Performance of FRAX in Women with Breast Cancer Initiating Aromatase Inhibitor Therapy: A Registry-Based Cohort Study

FRAX was developed to predict 10-year probability of major osteoporotic fracture (MOF) and hip fracture in the general population. Aromatase inhibitors (AI) used in breast cancer induce loss in bone mineral density (BMD) and are reported to increase fracture risk. AI exposure is not a direct input to FRAX but is captured under “secondary osteoporosis”. To inform use of FRAX in women treated with AI, we used a population-based registry for the Province of Manitoba, Canada, to identify women aged ≥40 years initiating AI for breast cancer with at least 12 months’ AI exposure (n = 1775), women with breast cancer not receiving AI (n = 1016), and women from the general population (n = 34,205). Among AI users, fracture probability estimated without BMD (AI use coded as secondary osteoporosis) significantly overestimated risk (10-year observed/predicted ratio 0.56, 95% confidence interval [CI] 0.45–0.68; 10-year hip fracture observed/predicted ratio 0.33, 95% CI 0.18–0.49). However, when BMD was included in the fracture probability, there was no significant difference between observed and predicted fracture risk. In Cox proportional hazards models, FRAX stratified risk of MOF, hip, and any fracture equally well in all subgroups (p-interaction >0.1). When adjusted for FRAX score without BMD, with AI use coded as secondary osteoporosis, AI users were at significantly lower risk for MOF (hazard ratio [HR] = 0.78, 95% CI 0.64–0.95), hip fracture (HR = 0.46, 95% CI 0.29–0.73) and any fracture (HR = 0.75, 95% CI 0.63–0.89). AI use was no longer significantly associated with fractures when AI use was not entered as secondary osteoporosis in FRAX without BMD or when BMD was included in the FRAX calculation. In conclusion, FRAX scores stratify fracture risk equally well in women receiving AI therapy as in non-users, but including secondary osteoporosis as a risk factor for AI users overestimates fracture risk. Our results call this practice into question. © 2019 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.     

Relationship Between Body Mass Index and Fracture Risk Is Mediated by Bone Mineral Density

The relationship between body mass index (BMI) and fracture risk is controversial. We sought to investigate the effect of collinearity between BMI and bone mineral density (BMD) on fracture risk, and to estimate the direct and indirect effect of BMI on fracture with BMD being the mediator. The study involved 2199 women and 1351 men aged 60 years or older. BMI was derived from baseline weight and height. Femoral neck BMD was measured by dual‐energy X‐ray absorptiometry (DXA; GE‐LUNAR, Madison, WI, USA). The incidence of fragility fracture was ascertained by X‐ray reports from 1991 through 2012. Causal mediation analysis was used to assess the mediated effect of BMD on the BMI‐fracture relationship. Overall, 774 women (35% of total women) and 258 men (19%) had sustained a fracture. Approximately 21% of women and 20% of men were considered obese (BMI ≥ 30). In univariate analysis, greater BMI was associated with reduced fracture risk in women (hazard ratio [HR] 0.92; 95% confidence interval [CI], 0.85 to 0.99) and in men (HR 0.77; 95% CI, 0.67 to 0.88). After adjusting for femoral neck BMD, higher BMI was associated with greater risk of fracture in women (HR 1.21; 95% CI, 1.11 to 1.31) but not in men (HR 0.96; 95% CI, 0.83 to 1.11). Collinearity had minimal impact on the BMD‐adjusted results (variance inflation factor [VIF] = 1.2 for men and women). However, in mediation analysis, it was found that the majority of BMI effect on fracture risk was mediated by femoral neck BMD. The overall mediated effect estimates were ?0.048 (95% CI, ?0.059 to ?0.036; p < 0.001) in women and ?0.030 (95% CI, ?0.042 to ?0.018; p < 0.001) in men. These analyses suggest that there is no significant direct effect of BMI on fracture, and that the observed association between BMI and fracture risk is mediated by femoral neck BMD in both men and women. © 2014 American Society for Bone and Mineral Research.     

Effect of Total Hip Bone Area on Osteoporosis Diagnosis and Fractures

DXA is affected by skeletal size, with smaller bones giving lower areal BMD despite equal material density. Whether this size effect confounds the use of BMD as a diagnostic and fracture risk assessment tool is unclear. We identified 16,205 women of white ethnicity ≥50 yr of age undergoing baseline hip assessment with DXA (1998–2002) from a population‐based database that contains all clinical DXA test results for the Province of Manitoba, Canada. Total hip measurements were categorized according to quartile in total hip bone area (Q1 = smallest, Q4 = largest). Longitudinal health service records were assessed for the presence of nontraumatic osteoporotic fracture codes during a mean of 3.2 yr of follow‐up after BMD testing (757 osteoporotic fractures, 186 hip fractures). Total hip bone area strongly affected osteoporosis diagnosis with much higher rates in Q1 (14.4%) than Q4 (8.9%). However, incident fracture rates were constant across all area quartiles, and prevalent fractures were paradoxically fewer in smaller area quartiles (p < 0.001 for trend). Age was a potential confounder that correlated positively with area (r = 0.12, p < 0.0001). When age was not included in a Cox regression model, Q1 seemed to have a lower rate of incident osteoporotic fractures (HR = 0.80, 95% CI = 0.66–0.98, reference Q4) and hip fractures (HR = 0.63, 95% CI = 0.43–0.94) for a given level of BMD. In age‐adjusted regression models, total hip BMD was strongly predictive of incident osteoporotic fractures (HR per SD = 1.83, 95% CI = 1.68–1.99) and hip fractures (HR per SD = 2.80, 95% CI = 2.33–3.35), but there was no independent effect of bone area (categorical or continuous). Nested matched subgroup analysis and ROC analysis confirmed that bone area had no appreciable effect on incident fractures. We conclude that total hip areal BMD categorizes a substantially higher fraction of women with smaller bone area as being osteoporotic despite younger age. Incident fracture rates correlate equally well with BMD across all bone area quartiles when adjusted for age.     

Effects of antiresorptive treatment on nonvertebral fracture outcomes

Various definitions of nonvertebral fracture have been used in osteoporosis trials, precluding comparisons of efficacy. Using only subgroups of nonvertebral fractures for trial outcomes may underestimate the benefits and cost‐effectiveness of treatments. The objectives of this study were to determine (1) the effect of antiresorptive treatment on various nonvertebral fracture outcomes, (2) whether risk reduction from antiresorptive treatment is greater for nonvertebral fractures that have stronger associations with low BMD, and (3) sample size estimates for clinical trials of osteoporosis treatments. Study‐level data were combined from five randomized fracture‐prevention trials of antiresorptive agents that reduce the risk of nonvertebral fracture in postmenopausal women: alendronate, clodronate, denosumab, lasofoxifene, and zoledronic acid. Pooled effect estimates were calculated with random‐effects models. The five trials included 30,118 women; 2997 women had at least one nonvertebral fracture. There was no significant heterogeneity between treatments for any outcome (all p > 0.10). Antiresorptive treatment had similar effects on all fractures (summary hazard ratio [HR] = 0.76, 95% CI 0.70–0.81), high‐trauma fractures (HR = 0.74, 95% CI 0.57–0.96), low‐trauma fractures (HR = 0.77, (95% CI 0.71–0.83), nonvertebral six (ie, hip, pelvis, leg, wrist, humerus, and clavicle) fractures (HR = 0.73, 95% CI 0.66–0.80), other than nonvertebral six fractures (HR = 0.78, 95% CI 0.70–0.87), and all fractures other than finger, face, and toe (HR = 0.75, 95% CI 0.70–0.81). Risk reduction was not greater for fractures with stronger associations with low BMD (p = 0.77). A trial of all nonvertebral fractures would require fewer participants (n = 2641 per arm) than one of a subgroup of six fractures (n = 3289), for example. In summary, antiresorptive treatments reduced all nonvertebral fractures regardless of degree of trauma or special groupings, supporting the use of all nonvertebral fractures as a standard endpoint of osteoporosis trials and the basis for estimating the benefits and cost‐effectiveness of treatments. © 2011 American Society for Bone and Mineral Research     

Wrist Fracture and Risk of Subsequent Fracture: Findings from the Women's Health Initiative Study

Wrist fractures are common in postmenopausal women and are associated with functional decline. Fracture patterns after wrist fracture are unclear. The goal of this study was to determine the frequency and types of fractures that occur after a wrist fracture among postmenopausal women. We carried out a post hoc analysis of data from the Women's Health Initiative Observational Study and Clinical Trials (1993–2010) carried out at 40 US clinical centers. Participants were postmenopausal women aged 50 to 79 years at baseline. Mean follow‐up duration was 11.8 years. Main measures included incident wrist, clinical spine, humerus, upper extremity, lower extremity, hip, and total non‐wrist fractures and bone mineral density (BMD) in a subset. Among women who experienced wrist fracture, 15.5% subsequently experienced non‐wrist fracture. The hazard for non‐wrist fractures was higher among women who had experienced previous wrist fracture than among women who had not experienced wrist fracture: non‐wrist fracture overall (hazard ratio [HR] = 1.40, 95% confidence interval [CI] 1.33–1.48), spine (HR = 1.48, 95% CI 1.32–1.66), humerus (HR = 1.78, 95% CI 1.57–2.02), upper extremity (non‐wrist) (HR = 1.88, 95% CI 1.70–2.07), lower extremity (non‐hip) (HR = 1.36, 95% CI 1.26–1.48), and hip (HR = 1.50, 95% CI 1.32–1.71) fracture. Associations persisted after adjustment for BMD, physical activity, and other risk factors. Risk of non‐wrist fracture was higher in women who were younger when they experienced wrist fracture (interaction p value 0.02). Associations between incident wrist fracture and subsequent non‐wrist fracture did not vary by baseline BMD category (normal, low bone density, osteoporosis). A wrist fracture is associated with increased risk of subsequent hip, vertebral, upper extremity, and lower extremity fractures. There may be substantial missed opportunity for intervention in the large number of women who present with wrist fractures. © 2015 American Society for Bone and Mineral Research.     

Change in Trabecular Bone Score (TBS) With Antiresorptive Therapy Does Not Predict Fracture in Women: The Manitoba BMD Cohort

Bone mineral density (BMD) and trabecular bone score (TBS), along with additional clinical risk factors, can be used to identify individuals at high fracture risk. Whether change in TBS in untreated or treated women independently affects fracture risk is unclear. Using the Manitoba (Canada) DXA Registry containing all BMD results for the population we identified 9044 women age ≥40 years with two consecutive DXA scans and who were not receiving osteoporosis treatment at baseline (baseline mean age 62 ± 10 years). We examined BMD and TBS change, osteoporosis treatment, and incident major osteoporotic fractures (MOFs) for each individual. Over a mean of 7.7 years follow‐up, 770 women developed an incident MOF. During the interval between the two DXA scans (mean, 4.1 years), 5083 women initiated osteoporosis treatment (bisphosphonate use 80%) whereas 3961 women did not receive any osteoporosis treatment. Larger gains in both BMD and TBS were seen in women with greater adherence to osteoporosis medication (p for trend <0.001), and the magnitude of the increase was consistently greater for BMD than for TBS. Among treated women there was greater antifracture effect for each SD increase in total hip BMD change (fracture decrease 20%; 95% CI, 13% to 26%; p < 0.001), femoral neck BMD change (19%; 95% CI, 12% to 26%; p < 0.001), and lumbar spine BMD change (9%; 95% CI, 0% to 17%; p = 0.049). In contrast, change in TBS did not predict fractures in women who initiated osteoporosis treatment (p = 0.10). Among untreated women neither change in BMD or TBS predicted fractures. We conclude that, unlike antiresorptive treatment–related changes in BMD, change in lumbar spine TBS is not a useful indicator of fracture risk irrespective of osteoporosis treatment. © 2016 American Society for Bone and Mineral Research.     

Differences in Site-Specific Fracture Risk Among Older Women with Discordant Results for Osteoporosis at Hip and Spine: Study of Osteoporotic Fractures

To examine the fracture pattern in older women whose bone mineral density (BMD) T-score criteria for osteoporosis at hip and spine disagree, hip and spine BMD were measured in Study of Osteoporotic Fractures participants using dual energy X-ray absorptiometry (DXA). Hip osteoporosis was defined as T-score ≤−2.5 at femoral neck or total hip, and spine osteoporosis as T-score ≤−2.5 at lumbar spine. Incident clinical fractures were self-reported and centrally adjudicated. Incident radiographic spine fractures were defined morphometrically. Compared to women with osteoporosis at neither hip nor spine, those osteoporotic only at hip had a 3.0-fold age- and weight-adjusted increased risk for hip fracture (95% confidence interval [CI]: 2.4–3.6), and smaller increases in risk of nonhip nonspine (hazard ratios [HR] = 1.6), clinical spine (odds ratio [OR] = 2.2), and radiographic spine fractures (OR = 1.5). Women osteoporotic only at spine had a 2.8-fold increased odds of radiographic spine fracture (95% CI: 2.1–3.8), and smaller increases in risk of clinical spine (OR = 1.4), nonhip nonspine (HR = 1.6), and hip fractures (HR = 1.2). Discordant BMD results predict different fracture patterns. DXA fracture risk estimation in these patients should be site specific. Women osteoporotic only at spine would not have been identified from hip BMD measurement alone, and may have a sufficiently high fracture risk to warrant preventive treatment.     

Trabecular Bone Score (TBS) Predicts Fracture in Ankylosing Spondylitis: The Manitoba BMD Registry

Introduction: Ankylosing spondylitis (AS) is a chronic inflammatory disease of the spine characterized among other features by spinal boney proliferation, back pain, loss of flexibility, and increased fracture risk. Overlying bone limits the utility of bone mineral density (BMD) by dual X-ray absorptiometry (DXA) in the spine. Trabecular bone score (TBS) is a bone texture measurement derived from the spine DXA image that indicates bone quality and fracture risk independent of BMD. Methodology: Using the Manitoba Bone Density Program database, patients with diagnosis codes for ankylosing spondylitis, baseline DXA and lumbar spine TBS were identified. Incident nontraumatic fractures (major osteoporotic [MOF], clinical spine, hip, and all fracture) were identified from population based databases. Cox-proportional hazard models are presented. Results: We identified 188 patients with diagnosed AS. TBS was lower in those with incident MOF (1.278 ± 0.126, compared to 1.178 ± 0.136, p < 0.001). Unadjusted TBS and FRAX-MOF-BMD adjusted predicted major osteoporotic fracture (N = 19) (hazard ratio [HR] 2.04, 95% confidence interval [CI]: 1.28–2.26, p = 0.003; HR 1.81, 95% CI: 1.11–2.96, p = 0.018). TBS unadjusted and FRAX-MOF-BMD adjusted also predicted clinical spine fracture (N = 7) (HR 2.50, 95% CI: 1.17–5.37; p = 0.019; HR 2.40 95% CI: 1.1–5.25; p = 0.028). Higher HRs were observed for prediction of hip fracture (N = 6), but these did not achieve statistical significance (FRAX-adjusted HR 1.74, 95% 0.73–4.17; p = 0.211). Unadjusted models show TBS was predictive of all fracture (N = 27) (HR 1.60, 95% CI: 1.08–2.39; p = 0.020), which was borderline significant after adjustment for FRAX-MOF-BMD (HR 1.51, 95% CI: 1.00–2.29; p = 0.052). Conclusion: We report the first analysis of TBS for fracture prediction as an incident event in AS. TBS independently predicted major osteoporotic and clinical spine fracture in AS independent of FRAX.     

Can BMD assessed by DXA at age 8 predict fracture risk in boys and girls during puberty?: an eight-year prospective study.

This study reports on the association between DXA at age 8 and subsequent fractures in both male and female children. Bone densitometry at the total body and spine (but not hip) is a strong predictor of fracture (especially upper limb) during puberty. INTRODUCTION: The aim of this study was to determine if prepubertal DXA can predict fracture risk during puberty. MATERIALS AND METHODS: We studied 183 children who were followed for 8 yr (1460 person-years). Bone densitometry was measured at the total body, hip, and spine by DXA and reported as BMC, BMD, and bone mineral apparent density (BMAD). Fractures were self-reported at age 16 with X-ray confirmation, RESULTS: There were a total of 63 fractures (43 upper limb). In unadjusted analysis, only total body BMD showed an inverse relationship with upper limb fracture risk (p = 0.03). However, after adjustment for height, weight, age (all at age 8), and sex, total body BMC (HR/SD, 2.47; 95% CI, 1.52-4.02), spine BMC (HR/SD, 1.97: 95% CI, 1.30-2.98), total body BMD (HR/SD, 1.67; 95% CI, 1.18-2.36), total body BMAD (HR/SD, 1.54; 95% CI, 1.01-2.37), and spine BMD (HR/SD, 1.53; 95% CI, 1.10, 2.22) were all significantly associated with upper limb fracture risk. Similar, but weaker associations were present for total fractures. There was a trend for overweight/obesity to be associated with increased upper limb fracture risk (HR, 1.53/category; p = 0.08). CONCLUSIONS: Measurement of bone mass by DXA is a good predictor of upper limb fracture risk during puberty. Although we did not measure true BMD, the constancy of fracture prediction after a single measure suggests bone strength remains relatively constant during puberty despite the large changes in bone size.     

Lower fracture risk in older men with higher sclerostin concentration: A prospective analysis from the MINOS study

Sclerostin is synthesized by osteocytes and inhibits bone formation. We measured serum sclerostin levels in 710 men aged 50 years and older. Bone mineral density (BMD) was measured at the lumbar spine, hip, and distal forearm. Serum sclerostin increased with age (unadjusted r = 0.30, p < 0.001). After adjustment for age, weight, and bioavailable 17β‐estradiol, serum sclerostin correlated positively with BMD (r = 0.24 to 0.35, p < 0.001) and negatively with the levels of bone turnover markers (r = ? 0.09 to ? 0.23, p < 0.05 to 0.001). During a 10‐year follow‐up, 75 men sustained fragility fractures. Fracture risk was lower in the two upper quintiles of sclerostin combined versus three lower quintiles combined (6.1 versus 13.5%, p < 0.01). We compared fracture risk in the two highest quintiles combined versus three lower quintiles combined using the Cox model adjusted for age, weight, leisure physical activity, BMD, bone width (tubular bones), prevalent fracture, prevalent falls, ischemic heart disease, and severe abdominal aortic calcification. Men with higher sclerostin concentration had lower fracture risk (adjusted for hip BMD, hazard ratio [HR] = 0.55, 95% confidence interval [CI] 0.31 to 0.96, p < 0.05). The results were similar in 47 men with major fragility fractures (adjusted for lumbar spine BMD: HR = 0.39, 95% CI 0.17 to 0.90, p < 0.05). Men who had higher sclerostin and higher BMD (two highest quintiles) had lower risk of fracture compared with men who had lower BMD and lower sclerostin levels (three lower quintiles) (HR = 0.24, 95% CI 0.10 to 0.62, p < 0.005). Circulating sclerostin was not associated with mortality rate or the incidence of major cardiovascular events. Thus, in older men, higher serum sclerostin levels are associated with lower risk of fracture, higher BMD, and lower bone turnover rate. © 2013 American Society for Bone and Mineral Research.     

Bone mineral density-independent association of quantitative ultrasound measurements and fracture risk in women

Osteoporotic fracture is considered to result from reduced bone strength and to be related to decreased bone mass and impaired bone architecture. Quantitative ultrasound measurements (QUS) of bone, that may reflect certain architectural aspects of bone, have been shown to be associated with fracture, but it is not clear whether the association is independent of bone mineral density (BMD). This study was designed to examine the contributions of cortical QUS and BMD measurements to the prediction of fracture risk in postmenopausal Caucasian women. Speed of sound (SOS) at the distal radius, tibia, and phalanx (Sunlight Omnisense) and BMD at the lumbar spine and femoral neck (GE Lunar) were measured in 549 women, aged 63.2 ± 12.3 years (mean ± SD; range, 49–88 years), including 77 fracture cases. Lower SOS at the distal radius, tibia, and phalanx, which were correlated with each other, were associated with increased risk of fracture. Independent predictors of fracture risk (in multivariate analysis) were distal radius SOS (OR per SD = 1.8; 95% CI, 1.3–2.4), femoral neck BMD (OR per SD = 1.9; 95% CI, 1.4–2.4), and age (OR per 5 years = 1.2; 95% CI, 1.0–1.5). Approximately 30% of the women had distal radius SOS T-scores <–2.5; however, only 6.6% of women had both BMD and SOS T-scores <–2.5. Among the 77 fracture cases, only 14 (18.2%) had both BMD and QUS T-scores below –2.5. These data in postmenopausal women suggest that speed of sound at the distal radius was associated with fracture risk, independent of BMD and age. The combination of QUS and BMD measurements may improve the accuracy of identification of women who will sustain a fracture.     

Assessment of incident spine and hip fractures in women and men using finite element analysis of CT scans

Finite element analysis of computed tomography (CT) scans provides noninvasive estimates of bone strength at the spine and hip. To further validate such estimates clinically, we performed a 5‐year case‐control study of 1110 women and men over age 65 years from the AGES‐Reykjavik cohort (case = incident spine or hip fracture; control = no incident spine or hip fracture). From the baseline CT scans, we measured femoral and vertebral strength, as well as bone mineral density (BMD) at the hip (areal BMD only) and lumbar spine (trabecular volumetric BMD only). We found that for incident radiographically confirmed spine fractures (n = 167), the age‐adjusted odds ratio for vertebral strength was significant for women (2.8, 95% confidence interval [CI] 1.8 to 4.3) and men (2.2, 95% CI 1.5 to 3.2) and for men remained significant (p = 0.01) independent of vertebral trabecular volumetric BMD. For incident hip fractures (n = 171), the age‐adjusted odds ratio for femoral strength was significant for women (4.2, 95% CI 2.6 to 6.9) and men (3.5, 95% CI 2.3 to 5.3) and remained significant after adjusting for femoral neck areal BMD in women and for total hip areal BMD in both sexes; fracture classification improved for women by combining femoral strength with femoral neck areal BMD (p = 0.002). For both sexes, the probabilities of spine and hip fractures were similarly high at the BMD‐based interventional thresholds for osteoporosis and at corresponding preestablished thresholds for “fragile bone strength” (spine: women ≤ 4500 N, men ≤ 6500 N; hip: women ≤ 3000 N, men ≤ 3500 N). Because it is well established that individuals over age 65 years who have osteoporosis at the hip or spine by BMD criteria should be considered at high risk of fracture, these results indicate that individuals who have fragile bone strength at the hip or spine should also be considered at high risk of fracture. © 2014 American Society for Bone and Mineral Research.     

Association Between Abdominal Aortic Calcification,Bone Mineral Density,and Fracture in Older Women

Although a relationship between vascular disease and osteoporosis has been recognized, its clinical importance for fracture risk evaluation remains uncertain. Abdominal aortic calcification (AAC), a recognized measure of vascular disease detected on single-energy images performed for vertebral fracture assessment, may also identify increased osteoporosis risk. In a prospective 10-year study of 1024 older predominantly white women (mean age 75.0 ± 2.6 years) from the Perth Longitudinal Study of Aging cohort, we evaluated the association between AAC, skeletal structure, and fractures. AAC and spine fracture were assessed at the time of hip densitometry and heel quantitative ultrasound. AAC was scored 0 to 24 (AAC24) and categorized into low AAC (score 0 and 1, n = 459), moderate AAC (score 2 to 5, n = 373), and severe AAC (score > 6, n = 192). Prevalent vertebral fractures were calculated using the Genant semiquantitative method. AAC24 scores were inversely related to hip BMD ( r _s = –0.077, p = 0.013), heel broadband ultrasound attenuation ( r _s = –0.074, p = 0.020), and the Stiffness Index ( r _s = –0.073, p = 0.022). In cross-sectional analyses, women with moderate to severe AAC were more likely to have prevalent fracture and lumbar spine imaging-detected lumbar spine fractures, but not thoracic spine fractures (Mantel-Haenszel test of trend p < 0.05). For 10-year incident clinical fractures and fracture-related hospitalizations, women with moderate to severe AAC (AAC24 score >1) had increased fracture risk (HR 1.48; 95% CI, 1.15 to 1.91; p = 0.002; HR 1.46; 95% CI, 1.07 to 1.99; p = 0.019, respectively) compared with women with low AAC. This relationship remained significant after adjusting for age and hip BMD for clinical fractures (HR 1.40; 95% CI, 1.08 to 1.81; p = 0.010), but was attenuated for fracture-related hospitalizations (HR 1.33; 95% CI, 0.98 to 1.83; p = 0.073). In conclusion, older women with more marked AAC are at higher risk of fracture, not completely captured by bone structural predictors. These findings further support the concept that vascular calcification and bone pathology may share similar mechanisms of causation that remain to be fully elucidated © 2019 American Society for Bone and Mineral Research     

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.     

Plasma Choline,Nicotine Exposure,and Risk of Low Bone Mineral Density and Hip Fracture: The Hordaland Health Study

Choline, obtained from diet and formed by biosynthesis, is the immediate precursor of betaine. Animal studies suggest an impact of choline on bone metabolism. We examined the associations of plasma choline and betaine with bone mineral density (BMD), the risk of hip fractures, and possible effect‐modification by nicotine exposure. The Hordaland Health Study (1998 to 2000) included 7074 women and men (ages 46 to 49 or 71 to 74 years). In 5315, BMD was measured. The oldest (n = 3311) were followed for hip fractures through 2009. Risk associations were studied by logistic and Cox regression by comparing the lowest and middle tertiles with the highest, as well as trends across tertiles of plasma choline and betaine. In analyses adjusted for sex and age, participants in the lowest (odds ratio [OR] = 2.00, 95% confidence interval [CI] 1.69–2.37) and middle (OR = 1.39, CI 1.17–1.66) tertiles of plasma choline had an increased risk of low BMD (lowest quintile) (p trend < 0.001). Separate analyses for sex and age groups revealed the strongest relations in elderly women (lowest tertile: OR = 2.84, CI 1.95–4.14; middle tertile: OR = 1.80, CI 1.22–2.67, p trend < 0.001), and highest OR among those in the lowest tertile who were exposed to nicotine (OR = 4.56, CI 1.87–11.11). Low plasma choline was also associated with an increased risk of hip fracture in elderly women and men (lowest tertile: hazard ratio [HR] = 1.45, CI 1.08–1.94; middle tertile: HR = 1.13, CI 0.83–1.54, p trend = 0.012). In elderly women, the HR for hip fracture was 1.90 (CI 1.32–2.73) and 1.36 (CI 0.92–1.99) (p trend < 0.001) for lowest and middle tertiles of choline, and the highest HR was found among women in the lowest tertile exposed to nicotine (HR = 2.68, CI 1.16–6.19). Plasma betaine was not related to BMD or hip fracture. Low plasma choline was associated with low BMD in both sexes and increased the risk of hip fracture in elderly women. These results should motivate further studies on choline, nicotine exposure, and bone metabolism. © 2014 American Society for Bone and Mineral Research.     

The relationship between social deprivation,osteoporosis, and falls

The aim of this study was to assess the relationship between heel BMD, risk factors for osteoporosis, falls history, and the Jarman Underprivileged Area Score in an older community population. From the general practice register, 1,187 women (mean age 70, range 60 to 94) were recruited. BMD of the heel was measured using the GE Lunar PIXI densitometer. A T-score cutoff for predicted osteoporosis at the spine or hip of –1.7 was used. A risk factor questionnaire was completed that included fracture history and falls history. The odds ratio (OR) with a 95% confidence interval (CI) was calculated for each risk factor for each quartile of Jarman score and for the diagnosis of osteoporosis. Logistic regression was used to identify the risk factors that predict lone bone mass in the heel. There were no significant differences between women in different quartiles of Jarman score in terms of age and body mass index (BMI). Women in the highest two quartiles of Jarman score (i.e., most deprived) had a significantly higher likelihood of osteoporosis (OR=1.82; 95% CI, 1.03 to 1.63; and OR=1.85; 95% CI, 1.04 to 1.64, respectively) and significantly lower BMD (p=0.008). Women in these two quartiles were significantly more likely to have had a history of previous fracture (OR=1.66; 95% CI, 1.01 to 1.53), but there was no difference in falls history. Women in the lowest quartile (least deprived) were also significantly less likely to smoke (p=0.011) but were not significantly different in terms of other risk factors (e.g., dietary calcium and activity). BMI, age, kyphosis, significant visual problems, and quartile of Jarman score were significant risk factors for low bone mass. Risk factors identified those with low bone mass at the heel with a sensitivity and specificity of 72%. In conclusion, women in the lowest quartile of Jarman score (i.e., least deprived) have significantly higher heel BMD compared with the rest of the population.     

Temporal Trends in Obesity,Osteoporosis Treatment,Bone Mineral Density,and Fracture Rates: A Population‐Based Historical Cohort Study

Diverging international trends in fracture rates have been observed, with most reports showing that fracture rates have stabilized or decreased in North American and many European populations. We studied two complementary population‐based historical cohorts from the Province of Manitoba, Canada (1996–2006) to determine whether declining osteoporotic fracture rates in Canada are attributable to trends in obesity, osteoporosis treatment, or bone mineral density (BMD). The Population Fracture Registry included women aged 50 years and older with major osteoporotic fractures, and was used to assess impact of changes in osteoporosis treatment. The BMD Registry included all women aged 50 years and older undergoing BMD tests, and was used to assess impact of changes in obesity and BMD. Model‐based estimates of temporal changes in fracture rates (Fracture Registry) were calculated. Temporal changes in obesity and BMD and their association with fracture rates (BMD Registry) were estimated. In the Fracture Registry (n = 27,341), fracture rates declined 1.6% per year (95% confidence interval [CI], 1.3% to 2.0%). Although osteoporosis treatment increased from 5.6% to 17.4%, the decline in fractures was independent of osteoporosis treatment. In the BMD Registry (n = 36,587), obesity increased from 12.7% to 27.4%. Femoral neck BMD increased 0.52% per year and lumbar spine BMD increased 0.32% per year after covariate adjustment (p < 0.001). Major osteoporotic fracture rates decreased in models that did not include femoral neck BMD (fully adjusted annual change –1.8%; 95% CI, –2.9 to –0.5), but adjusting for femoral neck BMD accounted for the observed reduction (annual change –0.5%; 95% CI, –1.8 to +1.0). In summary, major osteoporotic fracture rates declined substantially and linearly from 1996 to 2006, and this was explained by improvements in BMD rather than greater rates of obesity or osteoporosis treatment. © 2014 American Society for Bone and Mineral Research.     

Risk factors for prediction of inadequate response to antiresorptives

Some patients sustain fractures while on antiresorptives. Whether this represents an inadequate response (IR) to treatment or a chance event has not been elucidated. We performed a study to identify which patients are more likely to fracture while on treatment. This is a multicentric, cross‐sectional study of postmenopausal women on antiresorptives for osteoporosis in 12 Spanish hospitals, classified as adequate responders (ARs) if on treatment with antiresorptives for 5 years with no incident fractures or inadequate responders (IRs) if an incident fracture occurred between 1 and 5 years on treatment. Poor compliance, secondary osteoporosis, and previous anti‐osteoporosis treatment other than the assessed were exclusion criteria. Clinical, demographic, analytical, dual‐energy X‐ray absorptiometry (DXA) variables, and proximal femur structure analysis (ImaTx?) and structural/fractal analyses of distal radius were performed. A total of 179 women (76 IRs; mean (SD): age 68.2 (9.0) years; 103 ARs, age 68.5 (7.9) years) were included. History of prior fracture (p = 0.005), two or more falls in the previous year (p = 0.032), low lumbar spine bone mineral density (BMD) (p = 0.02), 25 hydroxyvitamin D (p = 0.017), and hip ImaTx fracture load index (p = 0.004) were associated with IR. In the logistic regression models a fracture before treatment (odds ratio [OR], 3.60; 95% confidence interval [CI], 1.47–8.82; p = 0.005) and levels of 25 hydroxyvitamin D below 20 ng/mL (OR, 3.89; 95% CI, 1.55–9.77; p = 0.004) significantly increased risk for IR, while increased ImaTx fracture load (OR, 0.96; 95% CI, 0.93–0.99; p = 0.006; per every 100 units) was protective, although the latter became not significant when all three variables were fitted into the model. Therefore, we can infer that severity of the disease, with microarchitectural and structure deterioration, as shown by previous fracture and hip analysis, and low levels of 25 hydroxy vitamin D carry higher risk of inadequate response to antiresorptives. More potent regimes should be developed and adequate supplementation implemented to solve this problem. © 2012 American Society for Bone and Mineral Research.     

Identification of osteopenic women at high risk of fracture: the OFELY study.

About one-half of women with incident fractures have BMD above the WHO diagnostic threshold of osteoporosis. In the OFELY study, low BMD, increased markers of bone turnover, and prior fracture could be used to identify, within osteopenic women, those at high risk of fracture. INTRODUCTION: Recent data suggest that about one-half of women with incident fractures have BMD above the World Health Organization (WHO) diagnostic threshold of osteoporosis (T score相似文献