in the age group below 60 to about 19% in the 70+ group in women, and from 7.5% to about 20% in men, with an overall prevalence of 11.8% in women and 13.8% in men (p = 0.07). Among those with fractures, only one fracture was the most common; two and more fractures were present in approximately 30% of the cases. Fractures were seen from the fourth lumbar to the fifth thoracic vertebrae, most common between first lumbar and sixth thoracic vertebrae. The most common type of fracture was the wedge type in both sexes. Bone mineral density at the hip differed significantly according to type of fracture, being highest in those with wedge fractures and lowest in those with compression fractures. CONCLUSIONS: The prevalence of vertebral fractures increased by age in women and men, but the overall prevalence was lower than expected, considering the high prevalence of hip and forearm fractures in Norway. In both sexes, the wedge type was the fracture type most frequently observed and most common in the thoracic region.

Development of a simple prognostic nomogram for individualising 5-year and 10-year absolute risks of fracture: a population-based prospective study among postmenopausal women.

OBJECTIVES: Previous fracture prediction models have been based on the assumption of a stable risk of subsequent fractures over time. The aim of the present work was to develop a nomogram for prediction of 5-year and 10-year individualised absolute fracture risks for postmenopausal women taking into account the time relation between fractures. METHODS: A population-based prospective study was performed in 23 general practice centres located in the southern part of The Netherlands. At baseline (1992-1994), 4203 postmenopausal women between 50 and 80 years participated and 2372 of them also participated 10 years later. Baseline measurements included lumbar spine bone mineral density (BMD) and clinical risk factor evaluation. The incidence of fractures was ascertained. Bayesian model averaging and Cox's proportional hazards model were used. RESULTS: After enrolment, 382 (16.1%) women had a clinical fracture. Fracture risk was associated with advancing age (HR 1.09 per SD (5 years); 95% CI 1.01 to 1.17), lumbar spine BMD (HR 1.23 per -1 SD; 95% CI 1.10 to 1.37) and a prior fracture, with HR 3.27 (95% CI 2.50 to 4.30) for a recent prior fracture (≤5 years previously) and HR 1.97 (95% CI 1.43 to 2.71) for a non-recent prior fracture after menopause (>5 years previously). Women with a recent prior fracture had 66% higher risk of an incident fracture than those with a non-recent prior fracture (HR 1.66; 95% CI 1.15 to 2.40). CONCLUSIONS: The nomogram developed can help doctors to inform patients more effectively and thus better manage patient care by providing an individualised fracture risk taking into account the time relationship for fractures.

Independent external validation of nomograms for predicting risk of low-trauma fracture and hip fracture.

BACKGROUND: A set of nomograms based on the Dubbo Osteoporosis Epidemiology Study predicts the five- and ten-year absolute risk of fracture using age, bone mineral density and history of falls and low-trauma fracture. We assessed the discrimination and calibration of these nomograms among participants in the Canadian Multicentre Osteoporosis Study. METHODS: We included participants aged 55-95 years for whom bone mineral density measurement data and at least one year of follow-up data were available. Self-reported incident fractures were identified by yearly postal questionnaire or interview (years 3, 5 and 10). We included low-trauma fractures before year 10, except those of the skull, face, hands, ankles and feet. We used a Cox proportional hazards model. RESULTS: Among 4152 women, there were 583 fractures, with a mean follow-up time of 8.6 years. Among 1606 men, there were 116 fractures, with a mean follow-up time of 8.3 years. Increasing age, lower bone mineral density, prior fracture and prior falls were associated with increased risk of fracture. For low-trauma fractures, the concordance between predicted risk and fracture events (Harrell C) was 0.69 among women and 0.70 among men. For hip fractures, the concordance was 0.80 among women and 0.85 among men. The observed fracture risk was similar to the predicted risk in all quintiles of risk except the highest quintile of women, where it was lower. The net reclassification index (19.2%, 95% confidence interval [CI] 6.3% to 32.2%), favours the Dubbo nomogram over the current Canadian guidelines for men. INTERPRETATION: The published nomograms provide good fracture-risk discrimination in a representative sample of the Canadian population.

Reference ranges for bone mineral density and prevalence of osteoporosis in Vietnamese men and women.

BACKGROUND: The aim of this study was to examine the effect of different reference ranges in bone mineral density on the diagnosis of osteoporosis. METHODS: This cross-sectional study involved 357 men and 870 women aged between 18 and 89 years, who were randomly sampled from various districts within Ho Chi Minh City, Vietnam. BMD at the femoral neck, lumbar spine and whole body was measured by DXA (Hologic QDR4500). Polynomial regression models and bootstraps method were used to determine peak BMD and standard deviation (SD). Based on the two parameters, we computed T-scores (denoted by TVN) for each individual in the study. A similar diagnosis was also done based on T-scores provided by the densitometer (TDXA), which is based on the US White population (NHANES III). We then compared the concordance between TVN and TDXA in the classification of osteoporosis. Osteoporosis was defined according to the World Health Organization criteria. RESULTS: In post-menopausal women, the prevalence of osteoporosis based on femoral neck TVN was 29%, but when the diagnosis was based on TDXA, the prevalence was 44%. In men aged 50+ years, the TVN-based prevalence of osteoporosis was 10%, which was lower than TDXA-based prevalence (30%). Among 177 women who were diagnosed with osteoporosis by TDXA, 35% were actually osteopenia by TVN. The kappa-statistic was 0.54 for women and 0.41 for men. CONCLUSION: These data suggest that the T-scores provided by the Hologic QDR4500 over-diagnosed osteoporosis in Vietnamese men and women. This over-diagnosis could lead to over-treatment and influence the decision of recruitment of participants in clinical trials.

Association between vitamin D insufficiency and tuberculosis in a Vietnamese population.

BACKGROUND: Recent in vitro evidence suggests a link between vitamin D status and the risk of tuberculosis (TB). This study sought to examine the association between vitamin D status, parathyroid hormone (PTH) and the risk of TB in a Vietnamese population. METHODS: The study was designed as a matched case-control study, which involved 166 TB patients (113 men and 53 women), who were age-and-sex matched with 219 controls (113 men and 106 women). The average age of men and women was 49 and 50, respectively. TB was diagnosed by the presence of acid-fast bacilli on smears from sputum, and the isolation of M. tuberculosis. All patients were hospitalized for treatment in a TB specialist hospital. Controls were randomly drawn from the general community within the Ho Chi Minh, Vietnam. 25-hydroxyvitamin D [25(OH)D] and PTH was measured prior to treatment by an electrochemiluminescence immunoassay (ECLIA) on a Roche Elecsys. A serum level of 25(OH)D below 30 ng/mL was deemed to be vitamin D insufficient. RESULTS: The prevalence of vitamin D insufficiency was 35.4% in men with TB and 19.5% in controls (P = 0.01). In women, there were no significant differences in serum 25(OH)D and serum PTH levels between TB patients and controls. The prevalence of vitamin D insufficiency in women with TB (45.3%) was not significantly different from those without TB (47.6%; P = 0.91). However, in both genders, serum calcium levels in TB patients were significantly lower than in non-TB individuals. Smoking (odds ratio [OR] 1.25; 95% confidence interval [CI] 1.10 - 14.7), reduced 25(OH)D (OR per standard deviation [SD]: 1.14; 95% CI 1.07 - 10.7) and increased PTH (OR per SD 1.13; 95% CI 1.05 - 10.4) were independently associated with increased risk of TB in men. CONCLUSION: These results suggest that vitamin D insufficiency was a risk factor for tuberculosis in men, but not in women. However, it remains to be established whether the association is a causal relationship.

Contributions of lean mass and fat mass to bone mineral density: a study in postmenopausal women.

BACKGROUND: The relative contribution of lean and fat to the determination of bone mineral density (BMD) in postmenopausal women is a contentious issue. The present study was undertaken to test the hypothesis that lean mass is a better determinant of BMD than fat mass. METHODS: This cross-sectional study involved 210 postmenopausal women of Vietnamese background, aged between 50 and 85 years, who were randomly sampled from various districts in Ho Chi Minh City (Vietnam). Whole body scans, femoral neck, and lumbar spine BMD were measured by DXA (QDR 4500, Hologic Inc., Waltham, MA). Lean mass (LM) and fat mass (FM) were derived from the whole body scan. Furthermore, lean mass index (LMi) and fat mass index (FMi) were calculated as ratio of LM or FM to body height in metre squared (m2). RESULTS: In multiple linear regression analysis, both LM and FM were independent and significant predictors of BMD at the spine and femoral neck. Age, lean mass and fat mass collectively explained 33% variance of lumbar spine and 38% variance of femoral neck BMD. Replacing LM and FM by LMi and LMi did not alter the result. In both analyses, the influence of LM or LMi was greater than FM and FMi. Simulation analysis suggested that a study with 1000 individuals has a 78% chance of finding the significant effects of both LM and FM, and a 22% chance of finding LM alone significant, and zero chance of finding the effect of fat mass alone. CONCLUSIONS: These data suggest that both lean mass and fat mass are important determinants of BMD. For a given body size -- measured either by lean mass or height --women with greater fat mass have greater BMD.

Enhancement of absolute fracture risk prognosis with genetic marker: the collagen I alpha 1 gene.

An important objective of genetic research in osteoporosis is to translate genotype data into the prognosis of fracture. The present study sought to develop a prognostic model for predicting osteoporotic fracture by using information from a genetic marker and clinical risk factors. It was designed as a prospective epidemiological study which involved 894 women of Caucasian background aged 60+ years who had been followed for a median of 9 years (from 1989 and 2008, range 0.2-18 years). During the follow-up period, fragility fracture was ascertained by X-ray reports for all women. Bone mineral density (BMD) at the femoral neck was measured by dual-energy X-ray absorptiometry. Genotypes of the Sp1 binding site in the first intron of the collagen I alpha 1 (COLIA1) gene polymorphism were determined by polymerase chain reaction, digestion with BalI restriction enzyme, and agarose gel electrophoresis. The relationship between COL1A1 genotype and fracture was assessed by the Cox proportional hazards model, from which nomograms were developed for individualizing the risk of fracture. The distribution of COL1A1 genotypes was consistent with the Hardy-Weinberg equilibrium law: GG (63.8%), GT (32.6%), and TT (3.6%). During the follow-up period, there were 322 fractures, including 77 hip and 127 vertebral fractures. There was an overrepresentation of the TT genotype in the fracture group (6.2%) compared with the nonfracture group (2.3%). Compared with carriers of GT and GG, women carrying the TT genotype had increased risk of any fracture (relative risk [RR] = 1.91, 95% CI 1.21-3.00), hip fracture (RR = 3.67, 95% CI 1.69-8.00), and vertebral fracture (RR = 3.36, 95% CI 1.81-6.24). The incorporation of COL1A1 genotypes improved the risk reclassification by 2% for any fragility fracture, 4% for hip fracture, and 5% for vertebral fracture, beyond age, BMD, prior fracture, and fall. Three nomograms were constructed for predicting fracture risk in an individual woman based on age, BMD, and COLIA1 genotypes. These data suggest that the COLIA1 Sp1 polymorphism is associated with the risk of fragility fracture in Caucasian women and that the polymorphism could enhance the predictive accuracy of fracture prognosis. The nonograms presented here can be useful for individualizing the short- and intermediate-term prognosis of fracture risk and help identify high-risk individuals for intervention for appropriate management of osteoporosis.

Mortality risk associated with low-trauma osteoporotic fracture and subsequent fracture in men and women.

CONTEXT: There are few data on long-term mortality following osteoporotic fracture and fewer following subsequent fracture. OBJECTIVES: To examine long-term mortality risk in women and men following all osteoporotic fractures and to assess the association of subsequent fracture with that risk. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort from the Dubbo Osteoporosis Epidemiology Study of community-dwelling women and men aged 60 years and older from Dubbo, Australia, who sustained a fracture between April 1989 and May 2007. MAIN OUTCOME MEASURES: Age- and sex-specific standardized mortality ratios (SMRs) compared with the overall Dubbo population for hip, vertebral, major, and minor fractures. RESULTS: In women, there were 952 low-trauma fractures followed by 461 deaths, and in men, 343 fractures were followed by 197 deaths. Age-adjusted SMRs were increased following hip fractures (SMRs, 2.43 [95% confidence interval [CI], 2.02-2.93] and 3.51 [95% CI, 2.65-4.66]), vertebral fractures (SMRs, 1.82 [95% CI, 1.52-2.17] and 2.12 [95% CI, 1.66-2.72]), major fractures (SMRs, 1.65 [95% CI, 1.31-2.08] and 1.70 [95% CI, 1.23-2.36]), and minor fractures (SMRs, 1.42 [95% CI, 1.19-1.70] and 1.33 [95% CI, 0.99-1.80]) for both women and men, respectively. Mortality was increased for all ages for all fractures except minor fractures for which increased mortality was only apparent for those older than 75 years. Increased mortality risk persisted for 5 years for all fractures and up to 10 years for hip fractures. Increases in absolute mortality that were above expected, for 5 years after fracture, ranged from 1.3 to 13.2 per 100 person-years in women and from 2.7 to 22.3 per 100 person-years in men, depending on fracture type. Subsequent fracture was associated with an increased mortality hazard ratio of 1.91 (95% CI, 1.54-2.37) in women and 2.99 (95% CI, 2.11-4.24) in men. Mortality risk following a subsequent fracture then declined but beyond 5 years still remained higher than in the general population (SMR, 1.41 [95% CI, 1.01-1.97] and SMR, 1.78 [95% CI, 0.96-3.31] for women and men, respectively). Predictors of mortality after any fragility fracture for both men and women included age, quadriceps weakness, and subsequent fracture but not comorbidities. Low bone mineral density, having smoked, and sway were also predictors for women and less physical activity for men. CONCLUSIONS: In a sample of older women and men, all low-trauma fractures were associated with increased mortality risk for 5 to 10 years. Subsequent fracture was associated with increased mortality risk for an additional 5 years.

Incidence and risk factors for low trauma fractures in men with prostate cancer.

BACKGROUND: Men with prostate cancer on androgen deprivation therapy (ADT) are at increased risk of bone loss. The present study sought to determine the incidence of low trauma fracture in men with prostate cancer (PC), and to characterize the association between potential risk factors and fracture risk in these men. METHODS: In the prospective, population-based Dubbo Osteoporosis Epidemiology Study, 43 men aged 60+ years reported a history of prostate cancer; among whom, 22 men received ADT, and 21 men did not. Low-trauma fractures were ascertained between 1989 and 2004. Bone mineral density at the femoral neck (FNBMD), postural instability and lifestyle factors were obtained at baseline. RESULTS: Men with prostate cancer had significantly higher lumbar spine BMD than those without cancer (p=0.013). During the follow-up period, 15 men with prostate cancer had sustained a fracture, yielding the age-adjusted incidence of fracture among this group was 31.6 per 1000 person-years, which was greater than those without cancer (22.1 per 1000 person-years). The age-adjusted incidence of fracture was more pronounced among those with prostate cancer on ADT (40.2 per 1000 person-years). After adjusting for age, the increase in fracture risk among prostate cancer patients was associated with lower femoral neck BMD (hazard ratio [HR] per SD=1.8, 95% CI: 1.0-3.4) and increased rate of bone loss (HR 2.3, 1.2-4.6). CONCLUSIONS: Men with prostate cancer, particularly those treated with ADT, had an increased fracture risk. Although the average BMD in men with prostate cancer was higher than men without cancer, a low BMD prior to treatment or increased rate of bone loss after initiating ADT treatment was each a significant predictor of fracture in these.

Association between LRP5 polymorphism and bone mineral density: a Bayesian meta-analysis.

BACKGROUND: The low-density lipoprotein receptor-related protein 5 gene (LRP5) was identified to be linked to the variation in BMD in high bone mass pedigrees. Subsequent population-based studies of the association between the LRP5 gene and BMD have yielded conflicting results. The present study was aimed at examining the association between LRP5 gene and BMD by using meta-analysis. METHODS: A systematic electronic search of literature was conducted to identify all published studies in English on the association between LRP5 gene and osteoporosis-related phenotypes, including bone mineral density and fracture. BMD data were summarized from individual studies by LRP5 genotype, and a synthesis of data was performed with random-effects meta-analyses. After excluding studies on animal and review papers, there were 19 studies for the synthesis. Among these studies, 10 studies used the rs3736228 (A1330V) polymorphism and reported BMD values. RESULTS: The 10 eligible studies comprised 16,705 individuals, with the majority being women (n = 8444), aged between 18 - 81 years. The overall distribution of genotype frequencies was: AA, 68%, AV and VV, 32%. However, the genotype frequency varied significantly within as well as between ethnic populations. On random-effects meta-analysis, lumbar spine BMD among individuals with the AA genotype was on average 0.018 (95% confidence interval [CI]: 0.012 to 0.023) g/cm2 higher than those with either AV or VV genotype. Similarly, femoral neck BMD among carriers of the AA genotype was 0.011 (95%CI: 0.004 to 0.017) g/cm2 higher than those without the genotype. While there was no significant heterogeneity in the association between the A1330V polymorphism and lumbar spine BMD (p = 0.55), the association was heterogeneous for femoral neck BMD (p = 0.05). The probability that the difference is greater than one standard deviation was 0.34 for femoral neck BMD and 0.54 for lumbar spine BMD. CONCLUSION: These results suggest that there is a modest effect of the A1330V polymorphism on BMD in the general population, and that the modest association may limit its clinical use.

The prevalence and correlates of physical inactivity among adults in Ho Chi Minh City.

BACKGROUND: Socioeconomic changes have led to profound changes in individuals' lifestyles, including the adoption of unhealthy food consumption patterns, prevalent tobacco use, alcohol abuse and physical inactivity, especially in large cities like Ho Chi Minh City (HCMC). The Stepwise Approach to Surveillance of Non-communicable Disease Risk Factors survey was conducted to identify physical activity patterns and factors associated with 'insufficient' levels of physical activity for health in adults in HCMC. METHODS: A cross-sectional survey was conducted in 2005 among 1906 adults aged 25-64 years using a probability proportional to size cluster sampling method to estimate the prevalence of non-communicable disease risk factors including physical inactivity. Data on socioeconomic status, health behaviours, and time spent in physical activity during work, commuting and leisure time were collected. Physical activity was measured using the validated Global Physical Activity Questionnaire (GPAQ). Responders were classified as 'sufficiently active' or 'insufficiently active' using the GPAQ protocol. Correlates of insufficient physical activity were identified using multivariable logistic regression. RESULTS: A high proportion of adults were physically inactive, with only 56.2% (95% CI = 52.1-60.4) aged 25-64 years in HCMC achieving the minimum recommendation of 'doing 30 minutes moderate-intensity physical activity for at least 5 days per week'. The main contributors to total physical activity among adults were from working and active commuting. Leisure-time physical activity represented a very small proportion (9.4%) of individuals' total activity level. Some differences in the pattern of physical activity between men and women were noted, with insufficient activity levels decreasing with age among women, but not among men. Physical inactivity was positively associated with high income (OR = 1.77, 95% CI = 1.05-2.97) and high household wealth index (OR = 1.86, 95% CI = 1.29-2.66) amongst men. CONCLUSION: Public health policies and programs to preserve active commuting in HCMC and to promote time spent in recreational physical activity in both genders and across all age groups, but especially among young adults, will be critical in any comprehensive national plan to tackle inactivity. Clear and consistent national recommendations about how much physical activity Vietnamese people need for preventing and managing non-communicable diseases should also be part of this population-wide promotional effort.

Bone loss, weight loss, and weight fluctuation predict mortality risk in elderly men and women.

UNLABELLED: Low baseline BMD, rate of BMD loss, weight loss, and weight fluctuation are significant predictors of all-cause mortality in elderly men and women, independent of each other and of age, incident fracture, and concomitant diseases. INTRODUCTION: Although low BMD has been shown to be associated with mortality in women, the effect of BMD is affected by weight and weight change and the contribution of these factors to mortality risk, particularly in men, is not known. This study examined the association between baseline BMD, rate of bone loss, weight loss, and weight fluctuation and all-cause mortality risk in elderly men and women. MATERIALS AND METHODS: Data from 1059 women and 644 men, >or=60 years of age (as of 1989), of white background who participated in the Dubbo Osteoporosis Epidemiology Study were analyzed. All-cause mortality was recorded annually between 1989 and 2004. BMD at the femoral neck was measured by DXA (GE-LUNAR) at baseline and at approximately every 2 yr afterward. Data on incident osteoporotic fractures and concomitant diseases, including cardiovascular diseases, all types of cancer, and type I/II diabetes mellitus, was also recorded. RESULTS: In the multivariable Cox's proportional hazards model with adjustment for age, incident fractures, and concomitant diseases, the following variables were independent risk factors of all-cause mortality in men: rate of BMD loss of at least 1%/yr, rate of weight loss of at least 1%/yr, and weight fluctuation (defined by the CV) of at least 3%. In women, in addition to the significant factors observed in men, lower baseline BMD was also an independent risk factor of mortality. In both sexes, baseline weight was not an independent and significant predictor of mortality risk. Approximately 36% and 22% of deaths in women and men, respectively, were attributable to the four risk factors. CONCLUSIONS: These data suggest that, although low BMD was a risk factor of mortality in women, it was not a risk factor of mortality in men. However, high rates of BMD loss, weight loss, and weight fluctuation were also independent predictors of all-cause mortality in elderly men and women, independent of age, incident fracture, and concomitant diseases.

Residual lifetime risk of fractures in women and men.

UNLABELLED: In a sample of 1358 women and 858 men, > or = 60 yr of age who have been followed-up for up to 15 yr, it was estimated that the mortality-adjusted residual lifetime risk of fracture was 44% for women and 25% for men. Among those with BMD T-scores < or = -2.5, the risks increased to 65% in women and 42% in men. INTRODUCTION: Risk assessment of osteoporotic fracture is shifting from relative risk to an absolute risk approach. Whereas BMD is a primary predictor of fracture risk, there has been no estimate of mortality-adjusted lifetime risk of fracture by BMD level. The aim of the study was to estimate the residual lifetime risk of fracture (RLRF) in elderly men and women. MATERIALS AND METHODS: Data from 1358 women and 858 men > or = 60 yr of age as of 1989 of white background from the Dubbo Osteoporosis Epidemiology Study were analyzed. The participants have been followed for up to 15 yr. During the follow-up period, incidence of low-trauma, nonpathological fractures, confirmed by X-ray and personal interview, were recorded. Incidence of mortality was also recorded. BMD at the femoral neck was measured by DXA (GE-LUNAR) at baseline. Residual lifetime risk of fracture from the age of 60 was estimated by the survival analysis taking into account the competing risk of death. RESULTS: After adjusting for competing risk of death, the RLRF for women and men from age 60 was 44% (95% CI, 40-48) and 25% (95% CI, 19-31), respectively. For individuals with osteoporosis (BMD T-scores < or = -2.5), the mortality-adjusted lifetime risk of any fracture was 65% (95% CI, 58-73) for women and 42% (95% CI, 24-71) for men. For the entire cohort, the lifetime risk of hip fracture was 8.5% (95% CI, 6-11%) for women and 4% (95% CI, 1.3-5.4%) for men; risk of symptomatic vertebral fracture was 18% (95% CI, 15-21%) for women and 11% (95% CI, 7-14%) for men. CONCLUSIONS: These estimates provide a means to communicate the absolute risk of fracture to an individual patient and can help promote the identification and targeting of high-risk individuals for intervention.

Risk factors for fracture in nonosteoporotic men and women.

CONTEXT AND OBJECTIVE: It is not known which factors are associated with fracture in nonosteoporotic elderly. The aim of this study was to assess the association between fall-related risk factors and fracture risk in men and women without osteoporosis. DESIGN: This study was part of the ongoing Dubbo Osteoporosis Epidemiology Study, which was designed as a prospective population-based cohort investigation. PARTICIPANTS: At baseline, 924 women and 723 men aged 60+ yr did not have osteoporosis [bone mineral density (BMD) T-scores > -2.5]. The individuals have been followed for up to 15 yr. MAIN OUTCOME MEASURES: Atraumatic fractures were prospectively identified through radiologists' reports. RISK FACTORS: At baseline, femoral neck BMD (FNBMD) was measured by dual energy x-ray absorptiometry (DXA); history of fall, postural stability, and quadriceps strength was obtained. RESULTS: During the follow-up period, among the nonosteoporotic group, 221 women and 105 men had sustained a fracture, accounting for 55 and 74% of total fractures in the entire Dubbo Osteoporosis Epidemiology Study sample, respectively. The following factors were independent risk factors for any fracture: in women, age per sd (hazard ratio, 1.2; 95% CI, 1.0-1.3), postural sway per sd (1.1, 1.0-1.2), FNBMD per sd (1.6, 1.3-1.9), fall in the previous 12 months (2.1, 1.6-2.7), and prior fracture (1.8, 1.2-2.7); in men, age (1.4, 1.1-1.6), postural sway (1.2, 1.0-1.3), FNBMD (1.2, 1.0-1.5), and fall in the previous 12 months (1.9, 1.2-3.0). Exposure to at least one of the risk factors could account for 49% (women) and 39% (men) of any fractures in this population. CONCLUSION: In nonosteoporotic elderly, the combination of low BMD, advancing age, fall during the last 12 months, and prior fracture could identify a subgroup of individuals with high risk of fracture.