Correlates of bone microarchitectural parameters and serum sclerostin levels in men: The STRAMBO study

Sclerostin is predominantly expressed by osteocytes. Serum sclerostin levels are positively correlated with areal bone mineral density (aBMD) measured by dual‐energy X‐ray absorptiometry (DXA) and bone microarchitecture assessed by high‐resolution peripheral quantitative computed tomography (HR‐pQCT) in small studies. We assessed the relation of serum sclerostin levels with aBMD and microarchitectural parameters based on HR‐pQCT in 1134 men aged 20 to 87 years using multivariable models adjusted for confounders (age, body size, lifestyle, comorbidities, hormones regulating bone metabolism, muscle mass and strength). The apparent age‐related increase in serum sclerostin levels was faster before the age of 63 years than afterward (0.43 SD versus 0.20 SD per decade). In 446 men aged ≤63 years, aBMD (spine, hip, whole body), trabecular volumetric BMD (Tb.vBMD), and trabecular number (Tb.N) at the distal radius and tibia were higher in the highest sclerostin quartile versus the three lower quartiles combined. After adjustment for aBMD, men in the highest sclerostin quartile had higher Tb.vBMD (mainly in the central compartment) and Tb.N at both skeletal sites (p < 0.05 to 0.001). In 688 men aged >63 years, aBMD was positively associated with serum sclerostin levels at all skeletal sites. Cortical vBMD (Ct.vBMD) and cortical thickness (Ct.Th) were lower in the first sclerostin quartile versus the three higher quartiles combined. Tb.vBMD increased across the sclerostin quartiles, and was associated with lower Tb.N and more heterogeneous trabecular distribution (higher Tb.Sp.SD) in men in the lowest sclerostin quartile. After adjustment for aBMD, men in the lowest sclerostin quartile had lower Tb.vBMD and Tb.N, but higher Tb.Sp.SD (p < 0.05 to 0.001) at both the skeletal sites. In conclusion, serum sclerostin levels in men are strongly positively associated with better bone microarchitectural parameters, mainly trabecular architecture, regardless of the potential confounders.     

Abdominal aortic calcification on vertebral morphometry images predicts incident myocardial infarction

Abdominal aortic calcification (AAC) measured on spine X‐rays is an established risk factor for cardiovascular disease. We investigated whether AAC assessed using vertebral morphometry and a recently developed scoring system (AAC‐8) is reliable and associated with cardiovascular risk factors or events. A total of 1471 healthy postmenopausal women and 323 healthy middle‐aged and older men participated in 5 and 2 year trials of calcium supplements, respectively. AAC‐8 was assessed on vertebral morphometry images at baseline and follow‐up. In addition, 163 men also had coronary artery calcification measured using computed tomography. Cardiovascular events during the trials were independently adjudicated. We found strong inter‐ and intrameasurer agreement for AAC‐8 (κ > 0.87). The prevalence of AAC increased with age (p < .01) in women and in men. AAC was associated with many established cardiovascular risk factors, with serum calcium in women (p = .002) and with higher coronary calcium scores in men (p = .03). Estimated 5 year cardiovascular risk increased with increasing AAC‐8 score (p < .001) in women and in men. The presence of AAC independently predicted myocardial infarction (MI) in women [hazards ratio (HR) = 2.30, p = .007] and men (HR = 5.32, p = .04), even after adjustment for estimated cardiovascular risk in women. In women, AAC independently predicted cardiovascular events (MI, stroke, or sudden death) (HR = 1.74, p = .007), and changes in AAC‐8 score over time were associated with MI and cardiovascular events, even after adjustment for estimated cardiovascular risk. In summary, scoring AAC on vertebral morphometric scans is a reproducible method of assessing cardiovascular risk that independently predicts incident MI and cardiovascular events, even after taking into account traditional cardiovascular risk factors. © 2010 American Society for Bone and Mineral Research     

QCT Volumetric Bone Mineral Density and Vascular and Valvular Calcification: The Framingham Study

There is increasing evidence that bone and vascular calcification share common pathogenesis. Little is known about potential links between bone and valvular calcification. The purpose of this study was to determine the association between spine bone mineral density (BMD) and vascular and valvular calcification. Participants included 1317 participants (689 women, 628 men) in the Framingham Offspring Study (mean age 60 years). Integral, trabecular, and cortical volumetric bone density (vBMD) and arterial and valvular calcification were measured from computed tomography (CT) scans and categorized by sex‐specific quartiles (Q4 = high vBMD). Calcification of the coronary arteries (CAC), abdominal aorta (AAC), aortic valve (AVC), and mitral valve (MVC) were quantified using the Agatston Score (AS). Prevalence of any calcium (AS >0) was 69% for CAC, 81% for AAC, 39% for AVC, and 20% for MVC. In women, CAC increased with decreasing quartile of trabecular vBMD: adjusted mean CAC = 2.1 (Q4), 2.2 (Q3), 2.5 (Q2), 2.6 (Q1); trend p = 0.04. However, there was no inverse trend between CAC and trabecular vBMD in men: CAC = 4.3 (Q4), 4.3 (Q3), 4.2 (Q2), 4.3 (Q1); trend p = 0.92. AAC increased with decreasing quartile of trabecular vBMD in both women (AAC = 4.5 [Q4], 4.8 [Q3], 5.4 [Q2], 5.1 [Q1]; trend p = 0.01) and men (AAC = 5.5 [Q4], 5.8 [Q3], 5.9 [Q2], 6.2 [Q1]; trend p = 0.01). We observed no association between trabecular vBMD and AVC or MVC in women or men. Finally, cortical vBMD was unrelated to vascular calcification and valvular calcification in women and men. Women and men with low spine vBMD have greater severity of vascular calcification, particularly at the abdominal aorta. The inverse relation between AAC and spine vBMD in women and men may be attributable to shared etiology and may be an important link on which to focus treatment efforts that can target individuals at high risk of both fracture and cardiovascular events. © 2015 American Society for Bone and Mineral Research.     

Early impairment of trabecular microarchitecture assessed with HR‐pQCT in patients with stage II‐IV chronic kidney disease

Bone fragility is a complication of chronic kidney disease (CKD). The aim of this study was to assess whether volumetric bone mineral density (vBMD) and microarchitecture could be impaired early in the course of CKD. Bone microarchitecture was examined with a noninvasive 3D imaging technique [high‐resolution peripheral quantitative computed tomography (HR‐pQCT)] at the tibia and radius in 70 stage II‐IV CKD patients older than 50 years of age; controls belonged to two cohorts of healthy subjects comparable for age and gender (OFELY cohort in women and STRAMBO cohort in men). We examined 46 men and 24 women; 19 patients were diabetic. Mean age was 70.8 ± 8.5 years, mean glomerular filtration rate (GFR) was 34 ± 12 mL/min per 1.73 m², and mean serum parathyroid hormone (PTH) level was 87 ± 59 pg/mL. Both CKD men and women experienced a moderate but significant trabecular (Tb) impairment, positioning CKD patient values between those of normal and osteopenic controls (e.g., CKD men versus healthy controls: Tb vBMD 172 ± 35 versus 188 ± 34 mg HA/cm³; Tb number 1.75 ± 0.27 versus 1.86 ± 0.26 mm^?1, and Tb separation 503 ± 94 versus 465 ± 78 µm; p < .05). Cortical thickness (Ct.Th) in men also was significantly decreased compared with healthy controls (e.g., CKD men versus healthy controls: tibial Ct.Th 1171 ± 331 versus 1288 ± 283 µm; p < .05). In conclusion, this study, using a noninvasive bone‐imaging device, shows for the first time an early impairment of trabecular microarchitecture in stage II‐IV CKD patients. Further longitudinal studies should be performed to validate HR‐pQCT as a tool for predicting the fracture risk in CKD. © 2010 American Society for Bone and Mineral Research.     

Poor bone microarchitecture in older men with impaired physical performance—the STRAMBO study

Summary

In 810 men ≥60?years, poor physical performance of lower limbs was associated with lower areal bone mineral density (aBMD) of total hip and poor bone microarchitecture at the distal tibia (assessed by HR-pQCT). Men who reported falls had lower hip aBMD and lower cortical density at the distal tibia.

Introduction

The aim of this study was to assess the association between bone microarchitecture and physical performance in older men.

Methods

Volumetric bone mineral density (vBMD) and bone microarchitecture were assessed in 810 men ≥60?years at the distal radius and tibia by high resolution pQCT. aBMD was measured at the spine, hip, whole body, and distal radius by dual energy X-ray absorptiometry. Clinical tests included chair stands and tests of static and dynamic balance. We calculated a composite score summarizing abilities and time required to perform the tests.

Results

In multivariable models, men who failed in ≥one test had lower total hip aBMD than men who accomplished all the tests. They had lower total vBMD (Tt.vBMD), cortical thickness (Ct.Th), trabecular vBMD (Tb.vBMD), and more heterogenous trabecular distribution (Tb.Sp.SD) at the distal tibia (p?<?0.05). Men who failed in ≥two tests had lower aBMD at the total hip, femoral neck, and trochanter as well as lower Tt.vBMD, cortical vBMD (Ct.vBMD), Ct.Th and trabecular number (Tb.N), and higher Tb.Sp.SD at the distal tibia (p?<?0.05). Men in the lowest quartile of the composite score had lower aBMD (total hip, distal radius), lower Tb.vBMD and Tb.N at the distal radius, and lower Tt.vBMD, Ct.vBMD, Ct.Th, Tb.vBMD, and Tb.N, and higher Tb.Sp.SD at the distal tibia compared with the highest quartile. In multivariables models, men reporting falls had lower total hip aBMD and lower distal tibia Ct.vBMD (p?<?0.01).

Conclusion

In older men, poor physical performance is associated with lower hip aBMD and poor bone microarchitecture (mainly at the distal tibia).     

Rates of and Risk Factors for Trabecular and Cortical BMD Loss in Middle‐Aged and Elderly African‐Ancestry Men

Low trabecular (Tb) and cortical (Ct) volumetric BMD (vBMD) are related to increased fracture risk, but little is known about the patterns and correlates of Tb and Ct vBMD loss with aging. We examined the rates of change in total, Tb.vBMD, and Ct.vBMD at the radius and tibia, and identified factors associated with vBMD loss among 1569 men of African descent aged 40 years and older. Quantitative computed tomography was used to measure vBMD 6 years apart. The annualized rate of loss in Tb.vBMD was significant at the radius (–0.047%/yr, p = 0.016) but not at the tibia. At the radius, a significant loss of Tb.vBMD was observed in men aged 40 to 49 years that appeared to be attenuated and not statistically significant among older age men. In contrast, the decline in Ct.vBMD was similar at both skeletal sites (–0.254 to –0.264%/yr, p < 0.0001) and was consistent across all age groups. Positive associations were found for vBMD changes with body weight (all but radius Ct.vBMD) and diabetes (Ct.vBMD only), whereas negative associations were found with hypertension (all but radius Tb.vBMD), smoking (Ct.vBMD only), and androgen deprivation therapy (cortical vBMD only). Trabecular and cortical vBMD loss appears to follow different patterns among middle‐ and older‐aged men of African ancestry. Factors associated with the decline in vBMD also varied by compartment and anatomical site. Additional studies are needed to better understand the physiological mechanisms underlying early BMD loss among African‐ancestry men. © 2014 American Society for Bone and Mineral Research.     

Impaired bone microarchitecture at the distal radius in older men with low muscle mass and grip strength: The STRAMBO study

The aim was to study the association between bone microarchitecture and muscle mass and strength in older men. Volumetric bone mineral density (vBMD) and bone microarchitecture were assessed in 810 men aged ≥60 years at the distal radius by high‐resolution peripheral computed tomography (HR‐pQCT). Areal bone mineral density (aBMD) and appendicular muscle mass (ASM) were assessed by dual‐energy X‐ray absorptiometry (DXA). Relative ASM of the upper limbs (RASM‐u.l.) was calculated as ASM of the upper limbs/(height)². Grip strength was measured by dynanometry. In multivariable models, men in the lowest RASM‐u.l. quartile had lower cross‐sectional area (CSA), cortical area (Ct.Ar), cortical thickness (Ct.Th), and trabecular area (Tb.Ar) at distal radius compared with men in the highest quartile. The trends remained significant after adjustment for grip strength. Men in the lowest quartile of the normalized grip strength (grip strength/[height]²) had lower aBMD, total vBMD, Ct.Ar, Ct.Th, Tb.vBMD, and Tb.N, and higher Tb.Sp and Tb.Sp.SD. The associations for Ct.Ar, total vBMD, Ct.Th, Tb.vBMD, and Tb.Sp remained significant after adjustment for RASM‐u.l. In the models including RASM‐u.l. and normalized grip strength, CSA and Tb.Ar were associated with RASM‐u.l. but not with the strength. Lower Ct.Th, Tb.vBMD, and Tb.N were associated with lower grip strength but not with RASM‐u.l. Lower Ct.Ar was associated with lower grip strength and with lower RASM‐u.l. In conclusion, in older men, low RASM‐u.l. and low grip strength are associated with poor cortical and trabecular microarchitecture partly independently of each other, after adjustment for confounders. © 2013 American Society for Bone and Mineral Research     

Decreased Quantity and Quality of the Periarticular and Nonperiarticular Bone in Patients With Rheumatoid Arthritis: A Cross‐Sectional HR‐pQCT Study

Rheumatoid arthritis (RA) is a highly bone destructive disease. Although it is well established that RA leads to bone loss and increased fracture risk, current knowledge on the microstructural changes of bone in RA is still limited. The purpose of this study was to assess the microstructure of periarticular and nonperiarticular bone in female and male RA patients and compare it with respective healthy controls. We performed two high‐resolution peripheral quantitative computed tomography (HR‐pQCT; Xtreme‐CT) scans, one of the distal radius and one of the ultradistal radius in 90 patients with RA (60 females, 30 males) and 70 healthy controls (40 females, 30 males) matched for sex, age, and body mass index. Volumetric bone mineral density (vBMD), bone geometry, and bone microstructure including trabecular bone volume fraction (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), cortical thickness (Ct.Th) and cortical porosity (Ct.Po) were assessed. At the distal and ultradistal radius, trabecular (p = 0.005 and p < 0.001) and cortical BMD (p < 0.001 and p < 0.001) were significantly decreased in male and female patients with RA, respectively. BV/TV was also decreased at both sites, based on lower Tb.N in female RA (p < 0.001 for both sites) and lower Tb.Th (p = 0.034 and p = 0.005) in male RA patients compared with respective healthy controls. Cortical thinning (p = 0.018 and p = 0.002) but not Ct.Po (p = 0.070 and p = 0.275) was pronounced in male and female RA patients at the distal radius. Cortical perimeter was increased in male and female RA patients at both sites. Multiple regression models showed that bone geometry (cortical perimeter) is predominantly influenced by age of the RA patient, cortical thickness by both age and disease duration, and trabecular microstructure predominantly by the disease duration. In summary, these data show profound deterioration of bone microstructure in the appendicular skeleton of RA patients at both periarticular and nonperiarticular sites. © 2014 American Society for Bone and Mineral Research.     

Bone Density,Microstructure and Strength in Obese and Normal Weight Men and Women in Younger and Older Adulthood

Obesity is associated with greater areal BMD (aBMD) and is considered protective against hip and vertebral fracture. Despite this, there is a higher prevalence of lower leg and proximal humerus fracture in obesity. We aimed to determine if there are site‐specific differences in BMD, bone structure, or bone strength between obese and normal‐weight adults. We studied 100 individually‐matched pairs of normal (body mass index [BMI] 18.5 to 24.9 kg/m²) and obese (BMI >30 kg/m²) men and women, aged 25 to 40 years or 55 to 75 years. We assessed aBMD at the whole body (WB), hip (TH), and lumbar spine (LS) with dual‐energy X‐ray absorptiometry (DXA), LS trabecular volumetric BMD (Tb.vBMD) by quantitative computed tomography (QCT), and vBMD and microarchitecture and strength at the distal radius and tibia with high‐resolution peripheral QCT (HR‐pQCT) and micro–finite element analysis. Serum type 1 procollagen N‐terminal peptide (P1NP) and collagen type 1 C‐telopeptide (CTX) were measured by automated electrochemiluminescent immunoassay (ECLIA). Obese adults had greater WB, LS, and TH aBMD than normal adults. The effect of obesity on LS and WB aBMD was greater in older than younger adults (p < 0.01). Obese adults had greater vBMD than normal adults at the tibia (p < 0.001 both ages) and radius (p < 0.001 older group), thicker cortices, higher cortical BMD and tissue mineral density, lower cortical porosity, higher trabecular BMD, and higher trabecular number than normal adults. There was no difference in bone size between obese and normal adults. Obese adults had greater estimated failure load at the radius (p < 0.05) and tibia (p < 0.01). Differences in HR‐pQCT measurements between obese and normal adults were seen more consistently in the older than the younger group. Bone turnover markers were lower in obese than in normal adults. Greater BMD in obesity is not an artifact of DXA measurement. Obese adults have higher BMD, thicker and denser cortices, and higher trabecular number than normal adults. Greater differences between obese and normal adults in the older group suggest that obesity may protect against age‐related bone loss and may increase peak bone mass. © 2014 American Society for Bone and Mineral Research.     

Bone mass and strength in older men with type 2 diabetes: The Osteoporotic Fractures in Men Study

The effects of type 2 diabetes mellitus (T2DM) on bone volumetric density, bone geometry, and estimates of bone strength are not well established. We used peripheral quantitative computed tomography (pQCT) to compare tibial and radial bone volumetric density (vBMD, mg/cm³), total (ToA, mm²) and cortical (CoA, mm²) bone area and estimates of bone compressive and bending strength in a subset (n = 1171) of men (≥65 years of age) who participated in the multisite Osteoporotic Fractures in Men (MrOS) study. Analysis of covariance–adjusted bone data for clinic site, age, and limb length (model 1) and further adjusted for body weight (model 2) were used to compare data between participants with (n = 190) and without (n = 981) T2DM. At both the distal tibia and radius, patients with T2DM had greater bone vBMD (+2% to +4%, model 1, p < .05) and a smaller bone area (ToA ?1% to ?4%, model 2, p < .05). The higher vBMD compensated for lower bone area, resulting in no differences in estimated compressive bone strength at the distal trabecular bone regions. At the mostly cortical bone midshaft sites of the radius and tibia, men with T2DM had lower ToA (?1% to ?3%, p < .05), resulting in lower bone bending strength at both sites after adjusting for body weight (?2% to ?5%, p < .05) despite the lack of difference in cortical vBMD at these sites. These data demonstrate that older men with T2DM have bone strength that is low relative to body weight at the cortical‐rich midshaft of the radius despite no difference in cortical vBMD. © 2010 American Society for Bone and Mineral Research     

Microarchitecture Influences Microdamage Accumulation in Human Vertebral Trabecular Bone

It has been suggested that accumulation of microdamage with age contributes to skeletal fragility. However, data on the age‐related increase in microdamage and the association between microdamage and trabecular microarchitecture in human vertebral cancellous bone are limited. We quantified microdamage in cancellous bone from human lumbar (L₂) vertebral bodies obtained from 23 donors 54–93 yr of age (8 men and 15 women). Damage was measured using histologic techniques of sequential labeling with chelating agents and was related to 3D microarchitecture, as assessed by high‐resolution μCT. There were no significant differences between sexes, although women tended to have a higher microcrack density (Cr.Dn) than men. Cr.Dn increased exponentially with age (r = 0.65, p < 0.001) and was correlated with bone volume fraction (BV/TV; r = ?0.55; p < 0.01), trabecular number (Tb.N; r = ?0.56 p = 0.008), structure model index (SMI; r = 0.59; p = 0.005), and trabecular separation (Tb.Sp; r = 0.59; p < 0.009). All architecture parameters were strongly correlated with each other and with BV/TV. Stepwise regression showed that SMI was the best predictor of microdamage, explaining 35% of the variance in Cr.Dn and 20% of the variance in diffuse damage accumulation. In addition, microcrack length was significantly greater in the highest versus lowest tertiles of SMI. In conclusion, in human vertebral cancellous bone, microdamage increases with age and is associated with low BV/TV and a rod‐like trabecular architecture.     

CT‐measured bone attenuation in patients with chronic obstructive pulmonary disease: Relation to clinical features and outcomes

Osteoporosis is highly prevalent in chronic obstructive pulmonary disease (COPD) patients and has been related to several clinical features. However, most studies have been in relatively small COPD cohorts. Therefore, the objectives of this study were to compare bone attenuation measured on low‐dose chest computed tomography (CT) between COPD subjects and smoker and nonsmoker controls, and to relate bone attenuation to clinical parameters, inflammatory biomarkers, and outcomes in a large, well‐characterized COPD cohort. We studied 1634 COPD subjects, 259 smoker controls, and 186 nonsmoker controls who participated in a large longitudinal study (ECLIPSE). We measured bone attenuation, extent of emphysema, and coronary artery calcification (Agatston score) on baseline CT scans, and clinical parameters, inflammatory biomarkers, and outcomes. Bone attenuation was lower in COPD subjects compared with smoker and nonsmoker controls (164.9 ± 49.5 Hounsfield units [HU] versus 183.8 ± 46.1 HU versus 212.1 ± 54.4 HU, p < 0.001). Bone attenuation was not significantly different between COPD subjects and smoker controls after adjustment for age, sex, and pack‐years of smoking. In the COPD subjects, bone attenuation correlated positively with forced expiratory volume in 1 second (FEV₁, r = 0.062, p = 0.014), FEV₁/forced vital capacity (FVC) ratio (r = 0.102, p < 0.001), body mass index (r = 0.243, p < 0.001), fat‐free mass index (FFMI, r = 0.265, p < 0.001), and C‐reactive protein (r = 0.104, p < 0.001), and correlated negatively with extent of emphysema (r = ?0.090, p < 0.001), Agatston score (r = ?0.177, p < 0.001), and interleukin‐8 (r = ?0.054, p = 0.035). In a multiple regression model, older age, lower FFMI and higher Agatston score were associated with lower bone attenuation. Lower bone attenuation was associated with higher exacerbation (r = ?0.057, p = 0.022) and hospitalization (r = ?0.078, p = 0.002) rates but was not associated with all‐cause mortality. In conclusion, CT‐measured bone attenuation was lower in COPD subjects compared with nonsmoker controls but not compared with smoker controls, after adjustment for age, sex, and pack‐years of smoking. In the COPD subjects, bone attenuation was associated with age, body composition, and coronary artery calcification but was not associated with all‐cause mortality.     

Gender differences in trabecular bone architecture of the distal radius assessed with magnetic resonance imaging and implications for mechanical competence

High-resolution magnetic resonance imaging (hrMRI) has recently made it possible to evaluate trabecular bone structure in vivo. Despite obvious gender differences in fracture incidence at the distal radius, little is known about gender differences in trabecular bone microarchitecture and its relationship to the structural strength of the forearm. The aim of this study was to determine trabecular bone structure in the distal radius of elderly women and men and its correlation with failure loads of the distal radius as determined in a fall configuration. Specifically, we tested the hypotheses that structural indices differ between women and men and that they offer information that is independent from BMD for predicting structural strength. Intact right arms were obtained from 73 formalin-fixed cadavers (age 80±11 years, 43 women, 30 men). Trabecular structural indices (apparent bone volume fraction [app. BV/TV], trabecular number [app. Tb.N], trabecular separation [app. Tb.Sp], trabecular thickness [app. Tb.Th] and fractal dimension [Frac.Dim]) were assessed in the distal metaphysis, using hrMRI with 156 µm in-plane resolution and proprietary digital image analysis, while BMD was measured with dual X-ray absorptiometry (DXA). Women displayed significantly lower BMD (–29.8%, p <0.001), app. BV/TV (–8.2%, p <0.05) and app. Tb.Th (–10.2%, p <0.001) than men, whereas app. Tb.N, app. Tb.Sp. and fractal dimension did not differ significantly. Structural parameters differed between normal and osteopenic women (BV/TV: –11%, p <0.01; Tb.Th: –8%, p <0.001) and between normal and osteoporotic women BV/TV: –21%, p <0.001; Tb.Th: –16%, p <0.001). App. BV/TV, app. Tb.Th and fractal dimension provided information independent from BMD in the prediction of radial failure loads in multiple regression models. These findings imply that it should be of clinical interest to monitor both bone mass and trabecular microstructure for predicting osteoporotic fracture risk.     

Association of volumetric bone mineral density with abdominal aortic calcification in African ancestry men

Summary

We tested for association between cortical and trabecular volumetric bone mineral density (vBMD) with abdominal aortic calcification (AAC) prevalence in 278 Afro-Caribbean men. AAC was present in 68.3 % of the men. Greater cortical, but not trabecular, vBMD was associated with significantly decreased odds of AAC independent of traditional risk factors.

Introduction

The aim of this study is to assess the prevalence and correlates of AAC in a sample of 278 Afro-Caribbean men (mean age 56) and to test for a largely unexplored association between cortical and trabecular vBMD with AAC prevalence.

Methods

Men were recruited consecutively as part of an ongoing prospective cohort study of body composition in men aged 40+. For this analysis, AAC was assessed by computed tomography of the abdomen from L3 to S1. Aortic calcium was scored using the Agatston method, and prevalence was defined as a score ≥10 to rule out false positives. Men also had BMD assessed using peripheral quantitative computed tomography at 4 % (trabecular vBMD) and 33 % (cortical vBMD) of the radius and tibia.

Results

Abdominal aortic calcification was present in 68.3 % of the men. Significant independent predictors of AAC prevalence were increased age, increased BMI, hypertension, and current smoking. Age was the strongest predictor, with each SD (7.8 year) increase in age conferring 2.7 times increased odds of having AAC (P?<?0.0001). A one SD greater cortical, but not trabecular, vBMD was associated with a significant decreased odds of AAC prevalence independent of other traditional risk factors (OR 0.65; 95 % CI 0.45–0.92).

Conclusions

Cortical vBMD is inversely associated with AAC presence. This finding suggests that there may be shared physiology between cortical bone compartment remodeling and vascular calcification.     

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 Geometry,Volumetric Density,Microarchitecture, and Estimated Bone Strength Assessed by HR‐pQCT in Adult Patients With Hypophosphatemic Rickets

Hypophosphatemic rickets (HR) is characterized by a generalized mineralization defect. Although densitometric studies have found the patients to have an elevated bone mineral density (BMD), data on bone geometry and microstructure are scarce. The aim of this cross‐sectional in vivo study was to assess bone geometry, volumetric BMD (vBMD), microarchitecture, and estimated bone strength in adult patients with HR using high‐resolution peripheral quantitative computed tomography (HR‐pQCT). Twenty‐nine patients (aged 19 to 79 years; 21 female, 8 male patients), 26 of whom had genetically proven X‐linked HR, were matched with respect to age and sex with 29 healthy subjects. Eleven patients were currently receiving therapy with calcitriol and phosphate for a median duration of 29.1 years (12.0 to 43.0 years). Because of the disproportionate short stature in HR, the region of interest in HR‐pQCT images at the distal radius and tibia were placed in a constant proportion to the entire length of the bone in both patients and healthy volunteers. In age‐ and weight‐adjusted models, HR patients had significantly higher total bone cross‐sectional areas (radius 36%, tibia 20%; both p < 0.001) with significantly higher trabecular bone areas (radius 49%, tibia 14%; both p < 0.001) compared with controls. In addition, HR patients had lower total vBMD (radius ?20%, tibia ?14%; both p < 0.01), cortical vBMD (radius ?5%, p < 0.001), trabecular number (radius ?13%, tibia ?14%; both p < 0.01), and cortical thickness (radius ?19%; p < 0.01) compared with controls, whereas trabecular spacing (radius 18%, tibia 23%; p < 0.01) and trabecular network inhomogeneity (radius 29%, tibia 40%; both p < 0.01) were higher. Estimated bone strength was similar between the groups. In conclusion, in patients with HR, the negative impact of lower vBMD and trabecular number on bone strength seems to be compensated by an increase in bone diameter, resulting in HR patients having normal estimates of bone strength. © 2014 American Society for Bone and Mineral Research.     

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.     

A longitudinal HR‐pQCT study of alendronate treatment in postmenopausal women with low bone density: Relations among density,cortical and trabecular microarchitecture,biomechanics, and bone turnover

The goal of this study was to characterize longitudinal changes in bone microarchitecture and function in women treated with an established antifracture therapeutic. In this double‐blind, placebo‐controlled pilot study, 53 early postmenopausal women with low bone density (age = 56 ± 4 years; femoral neck T‐score = ?1.5 ± 0.6) were monitored by high‐resolution peripheral quantitative computed tomography (HR‐pQCT) for 24 months following randomization to alendronate (ALN) or placebo (PBO) treatment groups. Subjects underwent annual HR‐pQCT imaging of the distal radius and tibia, dual‐energy X‐ray absorptiometry (DXA), and determination of biochemical markers of bone turnover (BSAP and uNTx). In addition to bone density and microarchitecture assessment, regional analysis, cortical porosity quantification, and micro‐finite‐element analysis were performed. After 24 months of treatment, at the distal tibia but not the radius, HR‐pQCT measures showed significant improvements over baseline in the ALN group, particularly densitometric measures in the cortical and trabecular compartments and endocortical geometry (cortical thickness and area, medullary area) (p < .05). Cortical volumetric bone mineral density (vBMD) in the tibia alone showed a significant difference between treatment groups after 24 months (p < .05); however, regionally, significant differences in Tb.vBMD, Tb.N, and Ct.Th were found for the lateral quadrant of the radius (p < .05). Spearman correlation analysis revealed that the biomechanical response to ALN in the radius and tibia was specifically associated with changes in trabecular microarchitecture (|ρ| = 0.51 to 0.80, p < .05), whereas PBO progression of bone loss was associated with a broad range of changes in density, geometry, and microarchitecture (|ρ| = 0.56 to 0.89, p < .05). Baseline cortical geometry and porosity measures best predicted ALN‐induced change in biomechanics at both sites (ρ > 0.48, p < .05). These findings suggest a more pronounced response to ALN in the tibia than in the radius, driven by trabecular and endocortical changes. © 2010 American Society for Bone and Mineral Research.     

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

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

Divergent Effects of Glucocorticoids on Cortical and Trabecular Compartment BMD in Childhood Nephrotic Syndrome

Glucocorticoid (GC) effects on skeletal development have not been established. The objective of this pQCT study was to assess volumetric BMD (vBMD) and cortical dimensions in childhood steroid‐sensitive nephrotic syndrome (SSNS), a disorder with minimal independent deleterious skeletal effects. Tibia pQCT was used to assess trabecular and cortical vBMD, cortical dimensions, and muscle area in 55 SSNS (age, 5–19 yr) and >650 control participants. Race‐, sex‐, and age‐, or tibia length‐specific Z‐scores were generated for pQCT outcomes. Bone biomarkers included bone‐specific alkaline phosphatase and urinary deoxypyridinoline. SSNS participants had lower height Z‐scores (p < 0.0001) compared with controls. In SSNS, Z‐scores for cortical area were greater (+0.37; 95% CI = 0.09, 0.66; p = 0.01), for cortical vBMD were greater (+1.17; 95% CI = 0.89, 1.45; p < 0.0001), and for trabecular vBMD were lower (?0.60; 95% CI, = ?0.89, ?0.31; p < 0.0001) compared with controls. Muscle area (+0.34; 95% CI = 0.08, 0.61; p = 0.01) and fat area (+0.56; 95% CI = 0.27, 0.84; p < 0.001) Z‐scores were greater in SSNS, and adjustment for muscle area eliminated the greater cortical area in SSNS. Bone formation and resorption biomarkers were significantly and inversely associated with cortical vBMD in SSNS and controls and were significantly lower in the 34 SSNS participants taking GCs at the time of the study compared with controls. In conclusion, GCs in SSNS were associated with significantly greater cortical vBMD and cortical area and lower trabecular vBMD, with evidence of low bone turnover. Lower bone biomarkers were associated with greater cortical vBMD. Studies are needed to determine the fracture implications of these varied effects.