Relationship between subclinical thyroid dysfunction and the risk of fracture: a meta-analysis of prospective cohort studies

Summary

To identify the relationship between subclinical thyroid dysfunction and the risk of fracture, we conducted a meta-analysis of prospective cohort studies. Results showed that subclinical hyperthyroidism is associated with an increased risk of fracture, especially in elder.

Introduction

There are conflicting data on the association between subclinical thyroid dysfunction and the risk of fracture. This study is aimed at providing a summary of prospective evidence of the relationship between subclinical thyroid dysfunction and the risk of fracture.

Methods

We systematically searched the MEDLINE, EMBASE, and the Chinese Biomedical literature database (CBM) from 1974 to August 2014 to identify prospective cohort studies which have studied the risk of fracture in patients with subclinical thyroid dysfunction. Various fractures were reported as the sole outcome.

Results

Five population-based cohort studies including 314,146 participants with relationship of endogenous or exogenous subclinical thyroid dysfunction or euthyroidism and fractures were identified as eligible for the meta-analysis. In an unadjusted model, the relative risk (RR) of subclinical hypothyroidism for fracture was 1.30 (CI 1.08–1.56). Risk estimates were lower in a multivariable-adjusted model (RR?=?1.20, CI 0.70–2.04) and when higher quality studies (RR?=?0.95, CI 0.58–1.57) were analyzed. For subclinical hyperthyroidism, the RR was 1.52 (CI 1.33–1.73) in unadjusted model and 1.25 (CI 1.11–1.41) in a multivariable-adjusted model. An analysis of higher quality studies revealed a RR 1.18 (CI 1.07–1.29). Subgroup analysis indicated that the RR for risk of fracture was higher in the endogenous group than the exogenous group, taking thyroid-altering medicine in subclinical hyperthyroidism. Similar finding was also demonstrated in subclinical hypothyroidism.

Conclusions

Despite heterogeneity across the studies, data suggest that subclinical hyperthyroidism is associated with an increased risk of fracture in the population older than 60 years. No evidence could prove a definite association between subclinical hypothyroidism and the risk of fracture yet.

     

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.     

Depression and low bone mineral density: a meta-analysis of epidemiologic studies

Summary

The association between depression and loss of bone mineral density (BMD) has been reported inconsistently. This meta-analysis, which pooled results from 14 qualifying individual studies, found that depression was associated with a significantly decreased BMD, with a substantially greater BMD decrease in depressed women and in cases of clinical depression.

Introduction

The reported association between depression and loss of BMD has been controversial. This meta-analysis was conducted to determine whether depression and BMD are associated and to identify the variation in some subgroups.

Methods

English-language articles published before October 2008 were used as the data source. A total of six case-controlled and eight cross-sectional studies met prestated inclusion criteria (N?=?10,523). Information on study design, participant characteristics, measurements of BMD and depression, and control for potential confounders was abstracted independently by two investigators using a standardized protocol.

Results

Overall, depression was associated with a significant decrease in mean BMD of spine (?0.053 g/cm² [95% confidence interval {CI} ?0.087 to ?0.018 g/cm²]) and hip (?0.052 g/cm² [95% CI ?0.083 to ?0.022 g/cm²]). A substantially greater BMD decrease was observed in depressed women (?0.076 g/cm² in spine; ?0.059 g/cm² in hip) and in cases of clinical depression (?0.074 g/cm² in spine; ?0.080 g/cm² in hip).

Conclusion

Depression is associated with low BMD, with a substantially greater BMD decrease in depressed women and in cases of clinical depression. Depression should be considered as an important risk factor for osteoporosis.     

Coffee consumption and urologic cancer risk: a meta-analysis of cohort studies

Objectives

Controversial results were reported among several epidemiologic studies on the relationship between coffee consumption and urologic cancer risk. We, therefore, conducted this meta-analysis to clarify these associations.

Methods

Electronic databases including Pubmed, Embase and Cochrane library were searched between January 1966 and August 2013 for eligible studies. Pooled relative risk (RR) and its 95 % confidence interval (CI) were calculated. All P values are two tailed.

Results

Thirteen cohorts were eligible for inclusion. As to prostate cancer (PCa), significant reverse association was found among highest versus none/lowest analysis with acceptable heterogeneity (RR 0.86, 95 % CI 0.79–0.95; I ² 25 %, P value for heterogeneity: 0.221). A pooled RR which assessed advanced PCa was 0.73 (with 95 % CI 0.50–1.07), and a slight stronger reverse association was found in fatal PCa. However, a slight insignificant reverse association, basing on 8 studies with 9 outcomes, was found in dose–response analysis (RR 0.98, 95 % CI 0.93–1.03). For kidney and bladder cancer, insignificant associations were found in both highest versus none/lowest analyses and dose–response analyses.

Conclusions

Our findings suggest that coffee consumption may reduce the risk of PCa. No associations were found with both bladder and kidney cancer. Further well-designed large-scaled cohort studies are warranted to provide more definitive conclusions.     

Risk of hip fracture following stroke,a meta-analysis of 13 cohort studies

This study systematically reviews prospective and retrospective cohort studies evaluating the risk of hip fracture following stroke. Stroke survivors are at high risk of hip fracture and had a 1.5-fold increased risk compared to stroke-free men and women of the same age. Hip fracture often occurs in ageing and female stroke patients. We performed a meta-analysis to summarize evidence from prospective and retrospective cohort studies about the risk of hip fracture following stroke. We identified English and non-English publications in MEDLINE and EMBASE using stroke and fracture as keywords to 31 December 2015. The data of the incidence of hip fracture were extracted to calculate raw incident rate in stroke survivors as well as risk of hip fractures in strokes comparing populations using a random-effects model. Subgroup analyses were performed to identify the potential influence of some factors. Six prospective and seven retrospective cohort studies were included, involving 512,214 stroke patients with 22,559 hip fractures. The pooled prevalence of hip fractures was 4.87 % (95 % CI, 4.05 to 5.68 %) in stoke patients. We conducted subgroup analysis according to sex, age, duration of follow-up, study design, and region, which showed that female (vs. male) stroke patients older than 70 years (vs. those less than 70 years) and duration of follow-up more than 2 years (vs. those less than 2 years) have higher proportions of hip fractures. Four studies showed that stroke patients had a significantly higher risk of hip fracture compared with the general population, while the other study had a non-significant higher risk. The overall prevalence of hip fracture was 3.28 % (3431 of 104,646) in stroke patients and 2.83 % (36,493 of 1,287,726) in general population, respectively, and the unadjusted combined relative risk of hip fracture was 1.54 (95 % CI, 1.06–2.25). Hip fractures often occur in ageing and female stroke patients.     

Smoking and fracture risk: a meta-analysis

Smoking is widely considered a risk factor for future fracture. The aim of this study was to quantify this risk on an international basis and to explore the relationship of this risk with age, sex and bone mineral density (BMD). We studied 59,232 men and women (74% female) from ten prospective cohorts comprising EVOS/EPOS, DOES, CaMos, Rochester, Sheffield, Rotterdam, Kuopio, Hiroshima and two cohorts from Gothenburg. Cohorts were followed for a total of 250,000 person-years. The effect of current or past smoking, on the risk of any fracture, any osteoporotic fracture and hip fracture alone was examined using a Poisson model for each sex from each cohort. Covariates examined were age, sex and BMD. The results of the different studies were merged using the weighted -coefficients. Current smoking was associated with a significantly increased risk of any fracture compared to non-smokers (RR=1.25; 95% Confidence Interval (CI)=1.15–1.36). Risk ratio (RR) was adjusted marginally downward when account was taken of BMD, but it remained significantly increased (RR=1.13). For an osteoporotic fracture, the risk was marginally higher (RR=1.29; 95% CI=1.13–1.28). The highest risk was observed for hip fracture (RR=1.84; 95% CI=1.52–2.22), but this was also somewhat lower after adjustment for BMD (RR=1.60; 95% CI=1.27–2.02). Risk ratios were significantly higher in men than in women for all fractures and for osteoporotic fractures, but not for hip fracture. Low BMD accounted for only 23% of the smoking-related risk of hip fracture. Adjustment for body mass index had a small downward effect on risk for all fracture outcomes. For osteoporotic fracture, the risk ratio increased with age, but decreased with age for hip fracture. A smoking history was associated with a significantly increased risk of fracture compared with individuals with no smoking history, but the risk ratios were lower than for current smoking. We conclude that a history of smoking results in fracture risk that is substantially greater than that explained by measurement of BMD. Its validation on an international basis permits the use of this risk factor in case finding strategies.     

Dietary magnesium intake,bone mineral density and risk of fracture: a systematic review and meta-analysis

Dietary magnesium intake has been related to osteoporosis and risk of fractures in earlier studies; however, findings were conflicting. This meta-analysis indicated that high magnesium intake was not associated with increased risk of fracture; however, a positive marginally significant correlation was found between magnesium intake and bone mineral density (BMD) in total hip as well as in femoral neck. Although there is some evidence on the association between magnesium intake, BMD and fractures, no previous study has summarized findings in this regard. We aimed to systematically review the current evidence on this association and to perform a meta-analysis of observational studies. We searched MEDLINE, Scopus, EMBASE and Google Scholar up to January 2015 for studies that examined the relationship between magnesium intake and BMD or fracture. Studies that had reported correlation coefficients between magnesium intake and BMD or those that reported odds ratios (ORs) or relative risks (RRs) for risk of fracture in different sites were included. In total, 12 studies were included in the meta-analysis. We found that high intakes of magnesium were not significantly associated with risk of total hip fracture (summary effect size 1.92; 95 % CI 0.81, 4.55) or total fractures (1.01; 0.94–1.07). Combining four effect sizes, a positive marginally significant correlation was observed between magnesium intake and total BMD (pooled r 0.16; 95 % CI 0.001, 032). Based on nine effect sizes, we found a marginally significant association between magnesium intake and femoral neck BMD (0.14; 0.001, 0.28). However, no significant correlation was found between magnesium intake and BMD in lumbar spine (0.09; ?0.01, 0.19). We found that high intakes of magnesium were not associated with increased risk of hip and total fractures. There was a positive marginally significant correlation between magnesium intake and BMD in femoral neck and total hip. No significant correlations were observed between magnesium intake and BMD in lumbar spine.     

A family history of fracture and fracture risk: a meta-analysis

The aims of the present study were to determine whether a parental history of any fracture or hip fracture specifically are significant risk factors for future fracture in an international setting, and to explore the effects of age, sex and bone mineral density (BMD) on this risk. We studied 34,928 men and women from seven prospectively studied cohorts followed for 134,374 person-years. The cohorts comprised the EPOS/EVOS study, CaMos, the Rotterdam Study, DOES and cohorts at Sheffield, Rochester and Gothenburg. The effect of family history of osteoporotic fracture or of hip fracture in first-degree relatives, BMD and age on all clinical fracture, osteoporotic fracture and hip fracture risk alone was examined using Poisson regression in each cohort and for each sex. The results of the different studies were merged from the weighted beta coefficients. A parental history of fracture was associated with a modest but significantly increased risk of any fracture, osteoporotic fracture and hip fracture in men and women combined. The risk ratio (RR) for any fracture was 1.17 (95% CI=1.07-1.28), for any osteoporotic fracture was 1.18 (95% CI=1.06-1.31), and for hip fracture was 1.49 (95% CI=1.17-1.89). The risk ratio was higher at younger ages but not significantly so. No significant difference in risk was seen between men and women with a parental history for any fracture (RR=1.17 and 1.17, respectively) or for an osteoporotic fracture (RR=1.17 and 1.18, respectively). For hip fracture, the risk ratios were somewhat higher, but not significantly higher, in men than in women (RR=2.02 and 1.38, respectively). A family history of hip fracture in parents was associated with a significant risk both of all osteoporotic fracture (RR 1.54; 95CI=1.25-1.88) and of hip fracture (RR=2.27; 95% CI=1.47-3.49). The risk was not significantly changed when BMD was added to the model. We conclude that a parental history of fracture (particularly a family history of hip fracture) confers an increased risk of fracture that is independent of BMD. Its identification on an international basis supports the use of this risk factor in case-finding strategies.     

Associations of APOE gene polymorphisms with bone mineral density and fracture risk: a meta-analysis

Summary  

To determine the association of the Apolipoprotein E (APOE) E4 gene polymorphism with bone mineral density (BMD) and fractures we conducted a meta-analysis of 17 reports. Despite lower trochanteric and lumbar BMD in APOE4 carriers, there is insufficient evidence to support a consistent association of APOE with bone health.     

Coffee, tea, and the risk of hip fracture: a meta-analysis

Summary

The present meta-analysis shows no clear association between coffee consumption and the risk of hip fractures. There was a nonlinear association between tea consumption and the risk of hip fracture. Compared to no tea consumption, drinking 1?4 cups of tea daily was associated with a lower risk of hip fracture.

Introduction

Prospective cohort and case–control studies have suggested that coffee and tea consumption may be associated with the risk of hip fracture; the results have, however, been inconsistent. We conducted a meta-analysis to assess the association between coffee and tea consumption and the risk of hip fracture.

Methods

We performed systematic searches using MEDLINE, EMBASE, and OVID until February 20, 2013, without limits of language or publication year. Relative risks (RRs) with 95 % confidence intervals (CI) were derived using random-effects models throughout all analyses. We conducted categorical, dose–response, heterogeneity, publication bias, and subgroup analyses.

Results

Our study was based on 195,992 individuals with 9,958 cases of hip fractures from 14 studies, including six cohort and eight case–control studies. The pooled RRs of hip fractures for the highest vs. the lowest categories of coffee and tea consumption were 0.94 (95 % CI 0.71–1.17) and 0.84 (95 % CI 0.66–1.02), respectively. For the dose–response analysis, we found evidence of a nonlinear association between tea consumption and the risk of hip fracture (p _nonlinearity?<?0.01). Compared to no tea consumption, 1–4 cups of tea per day may reduce the risk of hip fracture by 28 % (0.72; 95 % CI 0.56–0.88 for 1–2 cups/day), 37 % (0.63; 95 % CI 0.32–0.94 for 2–3 cups/day), and 21 % (0.79; 95 % CI 0.62–0.96 for 3–4 cups/day).

Conclusions

We found no significant association between coffee consumption and the risk of hip fracture. A nonlinear association emerged between tea consumption and the risk of hip fracture; individuals drinking 1–4 cups of tea per day exhibited a lower risk of hip fractures than those who drank no tea. The association between 5 daily cups of tea, or more, and hip fracture risk should be investigated.     

High-intensity resistance training and postmenopausal bone loss: a meta-analysis

Introduction Conflicting evidence exists regarding the optimum exercise for postmenopausal bone loss. A systematic review and meta-analysis was undertaken to evaluate the effects of randomised controlled trials (RCTs) of progressive, high-intensity resistance training on bone mineral density (BMD) amongst postmenopausal women.Methods Structured electronic searching of multiple databases and hand-searching of key journals and reference lists was undertaken to locate relevant studies up to December 2004. Study quality and possible publication bias were assessed using recognised methods. Primary outcomes were absolute changes in BMD at the lumbar spine (LS), femoral neck (FN) and total hip (TH). A priori defined subgroup analyses included concurrent hormonal or antiresorptive therapy or calcium supplementation during the intervention. The weighted mean difference method (WMD) was used for combining study group estimates. Random or fixed effect models were applied according to study heterogeneity observed from the I ² statistic.Results At the LS, 14 RCT study groups were homogenous (I ²=25.2%) in demonstrating a significant increase (P=0.006) in BMD of 0.006 g/cm² (fixed effect; 95% CI 0.002–0.011) following high-intensity resistance training. In contrast, marked heterogeneity (I ²=88.2%) was apparent within 11 RCT study groups evaluating FN. For this comparison, a random effects model showed a positive change in FN BMD of 0.010 g/cm² (95% CI −0.002 to 0.021; P = 0.11). Subgroup analyses showed more anatomical variability of BMD responses to resistance training according to participants’ hormone therapy use. Treatment effects for study groups increasing all participants’ calcium intake showed significant positive BMD changes at TH (P=0.007). Methodological quality of all included studies was low, and a reporting bias towards studies with positive BMD outcomes was evident.Conclusions These findings are relevant to the nonpharmacological treatment of postmenopausal bone loss.     

Predicting bone loss and fracture risk with biochemical markers: A review.

Numerous studies have reported associations of biochemical markers of bone turnover with rates of change in bone density. Increasing levels of both formation and resorption markers are associated with faster rates of decline in bone mineral density. The differences in bone loss rates among persons predicted from marker levels correspond to clinically significant differences in fracture risk. Markers have also been shown to predict fracture risk directly, although increases in certain markers are associated with increased risk in some studies, and other markers with decreased risk in other studies. The associations of biochemical markers with fracture risk are similar in magnitude to those for bone density and fractures. Taken together, existing data provide convincing evidence that biochemical markers can help determine which women are at increased risk of rapid bone loss and fracture.     

Effects of treatment with fluoride on bone mineral density and fracture risk - a meta-analysis

Summary Fluoride has fallen into discredit due to the absence of an anti-fracture effect. However, in this meta-analysis, a fracture reducing potential was seen at low fluoride doses [≤20 mg fluoride equivalents (152 mg monofluorophosphate/44 mg sodium fluoride)]: OR = 0.3, 95% CI: 0.1–0.9 for vertebral and OR = 0.5, 95% CI: 0.3–0.8 for non-vertebral fractures. Introduction Fluoride is incorporated into bone mineral and has an anabolic effect. However, the biomechanical competence of the newly formed bone may be reduced. Methods A systematic search of PubMed, Embase, and ISI web of science yielded 2,028 references. Results Twenty-five eligible studies were identified. Spine BMD increased 7.9%, 95% CI: 5.4–10.5%, and hip BMD 2.1%, 95% CI: 0.9–3.4%. A meta-regression showed increasing spine BMD with increasing treatment duration (5.04 ± 2.16%/year of treatment). Overall there was no significant effect on the risk of vertebral (OR = 0.8, 95% CI: 0.5–1.5) or non-vertebral fracture (OR = 0.8, 95% CI: 0.5–1.4). With a daily dose of ≤20 mg fluoride equivalents (152 mg monofluorophosphate/44 mg sodium fluoride), there was a statistically significant reduction in vertebral (OR = 0.3, 95% CI: 0.1–0.9) and non-vertebral (OR = 0.5, 95% CI: 0.3–0.8) fracture risk. With a daily dose >20 mg fluoride equivalents, there was no significant reduction in vertebral (OR = 1.3, 95% CI: 0.8–2.0) and non-vertebral (OR = 1.5, 95% CI: 0.8–2.8) fracture risk. Conclusions Fluoride treatment increases spine and hip BMD, depending on treatment duration. Overall there was no effect on hip or spine fracture risk. However, in subgroup analyses a low fluoride dose (≤20 mg/day of fluoride equivalents) was associated with a significant reduction in fracture risk.     

Effects of COLIA1 polymorphisms and haplotypes on perimenopausal bone mass, postmenopausal bone loss and fracture risk

Summary  

One thousand seven hundred seventeen perimenopausal women from the Danish Osteoporosis Prevention Study were genotyped for the −1997G/T, −1663indelT and +1245G/T polymorphisms in the COLIA1 gen. We found that the −1997T allele and a haplotype containing it were associated with reduced bone mineral density (BMD) and increased bone turnover at menopause and after 10 years of follow-up.     

Prediction of fracture risk in men: a cohort study

FRAX is a tool that identifies individuals with high fracture risk who will benefit from pharmacological treatment of osteoporosis. However, a majority of fractures among elderly occur in people without osteoporosis and most occur after a fall. Our aim was to accurately identify men with a high future risk of fracture, independent of cause. In the population‐based Uppsala Longitudinal Study of Adult Men (ULSAM) and using survival analysis we studied different models' prognostic values (R²) for any fracture and hip fracture within 10 years from age 50 (n = 2322), 60 (n = 1852), 71 (n = 1221), and 82 (n = 526) years. During the total follow‐up period from age 50 years, 897 fractures occurred in 585 individuals. Of these, 281 were hip fractures occurring in 189 individuals. The rates of any fracture were 5.7/1000 person‐years at risk from age 50 years and 25.9/1000 person‐years at risk from age 82 years. Corresponding hip fractures rates were 2.9 and 11.7/1000 person‐years at risk. The FRAX model included all variables in FRAX except bone mineral density. The full model combining FRAX variables, comorbidity, medications, and behavioral factors explained 25% to 45% of all fractures and 80% to 92% of hip fractures, depending on age. The corresponding prognostic values of the FRAX model were 7% to 17% for all fractures and 41% to 60% for hip fractures. Net reclassification improvement (NRI) comparing the full model with the FRAX model ranged between 40% and 53% for any fracture and between 40% and 87% for hip fracture. Within the highest quintile of predicted fracture risk with the full model, one‐third of the men will have a fracture within 10 years after age 71 years and two‐thirds after age 82 years. We conclude that the addition of comorbidity, medication, and behavioral factors to the clinical components of FRAX can substantially improve the ability to identify men at high risk of fracture, especially hip fracture. © 2012 American Society for Bone and Mineral Research.     

A meta-analysis of previous fracture and subsequent fracture risk

Previous fracture is a well-documented risk factor for future fracture. The aim of this study was to quantify this risk on an international basis and to explore the relationship of this risk with age, sex, and bone mineral density (BMD). We studied 15259 men and 44902 women from 11 cohorts comprising EVOS/EPOS, OFELY, CaMos, Rochester, Sheffield, Rotterdam, Kuopio, DOES, Hiroshima, and two cohorts from Gothenburg. Cohorts were followed for a total of 250000 person-years. The effect of a prior history of fracture on the risk of any fracture, any osteoporotic fracture, and hip fracture alone was examined using a Poisson model for each sex from each cohort. Covariates examined were age, sex, and BMD. The results of the different studies were merged by using the weighted beta-coefficients. A previous fracture history was associated with a significantly increased risk of any fracture compared with individuals without a prior fracture (RR = 1.86; 95% CI = 1.75-1.98). The risk ratio was similar for the outcome of osteoporotic fracture or for hip fracture. There was no significant difference in risk ratio between men and women. Risk ratio (RR) was marginally downward adjusted when account was taken of BMD. Low BMD explained a minority of the risk for any fracture (8%) and for hip fracture (22%). The risk ratio was stable with age except in the case of hip fracture outcome where the risk ratio decreased significantly with age. We conclude that previous history of fracture confers an increased risk of fracture of substantial importance beyond that explained by measurement of BMD. Its validation on an international basis permits the use of this risk factor in case finding strategies.     

Phytotherapy versus hormonal therapy for postmenopausal bone loss: a meta-analysis

This meta-analysis included 14 randomized controlled trials involving 780 patients to compare phytotherapy with hormonal therapy in the treatment of postmenopausal bone loss. Current evidence suggests that phytotherapy may possess a similar effect on bone mineral density (BMD) values but clinically is not associated with a high incidence of uterine bleeding and breast pain as is hormonal therapy. Clinical trials indicate that phytotherapy may be a potential treatment for postmenopausal osteoporosis. The objective of this meta-analysis was to compare the efficacy and safety of phytotherapy with that of hormonal therapy, to assess the quality of phytotherapy trials, and to identify herbs used commonly in the treatment of postmenopausal bone loss. A total of 43 electronic databases were searched. The quality of eligible trials was assessed using Jadad’s scale. Outcome measures were BMD values and adverse events. Revman 5.0 software was used for data syntheses and meta-analyses. The database search revealed 14 randomized controlled trials involving 780 patients that met the inclusion criteria, and four trials were graded as high quality (score 3–5). There was no significant difference in lumbar, femoral or forearm BMD values between subjects treated with phytotherapy and those treated with hormonal therapy (P>0.05), but the incidence of uterine bleeding and breast pain was significantly lower in those treated with phytotherapy than in those treated with hormonal therapy (P = 0.002 and P = 0.01). The six most commonly used herbs in the included trials were identified. Phytotherapy may not show effects beyond hormonal therapy, but may be safer than hormonal therapy in the treatment of postmenopausal bone loss. Further trials with high-quality study designs should be conducted in this field.     

Femoral neck bone loss predicts fracture risk independent of baseline BMD.

Whereas low BMD is known to be a risk factor for fracture, it is not clear whether loss of BMD is also a risk factor. In elderly women, greater loss of BMD at the femoral neck was associated with increased risk of fracture, independent of baseline BMD and age. INTRODUCTION: Baseline measurement of BMD predicts fracture risk. However, it is not clear whether short-term bone loss is an independent risk factor for fractures. This study was designed to investigate the relationship between changes in BMD and fracture risk in elderly women in the general population. MATERIALS AND METHODS: A total of 966 women > or = 60 years of age (mean, 70 +/- 6.7 [SD] years), who had been followed for an average of 10.7 years, were studied. Atraumatic fracture of the proximal femur (hip), symptomatic vertebral fracture, and other major fractures, excluding pathological fractures or those resulting from severe trauma, were recorded and confirmed by radiographs. Femoral neck and lumbar spine BMD was measured by DXA. RESULTS: During the follow-up period, 224 had sustained a fracture (including 43 hip, 71 symptomatic vertebrae, 37 proximal humerus, 46 forearm and wrist, and 27 rib and pelvis fractures). The annual rate of change in BMD in fracture women (-2.1 +/- 4.2%) was significantly higher than that in nonfracture women (-0.8 +/- 2.8%; p = 0.005). In the multivariable Cox's proportional hazards analysis, the following factors were significant predictors of fracture risk: femoral neck bone loss (relative hazard [RH], 1.4; 95% CI, 1.1-1.8 per 5% loss), baseline femoral neck BMD (RH, 2.0; 95% CI, 1.7-2.7 per SD), and advancing age (RH, 1.2; 95% CI, 1.1-1.4). The proportion of fractures attributable to the three factors was 45%. For hip fracture, the attributable risk fraction was approximately 90%. CONCLUSION: Bone loss at the femoral neck is a predictor of fracture risk in elderly women, independent of baseline BMD and age.