The Prevalence of Vertebral Fractures Is Associated With Reduced Hip Bone Density and Inferior Peripheral Appendicular Volumetric Bone Density and Structure in Older Women

Vertebral fractures (VFs) are among the most severe and prevalent osteoporotic fractures. Their association with bone microstructure have been investigated in several retrospective case‐control studies with spine radiography for diagnosis of VF. The aim of this population‐based cross‐sectional study of 1027 women aged 75 to 80 years was to investigate if prevalent VF, identified by vertebral fracture assessment (VFA) by dual‐energy X‐ray absorptiometry (DXA), was associated with appendicular volumetric bone density, structure, and bone material strength index (BMSi), independently of hip areal bone mineral density (aBMD). aBMD was measured using DXA (Discovery; Hologic); BMSi with microindentation (Osteoprobe); and bone geometry, volumetric BMD, and microstructure with high‐resolution peripheral quantitative computed tomography (HRpQCT) (XtremeCT; Scanco Medical AG). aBMD was lower (spine 3.2%, total hip [TH] 3.8%) at all sites in women with VF, but tibia BMSi did not differ significantly compared to women without VF. In multivariable adjusted logistic regression models, radius trabecular bone volume fraction and tibia cortical area (odds ratio [OR] 1.26; 95% confidence interval [CI], [1.06 to 1.49]; and OR 1.27 [95% CI, 1.08 to 1.49], respectively) were associated with VF prevalence, whereas BMSi and cortical porosity were not. The risk of having one, two, or more than two VFs was increased 1.27 (95% CI, 1.04 to 1.54), 1.83 (95% CI, 1.28 to 2.61), and 1.78 (95% CI, 1.03 to 3.09) times, respectively, for each SD decrease in TH aBMD. When including either cortical area, trabecular bone volume fraction or TBS in the model together with TH aBMD and covariates, only TH aBMD remained independently associated with presence of any VF. In conclusion, TH aBMD was consistently associated with prevalent VFA‐verified VF, whereas neither trabecular bone volume fraction, cortical area, cortical porosity, nor BMSi were independently associated with VF in older women. © 2017 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.     

Femoral Strength Changes Faster With Age Than BMD in Both Women and Men: A Biomechanical Study

Although a large number of studies have addressed the age‐related changes in bone mineral density (BMD), there is a paucity of data for the assessment of femoral strength loss with age in both genders. We determined the variation of strength with age in femurs of women and men by mechanical tests on a cohort of 100 cadaveric femurs. In addition, the age‐related neck BMD loss in our cadaveric cohort was found to be similar with BMD loss of four published population‐based studies. Given the strong correlation found in our cadaveric study between BMD and femoral strength, we also estimated the femoral strength of the four populations based on their reported neck BMDs. Our study showed that men's femurs in our cadaveric cohort were stronger than women's femurs by about 800 N at the same BMD level, and by 1750 N at the same age. The strength differences were not explained satisfactorily by the size difference between men's and women's bones. Similar to the findings of clinical studies, the BMD values of men at all ages were larger than that of women. The age‐related loss rates in BMD and strength were not statistically different between the two genders of our cadaveric cohort. After normalization, strength decreased more than 40% faster than BMD. On average, men reached a certain BMD value about 16 years later than women, and for strength about 23 years later, which may explain the higher rate of hip fracture in postmenopausal women. In patient population cohorts men reached a similar BMD value about 16 to 25 years later than women, whereas for estimated strength, sometimes more than 40 years later. © 2015 American Society for Bone and Mineral Research.     

Vertebral Fracture Risk in Diabetic Elderly Men: The MrOS Study

Type 2 diabetes (T2DM) is associated with a significant increase in risk of nonvertebral fractures, but information on risk of vertebral fractures (VFs) in subjects with T2DM, particularly among men, is lacking. Furthermore, it is not known whether spine bone mineral density (BMD) can predict the risk of VF in T2DM. We sought to examine the effect of diabetes status on prevalent and incident vertebral fracture, and to estimate the effect of lumbar spine BMD (areal and volumetric) as a risk factor for prevalent and incident morphometric vertebral fracture in T2DM (n = 875) and nondiabetic men (n = 4679). We used data from the Osteoporotic Fractures in Men (MrOS) Study, which enrolled men aged ≥65 years. Lumbar spine areal BMD (aBMD) was measured with dual‐energy X‐ray absorptiometry (DXA), and volumetric BMD (vBMD) by quantitative computed tomography (QCT). Prevalence (7.0% versus 7.7%) and incidence (4.4% versus 4.5%) of VFs were not higher in T2DM versus nondiabetic men. The risk of prevalent (OR, 1.05; 95% CI, 0.78 to 1.40) or incident vertebral‐fracture (OR, 1.28; 95% CI, 0.81 to 2.00) was not higher in T2DM versus nondiabetic men in models adjusted for age, clinic site, race, BMI, and aBMD. Higher spine aBMD was associated with lower risk of prevalent VF in T2DM (OR, 0.55; 95% CI, 0.48 to 0.63) and nondiabetic men (OR, 0.66; 95% CI, 0.5 to 0.88) (p for interaction = 0.24) and of incident VF in T2DM (OR, 0.50; 95% CI, 0.41 to 0.60) and nondiabetic men (OR, 0.54; 95% CI, 0.33 to 0.88) (p for interaction = 0.77). Results were similar for vBMD. In conclusion, T2DM was not associated with higher prevalent or incident VF in older men, even after adjustment for BMI and BMD. Higher spine aBMD and vBMD are associated with lower prevalence and incidence of VF in T2DM as well as nondiabetic men. © 2017 American Society for Bone and Mineral Research.     

Factors Associated With Kyphosis and Kyphosis Progression in Older Men: The MrOS Study

Hyperkyphosis (HK), or increased anterior curvature of the thoracic spine, is common in older persons. Although it is thought that vertebral fractures are the major cause of HK, only about a third of those with the worst degrees of kyphosis have underlying vertebral fractures. In older men, HK is associated with increased risk of poor physical function, injurious falls, and earlier mortality, but its causes are not well understood. We studied 1092 men from the Osteoporotic Fractures in Men (MrOS) Study aged 64 to 92 years (mean age 72.8 years) who had repeated standardized radiographic measures of Cobb angle of kyphosis to identify risk factors for HK (defined as ≥50 degrees) and kyphosis progression over an interval of 4.7 years. Specifically, we examined the associations with age, body mass index (BMI), weight, weight loss, health behaviors, family history of HK, muscle strength, degenerative disc disease (DDD), bone mineral density (BMD), prevalent thoracic vertebral fractures, and incident thoracic vertebral fractures (longitudinal analyses only). Men had an average baseline kyphosis of 38.9 (standard deviation [SD] 11.4) degrees. Fifteen percent had HK (n = 161) with a mean Cobb angle of 56.7 (SD = 6.0) degrees; these men were older (p < 0.01), had lower BMI (p < 0.01), lower BMD (p < 0.01), were more likely to have family history of HK (p = 0.01), and prevalent thoracic vertebral fracture (p < 0.01) compared with the men without HK. During follow-up, men experienced an average of 1.4 degrees of kyphosis progression with DDD (p = 0.04) and lower hip BMD (p < 0.01) being identified as statistically significant and incident vertebral fractures (p = 0.05) nearly significant factors associated with worse progression. These results suggest that in older men, HK results from not only low BMD and vertebral fractures but that DDD also may play a significant role in kyphosis progression. © 2020 American Society for Bone and Mineral Research (ASBMR).     

Heterogeneity and Spatial Distribution of Intravertebral Trabecular Bone Mineral Density in the Lumbar Spine Is Associated With Prevalent Vertebral Fracture

The spatial heterogeneity in trabecular bone density within the vertebral centrum is associated with vertebral strength and could explain why volumetric bone mineral density (vBMD) exhibits low sensitivity in identifying fracture risk. This study evaluated whether the heterogeneity and spatial distribution of trabecular vBMD are associated with prevalent vertebral fracture. We examined the volumetric quantitative computed tomography (QCT) scans of the L₃ vertebra in 148 participants in the Framingham Heart Study Multidetector CT study. Of these individuals, 37 were identified as cases of prevalent fracture, and 111 were controls, matched on sex and age with three controls per case. vBMD was calculated within 5-mm contiguous cubic regions of the centrum. Two measures of heterogeneity were calculated: (i) interquartile range (IQR); and (ii) quartile coefficient of variation (QCV). Ratios in the spatial distributions of the trabecular vBMD were also calculated: anterior/posterior, central/outer, superior/mid-transverse, and inferior/mid-transverse. Heterogeneity and spatial distributions were compared between cases and controls using Wilcoxon rank sum tests and t tests and tested for association with prevalent fractures with conditional logistic regressions independent of integral vBMD. Prevalent fracture cases had lower mean ± SD integral vBMD (134 ± 38 versus165 ± 42 mg/cm³, p < .001), higher QCV (0.22 ± 0.13 versus 0.17 ± 0.09, p = .003), and lower anterior/posterior rBMD (0.65 ± 0.13 versus 0.78 ± 0.16, p < .001) than controls. QCV was positively associated with increased odds of prevalent fracture (OR 1.61; 95% CI, 1.04 to 2.49; p = .034), but this association was not independent of integral vBMD (p = .598). Increased anterior/posterior trabecular vBMD ratio was associated with decreased odds of prevalent fracture independent of integral vBMD (OR 0.38; 95% CI, 0.20 to 0.71; p = .003). In conclusion, increased trabecular vBMD in the anterior versus posterior centrum, but not trabecular vBMD heterogeneity, was associated with decreased risk of prevalent fracture independent of integral vBMD. Regional measurements of trabecular vBMD could aid in determining the risk and underlying mechanisms of vertebral fracture. © 2019 American Society for Bone and Mineral Research.     

Muscle Strength and Physical Performance Are Associated With Risk of Postfracture Mortality But Not Subsequent Fracture in Men

Muscle strength and physical performance are associated with incident fractures and mortality. However, their role in the risk of subsequent fracture and postfracture mortality is not clear. We assessed the association between muscle strength (grip strength) and performance (gait speed and chair stands time) and the risk of subsequent fracture and mortality in 830 men with low-trauma index fracture, who participated in the Osteoporotic Fractures in Men (MrOS) USA Study and had their index measurements assessed within 5 years prior to the index fracture. The annual decline in muscle strength and performance following index fracture, estimated using linear mixed-effects regression, was also examined in relation to mortality. The associations were assessed using Cox proportional hazards models adjusted for age, femoral neck bone mineral density (FN BMD), prior fractures, falls, body mass index (BMI), index fracture site, lifestyle factors, and comorbidities. Over a median follow-up of 3.7 (interquartile range [IQR], 1.3–8.1) years from index fracture to subsequent fracture, 201 (24%) men had a subsequent fracture and over 5.1 (IQR, 1.8–9.6) years to death, and 536 (65%) men died. Index measurements were not associated with subsequent fracture (hazard ratios [HRs] ranging from 0.97 to 1.07). However, they were associated with postfracture mortality. HR (95% confidence interval [CI]) per 1 standard deviation (1-SD) decrement in grip strength: HR 1.12 (95% CI, 1.01–1.25) and gait speed: HR 1.14 (95% CI, 1.02–1.27), and 1-SD increment in chair stands time: HR 1.08 (95% CI, 0.97–1.21). Greater annual declines in these measurements were associated with higher mortality risk, independent of the index values and other covariates. HR (95% CI) per 1-SD annual decrement in change in grip strength: HR 1.15 (95% CI, 1.01–1.33) and in gait speed: HR 1.38 (95% CI, 1.13–1.68), and 1-SD annual increment in chair stands time: HR 1.28 (95% CI, 1.07–1.54). Men who were unable to complete one or multiple tests had greater risk of postfracture mortality (24%–109%) compared to those performed all tests. It remains to be seen whether improvement in these modifiable factors can reduce postfracture mortality. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

Prediction of Incident Major Osteoporotic and Hip Fractures by Trabecular Bone Score (TBS) and Prevalent Radiographic Vertebral Fracture in Older Men

Trabecular bone score (TBS) has been shown to predict major osteoporotic (clinical vertebral, hip, humerus, and wrist) and hip fractures in postmenopausal women and older men, but the association of TBS with these incident fractures in men independent of prevalent radiographic vertebral fracture is unknown. TBS was estimated on anteroposterior (AP) spine dual‐energy X‐ray absorptiometry (DXA) scans obtained at the baseline visit for 5979 men aged ≥65 years enrolled in the Osteoporotic Fractures in Men (MrOS) Study and its association with incident major osteoporotic and hip fractures estimated with proportional hazards models. Model discrimination was tested with Harrell's C‐statistic and with a categorical net reclassification improvement index, using 10‐year risk cutpoints of 20% for major osteoporotic and 3% for hip fractures. For each standard deviation decrease in TBS, there were hazard ratios of 1.27 (95% confidence interval [CI] 1.17 to 1.39) for major osteoporotic fracture, and 1.20 (95% CI 1.05 to 1.39) for hip fracture, adjusted for FRAX with bone mineral density (BMD) 10‐year fracture risks and prevalent radiographic vertebral fracture. In the same model, those with prevalent radiographic vertebral fracture compared with those without prevalent radiographic vertebral fracture had hazard ratios of 1.92 (95% CI 1.49 to 2.48) for major osteoporotic fracture and 1.86 (95% CI 1.26 to 2.74) for hip fracture. There were improvements of 3.3%, 5.2%, and 6.2%, respectively, of classification of major osteoporotic fracture cases when TBS, prevalent radiographic vertebral fracture status, or both were added to FRAX with BMD and age, with minimal loss of correct classification of non‐cases. Neither TBS nor prevalent radiographic vertebral fracture improved discrimination of hip fracture cases or non‐cases. In conclusion, TBS and prevalent radiographic vertebral fracture are associated with incident major osteoporotic fractures in older men independent of each other and FRAX 10‐year fracture risks, and these data support their use in conjunction with FRAX for fracture risk assessment in older men. © 2015 American Society for Bone and Mineral Research.     

Trabecular Bone Score (TBS) Predicts Vertebral Fractures in Japanese Women Over 10 Years Independently of Bone Density and Prevalent Vertebral Deformity: The Japanese Population‐Based Osteoporosis (JPOS) Cohort Study

Bone strength is predominantly determined by bone density, but bone microarchitecture also plays an important role. We examined whether trabecular bone score (TBS) predicts the risk of vertebral fractures in a Japanese female cohort. Of 1950 randomly selected women aged 15 to 79 years, we analyzed data from 665 women aged 50 years and older, who completed the baseline study and at least one follow‐up survey over 10 years, and who had no conditions affecting bone metabolism. Each survey included spinal imaging by dual‐energy X‐ray absorptiometry (DXA) for vertebral fracture assessment and spine areal bone mineral density (aBMD) measurement. TBS was obtained from spine DXA scans archived in the baseline study. Incident vertebral fracture was determined when vertebral height was reduced by 20% or more and satisfied McCloskey‐Kanis criteria or Genant's grade 2 fracture at follow‐up. Among eligible women (mean age 64.1 ± 8.1 years), 92 suffered incident vertebral fractures (16.7/10³ person‐years). These women were older with lower aBMD and TBS values relative to those without fractures. The unadjusted odds ratio of vertebral fractures for one standard deviation decrease in TBS was 1.98 (95% confidence interval [CI] 1.56, 2.51) and remained significant (1.64, 95% CI 1.25, 2.15) after adjusting for aBMD. The area under the receiver operating characteristic curve of TBS and aBMD combined was 0.700 for vertebral fracture prediction and was not significantly greater than that of aBMD alone (0.673). However, reclassification improvement measures indicated that TBS and aBMD combined significantly improved risk prediction accuracy compared with aBMD alone. Further inclusion of age and prevalent vertebral deformity in the model improved vertebral fracture prediction, and TBS remained significant in the model. Thus, lower TBS was associated with higher risk of vertebral fracture over 10 years independently of aBMD and clinical risk factors including prevalent vertebral deformity. TBS could effectively improve fracture risk assessment in clinical settings. © 2014 American Society for Bone and Mineral Research.     

Ultrasound-Based Estimates of Cortical Bone Thickness and Porosity Are Associated With Nontraumatic Fractures in Postmenopausal Women: A Pilot Study

Recent ultrasound (US) axial transmission techniques exploit the multimode waveguide response of long bones to yield estimates of cortical bone structure characteristics. This pilot cross-sectional study aimed to evaluate the performance at the one-third distal radius of a bidirectional axial transmission technique (BDAT) to discriminate between fractured and nonfractured postmenopausal women. Cortical thickness (Ct.Th) and porosity (Ct.Po) estimates were obtained for 201 postmenopausal women: 109 were nonfractured (62.6 ± 7.8 years), 92 with one or more nontraumatic fractures (68.8 ± 9.2 years), 17 with hip fractures (66.1 ± 10.3 years), 32 with vertebral fractures (72.4 ± 7.9 years), and 17 with wrist fractures (67.8 ± 9.6 years). The areal bone mineral density (aBMD) was obtained using DXA at the femur and spine. Femoral aBMD correlated weakly, but significantly with Ct.Th (R = 0.23, p < 0.001) and Ct.Po (R = -0.15, p < 0.05). Femoral aBMD and both US parameters were significantly different between the subgroup of all nontraumatic fractures combined and the control group (p < 0.05). The main findings were that (1) Ct.Po was discriminant for all nontraumatic fractures combined (OR = 1.39; area under the receiver operating characteristic curve [AUC] equal to 0.71), for vertebral (OR = 1.96; AUC = 0.84) and wrist fractures (OR = 1.80; AUC = 0.71), whereas Ct.Th was discriminant for hip fractures only (OR = 2.01; AUC = 0.72); there was a significant association (2) between increased Ct.Po and vertebral and wrist fractures when these fractures were not associated with any measured aBMD variables; (3) between increased Ct.Po and all nontraumatic fractures combined independently of aBMD neck; and (4) between decreased Ct.Th and hip fractures independently of aBMD femur. BDAT variables showed comparable performance to that of aBMD neck with all types of fractures (OR = 1.48; AUC = 0.72) and that of aBMD femur with hip fractures (OR = 2.21; AUC = 0.70). If these results are confirmed in prospective studies, cortical BDAT measurements may be considered useful for assessing fracture risk in postmenopausal women. © 2019 American Society for Bone and Mineral Research.     

Low‐Level Cadmium Exposure Is Associated With Decreased Bone Mineral Density and Increased Risk of Incident Fractures in Elderly Men: The MrOS Sweden Study

One risk factor for osteoporosis that has attracted increasing attention in recent years is exposure to cadmium. The aim of this study was to examine the associations between low‐level cadmium exposure, from diet and smoking, and bone mineral density (BMD) and incident fractures in elderly men. The study population consisted of 936 men from the Swedish cohort of the Osteoporotic Fractures in Men (MrOS) study, aged 70 to 81 years at inclusion (years 2002 to 2004), with reliable data on cadmium in urine (U‐Cd) analyzed using inductively coupled plasma mass spectrometry in baseline samples. The participants also answered a questionnaire on lifestyle factors and medical history. BMD was measured at baseline using dual‐energy X‐ray absorptiometry (DXA) in the total body, hip, and lumbar spine. During the follow‐up period (until 2013), all new fractures were registered by date and type. Associations between BMD and U‐Cd were assessed using multiple linear regression, and associations between incident fractures and baseline U‐Cd were analyzed using Cox regression. In both cases, a number of potential confounders and other risk factors (eg, age, smoking, body mass index [BMI], and physical activity) were included in the models. We found significant negative associations between U‐Cd and BMD, with lower BMD (4% to 8%) for all sites in the fourth quartile of U‐Cd, using the first quartile as the reference. In addition, we found positive associations between U‐Cd and incident fractures, especially nonvertebral osteoporosis fractures in the fourth quartile of U‐Cd, with hazard ratios of 1.8 to 3.3 in the various models. U‐Cd as a continuous variable was significantly associated with nonvertebral osteoporosis fractures (adjusted hazard ratio 1.3 to 1.4 per μg Cd/g creatinine), also in never‐smokers, but not with the other fracture groups (all fractures, hip fractures, vertebral fractures, and other fractures). Our results indicate that even relatively low cadmium exposure through diet and smoking increases the risk of low BMD and osteoporosis‐related fractures in elderly men. © 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).     

Vertebral Size,Bone Density,and Strength in Men and Women Matched for Age and Areal Spine BMD

To explore the possible mechanisms underlying sex‐specific differences in skeletal fragility that may be obscured by two‐dimensional areal bone mineral density (aBMD) measures, we compared quantitative computed tomography (QCT)‐based vertebral bone measures among pairs of men and women from the Framingham Heart Study Multidetector Computed Tomography Study who were matched for age and spine aBMD. Measurements included vertebral body cross‐sectional area (CSA, cm²), trabecular volumetric BMD (Tb.vBMD, g/cm³), integral volumetric BMD (Int.vBMD, g/cm³), estimated vertebral compressive loading and strength (Newtons) at L₃, the factor‐of‐risk (load‐to‐strength ratio), and vertebral fracture prevalence. We identified 981 male‐female pairs (1:1 matching) matched on age (± 1 year) and QCT‐derived aBMD of L₃ (± 1%), with an average age of 51 years (range 34 to 81 years). Matched for aBMD and age, men had 20% larger vertebral CSA, lower Int.vBMD (–8%) and Tb.vBMD (–9%), 10% greater vertebral compressive strength, 24% greater vertebral compressive loading, and 12% greater factor‐of‐risk than women (p < 0.0001 for all), as well as higher prevalence of vertebral fracture. After adjusting for height and weight, the differences in CSA and volumetric bone mineral density (vBMD) between men and women were attenuated but remained significant, whereas compressive strength was no longer different. In conclusion, vertebral size, morphology, and density differ significantly between men and women matched for age and spine aBMD, suggesting that men and women attain the same aBMD by different mechanisms. These results provide novel information regarding sex‐specific differences in mechanisms that underlie vertebral fragility. © 2014 American Society for Bone and Mineral Research.     

Major Osteoporotic to Hip Fracture Ratios in Canadian Men and Women With Swedish Comparisons: A Population‐Based Analysis

Fracture Risk Assessment (FRAX) tools are calibrated from country‐specific fracture epidemiology. Although hip fracture data are usually available, data on non‐hip fractures for most countries are often lacking. In such cases, rates are often estimated by assuming similar non‐hip to hip fracture ratios from historical (1987 to 1996) Swedish data. Evidence that countries share similar fracture ratios is limited. Using data from Manitoba, Canada (2000 to 2007, population 1.2 million), we identified 21,850 incident major osteoporotic fractures (MOF) in men and women aged >50 years. Population‐based age‐ and sex‐specific ratios of clinical vertebral, forearm, and humerus fractures to hip fractures were calculated, along with odds ratios (ORs) and 95% confidence intervals (CIs). All ratios showed decreasing trends with increasing age for both men and women. Men and women showed similar vertebral/hip fracture ratios (all p > 0.1, with ORs 0.86 to 1.25). Forearm/hip and humerus/hip fracture ratios were significantly lower among men than women (forearm/hip ratio: p < 0.01 for all age groups, with ORs 0.29 to 0.53; humerus/hip ratio: p < 0.05 for all age groups [except 80 to 84 years] with ORs 0.46 to 0.86). Ratios for any MOF/hip fracture were also significantly lower among men than women in all but two subgroups (p < 0.05 for all age groups [except 80 to 84 and 90+ years] with ORs 0.48 to 0.87). Swedish vertebral/hip fracture ratios were similar to the Canadian fracture ratios (within 7%) but significantly lower for other sites (men and women: 46% and 35% lower for forearm/hip ratios, 19% and 15% lower for humerus/hip ratios, and 19% and 23% lower for any MOF/hip ratios). These differences have implications for updating and calibrating FRAX tools, fracture risk estimation, and intervention rates. Moreover, wherever possible, it is important that countries try to collect accurate non‐hip fracture data. © 2014 American Society for Bone and Mineral Research     

Circulating Levels of Carboxy‐Methyl‐Lysine (CML) Are Associated With Hip Fracture Risk: The Cardiovascular Health Study

Advanced glycation end products (AGE) in bone tissue are associated with impaired biomechanical properties and increased fracture risk. Here we examine whether serum levels of the AGE carboxy‐methyl‐lysine (CML) are associated with risk of hip fracture. We followed 3373 participants from the Cardiovascular Health Study (age 78 years; range, 68–102 years; 39.8% male) for a median of 9.22 years (range, 0.01–12.07 years). Rates of incident hip fracture were calculated by quartiles of baseline CML levels, and hazard ratios were adjusted for covariates associated with hip fracture risk. A subcohort of 1315 participants had bone mineral density (BMD) measurement. There were 348 hip fractures during follow‐up, with incidence rates of hip fracture by CML quartiles of 0.94, 1.34, 1.18, and 1.69 per 100 participant‐years. The unadjusted hazard ratio of hip fracture increased with each 1 SD increase (189 ng/mL) of CML level (hazard ratio, 1.27; 95% confidence interval [CI], 1.16–1.40]; p < 0.001). Sequential adjustment for age, gender, race/ethnicity, body mass index (BMI), smoking, alcohol consumption, prevalent coronary heart disease (CHD), energy expenditure, and estimated glomerular filtration rate (based on cystatin C), moderately attenuated the hazard ratio for fracture (1.17; 95% CI, 1.05–1.31; p = 0.006). In the cohort with BMD testing, total hip BMD was not significantly associated with CML levels. We conclude that increasing levels of CML are associated with hip fracture risk in older adults, independent of hip BMD. These results implicate AGE in the pathogenesis of hip fractures. © 2014 American Society for Bone and Mineral Research.     

Progressive Temporal Change in Serum SHBG,But Not in Serum Testosterone or Estradiol,Is Associated With Bone Loss and Incident Fractures in Older Men: The Concord Health and Ageing in Men Project

This study aimed to examine progressive temporal relationships between changes in major reproductive hormones across three waves of a cohort study of older men and (1) changes in bone mineral density (BMD) and (2) incident fractures (any, hip or non‐vertebral) over an average of 6 years of follow‐up. The CHAMP cohort of men aged 70 years and older were assessed at baseline (2005 to 2007, n = 1705), 2‐year follow‐up (n = 1367), and 5‐year follow‐up (n = 958). Serum testosterone (T), dihydrotestosterone (DHT), estradiol (E2), and estrone (E1) (by liquid chromatography–tandem mass spectrometry [LC‐MS/MS]), and sex hormone–binding globulin (SHBG), luteinizing hormone (LH), and follicle‐stimulating hormone (FSH) (by immunoassay) were measured at all time‐points, whereas free testosterone (cFT) was calculated using a well‐validated formula. Hip BMD was measured by dual‐energy X‐ray absorptiometry (DXA) at all three time‐points, and fracture data were verified radiographically. Statistical modeling was done using general estimating equations (GEEs). For total hip BMD, univariable analyses revealed inverse associations with temporal changes in serum SHBG, FSH, and LH and positive associations for serum E1 and cFT across the three time‐points. In models adjusted for multiple covariables, serum SHBG (β = –0.029), FSH (β = –0.065), LH (β = –0.049), E1 (β = 0.019), and cFT (β = 0.033) remained significantly associated with hip BMD. However for femoral neck BMD, only FSH (β = –0.048) and LH (β = –0.036) remained associated in multivariable‐adjusted models. Temporal change in serum SHBG, but not T, E2, or other hormonal variables, was significantly associated with any, nonvertebral or hip fracture incidence in univariable analyses. In multivariable‐adjusted models, temporal increase in serum SHBG over time remained associated with any fracture (β = 0.060) and hip fracture (β = 0.041) incidence, but not nonvertebral fracture incidence. These data indicate that a progressive increase in circulating SHBG over time predicts bone loss and fracture risk in older men. Further studies are warranted to further characterize changes in circulating SHBG as a mechanism and/or biomarker of bone health during male ageing. © 2016 American Society for Bone and Mineral Research.     

Microarchitecture and Peripheral BMD are Impaired in Postmenopausal White Women With Fracture Independently of Total Hip T‐Score: An International Multicenter Study

Because single‐center studies have reported conflicting associations between microarchitecture and fracture prevalence, we included high‐resolution peripheral quantitative computed tomography (HR‐pQCT) data from five centers worldwide into a large multicenter analysis of postmenopausal women with and without fracture. Volumetric BMD (vBMD) and microarchitecture were assessed at the distal radius and tibia in 1379 white postmenopausal women (age 67 ± 8 years); 470 (34%) had at least one fracture including 349 with a major fragility fracture. Age, height, weight, and total hip T‐score differed across centers and were employed as covariates in analyses. Women with fracture had higher BMI, were older, and had lower total hip T‐score, but lumbar spine T‐score was similar between groups. At the radius, total and trabecular vBMD and cortical thickness were significantly lower in fractured women in three out of five centers, and trabecular number in two centers. Similar results were found at the tibia. When data from five centers were combined, however, women with fracture had significantly lower total, trabecular, and cortical vBMD (2% to 7%), lower trabecular number (4% to 5%), and thinner cortices (5% to 6%) than women without fracture after adjustment for covariates. Results were similar at the radius and tibia. Similar results were observed with analysis restricted to major fragility fracture, vertebral and hip fractures, and peripheral fracture (at the radius). When focusing on osteopenic women, each SD decrease of total and trabecular vBMD was associated with a significantly increased risk of major fragility fracture (OR = 1.55 to 1.88, p < 0.01) after adjustment for covariates. Moreover, trabecular architecture modestly improved fracture discrimination beyond peripheral total vBMD. In conclusion, we observed differences by center in the magnitude of fracture/nonfracture differences at both the distal radius and tibia. However, when data were pooled across centers and the sample size increased, we observed significant and consistent deficits in vBMD and microarchitecture independent of total hip T‐score in all postmenopausal white women with fracture and in the subgroup of osteopenic women, compared to women who never had a fracture. © 2016 American Society for Bone and Mineral Research.     

Density and Fat Fraction of the Psoas,Paraspinal, and Oblique Muscle Groups Are Associated With Lumbar Vertebral Bone Mineral Density in a Multi-Ethnic Community-Living Population: The Multi-Ethnic Study of Atherosclerosis

Low vertebral bone mass is a major risk factor for vertebral compression fractures. Although sarcopenia has been shown to be associated with low bone mineral density (BMD), it is not known whether trunk musculature is directly associated with lumbar BMD, and whether exercise modifies this association. Using data from the Multi-Ethnic Study of Atherosclerosis (MESA), we sought to determine the association of muscle density and fat fraction of the psoas, paraspinal, and oblique muscle groups with L₃ lumbar volumetric BMD, and whether these associations were modified by exercise. We obtained L₃ vBMD measurements, and fat and muscle measurements (in Hounsfield units [HU]) from abdominal computed tomography (CT) scans spanning the L₂–L₄ intervertebral disc spaces. Muscle density was defined as the mean HU value for a muscle group area. Fat fraction was calculated as the mean HU value for the muscle group fat area/total muscle group area (cm²). Exercise data were self-reported (MET-minute/week). We utilized multivariable linear regression to evaluate these associations, stratified by gender, and adjusting for demographics, body mass index (BMI), smoking status, impaired fasting glucose, and corticosteroid and anti-resorptive medication use. Among 1923 MESA participants, mean ± standard deviation (SD) age was 62 ± 10 years, 49% were female, 40% white, 21% black, 26% Hispanic/Latino, and 13% Chinese. In fully adjusted analysis, for every 1-SD higher psoas fat fraction, there was a 3.19-SD lower L₃ vBMD in men and 4.3-SD lower L₃ vBMD in women (p < 0.001). For every 1-SD higher psoas density, there was a 0.2-SD higher L₃ vBMD (p < 0.001) in men and 0.19-SD higher L₃ vBMD (p < 0.001) in women. Findings were similar for paraspinal and oblique muscles. Intentional exercise did not modify these associations. In men and women, trunk muscle density was positively associated with higher lumbar BMD, suggesting a local association. Future studies are warranted to determine the temporality of this association. © 2022 American Society for Bone and Mineral Research (ASBMR).