Quantitative ultrasound predicts hip and non-spine fracture in men: the MrOS study

Summary Quantitative ultrasound (QUS) is associated with fracture risk in women, but there are few data in men. We studied 5,607 older men and found that QUS predicts hip and any non-spine fracture risk nearly as well as BMD. Combined measurements of QUS and BMD are not superior to either measurement alone. Introduction Quantitative ultrasound (QUS) predicts fracture risk among older women, but there are few prospective studies among older men. We studied the ability of QUS and BMD measurements to predict hip and other non-spine fractures in a population-based study of older men. Methods Calcaneal QUS and hip BMD were measured in 5,607 men aged ≥65 years recruited from six US centers. At baseline duplicate QUS measurements with repositioning were obtained, and subsequent hip and other non-spine fractures were documented by review of x-rays or x-ray reports. The relationships between QUS and fractures were examined with proportional hazard models adjusted for age and clinic. We used receiver operating characteristic curves and predicted fracture risk models to determine the utility of QUS alone, BMD alone or the combination of QUS+BMD. Results During a mean follow-up of 4.2 years with 99% complete follow-up, 239 men suffered a non-spine fracture, including 49 hip fractures. Each standard deviation reduction in broadband ultrasonic attenuation (BUA) was associated with an increased risk of hip (relative hazard=2.0, CI: 1.5, 2.8) and any non-spine fracture (relative hazard=1.6, CI: 1.4, 1.8). The area under the receiver operating characteristic curve and the predicted probability of fracture were similar for BUA alone, BMD alone and the combination of BUA+BMD, indicating that once BUA or BMD is known, the other measurement does not add useful information. Other QUS parameters gave similar results. Conclusions QUS measurements predict the risk of hip and any non-spine fracture in older men, and do so nearly as well as hip BMD measurements. Combined measurements of QUS and BMD are not superior to either measurement alone. Funding: The Osteoporotic Fractures in Men (MrOS) Study is supported by National Institutes of Health funding. The following institutes provide support: the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Institute on Aging (NIA), and the National Cancer Institute (NCI), under the following grant numbers: UO1 AG18197-02, UO1 AR45580-02, UO1 AR45614, UO1 AR45632, UO1 AR45647, UO1 AR45654, UO1 AR45583 and M01 RR00334.     

Identification of vertebral fracture and non-osteoporotic short vertebral height in men: the MrOS study.

Non-osteoporotic SVH may mimic VF but is excluded in ABQ. In men, this led to discordance between ABQ and other methods, but SVH was not linked to low bone density. Exclusion of SVH could reduce false positives. INTRODUCTION: Non-osteoporotic short vertebral height (SVH) may mimic vertebral fracture (VF). The aims were to (1) compare the prevalence of VF in elderly men using the algorithm-based qualitative (ABQ), semiquantitative (SQ), and triage-quantitative morphometric (triage-QM) methods; (2) identify reasons for discordance between methods; and (3) determine whether SVH identified by ABQ is linked to low BMD. MATERIALS AND METHODS: We studied a subset of 732 men ages > or =65 yr participating in the Osteoporotic Fractures in Men (MrOS) Study. Criteria for VF were (1) ABQ: endplate depression; (2) SQ: estimated vertebral height reduction > or =20%; (3) triage-QM: vertebral height ratio >3 SD below the reference mean, on radiographs showing evidence of VF. Criteria for SVH (ABQ) were apparent "reduction" in vertebral height > or = approximately 15%, without evidence of endplate depression. RESULTS: The prevalence of at least one VF was 10% (ABQ); 13% (SQ) and 11% (QM-triage) and of at least one SVH (ABQ) was >50%. Agreement between methods was moderate (kappa = 0.42-0.62). Discordance between methods related mainly to classification of mild thoracic wedging or possible traumatic VF by ABQ. Mean BMD was lower in men with VF (any diagnostic method) than in those without (two-sample t-test, p < 0.05). For ABQ, BMD was similar in men with SVH (no VF) and men with normal vertebrae (ANOVA, p > 0.05). Mean BMD was significantly lower than expected in 40 men with VF identified by all three methods and average or more than average in those identified by a single method. CONCLUSIONS: Among elderly men (1) the prevalence of VF ranges from 10% to 13%: (2) agreement between diagnostic methods is moderate: discordance relates mainly to differential classification of mild thoracic deformities or ABQ definition of VF as traumatic; and (3) SVH identified by ABQ is common and not linked to low BMD.     

Waning predictive value of serum adiponectin for fracture risk in elderly men: MrOS Sweden

Summary

Serum adiponectin is a risk factor for fracture. The predictive value attenuates with time in elderly men so that its use for the risk assessment in the long term is questionable. The study underlines the importance of testing the long-term stability of potential risk factors.

Introduction

High serum adiponectin is associated with an increased risk of fracture in elderly men. The aim of the present study was to determine the impact of adiponectin on the probability of fracture as a function of time.

Methods

The probability of osteoporotic fracture was computed in 989 elderly men from the MrOS study in Sweden. Baseline data included clinical risk factors for fracture, femoral neck BMD and serum adiponectin. Men were followed for up to 7.4 years with a mean follow up of 5.3 years (range 0.0–7.4 years). Poisson regression was used to model the hazard function for osteoporotic fracture and death to determine the 10 year probability of fracture.

Results

During follow up, 124 men sustained one or more osteoporotic fracture. There was a significant interaction between adiponectin and time since baseline (p?=?0.026) such that the longer time since baseline, the lower the gradient of fracture risk. When using this interaction in the calculation of 10-year probability of fracture, the probabilities of osteoporotic fracture varied little over the range of adiponectin values.

Conclusion

Serum adiponectin is a risk factor for fracture. Nevertheless, the predictive value attenuates with time so that its use for the risk assessment in the long term is questionable. This study underlines the importance of testing the long-term stability of potential risk factors that might be used in fracture risk assessment.     

High hip fracture risk in men with severe aortic calcification: MrOS study

A significant link between cardiovascular disease and osteoporosis is established in postmenopausal women, but data for men are scarce. We tested the hypothesis that greater severity of abdominal aortic calcification (AAC) was associated with an increased risk of nonspine fracture in 5994 men aged ≥65 years. AAC was assessed on 5400 baseline lateral thoracolumbar radiographs using a validated visual semiquantitative score. Total hip bone mineral density (BMD) was measured using dual‐energy X‐ray absorptiometry. Incident nonspine fractures were centrally adjudicated. After adjustment for age, body mass index (BMI), total hip BMD, fall history, prior fracture, smoking status, comorbidities, race, and clinical center, the risk of nonspine fracture (n = 805) was increased among men with higher AAC (hazard ratio [HR] quartile 4 [Q4] [AAC score ≥9] versus quartile 1 [Q1] [0–1], 1.36; 96% confidence interval [CI], 1.10–1.68). This association was due to an increased risk of hip fracture (n = 178) among men with higher AAC (HR Q4 versus Q1, 2.33; 95% CI, 1.41–3.87). By contrast, the association between AAC and the risk of nonspine, nonhip fracture was weaker and not significant (HR Q4 versus Q1, 1.22; 95% CI, 0.96–1.55). The findings regarding higher AAC and increased risk of fracture were not altered in additional analyses accounting for degree of trauma, estimated glomerular filtration rate, presence of lumbar vertebral fractures (which may bias AAC assessment), preexisting cardiovascular disease, ankle brachial index, or competing risk of death. Thus, in this large cohort of elderly men, greater AAC was independently associated with an increased risk of hip fracture, but not with other nonspine fractures. These findings suggest that AAC assessment may be a useful method for identification of older men at high risk of hip fracture. © 2014 American Society for Bone and Mineral Research.     

BMI and fracture risk in older men: The osteoporotic fractures in men study (MrOS)

Low body mass index (BMI) is a risk factor for fracture, but little is known about the association between high BMI and fracture risk. We evaluated the association between BMI and fracture in the Osteoporotic Fractures in Men Study (MrOS), a cohort of 5995 US men 65 years of age and older. Standardized measures included weight, height, and hip bone mineral density (BMD) by dual‐energy X‐ray absorptiometry (DXA); medical history; lifestyle; and physical performance. Only 6 men (0.1%) were underweight (<18.5 kg/m²); therefore, men in this category were excluded. Also, 27% of men had normal BMI (18.5 to 24.9 kg/m²), 52% were overweight (25 to 29.9 kg/m²), 18% were obese I (30 to 34.9 kg/m²), and 3% were obese II (35 to 39.9 kg/m²). Overall, nonspine fracture incidence was 16.1 per 1000 person‐years, and hip fracture incidence was 3.1 per 1000 person‐years. In age‐, race‐, and BMD‐adjusted models, compared with normal weight, the hazard ratio (HR) for nonspine fracture was 1.04 [95% confidence interval (CI) 0.87–1.25] for overweight, 1.29 (95% CI 1.00–1.67) for obese I, and 1.94 (95% CI 1.25–3.02) for obese II. Associations were weaker and not statistically significant after adjustment for mobility limitations and walking pace (HR = 1.02, 95% CI 0.84–1.23, for overweight; HR = 1.12, 95% CI 0.86–1.46, for obese I, and HR = 1.44, 95% CI 0.90–2.28, for obese II). Obesity is common among older men, and when BMD is held constant, it is associated with an increased risk of fracture. This association is at least partially explained by worse physical function in obese men. © 2011 American Society for Bone and Mineral Research.     

Heel bone ultrasound predicts non-spine fracture in Japanese men and women

A number of prospective studies in the USA and Europe have demonstrated that quantitative ultrasound (QUS) measurements predict fracture risk. To our knowledge, there has been no such study in a Japanese population, and very few studies have measured the prognostic value of QUS measurements among men, even in the USA and Europe. We performed a three-center prospective study to investigate the relationship between baseline heel QUS measurements and non-spine fracture risk. There were 4,028 subjects (1,004 men and 3,024 women), 67.5±8.9 years [mean ± standard deviation (SD)] of age), who underwent heel QUS (Achilles device) at three centers between 1993 and 2000. In 2002, the subjects were mailed a standardized questionnaire that asked about their history of fracture. The mean follow-up period was approximately 5 years. The Achilles measured speed of sound (SOS) and broadband ultrasound attenuation (BUA). We used Cox regression analysis to determine the hazard ratio (HR), using weighted coefficients. SOS, BUA, and stiffness index (SI) predicted self-reported hip, wrist, and total non-spine fractures. After we had adjusted for age, gender, and weight, the HRs of total non-spine fracture were 1.54 [95% confidence interval (CI) 1.39–1.69], 1.53 (1.37–1.70), and 1.80 (1.62–1.98) for 1 SD decrease in SOS, BUA, and SI, respectively. In men, SOS and SI also predicted total non-spine fractures with HRs similar to those in women. The HR of prediction for hip fracture by SOS and SI was better in the short term than in the long term, and the prediction for hip, wrist, and non-spine fracture remained significant between 5 to 10 years of follow-up. Measurements obtained from heel QUS predicted non-spine fracture in Japanese men and women, and the HRs of Japanese of both genders was similar to the risk ratio (RR) of Caucasian men and women. QUS parameters can predict hip, wrist, and non-spine fracture up to 10 years.     

Low holotranscobalamin and cobalamins predict incident fractures in elderly men: the MrOS Sweden

Summary

In a population-based study on cobalamin status and incident fractures in elderly men (n?=?790) with an average follow-up of 5.9 years, we found that low levels of metabolically active and total cobalamins predict incident fractures, independently of body mass index (BMI), bone mineral density (BMD), plasma total homocysteine (tHcy), and cystatin C.

Introduction

Cobalamin deficiency in elderlies may affect bone metabolism. This study aims to determine whether serum cobalamins or holotranscobalamin (holoTC; the metabolic active cobalamin) predict incident fractures in old men.

Methods

Men participating in the Gothenburg part of the population-based Osteoporotic Fractures in Men (MrOS) Sweden cohort and without ongoing vitamin B medication were included in the present study (n?=?790; age range, 70–81 years).

Results

During an average follow-up of 5.9 years, 110 men sustained X-ray-verified fractures including 45 men with clinical vertebral fractures. The risk of fracture (adjusted for age, smoking, BMI, BMD, falls, prevalent fracture, tHcy, cystatin C, 25-OH-vitamin D, intake of calcium, and physical activity (fully adjusted)), increased per each standard deviation decrease in cobalamins (hazard ratio (HR), 1.38; 95 % confidence intervals (CI), 1.11–1.72) and holoTC (HR, 1.26; 95 % CI, 1.03–1.54), respectively. Men in the lowest quartile of cobalamins and holoTC (fully adjusted) had an increased risk of all fracture (cobalamins, HR?=?1.67 (95 % CI, 1.06–2.62); holoTC, HR?=?1.74 (95 % CI, 1.12–2.69)) compared with quartiles 2–4. No associations between folate or tHcy and incident fractures were seen.

Conclusions

We present novel data showing that low levels of holoTC and cobalamins predicting incident fracture in elderly men. This association remained after adjustment for BMI, BMD, tHcy, and cystatin C. However, any causal relationship between low cobalamin status and fractures should be explored in a prospective treatment study.     

Abdominal body composition measured by quantitative computed tomography and risk of non-spine fractures: the Osteoporotic Fractures in Men (MrOS) study

Summary

The effect of abdominal adiposity and muscle on fracture is unclear in older men; therefore, we examined the association among 749 men aged 65+. Among various adipose tissues and muscle groups, lower psoas muscle volume and higher fatty infiltration of abdominal muscle contribute to higher fracture risk independent of BMD.

Introduction

The association of abdominal adiposity and muscle composition with incident fracture is unclear, especially in older men. Therefore, we examined the relationship of subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), abdominal intermuscular adipose tissue (IMAT), and muscle volume with incident non-spine fractures among 749 men aged 65 and older.

Methods

A case–cohort study design was used with a total of 252 fracture cases and 497 non-cases. We measured volumes (in centimeters) of adipose and muscle tissues obtained from quantitative computed tomography scan at the L4–5 intervertebral space. Three groups of muscle and IMAT were evaluated: total abdominal, psoas, and paraspinal. Cox proportional hazards regression with a robust variance estimator was used to estimate the hazard ratio (HR) of non-spine fractures per standard deviation (SD) increase in the abdominal body composition measures. The mean age among men in the random subcohort was 74.2?±?6.1 years, and the average follow-up time was 5.2?±?1.1 years.

Results

After adjusting for age, race, clinic site, percent body fat, and femoral neck bone mineral density (BMD), no significant relationship was found between incident fractures and SAT or VAT. One SD increase in muscle volume at the psoas, but not paraspinal, was associated with 28 % lower fracture risk (95 % CI?=?0.55–0.95). When IMAT models were further adjusted for corresponding muscle volumes, only abdominal IMAT was significantly associated with fracture risk (HR?=?1.30 (95 % CI?=?1.04–1.63)).

Conclusion

Our findings suggest that lower total psoas muscle volume and higher IMAT of the total abdominal muscle contribute to higher fracture risk in older men independent of BMD.     

High serum adiponectin predicts incident fractures in elderly men: Osteoporotic fractures in men (MrOS) Sweden

Adipocytes and osteoblasts share a common progenitor, and there is, therefore, potential for both autocrine and endocrine effects of adiponectin on skeletal metabolism. The aim of the present study was to determine whether high serum adiponectin was associated with an increased risk of fracture in elderly men. We studied the relationship between serum adiponectin and the risk of fracture in 999 elderly men drawn from the general population and recruited to the Osteoporotic Fractures in Men (MrOS) study in Gothenburg, Sweden. Baseline data included general health questionnaires, lifestyle questionnaires, body mass index (BMI), bone mineral density (BMD), serum adiponectin, osteocalcin, and leptin. Men were followed for up to 7.4 years (average, 5.2 years). Poisson regression was used to investigate the relationship between serum adiponectin, other risk variables and the time‐to‐event hazard function of fracture. Median levels of serum adiponectin at baseline were 10.4 µg/mL (interquartile range, 7.7–14.3). During follow‐up, 150 men sustained one or more fractures. The risk of fracture increased in parallel with increasing serum adiponectin (hazard ratio [HR]/SD, 1.46; 95% confidence interval [CI], 1.23–1.72) and persisted after multivariate‐adjusted analysis (HR/SD, 1.30; 95% CI, 1.09–1.55). Serum adiponectin shows graded stepwise association with a significant excess risk of fracture in elderly men that was independent of several other risk factors for fracture. Its measurement holds promise as a risk factor for fracture in men. © 2012 American Society for Bone and Mineral Research.     

Free testosterone is an independent predictor of BMD and prevalent fractures in elderly men: MrOS Sweden.

The role of androgens for bone health in elderly men is unclear. We show that free testosterone within the normal range is a predictor of BMD at predominantly cortical bone sites and of previous osteoporosis-related fractures in elderly Swedish men. INTRODUCTION: Osteoporosis-related fractures constitute a major health concern not only in women but also in men. Previous studies have clearly shown that serum levels of estradiol are associated with BMD, whereas more conflicting data have been presented regarding the predictive value of testosterone (T) for bone health in elderly men. The aim of this study was to investigate if serum levels of T are associated with BMD and/or prevalent fractures in a large cohort of elderly men. MATERIALS AND METHODS: In the Swedish part of the MrOS study (n = 2908; average age, 75.4 years), bone parameters were measured using DXA, and prevalent fractures were recorded using standardized questionnaires and by vertebral X-ray analyses. Serum levels of total T, total estradiol (E2), and sex hormone-binding globulin (SHBG) were measured by radioimmunoassay, and free T (FT) and free E2 (FE2) were derived from the mass action equations. Height, weight, age, physical activity, smoking habits, and calcium intake were included together with FT and FE2 in regression models for BMD. RESULTS: FT was an independent positive predictor of BMD in total body, total hip, femur trochanter, and arm but not in the lumbar spine. The highest independent predictive value of FT was found in the arm and the hip (with a relatively high content of cortical bone). FE2 was an independent predictor of BMD at all bone sites studied, and the highest predictive value was seen for lumbar spine (with relatively high content of trabecular bone) BMD. FT but not FE2 was a positive predictor of total body bone area and BMC. FT levels below the median were independent predictors of prevalent osteoporosis-related fractures (OR, 1.56; 95% CI, 1.14-2.14; p < 0.01) and X-ray-verified vertebral fractures (OR, 2.00; 95% CI, 1.34-2.86; p < 0.001). The predictive value of FT for prevalent fractures was not affected by adjustment for BMD. CONCLUSIONS: These findings show that variation of FT within the normal range is an independent but modest predictor of BMD at predominantly cortical bone sites and of previous osteoporosis-related fractures in elderly men. Our data indicate that not only estrogens but also androgens are of importance for bone health in elderly men. Longitudinal studies investigating the predictive value of T for fracture risk in elderly men are required.     

Low serum vitamin D is associated with increased mortality in elderly men: MrOS Sweden

Summary

In elderly man, low serum 25-hydroxyvitamin D (25(OH)D) was associated with a substantial excess risk of death compared to 25(OH)D values greater than 50?C70?nmol/l, but the association attenuated with time.

Introduction

The aim of the present study was to determine whether poor vitamin D status was associated with an increase in the risk of death in elderly men.

Methods

We studied the relationship between serum 25(OH)D and the risk of death in 2,878 elderly men drawn from the population and recruited to the MrOS study in Sweden. Baseline data included general health and lifestyle measures and serum 25(OH)D measured by competitive RIA. Men were followed for up to 8.2?years (average 6.0?years).

Results

Mortality adjusted for comorbidities decreased by 5% for each SD increase in 25(OH)D overall (gradient of risk 1.05; 95% confidence interval 0.96?C1.14). The predictive value of 25(OH)D for death was greatest below a threshold value of 50?C70?nmol/l, was greatest at approximately 3?years after baseline and thereafter decreased with time.

Conclusions

Low serum 25(OH)D is associated with a substantial excess risk of death compared to 25(OH)D values greater than 50?C70?nmol/l, but the association attenuates with time. These findings, if causally related, have important implications for intervention in elderly men.     

Low bone mineral density is associated with increased mortality in elderly men: MrOS Sweden

Summary

We studied the nature of the relationship between bone mineral density (BMD) and the risk of death among elderly men. BMD was associated with mortality risk and was independent of adjustments for other co-morbidities. A piecewise linear function described the relationship more accurately than assuming the same gradient of risk over the whole range of BMD (p?=?0.020). Low BMD was associated with a substantial excess risk of death, whilst a higher than average BMD had little impact on mortality.

Introduction

Previous studies have demonstrated an association between low BMD and an increased risk of death among men and women. The aim of the present study was to examine the pattern of the risk in men and its relation to co-morbidities.

Methods

We studied the nature of the relationship between BMD and death among 3,014 elderly men drawn from the population and recruited to the MrOS study in Sweden. Baseline data included general health questionnaires, life style questionnaires and BMD measured using DXA. Men were followed for up to 6.5?years (average 4.5?years). Poisson regression was used to investigate the relationship between BMD, co-morbidities and the hazard function of death.

Results

During follow-up, 382 men died (all-cause mortality). Low BMD at all measured skeletal sites was associated with increased mortality. In multivariate analyses, the relationship between BMD and mortality was non-linear, and a piecewise linear function described the relationship more accurately than assuming the same gradient of risk over the whole range of BMD (p?=?0.020).

Conclusions

Low BMD is associated with a substantial excess risk of death compared to an average BMD, whereas a higher than average BMD has a more modest effect on mortality. These findings, if confirmed elsewhere, have implications for the constructing of probability-based fracture risk assessment tools.     

Risk factors for fracture in elderly men: a population-based prospective study

Summary  

Risk factors for fractures were assessed in a random sample of 4,696 elderly men followed for 5.4 years. Results highlighted the importance of assessment of falls and dizziness as well as novel risk factors including frequent urination and erectile dysfunction.     

Distribution of bone density in the proximal femur and its association with hip fracture risk in older men: The osteoporotic fractures in men (MrOS) study

This prospective case‐cohort study aimed to map the distribution of bone density in the proximal femur and examine its association with hip fracture. We analyzed baseline quantitative computed tomography (QCT) scans in 250 men aged 65 years or older, which comprised a randomly‐selected subcohort of 210 men and 40 cases of first hip fracture during a mean follow‐up period of 5.5 years. We quantified cortical, trabecular, and integral volumetric bone mineral density (vBMD), and cortical thickness (CtTh) in four quadrants of cross‐sections along the length of the femoral neck (FN), intertrochanter (IT), and trochanter (TR). In most quadrants, vBMDs and CtTh were significantly (p < 0.05) lower in cases compared to the subcohort and these deficits were present across the entire proximal femur. To examine the association of QCT measurements with hip fracture, we merged the two quadrants in the medial and lateral aspects of the FN, IT, and TR. At most sites, QCT measurements were associated significantly (p < 0.001) with hip fracture, the hazard ratio (HR) adjusted for age, body mass index (BMI), and clinical site for a 1‐SD decrease ranged between 2.28 (95% confidence interval [CI], 1.44–3.63) to 6.91 (95% CI, 3.11–15.53). After additional adjustment for total hip (TH) areal BMD (aBMD), trabecular vBMDs at the FN, TR, and TH were still associated with hip fracture significantly (p < 0.001), the HRs ranged from 3.21 (95% CI, 1.65–6.24) for the superolateral FN to 6.20 (95% CI, 2.71–14.18) for medial TR. QCT measurements alone or in combination did not predict fracture significantly (p > 0.05) better than TH aBMD. With an area under the receiver operating characteristic curve (AUC) of 0.901 (95% CI, 0.852–0.950), the regression model combining TH aBMD, age, and trabecular vBMD predicted hip fracture significantly (p < 0.05) better than TH aBMD alone or TH aBMD plus age. These findings confirm that both cortical and trabecular bone contribute to hip fracture risk and highlight trabecular vBMD at the FN and TR as an independent risk factor. © 2012 American Society for Bone and Mineral Research.     

ApoE gene polymorphisms, BMD, and fracture risk in elderly men and women: the Rotterdam study.

To study the association between the ApoE gene polymorphism and osteoporosis, we performed an association study in 5,857 subjects from the Rotterdam Study. We did not observe an association between the ApoE polymorphism and osteoporosis in this study, which is thus far the largest study on ApoE and osteoporosis. INTRODUCTION: The E*4 allele of the E*2, E*3, E*4 protein isoform polymorphism in the gene encoding apolipoprotein E (ApoE) has previously been associated with an increased fracture risk. We investigated the association between the ApoE polymorphism and BMD, bone loss, and incident fractures as part of the Rotterdam Study a prospective population-based cohort study of diseases in the elderly. MATERIALS AND METHODS: The study population consisted of 5,857 subjects (2,560 men; 3,297 women) for whom data on ApoE genotypes, confounding variables, and follow-up of nonvertebral fractures were available. Data on femoral neck and lumbar spine BMD were available for 4,814 participants. Genotype analyses for bone loss (defined as annualized percent change in BMD at the hip and lumbar spine) and BMD were performed using ANOVA. Fractures were analyzed using a Cox proportional-hazards model and logistic regression. All relative risks were adjusted for age and body mass index. RESULTS AND CONCLUSIONS: The genotype distribution of the study population was in Hardy-Weinberg equilibrium (p = 0.98) and did not differ by gender. At baseline, mean BMD of the lumbar spine and femoral neck did not differ between the ApoE genotypes of men and women. Bone loss (mean follow-up, 2.0 years) did not differ by ApoE genotype for women and men. During a mean follow-up of 6.6 years, 708 nonvertebral fractures (198 hip fractures and 179 wrist fractures) and 149 incident vertebral fractures occurred. No consistent differences in the distribution of alleles could be observed between subjects with or without these fractures. Our data do not support the hypothesis that the ApoE*4 risk allele is associated with BMD, increased bone loss, or an increased risk of osteoporotic fractures.     

Association of stressful life events with accelerated bone loss in older men: the osteoporotic fractures in men (MrOS) study

Summary

Prior studies suggest an association between stressful life events and fractures that may be mediated by BMD. In the current study, risk of accelerated hip BMD loss was higher in older men with any type of stressful life event and increased with the number of types of stressful life events.

Introduction

Prior studies suggest that stressful life events may increase adverse health outcomes, including falls and possibly fractures. The current study builds on these findings and examines whether stressful life events are associated with increased bone loss.

Methods

Four thousand three hundred eighty-eight men aged ≥65 years in the Osteoporotic Fractures in Men study completed total hip bone mineral density (BMD) measures at baseline and visit 2, approximately 4.6 years later, and self-reported stressful life events data mid-way between baseline and visit 2, and at visit 2. We used linear regression to model the association of stressful life events with concurrent annualized total hip BMD loss, and log binomial regression or Poisson regression to model risk of concurrent accelerated BMD loss (>1 SD more than mean annualized change).

Results

Men (75.3 %) reported ≥1 type of stressful life event, including 43.3 % with ≥2 types of stressful life events. Mean annualized BMD loss was ?0.36 % (SD 0.88), and 13.9 % of men were categorized with accelerated BMD loss (about 5.7 % or more total loss). Rate of annualized BMD loss increased with the number of types of stressful life events after adjustment for age (p?p?=?0.07). Multivariable-adjusted risk of accelerated BMD loss increased with the number of types of stressful life events (RR, 1.10 [95 % confidence interval (CI), 1.04–1.16]) per increase of one type of stressful life event). Fracture risk was not significantly different between stressful life event-accelerated bone loss subgroups (p?=?0.08).

Conclusions

In these older men, stressful life events were associated with a small, dose-related increase in risk of concurrent accelerated hip bone loss. Low frequency of fractures limited assessment of whether rapid bone loss mediates any association of stressful life events with incident fractures. Future studies are needed to confirm these findings and to investigate the mechanism that may underlie this association.     

The association of concurrent vitamin D and sex hormone deficiency with bone loss and fracture risk in older men: The osteoporotic fractures in men (MrOS) study

Low 25‐hydroxyvitamin D (VitD), low sex hormones (SH), and high sex hormone binding globulin (SHBG) levels are common in older men. We tested the hypothesis that combinations of low VitD, low SH, and high SHBG would have a synergistic effect on bone mineral density (BMD), bone loss, and fracture risk in older men. Participants were a random subsample of 1468 men (mean age 74 years) from the Osteoporotic Fractures in Men Study (MrOS) plus 278 MrOS men with incident nonspine fractures studied in a case‐cohort design. “Abnormal” was defined as lowest quartile for VitD (<20 ng/mL), bioavailable testosterone (BioT, <163 ng/dL), and bioavailable estradiol (BioE, <11 pg/mL); and highest quartile for SHBG (>59 nM). Overall, 10% had isolated VitD deficiency; 40% had only low SH or high SHBG; 15% had both SH/SHBG and VitD abnormality; and 35% had no abnormality. Compared to men with all normal levels, those with both SH/SHBG and VitD abnormality tended to be older, more obese, and to report less physical activity. Isolated VitD deficiency, and low BioT with or without low VitD, was not significantly related to skeletal measures. The combination of VitD deficiency with low BioE and/or high SHBG was associated with significantly lower baseline BMD and higher annualized rates of hip bone loss than SH abnormalities alone or no abnormality. Compared to men with all normal levels, the multivariate‐adjusted hazard ratio (95% confidence interval [CI]) for incident nonspine fracture during 4.6‐year median follow‐up was 1.2 (0.8–1.8) for low VitD alone; 1.3 (0.9–1.9) for low BioE and/or high SHBG alone; and 1.6 (1.1–2.5) for low BioE/high SHBG plus low VitD. In summary, adverse skeletal effects of low sex steroid levels were more pronounced in older men with low VitD levels. The presence of low VitD in the presence of low BioE/high SHBG may contribute substantially to poor skeletal health. © 2012 American Society for Bone and Mineral Research.     

Predictors of functional outcome following intracapsular hip fracture in elderly women. A one-year prospective cohort study

OBJECTIVES: To explore potential predictors of functional outcome one year after the injury in elderly women who sustained a displaced intracapsular hip fracture and who were treated with internal fixation, hemiarthroplasty, or total hip arthroplasty. PARTICIPANTS AND METHODS: Eighty-four women aged > or =50 years were enrolled on a consecutive basis in this one-year prospective cohort study reflecting standard day-to-day clinical practice. The main outcome measure was the rapid disability rating scale version-2 (RDRS-2) applied at hospital discharge and one year later. RESULTS: At hospital discharge, the total hip arthroplasty group was younger and had a better functional status than the internal fixation or hemiarthroplasty groups. One year later, the best function was still observed in the total arthroplasty group, but the differences were small and failed to achieve the level of statistical significance. During that one-year period, walking ability or mobility did not change significantly after total hip arthroplasty, but a significant proportion of the women developed cognitive impairment, including mental confusion, uncooperativeness, and depression. Overall, the most significant predictors of poor functional status one year after fracture were increasing age, living in an institution at time of injury, and poor functional status at discharge. CONCLUSIONS: In elderly women with a displaced intracapsular hip fracture, total hip arthroplasty is associated with a functional benefit within the first months after surgery. However, the extent to which this functional benefit is maintained over time, is less clear. These results support the need for randomised studies to quantify the extent to which, in elderly women, the early functional benefit of total hip arthroplasty is maintained in the long run or compromised by progressive cognitive impairment and other negative determinants of functional outcome.