An Assessment Tool for Predicting Fracture Risk in Postmenopausal Women

Due to the magnitude of the morbidity and mortality associated with untreated osteoporosis, it is essential that high-risk individuals be identified so that they can receive appropriate evaluation and treatment. The objective of this investigation was to develop a simple clinical assessment tool based on a small number of risk factors that could be used by women or their clinicians to assess their risk of fractures. Using data from the Study of Osteoporotic Fractures (SOF), a total of 7782 women age 65 years and older with bone mineral density (BMD) measurements and baseline risk factors were included in the analysis. A model with and without BMD T-scores was developed by identifying variables that could be easily assessed in either clinical practice or by self-administration. The assessment tool, called the FRACTURE Index, is comprised of a set of seven variables that include age, BMD T-score, fracture after age 50 years, maternal hip fracture after age 50, weight less than or equal to 125 pounds (57 kg), smoking status, and use of arms to stand up from a chair. The FRACTURE Index was shown to be predictive of hip fracture, as well as vertebral and nonvertebral fractures. In addition, this index was validated using the EPIDOS fracture study. The FRACTURE Index can be used either with or without BMD testing by older postmenopausal women or their clinicians to assess the 5-year risk of hip and other osteoporotic fractures, and could be useful in helping to determine the need for further evaluation and treatment of these women. Received: 7 November 2000 / Accepted: 23 May 2001     

Simplified 10-Year Absolute Fracture Risk Assessment: A Comparison of Men and Women

A simplified (semiquantitative) approach developed by the Canadian Association of Radiologists and Osteoporosis Canada (denoted as CAROC) for absolute fracture risk assessment incorporates age, sex, prior fragility fracture, and systemic corticosteroid use, together with bone mineral density (BMD) to define absolute fracture risk. The CAROC system has been shown to predict fracture rates in women referred for clinical BMD testing, but it is uncertain how this system performs in routine clinical practice in men who are much less likely to undergo BMD testing with potential for referral biases. Thirty-six thousand seven hundred and thirty women and 2873 men aged 50 yr or older at the time of baseline BMD testing were identified in a database containing all clinical dual-energy X-ray absorptiometry test results for the Province of Manitoba, Canada. Population-based health service records from 1987 to 2008 were assessed for fracture codes and medication use. Fracture risk under the CAROC model was categorized as low (<10%), moderate (10–20%), or high (>20%). Ten-year fracture risk estimated by the Kaplan-Meier method showed the same gradient in observed fracture risk for men and women. Despite evidence of greater referral bias in men resulting in a higher rate of clinical risk factors, the performance of the prediction algorithm was not affected.     

Increase in Vertebral Fracture Risk in Postmenopausal Women Using Omeprazole

Proton pump inhibitors are taken by millions of patients for prevention and treatment of gastroesophageal diseases. Case-control studies have suggested that use of omeprazole is associated with an increased risk of hip fractures. The aim of this prospective study was to assess the risk of vertebral fractures in postmenopausal women using omeprazole. We studied 1,211 postmenopausal women enrolled in the Osteoporosis and Ultrasound Study from the general population. Information on omeprazole and other risk factors for fractures including prevalent fractures and bone mineral density was obtained at baseline. Vertebral fractures were assessed on X-rays obtained at baseline and at the end of the 6-year follow-up and analyzed centrally. At baseline, 5% of this population was using omeprazole. Age-adjusted rates for vertebral fractures were 1.89 and 0.60 for 100 person-years for omeprazole users and nonusers, respectively (P = 0.009). In the multivariate analysis, omeprazole use was a significant and independent predictor of vertebral fractures (RR = 3.50, 95% CI 1.14–8.44). The other predictors were age higher than 65 years (RR = 2.34, 95% CI 1.02–5.34), prevalent vertebral fractures (RR = 3.62, 95% CI 1.63–8.08), and lumbar spine T score ≤ −2.5 (RR = 2.38, 95% CI 1.03–5.49). Omeprazole use is associated with an increased risk of vertebral fractures in postmenopausal women. Further studies are required to determine the mechanism of the association between the underlying gastric disease, omeprazole use, and risk of osteoporotic fractures.     

Endogenous Estradiol and The Risk of Incident Fracture in Postmenopausal Women: The OPUS Study

Some, but not all, studies have found that low endogenous estradiol levels in postmenopausal women are predictive of fractures. The aim of this study was to examine the roles of endogenous estradiol (E(2)), sex hormone binding globulin (SHBG), and dehydroepiandrosterone sulfate (DHEAS) in the prediction of incident vertebral and nonvertebral fractures. The study subjects were 797 postmenopausal women from the population-based OPUS (Osteoporosis and Ultrasound Study) study. Spine radiographs and dual-energy X-ray absorptiometry scans were obtained for all subjects at baseline and 6-year follow-up. Nonfasting blood samples were taken at baseline for E(2), SHBG, DHEAS, and bone turnover markers. Incident nonvertebral fractures were self-reported and verified; vertebral fractures were diagnosed at a single center from spinal radiographs. Medical and lifestyle data were obtained by questionnaire at each visit. Thirty-nine subjects had an incident vertebral fracture and 119 a nonvertebral fracture. Estradiol in the lowest quartile predicted vertebral fracture independent of confounders including age, body mass index, bone mineral density, bone turnover, fracture history, and use of antiresorptive therapy, with an OR of 2.97 (95 % confidence interval [CI] 1.52-5.82) by logistic regression. A calculated free estradiol index was not a stronger predictor than total E(2). Higher SHBG predicted vertebral fracture independently of age and body mass index, but not independently of E(2), bone mineral density, or prevalent fracture. Low DHEAS did not predict vertebral fracture. Nonvertebral fractures were not predicted by any of E(2), SHBG, or DHEAS, either in univariate or multivariate analyses. These findings suggest that there may be mechanistic differences in the protective effect of E(2) at vertebral compared with nonvertebral sites.     

Relationship of Height to Site‐Specific Fracture Risk in Postmenopausal Women

Height has been associated with increased risk of fracture of the neck of femur. However, information on the association of height with fractures at other sites is limited and conflicting. A total of 796,081 postmenopausal women, who reported on health and lifestyle factors including a history of previous fractures and osteoporosis, were followed for 8 years for incident fracture at various sites by record linkage to National Health Service hospital admission data. Adjusted relative risks of fracture at different sites per 10‐cm increase in height were estimated using Cox regression. Numbers with site‐specific fractures were: humerus (3036 cases), radius and/or ulna (1775), wrist (9684), neck of femur (5734), femur (not neck) (713), patella (649), tibia and/or fibula (1811), ankle (5523), and clavicle/spine/rib (2174). The risk of fracture of the neck of femur increased with increasing height (relative risk [RR] = 1.48 per 10‐cm increase, 99% confidence interval [CI] 1.39–1.57) and the proportional increase in risk was significantly greater than for all other fracture sites (p_{heterogeneity} < 0.001). For the other sites, fracture risk also increased with height (RR = 1.15 per 10 cm, CI 1.12–1.18), but there was only very weak evidence of a possible difference in risk between the sites (p_{heterogeneity} = 0.03). In conclusion, taller women are at increased risk of fracture, especially of the neck of femur. © 2015 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research (ASBMR).     

Determinants of Bone Mineral Density and Spinal Fracture Risk in Postmenopausal Japanese Women

The present study analyzed the factors that determine bone mineral density (BMD) and predict spinal fracture risk in postmenopausal Japanese women. Two hundred and five postmenopausal Japanese women aged 48–84 years (mean age 64 years) were enrolled in the cross-sectional study. BMD of the lumbar spine, femoral neck and total body as well as body composition were measured by dual-energy X-ray absorptiometry (DXA). Mid-radial BMD was measured by single-photon absorptiometry. We also determined serum levels of insulin-like growth factor (IGF)-I, IGF binding protein-2, -3 and osteocalcin as well as urinary levels of pyridinoline (Pyr), deoxy-Pyr (D-Pyr) and growth hormone. Multiple regression analysis revealed that lean body mass (LBM) was positively correlated with BMD at all sites. In contrast, femoral neck BMD was highly related to fat mass as well as LBM, although fat mass was not an independent correlate of total body and mid-radial BMD. LBM and urinary D-Pyr were crucial determinants at all sites except the mid-radius in stepwise regression analysis. Fat mass and serum IGF-I were determinants of femoral neck and mid-radial BMD, respectively. In terms of reproductive history, parity affected lumbar BMD. Factors affecting BMD differed according to the site. On the other hand, lumbar BMD as well as serum levels of IGF-I and albumin were selected as predictors of spinal fracture risk in multiple logistic regression analysis. Lumbar BMD, serum IGF-I and LBM were selected in women with lumbar BMD above 0.727 g/cm². In conclusion, the present study indicates that LBM is a more important determinant of BMD than fat mass at any site except the femoral neck. Age, serum IGF-I and urinary D-Pyr were also determinants of BMD, dependent on the regions measured. Lumbar BMD and LBM as well as serum levels of IGF-I and albumin were useful markers which predicted the risk of osteoporotic spinal fractures in postmenopausal Japanese women. Received: 6 June 2000 / Accepted: 11 January 2001     

Increased Fracture Risk in Normocalcemic Postmenopausal Women with High Parathyroid Hormone Levels: A 16-Year Follow-Up Study

High PTH levels increase bone turnover and decrease bone mineral density (BMD). Low plasma 25-hydroxyvitamin D (25OHD) levels cause secondary hyperparathyroidism, but the relative contribution of low 25OHD and high PTH levels on risk of fracture is largely unknown. Within the cohort of women (n = 2,016) included in the Danish Osteoporosis Prevention Study (DOPS), we studied risk of fracture according to parathyroid status. Analyses were performed on effects of high PTH levels (i.e., in the upper tertile, ≥4.5 pmol/L) on risk of incident fractures at different 25OHD levels during 16 years of follow-up. Incident fractures were assessed using a nationwide hospital discharge register. In addition, effects of high PTH levels on BMD and vertebral fractures were assessed by DXA scans and spinal X-ray examination after 10 years of follow-up. High PTH levels were associated with a decreased body mass index, adjusted BMD, and an increased risk of any fracture (HR = 1.41, 95% CI 1.11–1.79) as well as an increased risk of osteoporotic fractures (HR = 1.59, 95% CI 1.20–2.10). Plasma 25OHD levels per se did not affect fracture risk, but high PTH levels were associated with an increased fracture risk only at 25OHD levels <50 nmol/L and 50–80 nmol/L. High PTH levels did not increase risk of fracture at 25OHD levels >80 nmol/L. In conclusion, PTH levels in the upper part or above the upper level of the reference interval increase risk of fracture in the presence of low vitamin D levels.     

Increase in Fracture Risk Following Unintentional Weight Loss in Postmenopausal Women: The Global Longitudinal Study of Osteoporosis in Women

Increased fracture risk has been associated with weight loss in postmenopausal women, but the time course over which this occurs has not been established. The aim of this study was to examine the effects of unintentional weight loss of ≥10 lb (4.5 kg) in postmenopausal women on fracture risk at multiple sites up to 5 years after weight loss. Using data from the Global Longitudinal Study of Osteoporosis in Women (GLOW), we analyzed the relationships between self‐reported unintentional weight loss of ≥10 lb at baseline, year 2, or year 3 and incident clinical fracture in the years after weight loss. Complete data were available in 40,179 women (mean age ± SD 68 ± 8.3 years). Five‐year cumulative fracture rate was estimated using the Kaplan‐Meier method, and adjusted hazard ratios for weight loss as a time‐varying covariate were calculated from Cox multiple regression models. Unintentional weight loss at baseline was associated with a significantly increased risk of fracture of the clavicle, wrist, spine, rib, hip, and pelvis for up to 5 years after weight loss. Adjusted hazard ratios showed a significant association between unintentional weight loss and fracture of the hip, spine, and clavicle within 1 year of weight loss, and these associations were still present at 5 years. These findings demonstrate increased fracture risk at several sites after unintentional weight loss in postmenopausal women. This increase is found as early as 1 year after weight loss, emphasizing the need for prompt fracture risk assessment and appropriate management to reduce fracture risk in this population. © 2016 American Society for Bone and Mineral Research.     

Relationship Between Obesity and Risk of Major Osteoporotic Fracture in Postmenopausal Women: Taking Frailty Into Consideration

The role of obesity in fracture risk remains uncertain and inconclusive in postmenopausal women. Our study aimed to assess the relationship between obesity and risk of major osteoporotic fracture (MOF; ie, a clinical fracture of upper arm or shoulder, hip, spine, or wrist) in postmenopausal women, after taking frailty into consideration. We used the data from the Global Longitudinal Study of Osteoporosis in Women (GLOW) 5-year Hamilton cohort for this study. Frailty was measured by a frailty index (FI) of deficit accumulation at baseline. We incorporated an interaction term (obesity × FI) in the Cox proportional hazards regression model. We included 3985 women (mean age 69.4 years) for analyses, among which 29% were obese (n = 1118). There were 200 (5.02%) MOF events documented during follow-up: 48 (4.29%) in obese women and 152 (5.65%) in the nonobese group. Significant relationships between obesity, frailty, and MOF risk were found: hazard ratio (HR) = 0.72 (95% confidence interval [CI] 0.67–0.78) for those with an FI of zero regarding MOF risk among obese women, and HR = 1.34 (95% CI 1.11–1.62) per SD increase in the FI among nonobese women. The interaction term was also significant: HR = 1.16 (95% CI 1.02–1.34) per SD increase in the FI among obese women. Increased HRs were found with higher FIs regarding the relationship between obesity and MOF risk, indicating increasing frailty attenuated the protective effect of obesity. For example, although the HR for obesity and MOF risk among those who were not frail (FI = 0) was 0.72 (95% CI 0.67–0.78), among those who were very frail (FI = 0.70), the HR was 0.91 (95% CI 0.85–0.98). To conclude, after taking frailty into consideration, obesity was significantly associated with decreased risk of MOF in postmenopausal women among those who were not frail; however, increasing frailty attenuated this protective effect of obesity. Evaluating frailty status may aid in understanding of the complex relationship between obesity and fracture risk. © 2020 American Society for Bone and Mineral Research (ASBMR).     

Evaluation of Different Screening Tools for Predicting Femoral Neck Osteoporosis in Rural South Indian Postmenopausal Women

The measurement of bone mineral density by dual-energy X-ray absorptiometry scan is the “gold standard” for the diagnosis of osteoporosis, which has limited availability in many parts of India. This study was done to assess the diagnostic performance of 6 internationally validated tools (Simple Calculated Osteoporosis Risk Estimation [SCORE], age, bulk, one or never estrogen [ABONE], Osteoporosis Risk Assessment Instrument [ORAI] and Osteoporosis Self-Assessment Tool for Asians [OSTA], Fracture Risk Assessment Tool [FRAX®], and calcaneal quantitative ultrasound [QUS]) for the diagnosis of osteoporosis at the femoral neck (FN). This was a cross-sectional study conducted in 2108 ambulatory South Indian rural postmenopausal women who were assessed with SCORE, ABONE, ORAI, OSTA, and FRAX® tools. QUS was performed in 850 subjects. Bone mineral density was estimated by dual-energy X-ray absorptiometry scan at the FN, and sensitivity and specificity were calculated for all tools for predicting FN osteoporosis. The receiver operating characteristic curve was constructed for each tool and the area under the curve (AUC) was calculated. FN osteoporosis was seen in 27%. The sensitivities of SCORE, ABONE, OSTA, ORAI, FRAX®, and QUS were 91.3%, 91.0%, 88.5%, 81.0%, 72.7%, and 81.9%, and the specificities were 36.0%, 33.5%, 41.7%, 52.0%, 60.5%, and 50.3%, respectively, for the FN osteoporosis. When the receiver operating characteristics were constructed, the AUC was good only for SCORE (0.806), and the performance of the rest was under fair category (0.713–0.766). In our large cohort of rural postmenopausal women, the SCORE screening tool was found to be useful with good sensitivity and good AUC for predicting FN osteoporosis. Thus, this tool may be used in resource-limited countries to screen the population at risk and to enable treating physicians to make appropriate management decisions.     

Three-Year Prospective Study on Fracture Risk in Postmenopausal Women by Quantitative Ultrasound at the Phalanges

The purpose of this study was the calculation of fracture risk in a prospective study on postmenopausal women by quantitative ultrasound (QUS) at the phalanges. A total of 2341 postmenopausal women were recruited in 5 centers in Italy during 2006 and 2007 for QUS measurement during a screening program for osteoporosis. Two ultrasound parameters were collected: amplitude-dependent speed of sound (AD-SoS) and ultrasound bone profile index (UBPI). Women were then recontacted in 2010 and were asked about fracture occurrence during the period since previous QUS measurement. Data about new fracture occurred in this period, site and cause of fracture were requested. Two thousand two hundred eleven women were successfully recontacted. Mean age of the recruited women was 60.9 ± 10.0 yr, mean age at menopause was 49.3 ± 4.4 yr, mean body mass index (BMI) was 26.5 ± 4.6 kg/m². A total number of 108 new major osteoporotic fractures occurred during the 3-yr period, of which 23 are hip fractures, 51 are vertebral fractures. Relative risk (RR) per standard deviation (SD) decrease for major fractures was 1.77 (confidence interval [CI]: 1.59–1.97) for AD-SoS and 2.06 (CI: 1.78–2.37) for UBPI. When corrected for age, BMI, age at menopause, the RRs are still significant and equal to 1.44 (CI: 1.26–1.65) for AD-SoS and 1.67 (CI: 1.39–2.00) for UBPI. RR for vertebral fractures was 1.63 (CI: 1.41–1.88) for AD-SoS and 1.73 (CI: 1.44–2.08) for UBPI. RR for hip fractures was 1.92 (CI: 1.55–2.37) for AD-SoS and 2.68 (CI: 1.86–3.86) for UBPI. Ultrasound parameters AD-SoS and UBPI are able to significantly predict future major fractures in a prospective cohort of more than 2000 postmenopausal women.     

Multisite Quantitative Ultrasound: Colles’ Fracture Discrimination in Postmenopausal Women

Distal forearm fractures are the most common perimenopausal fracture and are generally associated with osteoporosis. The aim of this study was to evaluate the capability of speed of sound (SOS) measurements in cortical bone at the phalanx, radius, tibia and metatarsal to discriminate Colles’ fracture cases from controls in postmenopausal women and to compare this with bone mineral density (BMD) measurements obtained by dual-energy X-ray absorptiometry (DXA). Sixty-three postmenpausal Colles’ fracture cases and 191 postmenopausal controls had SOS measurements of the radius, tibia, phalanx and metatarsal using a semi-reflection ultrasound technique and BMD measurements of the lumbar spine and proximal femur using DXA. The age-adjusted odds ratios (ORs) for fracture for the SOS measurement sites were 1.50 [95% CI 1.07–2.10] for the radius, 1.23 [0.86-1.76] for the tibia, 1.85 [1.06–3.23] for the phalanx and 1.74 [1.12–2.71] for the metatarsal site. For the BMD measurements the ORs were 1.95 [1.34–2.85] for the lumbar spine, 2.21 [1.43–3.40] for the femoral neck and 2.62 [1.69–4.08] for the total hip. The benefits of combining sites either by taking their average Z-score or by using the manufacturer’s ORI algorithm were evaluated. The two methods yielded similar results and the ORs for the combination of the radius and phalanx were 2.00 [1.21–3.33], for the radius and metatarsal 1.67 [1.05–2.67], for the phalanx and metatarsal 1.86 [1.11–3.08] and for the radius, phalanx and metatarsal 1.81 [1.07–3.06]. Combinations of DXA sites gave 2.22 [1.44–3.41] for the lumbar spine and femoral neck and 2.41 [1.57–3.70] for the lumbar spine and total hip. In conclusion, semi-reflection ultrasound measurements at the radius, phalanx or metatarsal demonstrated an ability to discriminate fracture cases from controls in postmenopausal Colles’ fracture patients, although the odds ratios were lower than with spine and femur BMD. Received: 6 July 2001 / Accepted: 11 December 2001     

Simplified System for Absolute Fracture Risk Assessment: Clinical Validation in Canadian Women

Absolute 10‐yr fracture risk based on multiple factors is the preferred method for risk assessment. A simplified risk assessment system from sex, age, DXA, and two clinical risk factors (CRFs)—prior fracture and systemic corticosteroid (CS) use‐has been used in Canada since 2005. This study was undertaken to evaluate this system in the Canadian female population. A total of 16,205 women ≥50 yr of age at the time of baseline BMD (1998–2002) were identified in a database containing all clinical DXA test results for the Province of Manitoba, Canada. Basal 10‐yr fracture risk from age and minimum T‐score (lumbar spine, femur neck, trochanter, total hip) was categorized as low (<10%), moderate (10–20%), or high (>20%). Health service records since 1987 were assessed for prior fracture codes (N = 5224), recent major CS use (N = 616), and fracture codes after BMD testing (mean, 3.1 yr of follow‐up) for the hip, vertebrae, forearm, or humerus (designated osteoporotic, N = 757). Fracture risk predicted from age and minimum T‐score alone showed a significant gradient in observed fracture rates (low 5.1 [95% CI, 4.1–6.4], moderate 11.5 [95% CI, 10.1–13.0], high 25.4 [95% CI, 23.2–27.9] per 1000 person‐years; p‐for‐trend <0.0001). There was an incremental increase in incident fracture rates from a prior fracture (13.9 [95% CI, 11.3–16.4] per 1000 person‐years) or major CS use (11.2 [95% CI, 4.1–18.2] per 1000 person‐years). This simplified fracture risk assessment system provides an assessment of fracture risk that is consistent with observed fracture rates.     

Comparison of Two Methods for Measuring Ultrasound Properties of the Heel in Postmenopausal Women

Combined indices of ultrasound measurements have been proposed, such as "stiffness index" (SI) for the Lunar Achilles+ and 'quantitative ultrasound index' (QUI) for the Hologic Sahara ultrasound devices. We used the Bland and Altman approach and the kappa (kappa) score (classifying women by tertile, independent of age) to compare these methods. We studied 105 postmenopausal women (ages 57 to 88 years). We measured the heel (in duplicate) using both devices. Single lumbar spine (LS) bone mineral density (BMD) measurements were also made using the same two manufacturers' densitometers. QUI values were higher than SI values with a mean difference of 2.4 units (95% CI, 1.5-3.2). This difference in SI and QUI was most marked at higher ultrasound values (r = 0.61, p<0.0001). The kappa score between SI and QUI was 0.69 (95% CI, 0.57-0.80). When we calculated the kappa scores based on the mean of duplicate SI and QUI measurements, the kappa score increased to 0.90 (95% CI, 0.77-0.94). Lunar DPX LS-BMD values were higher than Hologic QDR 1000/W LS-BMD values with a mean difference of 0.18 g/cm2 (95% CI, 0.17-0.19). The difference between the machines was most marked at higher BMD values (r = 0.38, p<0.001). The kappa score between the DPX and QDR 1000/W was good (kappa = 0.79, 95% CI = 0.66-0.88), and was similar to the agreement of SI and QUI. Based on a single measurement, some women would be classified in different tertiles using the two heel ultrasound machines (about 20%). However, this is not significantly greater than the misclassification rate using two machines to measure spinal BMD (about 15%). Although there are significant differences between SI and QUI measurements, the misclassification rates are similar to those observed measuring LS-BMD using two different manufacturers' DXA machines. The misclassification rate using quantitative ultrasound improves when based on duplicate measurements.     

Prediction and Discrimination of Osteoporotic Hip Fracture in Postmenopausal Women

Osteoporotic hip fractures increase dramatically with age and are responsible for considerable morbidity and mortality. Several treatments to prevent the occurrence of hip fracture have been validated in large randomized trials and the current challenge is to improve the identification of individuals at high risk of fracture who would benefit from therapeutic or preventive intervention. We have performed an exhaustive literature review on hip fracture predictors, focusing primarily on clinical risk factors, dual X-ray absorptiometry (DXA), quantitative ultrasound, and bone markers. This review is based on original articles and meta-analyses. We have selected studies that aim both to predict the risk of hip fracture and to discriminate individuals with or without fracture. We have included only postmenopausal women in our review. For studies involving both men and women, only results concerning women have been considered. Regarding clinical factors, only prospective studies have been taken into account. Predictive factors have been used as stand-alone tools to predict hip fracture or sequentially through successive selection processes or by combination into risk scores. There is still much debate as to whether or not the combination of these various parameters, as risk scores or as sequential or concurrent combinations, could help to better predict hip fracture. There are conflicting results on whether or not such combinations provide improvement over each method alone. Sequential combination of bone mineral density and ultrasound parameters might be cost-effective compared with DXA alone, because of fewer bone mineral density measurements. However, use of multiple techniques may increase costs. One problem that precludes comparison of most published studies is that they use either relative risk, or absolute risk, or sensitivity and specificity. The absolute risk of individuals given their risk factors and bone assessment results would be a more appropriate model for decision-making than relative risk. Currently, a group appointed by the World Health Organization and lead by Professor John Kanis is working on such a model. It will therefore be possible to further assess the best choice of threshold to optimize the number of women needed to screen for each country and each treatment.     

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.