The Effects of Age,Adiposity, and Physical Activity on the Risk of Seven Site‐Specific Fractures in Postmenopausal Women

Risk factors for fracture of the neck of the femur are relatively well established, but those for fracture at other sites are little studied. In this large population study we explore the role of age, body mass index (BMI), and physical activity on the risk of fracture at seven sites in postmenopausal women. As part of the Million Women Study, 1,154,821 postmenopausal UK women with a mean age of 56.0 (SD 4.8) years provided health and lifestyle data at recruitment in 1996 to 2001. All participants were linked to National Health Service (NHS) hospital records for day‐case or overnight admissions with a mean follow‐up of 11 years per woman. Adjusted absolute and relative risks for seven site‐specific incident fractures were calculated using Cox regression models. During follow‐up, 4931 women had a fracture of the humerus; 2926 of the forearm; 15,883 of the wrist; 9887 of the neck of the femur; 1166 of the femur (not neck); 3199 a lower leg fracture; and 10,092 an ankle fracture. Age‐specific incidence rates increased gradually with age for fractures of forearm, lower leg, ankle, and femur (not neck), and steeply with age for fractures of neck of femur, wrist, and humerus. When compared to women with desirable BMI (20.0 to 24.9 kg/m²), higher BMI was associated with a reduced risk of fracture of the neck of femur, forearm, and wrist, but an increased risk of humerus, femur (not neck), lower leg, and ankle fractures (p < 0.001 for all). Strenuous activity was significantly associated with a decreased risk of fracture of the humerus and femur (both neck and remainder of femur) (p < 0.001), but was not significantly associated with lower leg, ankle, wrist, and forearm fractures. Postmenopausal women are at a high lifetime risk of fracture. BMI and physical activity are modifiable risk factors for fracture, but their associations with fracture risk differ substantially across fracture sites. © 2016 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research (ASBMR)     

The Associations Between Seven Different Types of Physical Activity and the Incidence of Fracture at Seven Sites in Healthy Postmenopausal UK Women

There is a paucity of information on associations between specific types of physical activity and fracture risk at different sites in otherwise healthy postmenopausal women. Therefore, we examined risk of fracture at seven different sites associated with seven different types of physical activity in the population-based prospective UK Million Women Study. A total of 371,279 postmenopausal women (mean age 59.8 years), rating their health as good or excellent and reporting participation in walking, cycling, gardening, doing housework, yoga, dance, and sports club activities, were followed for site-specific incident fracture through record linkage to national databases on day-case and overnight hospital admissions. Cox regression yielded adjusted relative risks (RRs) and, because of the large number of statistical tests done, 99% confidence intervals (CIs) for fracture at seven different sites in relation to seven different physical activities. During an average follow-up of 12 years, numbers with a first site-specific fracture were as follows: humerus (2341), forearm (1238), wrist (7358), hip (4354), femur (not neck) (617), lower leg (1184), and ankle (3629). For upper limb fractures there was significant heterogeneity across the seven activity types (test for heterogeneity p = 0.004), with gardening more than 1 hour/week associated with a lower risk (RR = 0.91; 99% CI, 0.86 to 0.96; p < 0.0001), whereas cycling more than 1 hour/week was associated with an increased risk (RR = 1.11; 99% CI, 1.00 to 1.23; p = 0.008). For fractures of the lower limb (including hip) there was no significant heterogeneity by type of activity, with significant approximately 5% to 15% reductions in risk associated with most activities, except cycling. For hip fractures, there was no significant heterogeneity by type of activity, but with significant 15% to 20% reductions in risk associated with walking for 1 hour/day and participating in yoga and sporting activities. Physical activity is a modifiable risk factor for fracture, but the effects differ between different types of activities and different fracture sites. © 2019 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.     

Height loss in older women: Risk of hip fracture and mortality independent of vertebral fractures

We examined if height loss in older women predicts risk of hip fractures, other nonspine fractures, and mortality, and whether this risk is independent of both vertebral fractures (VFx) and bone mineral density (BMD) by dual‐energy X‐ray absorptiometry. Among 3124 women age 65 and older in the Study of Osteoporotic Fractures, we assessed the association with measured height change between year 0 (1986–1988) and year 15 (2002–2004) and subsequent risk of radiologically confirmed hip fractures, other nonspine fractures, and mortality assessed via death certificates. Follow‐up occurred every 4 months for fractures and vital status (>95% contacts complete). Cox proportional hazards models assessed risk of hip fracture, nonspine fracture, and mortality over a mean of 5 years after height change was assessed (ie, after final height measurement). After adjustment for VFx, BMD, and other potential covariates, height loss >5 cm was associated with a marked increased risk of hip fracture [hazard ratio (HR) 1.50, 95% confidence interval (CI) 1.06, 2.12], nonspine fracture (HR 1.48; 95% CI 1.20, 1.83), and mortality (1.45; 95% CI 1.21, 1.73). Although primary analyses were a subset of 3124 survivors healthy enough to return for a year 15 height measurement, a sensitivity analysis in the entire cohort (n = 9677) using initial height in earlier adulthood [self‐reported height at age 25 (?40 years) to measured height age >65 years (Year 0)] demonstrated consistent results. Height loss >5 cm (2″) in older women was associated with a nearly 50% increased risk of hip fracture, nonspine fracture, and mortality—independent of incident VFx and BMD. © 2012 American Society for Bone and Mineral Research     

Relationship of Weight,Height, and Body Mass Index With Fracture Risk at Different Sites in Postmenopausal Women: The Global Longitudinal Study of Osteoporosis in Women (GLOW)

Low body mass index (BMI) is a well‐established risk factor for fracture in postmenopausal women. Height and obesity have also been associated with increased fracture risk at some sites. We investigated the relationships of weight, BMI, and height with incident clinical fracture in a practice‐based cohort of postmenopausal women participating in the Global Longitudinal study of Osteoporosis in Women (GLOW). Data were collected at baseline and at 1, 2, and 3 years. For hip, spine, wrist, pelvis, rib, upper arm/shoulder, clavicle, ankle, lower leg, and upper leg fractures, we modeled the time to incident self‐reported fracture over a 3‐year period using the Cox proportional hazards model and fitted the best linear or nonlinear models containing height, weight, and BMI. Of 52,939 women, 3628 (6.9%) reported an incident clinical fracture during the 3‐year follow‐up period. Linear BMI showed a significant inverse association with hip, clinical spine, and wrist fractures: adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) per increase of 5 kg/m² were 0.80 (0.71–0.90), 0.83 (0.76–0.92), and 0.88 (0.83–0.94), respectively (all p < 0.001). For ankle fractures, linear weight showed a significant positive association: adjusted HR per 5‐kg increase 1.05 (1.02–1.07) (p < 0.001). For upper arm/shoulder and clavicle fractures, only linear height was significantly associated: adjusted HRs per 10‐cm increase were 0.85 (0.75–0.97) (p = 0.02) and 0.73 (0.57–0.92) (p = 0.009), respectively. For pelvic and rib fractures, the best models were for nonlinear BMI or weight (p = 0.05 and 0.03, respectively), with inverse associations at low BMI/body weight and positive associations at high values. These data demonstrate that the relationships between fracture and weight, BMI, and height are site‐specific. The different associations may be mediated, at least in part, by effects on bone mineral density, bone structure and geometry, and patterns of falling. © 2014 American Society for Bone and Mineral Research.     

Physical activity slows femoral bone loss but promotes wrist fractures in postmenopausal women: A 15‐year follow‐up of the OSTPRE study

Results on fracture risk among physically active persons are contradictory. The aim of this study was to investigate the long‐term association between the self‐reported physical activity (PA), the risk of fractures, and bone loss among peri‐ and postmenopausal women. The association between PA and fracture risk was examined during 15 years of follow‐up in the population‐based Osteoporosis Risk Factor and Prevention (OSTPRE) Study among 8560 women with a mean age of 52.2 years (range 47 to 56 years) at baseline. The amount and type of PA, as well as the types and mechanisms of fractures, were registered with self‐administered questionnaires at 5‐year intervals (ie, 1989, 1994, 1999, and 2004). A total of 2641 follow‐up fractures were verified in 2073 women (24.2%). The study cohort was divided into quartiles by average hours of reported PA during the whole follow‐up. Areal bone mineral density (aBMD) at the proximal femur (n = 2050) and lumbar spine (L₂–L₄; n = 1417) was followed at 5‐year intervals from a random stratified subsample with dual X‐ray absorptiometry (DXA). Risk of fracture was estimated by using the Cox proportional hazards model with a mean follow‐up time of 15.2 years. Weekly average time spent on leisure‐time PA was 0.4, 1.7, 3.3, and 7.0 hours from the least to the most active quartiles, respectively. The risk of wrist fracture was higher in the active quartiles (II to IV) than in the most inactive quartile (I), with hazard ratios (HRs) of 1.3 [95% confidence interval (CI) 1.05–1.57, p = .014] for the second (II), 1.2 (95% CI 1.01–1.51, p = .045) for the third (III), and 1.4 (95% CI 1.14–1.69, p = .001) for the fourth (IV) quartile, respectively. Overall, most of the fractures were reported as a result of a fall (69.0%), with a 2.1 times higher rate of wrist fractures during the winter (November to April) than during summer season. There were no significant associations of PA with any other fracture types. Bone loss at the femoral neck, trochanter, and Ward's triangle was significantly associated with long‐term PA (ANCOVA p < .05), whereas no associations of bone loss and PA in lumbar spine were seen. PA is associated with a moderate rise in wrist fracture risk, which might be explained in part by a higher number of outdoor activities. Regular PA of at least 1½ hours per week does not seem to increase the risk of other fractures and might significantly decrease proximal femur bone loss among peri‐ and postmenopausal women. © 2010 American Society for Bone and Mineral Research.     

Milk intake and risk of hip fracture in men and women: A meta‐analysis of prospective cohort studies

Milk contains calcium, phosphorus, and protein and is fortified with vitamin D in the United States. All these ingredients may improve bone health. However, the potential benefit of milk on hip fracture prevention is not well established. The objective of this study was to assess the association of milk intake with risk of hip fracture based on a meta‐analysis of cohort studies in middle‐aged or older men and women. Data sources for this study were English and non‐English publications via Medline (Ovid, PubMed) and EMBASE search up to June 2010, experts in the field, and reference lists. The idea was to compare prospective cohort studies on the same scale so that we could calculate the relative risk (RR) of hip fracture per glass of milk intake daily (approximately 300 mg calcium per glass of milk). Pooled analyses were based on random effects models. The data were extracted by two independent observers. The results show that in women (6 studies, 195,102 women, 3574 hip fractures), there was no overall association between total milk intake and hip fracture risk (pooled RR per glass of milk per day = 0.99; 95% confidence interval [CI] 0.96–1.02; Q‐test p = .37). In men (3 studies, 75,149 men, 195 hip fractures), the pooled RR per daily glass of milk was 0.91 (95% CI 0.81–1.01). Our conclusion is that in our meta‐analysis of cohort studies, there was no overall association between milk intake and hip fracture risk in women but that more data are needed in men. © 2011 American Society for Bone and Mineral Research.     

In vivo discrimination of hip fracture with quantitative computed tomography: Results from the prospective European Femur Fracture Study (EFFECT)

In assessing osteoporotic fractures of the proximal femur, the main objective of this in vivo case‐control study was to evaluate the performance of quantitative computed tomography (QCT) and a dedicated 3D image analysis tool [Medical Image Analysis Framework—Femur option (MIAF‐Femur)] in differentiating hip fracture and non–hip fracture subjects. One‐hundred and seven women were recruited in the study, 47 women (mean age 81.6 years) with low‐energy hip fractures and 60 female non–hip fracture control subjects (mean age 73.4 years). Bone mineral density (BMD) and geometric variables of cortical and trabecular bone in the femoral head and neck, trochanteric, and intertrochanteric regions and proximal shaft were assessed using QCT and MIAF‐Femur. Areal BMD (aBMD) was assessed using dual‐energy X‐ray absorptiometry (DXA) in 96 (37 hip fracture and 59 non–hip fracture subjects) of the 107 patients. Logistic regressions were computed to extract the best discriminates of hip fracture, and area under the receiver characteristic operating curve (AUC) was calculated. Three logistic models that discriminated the occurrence of hip fracture with QCT variables were obtained (AUC = 0.84). All three models combined one densitometric variable—a trabecular BMD (measured in the femoral head or in the trochanteric region)—and one geometric variable—a cortical thickness value (measured in the femoral neck or proximal shaft). The best discriminant using DXA variables was obtained with total femur aBMD (AUC = 0.80, p = .003). Results highlight a synergistic contribution of trabecular and cortical components in hip fracture risk and the utility of assessing QCT BMD of the femoral head for improved understanding and possible insights into prevention of hip fractures. © 2011 American Society for Bone and Mineral Research.     

The Importance of Previous Fracture Site on Osteoporosis Diagnosis and Incident Fractures in Women

Previous fracture increases the risk of subsequent fractures regardless of the site of the initial fracture. Fracture risk assessment tools have been developed to guide clinical management; however, no discrimination is made as to the site of the prior fracture. Our objective was to determine which sites of previous nontraumatic fractures are most strongly associated with a diagnosis of osteoporosis, defined by a bone mineral density (BMD) T‐score of ≤ ?2.5 at the femoral neck, and an incident major osteoporotic fracture. Using administrative health databases, we conducted a retrospective historical cohort study of 39,991women age 45 years and older who had BMD testing with dual‐energy X‐ray absorptiometry (DXA). Logistic regression and Cox proportional multivariate models were used to test the association of previous fracture site with risk of osteoporosis and incident fractures. Clinical fractures at the following sites were strongly and independently associated with higher risk of an osteoporotic femoral neck T‐score after adjustment for age: hip (odds ratio [OR], 3.58; 95% confidence interval [CI], 3.04–4.21), pelvis (OR, 2.23; 95% CI, 1.66–3.0), spine (OR, 2.16; 95% CI, 1.77–2.62), and humerus (OR, 1.74; 95% CI, 1.49–2.02). Cox proportional hazards models, with adjustment for age and femoral neck BMD, showed the greatest increase in risk for a major osteoporotic fracture for women who had sustained previous fractures of the spine (hazard ratio [HR], 2.08; 95% CI, 1.72–2.53), humerus (HR, 1.70; 95% CI, 1.44–2.01), patella (HR, 1.54; 95% CI, 1.10–2.18), and pelvis (HR, 1.45; 95% CI, 1.04–2.02). In summary, our results confirm that nontraumatic fractures in women are associated with osteoporosis at the femoral neck and that the site of previous fracture impacts on future osteoporotic fracture risk, independent of BMD. © 2014 American Society for Bone and Mineral Research.     

Progressively increasing fracture risk with advancing age after initial incident fragility fracture: The Tromsø Study

The risk of subsequent fracture is increased after initial fractures; however, proper understanding of its magnitude is lacking. This population‐based study examines the subsequent fracture risk in women and men by age and type of initial incident fracture. All incident nonvertebral fractures between 1994 and 2009 were registered in 27,158 participants in the Tromsø Study, Norway. The analysis included 3108 subjects with an initial incident fracture after the age of 49 years. Subsequent fracture (n = 664) risk was expressed as rate ratios (RR) and absolute proportions irrespective of death. The rates of both initial and subsequent fractures increased with age, the latter with the steepest curve. Compared with initial incident fracture rate of 30.8 per 1000 in women and 12.9 per 1000 in men, the overall age‐adjusted RR of subsequent fracture was 1.3 (95% CI, 1.2–1.5) in women, and 2.0 (95% CI, 1.6–2.4) in men. Although the RRs decreased with age, the absolute proportions of those with initial fracture who suffered a subsequent fracture increased with age; from 9% to 30% in women and from 10% to 26% in men, between the age groups 50–59 to 80+ years. The type of subsequent fracture varied by age from mostly minor fractures in the youngest to hip or other major fractures in the oldest age groups, irrespective of type and severity of initial fracture. In women and men, 45% and 38% of the subsequent hip or other major fractures, respectively, were preceded by initial minor fractures. The risk of subsequent fracture is high in all age groups. At older age, severe subsequent fracture types follow both clinically severe and minor initial incident fractures. Any fragility fracture in the elderly reflects the need for specific osteoporosis management to reduce further fracture risk. © 2013 American Society for Bone and Mineral Research.     

Predicting Hip Fracture Type With Cortical Bone Mapping (CBM) in the Osteoporotic Fractures in Men (MrOS) Study

Hip fracture risk is known to be related to material properties of the proximal femur, but fracture prediction studies adding richer quantitative computed tomography (QCT) measures to dual‐energy X‐ray (DXA)‐based methods have shown limited improvement. Fracture types have distinct relationships to predictors, but few studies have subdivided fracture into types, because this necessitates regional measurements and more fracture cases. This work makes use of cortical bone mapping (CBM) to accurately assess, with no prior anatomical presumptions, the distribution of properties related to fracture type. CBM uses QCT data to measure the cortical and trabecular properties, accurate even for thin cortices below the imaging resolution. The Osteoporotic Fractures in Men (MrOS) study is a predictive case‐cohort study of men over 65 years old: we analyze 99 fracture cases (44 trochanteric and 55 femoral neck) compared to a cohort of 308, randomly selected from 5994. To our knowledge, this is the largest QCT‐based predictive hip fracture study to date, and the first to incorporate CBM analysis into fracture prediction. We show that both cortical mass surface density and endocortical trabecular BMD are significantly different in fracture cases versus cohort, in regions appropriate to fracture type. We incorporate these regions into predictive models using Cox proportional hazards regression to estimate hazard ratios, and logistic regression to estimate area under the receiver operating characteristic curve (AUC). Adding CBM to DXA‐based BMD leads to a small but significant (p < 0.005) improvement in model prediction for any fracture, with AUC increasing from 0.78 to 0.79, assessed using leave‐one‐out cross‐validation. For specific fracture types, the improvement is more significant (p < 0.0001), with AUC increasing from 0.71 to 0.77 for trochanteric fractures and 0.76 to 0.82 for femoral neck fractures. In contrast, adding DXA‐based BMD to a CBM‐based predictive model does not result in any significant improvement. © 2015 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.     

Cortical Bone Assessed With Clinical Computed Tomography at the Proximal Femur

Hip fractures are the most serious of all fragility fractures in older people of both sexes. Trips, stumbles, and falls result in fractures of the femoral neck or trochanter, and the incidence of these two common fractures is increasing worldwide as populations age. Although clinical risk factors and chance are important in causation, the ability of a femur to resist fracture also depends on the size and spatial distribution of the bone, its intrinsic material properties, and the loads applied. Over the past two decades, clinical quantitative computed tomography (QCT) studies of living volunteers have provided insight into how the femur changes with advancing age to leave older men and women at increased risk of hip fractures. In this review, we focus on patterns of cortical bone loss associated with hip fracture, age‐related changes in cortical bone, and the effects of drugs used to treat osteoporosis. There are several methodologies available to measure cortical bone in vivo using QCT. Most techniques quantify bone density (g/cm³), mass (g), and thickness (mm) in selected, predefined or “traditional” regions of interest such as the “femoral neck” or “total hip” region. A recent alternative approach termed “computational anatomy,” uses parametric methods to identify systematic differences, before displaying statistically significant regions as color‐scaled maps of density, mass, or thickness on or within a representative femur model. This review will highlight discoveries made using both traditional and computational anatomy methods, focusing on cortical bone of the proximal femur. © 2014 American Society for Bone and Mineral Research.     

Post-fracture Risk Assessment: Target the Centrally Sited Fractures First! A Substudy of NoFRACT

The location of osteoporotic fragility fractures adds crucial information to post-fracture risk estimation. Triaging patients according to fracture site for secondary fracture prevention can therefore be of interest to prioritize patients considering the high imminent fracture risk. The objectives of this cross-sectional study were therefore to explore potential differences between central (vertebral, hip, proximal humerus, pelvis) and peripheral (forearm, ankle, other) fractures. This substudy of the Norwegian Capture the Fracture Initiative (NoFRACT) included 495 women and 119 men ≥50 years with fragility fractures. They had bone mineral density (BMD) of the femoral neck, total hip, and lumbar spine assessed using dual-energy X-ray absorptiometry (DXA), trabecular bone score (TBS) calculated, concomitantly vertebral fracture assessment (VFA) with semiquantitative grading of vertebral fractures (SQ1–SQ3), and a questionnaire concerning risk factors for fractures was answered. Patients with central fractures exhibited lower BMD of the femoral neck (765 versus 827 mg/cm²), total hip (800 versus 876 mg/cm²), and lumbar spine (1024 versus 1062 mg/cm²); lower mean TBS (1.24 versus 1.28); and a higher proportion of SQ1-SQ3 fractures (52.0% versus 27.7%), SQ2–SQ3 fractures (36.8% versus 13.4%), and SQ3 fractures (21.5% versus 2.2%) than patients with peripheral fractures (all p < 0.05). All analyses were adjusted for sex, age, and body mass index (BMI); and the analyses of TBS and SQ1–SQ3 fracture prevalence was additionally adjusted for BMD). In conclusion, patients with central fragility fractures revealed lower femoral neck BMD, lower TBS, and higher prevalence of vertebral fractures on VFA than the patients with peripheral fractures. This suggests that patients with central fragility fractures exhibit more severe deterioration of bone structure, translating into a higher risk of subsequent fragility fractures and therefore they should get the highest priority in secondary fracture prevention, although attention to peripheral fractures should still not be diminished. © 2019 American Society for Bone and Mineral Research. © 2019 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.     

Pain at Multiple Sites Is Associated With Prevalent and Incident Fractures in Older Adults

Musculoskeletal pain is common and typically occurs at multiple sites. Pain has been shown to be associated with falls risk; however, whether an increased risk for falls associated with multisite pain (MSP) translates into an increased risk of fractures has not been investigated. This study aimed to examine the association of number of painful sites with prevalent and incident fractures. Data from a longitudinal population-based study of older adults (mean age 63 years) were utilized. Follow-up was performed at 2.6, 5.1, and 10.7 years later, respectively. Presence/absence of pain at the neck, back, hands, shoulders, hips, knees, and feet was assessed by questionnaire at baseline. Participants were classified into three groups according to the total number of painful sites: zero to two, three to four, and five to seven. Fractures were self-reported at each time point. BMD was measured by DXA. Falls risk was calculated based on the Short-Form Physiological Profile Assessment. Log-binomial regression was used for the analyses. There were 450 fractures at baseline and 154 new fractures reported during a mean follow-up period of 10.7 years (range 9.2 to 12.5 years). In multivariable analyses, number of painful sites was associated with prevalent fractures at any and nonvertebral site. Furthermore, participants with five to seven painful sites had an increased risk of incident fractures at any site (RR 1.69; 95% CI, 1.13 to 2.53); major site, including the femur, radius, ulnar, vertebral, rib, and humerus (RR 2.17; 95% CI 1.12 to 4.22); and vertebral site (RR 6.44, 95% CI, 1.64 to 25.33) compared with those with pain at zero to two sites. These associations remained statistically significant after further adjustment for falls risk and BMD. Pain at multiple sites was associated with incident fracture risk in a dose-response manner, suggesting that widespread pain is an independent contributor to fracture risk. The potential for pain management in fracture prevention warrants further exploration. © 2019 American Society for Bone and Mineral Research.     

Inflammatory bowel disease and the risk of fracture after controlling for FRAX

Subjects with inflammatory bowel disease (IBD) are at increased risk for hip and other major osteoporotic fractures. However, previous analyses have not fully accounted for differences in bone mineral density (BMD) and other clinical factors that affect the risk of fracture. The World Health Organization Fracture Risk Assessment tool (FRAX) can be used to predict the 10‐year fracture risk from BMD and clinical risk factors. A population‐based database containing clinical information on all IBD subjects in the province of Manitoba, Canada, was linked with the Manitoba Bone Mineral Density Database, which contains results of all dual X‐ray absorptiometry (DXA) scans in the province. FRAX probabilities were calculated for all subjects aged 50 years or more undergoing baseline DXA testing. Subjects were followed for occurrence of major osteoporotic fractures (MOF; hip, clinical spine, wrist, humerus). Cox proportional hazards models were used to determine whether IBD was independently predictive of MOF or hip fracture. After controlling for FRAX fracture probability computed with BMD, IBD was not associated with a significantly increased risk for MOF (hazard ratio [HR] = 1.12, 95% confidence interval [CI], 0.83–1.55) but was associated with an increased risk for hip fracture (HR = 2.14; 95% CI, 1.26–3.65). The addition of femoral neck T‐score to FRAX probability without knowledge of BMD had a negligible effect on the estimated HRs for IBD, suggesting that IBD mediates any effect on fracture risk independently of femoral neck BMD. After controlling for FRAX probability, subjects with IBD are not at an increased risk for overall MOF, but may be at increased risk of hip fracture. © 2013 American Society for Bone and Mineral Research.     

Fruit and Vegetable Intake and Hip Fracture Incidence in Older Men and Women: The CHANCES Project

The role of fruit and vegetable intake in relation to fracture prevention during adulthood and beyond is not adequately understood. We investigated the potential association between fruit and vegetable intake and hip fracture incidence in a large sample of older adults from Europe and the United States. A total of 142,018 individuals (116,509 women) aged ≥60 years, from five cohorts, were followed up prospectively for 1,911,482 person‐years, accumulating 5552 hip fractures. Fruit and vegetable intake was assessed by validated, cohort‐specific, food‐frequency questionnaires (FFQ). Ηip fractures were ascertained through national patient registers or telephone interviews/questionnaires. Adjusted hazard ratios (HRs) derived by Cox proportional hazards regression were estimated for each cohort and subsequently pooled using random effects meta‐analysis. Intake of ≤1 serving/day of fruit and vegetables combined was associated with 39% higher hip fracture risk (pooled adjusted HR, 1.39; 95% confidence interval [CI], 1.20 to 1.58) in comparison with moderate intake (>3 and ≤5 servings/day) (p_{for heterogeneity} = 0.505), whereas higher intakes (>5 servings/day) were not associated with lower risk in comparison with the same reference. Associations were more evident among women. We concluded that a daily intake of 1 or <1 servings of fruits and vegetables was associated with increased hip fracture risk in relation to moderate daily intakes. Older adults with such low fruit and vegetable consumption may benefit from raising their intakes to moderate amounts in order to reduce their hip fracture risk. © 2016 American Society for Bone and Mineral Research.     

Risk Factors for Hip Fracture in Older Men: The Osteoporotic Fractures in Men Study (MrOS)

Almost 30% of hip fractures occur in men; the mortality, morbidity, and loss of independence after hip fractures are greater in men than in women. To comprehensively evaluate risk factors for hip fracture in older men, we performed a prospective study of 5994 men, primarily white, age 65+ years recruited at six US clinical centers. During a mean of 8.6 years of 97% complete follow‐up, 178 men experienced incident hip fractures. Information on risk factors including femoral neck bone mineral density (FNBMD) was obtained at the baseline visit. Cox proportional hazards models were used to calculate the hazard ratio (HR) with 95% confidence intervals; Fine and Gray models adjusted for competing mortality risk. Older age (≥75 years), low FNBMD, currently smoking, greater height and height loss since age 25 years, history of fracture, use of tricyclic antidepressants, history of myocardial infarction or angina, hyperthyroidism or Parkinson's disease, lower protein intake, and lower executive function were all associated with an increased hip fracture risk. Further adjustment for competing mortality attenuated HR for smoking, hyperthyroidism, and Parkinson's disease. The incidence rate of hip fracture per 1000 person‐years (PY) was greatest in men with FNBMD T‐scores <–2.5 (white women reference database) who also had 4+ risk factors, 33.4. Men age ≥80 years with 3+ major comorbidities experienced hip fracture at rates of 14.52 versus 0.88 per 1000 PY in men age <70 years with zero comorbidities. Older men with low FNBMD, multiple risk factors, and multimorbidity have a high risk of hip fracture. Many of these assessments can easily be incorporated into routine clinical practice and may lead to improved risk stratification. © 2016 American Society for Bone and Mineral Research.     

Efficacy of continued alendronate for fractures in women with and without prevalent vertebral fracture: The FLEX Trial

In the Fracture Intervention Trial (FIT) Long Term Extension (FLEX) Trial, 10 years of alendronate (ALN) did not significantly reduce the risk of nonvertebral fractures (NVFs) compared with 5 years of ALN. Continuing ALN reduced the risk of clinical but not morphometric vertebral fractures regardless of baseline vertebral fracture status. In previous studies, ALN efficacy for NVF prevention in women without prevalent vertebral fracture was limited to those with femoral neck (FN) T‐scores of ?2.5 or less. To determine whether the effect of long‐term ALN on fracture differs by vertebral fracture status and femoral neck (FN) T‐score, we performed a post hoc analysis using FLEX data, a randomized, double‐blind, placebo‐controlled trial among 1099 postmenopausal women originally randomized to ALN in the FIT with mean ALN use of 5 years. In the FLEX Trial, women were randomized to placebo (40%) or ALN 5 mg/day (30%) or ALN 10 mg/day (30%) for an additional 5 years. Among women without vertebral fracture at FLEX baseline (n = 720), continuation of ALN reduced NVF in women with FLEX baseline FN T‐scores of ?2.5 or less [relative risk (RR) = 0.50, 95% confidence interval (CI) 0.26–0.96] but not with T‐scores of greater than ?2.5 and ?2 or less (RR 0.79, 95% CI 0.37–1.66) or with T‐scores of greater than ?2 (RR 1.41, 95% CI 0.75–2.66; p for interaction = .019). Continuing ALN for 10 years instead of stopping after 5 years reduces NVF risk in women without prevalent vertebral fracture whose FN T‐scores, achieved after 5 years of ALN, are ?2.5 or less but does not reduce risk of NVF in women whose T‐scores are greater than ?2. © 2010 American Society for Bone and Mineral Research     

Diabetes mellitus and the incidence and mortality of colorectal cancer: a meta‐analysis of 24 cohort studies

Aim The incidence and mortality of colorectal cancer (CRC) were quantified in persons with and without diabetes mellitus (DM). Method Medline and Embase were searched for articles published before July 2010. Cohort studies that evaluated incidence and mortality of DM and CRC were included. The initial search identified 1887 titles, of which 24 articles met the inclusion criteria. We defined the relative risk (RR) as the metric of choice; 95% confidence intervals (CIs) were calculated with a random‐effects model. Results There was an increase in the RR of developing CRC in persons with DM compared with those without DM (RR 1.28; 95% CI 1.19–1.39), without heterogeneity between studies (P_{heterogeneity} = 0.13). The association between duration of DM and CRC incidence was stronger in the 11–15‐year group (RR 1.51; 95% CI 1.12–2.03) than in the <10‐year group (RR 1.05; 95% CI 0.90–1.22) and the >15‐year group (RR 1.25; 95% CI 0.80–1.94), and there was significant heterogeneity among subgroups (P_{heterogeneity} = 0.01). In studies reporting standardized incidence ratios (SIRs), there was an increased incidence of CRC with DM (RR 1.27; 95% CI 1.14–1.42; P_{heterogeneity} = 0.09), and the association was stronger among men (RR 1.47; 95% CI 1.15–1.86) than women (RR 1.08; 95% CI 1.00–1.17); there was significant heterogeneity among gender (P_{heterogeneity} = 0.01). Conclusion This meta‐analysis suggests that individuals with DM have a significant increase in risk of developing CRC.     

Older men with low serum IGF‐1 have an increased risk of incident fractures: The MrOS Sweden study

Osteoporosis‐related fractures constitute a major health concern not only in women but also in men. Insulin‐like growth factor 1 (IGF‐1) is a key determinant of bone mass, but the association between serum IGF‐1 and incident fractures in men remains unclear. To determine the predictive value of serum IGF‐1 for fracture risk in men, older men (n = 2902, mean age of 75 years) participating in the prospective, population‐based Osteoporotic Fractures in Men (MrOS) Sweden study were followed for a mean of 3.3 years. Serum IGF‐1 was measured at baseline by radioimmunoassay. Fractures occurring after the baseline visit were validated. In age‐adjusted hazards regression analyses, serum IGF‐1 associated inversely with risk of all fractures [hazard ratio (HR) per SD decrease = 1.23, 95% confidence interval (CI) 1.07–1.41], hip fractures (HR per SD decrease = 1.45, 95% CI 1.07–1.97), and clinical vertebral fractures (HR per SD decrease = 1.40, 95% CI 1.10–1‐78). The predictive role of serum IGF‐1 for fracture risk was unaffected by adjustment for height, weight, prevalent fractures, falls, and major prevalent diseases. Further adjustment for bone mineral density (BMD) resulted in an attenuated but still significant association between serum IGF‐1 and fracture risk. Serum IGF‐1 below but not above the median was inversely related to fracture incidence. The population‐attributable risk proportion was 7.5% for all fractures and 22.9% for hip fractures. Taken together, older men with low serum IGF‐1 have an increased fracture risk, especially for the two most important fracture types, hip and vertebral fractures. The association between serum IGF‐1 and fracture risk is partly mediated via BMD. © 2011 American Society for Bone and Mineral Research.     

Active shape modeling of the hip in the prediction of incident hip fracture

The objective of this study was to evaluate right proximal femur shape as a risk factor for incident hip fracture using active shape modeling (ASM). A nested case‐control study of white women 65 years of age and older enrolled in the Study of Osteoporotic Fractures (SOF) was performed. Subjects (n = 168) were randomly selected from study participants who experienced hip fracture during the follow‐up period (mean 8.3 years). Controls (n = 231) had no fracture during follow‐up. Subjects with baseline radiographic hip osteoarthritis were excluded. ASM of digitized right hip radiographs generated 10 independent modes of variation in proximal femur shape that together accounted for 95% of the variance in proximal femur shape. The association of ASM modes with incident hip fracture was analyzed by logistic regression. Together, the 10 ASM modes demonstrated good discrimination of incident hip fracture. In models controlling for age and body mass index (BMI), the area under receiver operating characteristic (AUROC) curve for hip shape was 0.813, 95% confidence interval (CI) 0.771–0.854 compared with models containing femoral neck bone mineral density (AUROC = 0.675, 95% CI 0.620–0.730), intertrochanteric bone mineral density (AUROC = 0.645, 95% CI 0.589–0.701), femoral neck length (AUROC = 0.631, 95% CI 0.573–0.690), or femoral neck width (AUROC = 0.633, 95% CI 0.574–0.691). The accuracy of fracture discrimination was improved by combining ASM modes with femoral neck bone mineral density (AUROC = 0.835, 95% CI 0.795–0.875) or with intertrochanteric bone mineral density (AUROC = 0.834, 95% CI 0.794–0.875). Hips with positive standard deviations of ASM mode 4 had the highest risk of incident hip fracture (odds ratio = 2.48, 95% CI 1.68–3.31, p < .001). We conclude that variations in the relative size of the femoral head and neck are important determinants of incident hip fracture. The addition of hip shape to fracture‐prediction tools may improve the risk assessment for osteoporotic hip fractures. © 2011 American Society for Bone and Mineral Research.