Lower trabecular volumetric BMD at metaphyseal regions of weight‐bearing bones is associated with prior fracture in young girls

Understanding the etiology of skeletal fragility during growth is critical for the development of treatments and prevention strategies aimed at reducing the burden of childhood fractures. Thus we evaluated the relationship between prior fracture and bone parameters in young girls. Data from 465 girls aged 8 to 13 years from the Jump‐In: Building Better Bones study were analyzed. Bone parameters were assessed at metaphyseal and diaphyseal sites of the nondominant femur and tibia using peripheral quantitative computed tomography (pQCT). Dual‐energy X‐ray absorptiometry (DXA) was used to assess femur, tibia, lumbar spine, and total body less head bone mineral content. Binary logistic regression was used to evaluate the relationship between prior fracture and bone parameters, controlling for maturity, body mass, leg length, ethnicity, and physical activity. Associations between prior fracture and all DXA and pQCT bone parameters at diaphyseal sites were nonsignificant. In contrast, lower trabecular volumetric BMD (vBMD) at distal metaphyseal sites of the femur and tibia was significantly associated with prior fracture. After adjustment for covariates, every SD decrease in trabecular vBMD at metaphyseal sites of the distal femur and tibia was associated with 1.4 (1.1–1.9) and 1.3 (1.0–1.7) times higher fracture prevalence, respectively. Prior fracture was not associated with metaphyseal bone size (ie, periosteal circumference). In conclusion, fractures in girls are associated with lower trabecular vBMD, but not bone size, at metaphyseal sites of the femur and tibia. Lower trabecular vBMD at metaphyseal sites of long bones may be an early marker of skeletal fragility in girls. © 2011 American Society for Bone and Mineral Research.     

Bone density,geometry, microstructure,and stiffness: Relationships between peripheral and central skeletal sites assessed by DXA,HR‐pQCT,and cQCT in premenopausal women

High‐resolution peripheral quantitative computed tomography (HR‐pQCT) is a new in vivo imaging technique for assessing 3D microstructure of cortical and trabecular bone at the distal radius and tibia. No studies have investigated the extent to which measurements of the peripheral skeleton by HR‐pQCT reflect those of the spine and hip, where the most serious fractures occur. To address this research question, we performed dual‐energy X‐ray absorptiometry (DXA), central QCT (cQCT), HR‐pQCT, and image‐based finite‐element analyses on 69 premenopausal women to evaluate relationships among cortical and trabecular bone density, geometry, microstructure, and stiffness of the lumbar spine, proximal femur, distal radius, and distal tibia. Significant correlations were found between the stiffness of the two peripheral sites (r = 0.86), two central sites (r = 0.49), and between the peripheral and central skeletal sites (r = 0.56–0.70). These associations were explained in part by significant correlations in areal bone mineral density (aBMD), volumetric bone mineral density (vBMD), and cross‐sectional area (CSA) between the multiple skeletal sites. For the prediction of proximal femoral stiffness, vBMD (r = 0.75) and stiffness (r = 0.69) of the distal tibia by HR‐pQCT were comparable with direct measurements of the proximal femur: aBMD of the hip by DXA (r = 0.70) and vBMD of the hip by cQCT (r = 0.64). For the prediction of vertebral stiffness, trabecular vBMD (r = 0.58) and stiffness (r = 0.70) of distal radius by HR‐pQCT were comparable with direct measurements of lumbar spine: aBMD by DXA (r = 0.78) and vBMD by cQCT (r = 0.67). Our results suggest that bone density and microstructural and mechanical properties measured by HR‐pQCT of the distal radius and tibia reflect the mechanical competence of the central skeleton. © 2010 American Society for Bone and Mineral Research.     

Leptin is a negative independent predictor of areal BMD and cortical bone size in young adult Swedish men.

The association between leptin and areal BMD has been controversial, and the predictive role of leptin on cortical volumetric BMD and bone size has not previously been studied. We show that leptin is a negative independent predictor of aBMD (DXA), at several measured sites, and of cortical bone size (pQCT) in a large population of young men. INTRODUCTION: Recent findings suggest that both adipose tissue (AT) and bone mass are regulated by leptin. Previous reports studying the association between leptin and areal BMD (aBMD) have yielded conflicting results. The role of leptin on volumetric BMD (vBMD) and bone size of the cortical and trabecular bone compartments has not previously been studied. MATERIALS AND METHODS: The Gothenburg Osteoporosis and Obesity Determinants (GOOD) study is a population-based study of 1068 men (age, 18.9 +/- 0.6 [SD] years). aBMD of the total body, lumbar spine, femoral neck, both radii, and trochanter, as well as total body AT and lean mass (LM) were measured using DXA, whereas cortical and trabecular vBMD and bone size were measured by pQCT. RESULTS: Total body LM could explain a larger magnitude of the difference in the variation in aBMD and cortical bone size than what total body AT could (total body aBMD: LM 37.4% versus AT 8.7%; tibia cross-sectional area [CSA]: LM 46.8% versus AT 5.6%). The independent role of leptin on bone parameters was studied using a multiple linear regression model, including age, total body LM and AT, height, present physical activity, calcium intake, and smoking as covariates. Leptin was found to be a negative independent predictor of aBMD (total body: beta = -0.08, p = 0.01; lumbar spine: beta = -0.13, p < 0.01; trochanter: beta = -0.09, p = 0.01), as well as of the cortical bone size (CSA and thickness) of both the radius (CSA: beta = -0.12, p < 0.001) and tibia (CSA: beta = -0.08, p < 0.01), but not of the cortical or trabecular vBMD of these bones. CONCLUSION: Our results indicate that LM has a greater impact on bone mass than AT. Our findings further show that leptin is a negative independent predictor of aBMD at several measured sites and of bone parameters reflecting cortical bone size, but not vBMD, in a large population of young Swedish men.     

Abnormal microarchitecture and reduced stiffness at the radius and tibia in postmenopausal women with fractures

Measurement of areal bone mineral density (aBMD) by dual‐energy x‐ray absorptiometry (DXA) has been shown to predict fracture risk. High‐resolution peripheral quantitative computed tomography (HR‐pQCT) yields additional information about volumetric BMD (vBMD), microarchitecture, and strength that may increase understanding of fracture susceptibility. Women with (n = 68) and without (n = 101) a history of postmenopausal fragility fracture had aBMD measured by DXA and trabecular and cortical vBMD and trabecular microarchitecture of the radius and tibia measured by HR‐pQCT. Finite‐element analysis (FEA) of HR‐pQCT scans was performed to estimate bone stiffness. DXA T‐scores were similar in women with and without fracture at the spine, hip, and one‐third radius but lower in patients with fracture at the ultradistal radius (p < .01). At the radius fracture, patients had lower total density, cortical thickness, trabecular density, number, thickness, higher trabecular separation and network heterogeneity (p < .0001 to .04). At the tibia, total, cortical, and trabecular density and cortical and trabecular thickness were lower in fracture patients (p < .0001 to .03). The differences between groups were greater at the radius than at the tibia for inner trabecular density, number, trabecular separation, and network heterogeneity (p < .01 to .05). Stiffness was reduced in fracture patients, more markedly at the radius (41% to 44%) than at the tibia (15% to 20%). Women with fractures had reduced vBMD, microarchitectural deterioration, and decreased strength. These differences were more prominent at the radius than at the tibia. HR‐pQCT and FEA measurements of peripheral sites are associated with fracture prevalence and may increase understanding of the role of microarchitectural deterioration in fracture susceptibility. © 2010 American Society for Bone and Mineral Research.     

Decreased tibial bone strength in postmenopausal women with aseptic loosening of cemented femoral implants measured by peripheral quantitative computed tomography (pQCT)

Aseptic loosening after total hip arthroplasty is related to bone loss of the operated leg. The aim of the present study was to investigate the effect of aseptic loosening on volumetric bone mineral density (vBMD) and bone geometry in the operated leg, in postmenopausal women with a loosened cemented femoral implant using peripheral quantitative computed tomography (pQCT). We matched 12 postmenopausal women with aseptic loosening of cemented femoral implant, with 12 women without aseptic loosening (control group) according to age, BMI, and years from operation. All patients underwent pQCT of both tibias, DXA of the lumbar spine, and determination of biochemical markers of bone turnover. pQCT values in the control group as well as the nonoperated legs between groups had no significant difference. In the aseptic loosening group, there was significant reduction of cortical vBMD (cort vBMD) at 14% and 38% sites (cortical site), cortical thickness at 38% site, and of polar stress strength index (SSIp) at 14% site (transition zone) in the operated compared with the nonoperated leg. Similarly, there was significant reduction of cort vBMD at 14% and 38% sites and total vBMD and trabecular vBMD (trab vBMD) at the 14% site in the operated legs between the two groups. The aseptic loosening group had increased osteocalcin and serum collagen cross-linked N- and C-telopeptides (sNTX and sCTX) levels compared with controls. Aseptic loosening is associated with significant decrease of cortical and trabecular vBMD, and impairment of bone geometry and strength only in the operated leg. Increased bone turnover probably represents a local phenomenon, and is not associated with systemic skeletal disease.     

Effects of Odanacatib on the Radius and Tibia of Postmenopausal Women: Improvements in Bone Geometry,Microarchitecture, and Estimated Bone Strength

The cathepsin K inhibitor odanacatib (ODN), currently in phase 3 development for postmenopausal osteoporosis, has a novel mechanism of action that reduces bone resorption while maintaining bone formation. In phase 2 studies, odanacatib increased areal bone mineral density (aBMD) at the lumbar spine and total hip progressively over 5 years. To determine the effects of ODN on cortical and trabecular bone and estimate changes in bone strength, we conducted a randomized, double‐blind, placebo‐controlled trial, using both quantitative computed tomography (QCT) and high‐resolution peripheral (HR‐p)QCT. In previously published results, odanacatib was superior to placebo with respect to increases in trabecular volumetric BMD (vBMD) and estimated compressive strength at the spine, and integral and trabecular vBMD and estimated strength at the hip. Here, we report the results of HR‐pQCT assessment. A total of 214 postmenopausal women (mean age 64.0 ± 6.8 years and baseline lumbar spine T‐score –1.81 ± 0.83) were randomized to oral ODN 50 mg or placebo, weekly for 2 years. With ODN, significant increases from baseline in total vBMD occurred at the distal radius and tibia. Treatment differences from placebo were also significant (3.84% and 2.63% for radius and tibia, respectively). At both sites, significant differences from placebo were also found in trabecular vBMD, cortical vBMD, cortical thickness, cortical area, and strength (failure load) estimated using finite element analysis of HR‐pQCT scans (treatment differences at radius and tibia = 2.64% and 2.66%). At the distal radius, odanacatib significantly improved trabecular thickness and bone volume/total volume (BV/TV) versus placebo. At a more proximal radial site, odanacatib attenuated the increase in cortical porosity found with placebo (treatment difference = –7.7%, p = 0.066). At the distal tibia, odanacatib significantly improved trabecular number, separation, and BV/TV versus placebo. Safety and tolerability were similar between treatment groups. In conclusion, odanacatib increased cortical and trabecular density, cortical thickness, aspects of trabecular microarchitecture, and estimated strength at the distal radius and distal tibia compared with placebo. © 2014 American Society for Bone and Mineral Research     

Calcium supplementation and weight bearing physical activity--do they have a combined effect on the bone density of pre-pubertal children?

The adaptation of bone to exercise has been shown to be modified by dietary calcium intake. The aim of this randomised controlled trial was to investigate whether there was a differential response to calcium supplementation in elite gymnasts and school children controls. The primary hypothesis was that gymnasts who took calcium supplements would have greater increases in cortical and trabecular volumetric bone mineral density (vBMD) at the radius and tibia. Secondary outcomes studied were changes in bone geometry at the radius and tibia and lumbar spine and whole body measurements. Children were randomised to 12 months daily supplementation of 500 mg elemental calcium (1250 mg (in the form of calcium carbonate salt)) or placebo. Outcome measures were assessed using peripheral quantitative computed tomography (pQCT) (distal and diaphyseal radius and tibia) and dual energy X-ray absorptiometry (DXA) (lumbar spine and whole body). Eighty-six subjects participated in the trial (44 gymnasts, 42 controls) and 75 subjects completed the trial (39 gymnasts, 36 controls). Data were analysed by analysis of covariance adjusting for baseline value of bone parameters, age, height, gender and puberty, and delay between baseline measurement and start of intervention. The primary analysis was for a calcium-exercise interaction; a pooled calcium effect with no interaction was also tested. Results are presented as ratios (95% confidence intervals). At the distal tibia, trabecular vBMD showed a significant interaction (p=0.04), with controls (1.00: 0.99, 1.09) responding more than gymnasts (0.98: 0.94, 1.02) to supplementation. At the distal radius, change in trabecular vBMD was not significant (p=0.05). There were no differences in change in cortical vBMD at either site between the gymnasts and controls (tibia: p=0.82, radius: p=0.88). For all other secondary outcomes at radius, tibia, spine and whole body no significant interactions were found. In conclusion, there was no beneficial effect of additional calcium in gymnasts who already consume their recommended nutrient intake (888 mg/day; United Kingdom reference nutrient intake for 8- to 11-year-olds is 555-800 mg/day) for calcium. We speculate that gymnasts have already adapted their bones (geometry and vBMD) to the demands imposed upon them by the loading they are subjected to during gymnastics and do not benefit from additional calcium supplementation.     

A structural approach to the assessment of fracture risk in children and adolescents with chronic kidney disease

Children with chronic kidney disease (CKD) have multiple risk factors for impaired accretion of trabecular and cortical bone. CKD during childhood poses an immediate fracture risk and compromises adult bone mass, resulting in significantly greater skeletal fragility throughout life. High-turnover disease initially results in thickened trabeculae, with greater bone volume. As disease progresses, resorption cavities dissect trabeculae, connectivity degrades, and bone volume decreases. Increased bone turnover also results in increased cortical porosity and decreased cortical thickness. Dual-energy X-ray absorptiometry (DXA)-based measures of bone mineral density (BMD) are derived from the total bone mass within the projected bone area (g/cm²), concealing distinct disease effects in trabecular and cortical bone. In contrast, peripheral quantitative computed tomography (pQCT) estimates volumetric BMD (vBMD, g/cm³), distinguishes between cortical and trabecular bone, and provides accurate estimates of cortical dimensions. Recent data have confirmed that pQCT measures of cortical vBMD and thickness provide substantially greater fracture discrimination in adult dialysis patients compared with hip or spine DXA. The following review considers the structural effects of renal osteodystrophy as it relates to fracture risk and the potential advantages and disadvantages of DXA and alternative measures of bone density, geometry, and microarchitecture, such as pQCT, micro-CT (μCT), and micro magnetic resonance imaging (μMRI) for fracture risk assessment.     

Skeletal outcomes by peripheral quantitative computed tomography and dual-energy X-ray absorptiometry in adolescent girls with anorexia nervosa

Summary

We conducted the first comparison of dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT) outcomes in adolescent girls with anorexia nervosa. We observed deficits in bone density by both tools. pQCT assessments were associated with many of the same clinical parameters as have been previously established for DXA.

Introduction

Adolescents with anorexia nervosa (AN) commonly exhibit bone loss, but effects on bone geometry are less clear. We compared measures obtained by DXA and pQCT in girls with AN.

Methods

Seventy females (age 15.5 ± 1.9 years ) with AN and 132 normal-weighted controls underwent tibial measures by pQCT including trabecular volumetric bone mineral density (vBMD) at the 3 % site, cortical vBMD and dimensions at the 38 % site, and muscle cross-sectional area (CSA) at the 66 % site. Participants with AN also underwent standard DXA measures. Independent t tests compared the pQCT results, while Pearson coefficient assessed correlations among DXA and pQCT measures.

Results

Trabecular vBMD Z-scores were lower in AN compared to controls (AN ?0.31 ± 1.42 vs +0.11 ± 1.01, p = 0.01) and cortical vBMD Z-scores were higher (AN +0.18 ± 0.92 vs ?0.50 ± 0.88, p < 0.001). Trabecular vBMD and cortical CSA Z-scores positively correlated with DXA BMD Z-scores (r range 0.57–0.82, p < 0.001). Markers of nutritional status positively correlated with Z-scores for trabecular vBMD, cortical CSA, section modulus, and muscle CSA (p < 0.04 for all).

Conclusions

This study is the first to compare DXA and pQCT measurements in adolescent girls with AN. We observed deficits in BMD by both DXA and pQCT. pQCT assessments correlated well with DXA bone and body composition measures and were associated with many of the same clinical parameters and disease severity markers as have been previously established for DXA. The differences in cortical vBMD merit further study.

     

Increased fat mass is associated with increased bone size but reduced volumetric density in pre pubertal children

Recent studies have shown that obesity is associated with an increased risk of fracture in both adults and children. It has been suggested that, despite greater bone size, obese individuals may have reduced true volumetric density; however this is difficult to assess using two dimensional techniques such as DXA. We evaluated the relationship between fat mass, and bone size and density, in a population cohort of children in whom DXA and pQCT measurements had been acquired. We recruited 530 children at 6 years old from the Southampton Women's Survey. The children underwent measurement of bone mass at the whole body, lumbar spine and hip, together with body composition, by DXA (Hologic Discovery, Hologic Inc., Bedford, MA, USA). In addition 132 of these children underwent pQCT measurements at the tibia (Stratec XCT2000, Stratec Biomedical Systems, Birkenfeld, Germany). Significant positive associations were observed between total fat mass and both bone area (BA) and bone mineral content (BMC) at the whole body minus head, lumbar spine and hip sites (all p<0.0001). When true volumetric density was assessed using pQCT data from the tibia, fat mass (adjusted for lean mass) was negatively associated with both trabecular and cortical density (β=-14.6 mg/mm(3) per sd, p=0.003; β=-7.7 mg/mm(3) per sd, p=0.02 respectively). These results suggest that fat mass is negatively associated with volumetric bone density at 6 years old, independent of lean mass, despite positive associations with bone size.     

Skeletal Structure in Postmenopausal Women With Osteopenia and Fractures Is Characterized by Abnormal Trabecular Plates and Cortical Thinning

The majority of fragility fractures occur in women with osteopenia rather than osteoporosis as determined by dual‐energy X‐ray absorptiometry (DXA). However, it is difficult to identify which women with osteopenia are at greatest risk. We performed this study to determine whether osteopenic women with and without fractures had differences in trabecular morphology and biomechanical properties of bone. We hypothesized that women with fractures would have fewer trabecular plates, less trabecular connectivity, and lower stiffness. We enrolled 117 postmenopausal women with osteopenia by DXA (mean age 66 years; 58 with fragility fractures and 59 nonfractured controls). All had areal bone mineral density (aBMD) measured by DXA. Trabecular and cortical volumetric bone mineral density (vBMD), trabecular microarchitecture, and cortical porosity were measured by high‐resolution peripheral computed tomography (HR‐pQCT) of the distal radius and tibia. HR‐pQCT scans were subjected to finite element analysis to estimate whole bone stiffness and individual trabecula segmentation (ITS) to evaluate trabecular type (as plate or rod), orientation, and connectivity. Groups had similar age, race, body mass index (BMI), and mean T‐scores. Fracture subjects had lower cortical and trabecular vBMD, thinner cortices, and thinner, more widely separated trabeculae. By ITS, fracture subjects had fewer trabecular plates, less axially aligned trabeculae, and less trabecular connectivity. Whole bone stiffness was lower in women with fractures. Cortical porosity did not differ. Differences in cortical bone were found at both sites, whereas trabecular differences were more pronounced at the radius. In summary, postmenopausal women with osteopenia and fractures had lower cortical and trabecular vBMD; thinner, more widely separated and rodlike trabecular structure; less trabecular connectivity; and lower whole bone stiffness compared with controls, despite similar aBMD by DXA. Our results suggest that in addition to trabecular and cortical bone loss, changes in plate and rod structure may be important mechanisms of fracture in postmenopausal women with osteopenia. © 2014 American Society for Bone and Mineral Research.     

Mechanical strength of the thoracolumbar spine in the elderly: prediction from in situ dual-energy X-ray absorptiometry,quantitative computed tomography (QCT), upper and lower limb peripheral QCT,and quantitative ultrasound

The objective of this study was to compare the ability of clinically available densitometric measurement techniques for evaluating vertebral strength in elderly individuals. Measurements were related to experimentally determined failure strength in the thoracic and lumbar spine. In 127 specimens (82 women and 45 men, age 80 +/- 10 years), dual-energy X-ray absorptiometry (DXA) was performed at the lumbar spine, femur, radius, and total body, and peripheral-quantitative computed tomography (pQCT) at the distal radius, tibia, and femur under in situ conditions with intact soft tissues. Spinal QCT and calcaneal ultrasound parameters were performed ex situ in degassed specimens. Mechanical failure loads of thoracic vertebrae 6 and 10 (T-6 and -10), and lumbar vertebra 3 (L-3) were determined in axial compression on functional three-segment units. In situ anteroposterior DXA and QCT of the lumbar spine explained approximately 65% of the variability of thoracolumbar failure. A combination of cortical and trabecular density (QCT) provided the best prediction in the lumbar spine. However, this was not the case in the thoracic spine, for which lumbar cortical density (QCT) and DXA provided significantly better estimates than trabecular density (QCT). pQCT was significantly less correlated with the strength of lumbar and thoracic vertebrae (r(2) = 40%), but was equivalent to femoral or radial DXA. pQCT measurements in the lower limb showed no advantage over those at the distal radius. Ultrasound explained approximately 25% of the variability of vertebral failure strength and added independent information to spinal QCT, but not to spinal DXA. These experimental results advocate site-specific assessment of vertebral strength by either spinal DXA or QCT.     

Alterations of Bone Density,Microstructure, and Strength of the Distal Radius in Male Patients With Rheumatoid Arthritis: A Case‐Control Study With HR‐pQCT

In this cross‐sectional study, we investigated volumetric bone mineral density (vBMD), bone microstructure, and biomechanical competence of the distal radius in male patients with rheumatoid arthritis (RA). The study cohort comprised 50 male RA patients of average age of 61.1 years and 50 age‐matched healthy males. Areal BMD (aBMD) of the hip, lumbar spine, and distal radius was measured by dual‐energy X‐ray absorptiometry. High‐resolution peripheral quantitative computed tomography (HR‐pQCT) of the distal radius provided measures of cortical and trabecular vBMD, microstructure, and biomechanical indices. aBMD of the hip but not the lumbar spine or ultradistal radius was significantly lower in RA patients than controls after adjustment for body weight. Total, cortical, and trabecular vBMD at the distal radius were, on average, –3.9% to –23.2% significantly lower in RA patients, and these differences were not affected by adjustment for body weight, testosterone level, or aBMD at the ultradistal radius. Trabecular microstructure indices were, on average, –8.1% (trabecular number) to 28.7% (trabecular network inhomogeneity) significantly inferior, whereas cortical pore volume and cortical porosity index were, on average, 80.3% and 63.9%, respectively, significantly higher in RA patients. RA patients also had significantly lower whole‐bone stiffness, modulus, and failure load, with lower and more unevenly distributed cortical and trabecular stress. Density and microstructure indices significantly correlated with disease activity, severity, and levels of pro‐inflammatory cytokines (interleukin [IL] 12p70, tumor necrosis factor, IL‐6 and IL‐1β). Ten RA patients had focal periosteal bone apposition most prominent at the ulnovolar aspect of the distal radius. These patients had shorter disease duration and significantly higher cortical porosity. In conclusion, HR‐pQCT reveals significant alterations of bone density, microstructure, and strength of the distal radius in male RA patients and provides new insight into the microstructural basis of bone fragility accompanying chronic inflammation. © 2014 American Society for Bone and Mineral Research.     

Catch up in bone acquisition in young adult men with late normal puberty

The aim of this study was to investigate the development of bone mineral density (BMD) and bone mineral content (BMC) in relation to peak height velocity (PHV), and to investigate whether late normal puberty was associated with remaining low BMD and BMC in early adulthood in men. In total, 501 men (mean ± SD, 18.9 ± 0.5 years of age at baseline) were included in this 5‐year longitudinal study. Areal BMD (aBMD) and BMC, volumetric BMD (vBMD) and cortical bone size were measured using dual‐energy X‐ray absorptiometry (DXA) and pQCT. Detailed growth and weight charts were used to calculate age at PHV, an objective assessment of pubertal timing. Age at PHV was a strong positive predictor of the increase in aBMD and BMC of the total body (R² aBMD 11.7%; BMC 4.3%), radius (R² aBMD 23.5%; BMC 22.3%), and lumbar spine (R² aBMD 11.9%; BMC 10.5%) between 19 and 24 years (p < 0.001). Subjects were divided into three groups according to age at PHV (early, middle, and late). Men with late puberty gained markedly more in aBMD and BMC at the total body, radius, and lumbar spine, and lost less at the femoral neck (p < 0.001) than men with early puberty. At age 24 years, no significant differences in aBMD or BMC of the lumbar spine, femoral neck, or total body were observed, whereas a deficit of 4.2% in radius aBMD, but not in BMC, was seen for men with late versus early puberty (p < 0.001). pQCT measurements of the radius at follow‐up demonstrated no significant differences in bone size, whereas cortical and trabecular vBMD were 0.7% (p < 0.001) and 4.8% (p < 0.05) lower in men with late versus early puberty. In conclusion, our results demonstrate that late puberty in males was associated with a substantial catch up in aBMD and BMC in young adulthood, leaving no deficits of the lumbar spine, femoral neck, or total body at age 24 years. © 2012 American Society for Bone and Mineral Research.     

Correlates of trabecular and cortical volumetric bone mineral density of the radius and tibia in older men: The osteoporotic fractures in men study

Quantitative computed tomography (QCT) can estimate volumetric bone mineral density (vBMD) and distinguish trabecular from cortical bone. Few comprehensive studies have examined correlates of vBMD in older men. This study evaluated the impact of demographic, anthropometric, lifestyle, and medical factors on vBMD in 1172 men aged 69 to 97 years and enrolled in the Osteoporotic Fractures in Men Study (MrOS). Peripheral quantitative computed tomography (pQCT) was used to measure vBMD of the radius and tibia. The multivariable linear regression models explained up to 10% of the variance in trabecular vBMD and up to 9% of the variance in cortical vBMD. Age was not correlated with radial trabecular vBMD. Correlates associated with both cortical and trabecular vBMD were age (?), caffeine intake (?), total calcium intake (+), nontrauma fracture (?), and hypertension (+). Higher body weight was related to greater trabecular vBMD and lower cortical vBMD. Height (?), education (+), diabetes with thiazolidinedione (TZD) use (+), rheumatoid arthritis (+), using arms to stand from a chair (?), and antiandrogen use (?) were associated only with trabecular vBMD. Factors associated only with cortical vBMD included clinic site (?), androgen use (+), grip strength (+), past smoker (?), and time to complete five chair stands (?). Certain correlates of trabecular and cortical vBMD differed among older men. An ascertainment of potential risk factors associated with trabecular and cortical vBMD may lead to better understanding and preventive efforts for osteoporosis in men. © 2010 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.     

Effect of aging on trabecular and compact bone components of proximal and ultradistal radius

Bone densitometry has become a major tool for osteoporosis risk assessment. The traditional dual-energy X-ray absorptiometry (DXA) methods are able to evaluate the bone mineral content (BMC; mg/cm) and the areal density (BMD; mg/cm²), but only quantitative computed tomography (QCT) has the potential to measure the true volumetric bone density in the sense of mass per unit volume (mg/cm³). Peripheral QCT (pQCT) measurements were carried out at the non-dominant radius using a Stratec XCT 960 (Unitrem, Roma) in 241 postmenopausal and 29 premenopausal women. The sites of evaluation were both the ultradistal and the proximal radius. The technique used has a coefficient of variation of 2% and it allows separation of the bone section into trabecular and cortical bone on the basis of density threshold. Bone mass of radius, hip and spine was also evaluated by DXA procedures. The bone density data obtained by pQCT were significantly correlated with all DXA measurements. The correlation coefficients between their respective BMD values ranged from 0.48 to 0.75, but for the BMC values of the radius the correlation coefficients ranged from 0.82 to 0.93. The BMD values measured by DXA, but not by pQCT, were positively related with patient heights. All pQCT density measurements, including those obtained at the proximal radius and containing exclusively cortical bone, where negatively related with age and years since menopause. A partial volume effect, which is increasingly relevant the thinner are the bone cortices, might explain that. However, by applying increasing density thresholds, cortical bone density seems to decrease with age as a consequence of a gradual density diminution from the inner part of the bone cortex outwards. Trabecular bone density decreases with aging, but its overall mass does not change as a consequence of an age-related enlargement of trabecular area. Thus, the proportion of trabecular bone over total bone rises, and this might be relevant for our understanding of the age-related changes in bone turnover and rate of bone loss.     

Structure and strength of the distal radius in female patients with rheumatoid arthritis: A case‐control study

The purpose of this work was to investigate the volumetric bone mineral density (vBMD), bone microstructure, and mechanical indices of the distal radius in female patients with rheumatoid arthritis (RA). We report a cross‐sectional study of 66 middle‐aged female RA patients and 66 age‐matched healthy females. Areal BMD (aBMD) of the hip, lumbar spine, and distal radius was measured by dual‐energy X‐ray absorptiometry (DXA). High‐resolution peripheral quantitative computed tomography (HR‐pQCT) was performed at the distal radius, yielding vBMD, bone microstructure, and mechanical indices. Cortical and trabecular vBMD were 3.5% and 10.7% lower, respectively, in RA patients than controls, despite comparable aBMD. Trabecular microstructural indices were –5.7% to –23.1% inferior, respectively, in RA patients compared to controls, with significant differences in trabecular bone volume fraction, separation, inhomogeneity, and structural model index. Cortical porosity volume and percentage were 128% and 93% higher, respectively, in RA patients, with stress being distributed more unevenly. Fourteen RA patients had exaggerated periosteal bone apposition primarily affecting the ulnovolar aspect of the distal radius. These particular patients were more likely to have chronic and severe disease and coexisting wrist deformity. The majority of the differences in density and microstructure between RA patients and controls did not depend on menstrual status. Recent exposure to glucocorticoids did not significantly affect bone density and microstructure. HR‐pQCT provides new insight into inflammation‐associated bone fragility in RA. It detects differences in vBMD, bone microstructure, and mechanical indices that are not captured by DXA. At the distal radius, deterioration in density and microstructure in RA patients involved both cortical and trabecular compartments. Excessive bone resorption appears to affect cortical more than trabecular bone at distal radius, particularly manifested as increased cortical porosity. Ulnovolar periosteal apposition of the distal radius is a feature of chronic, severe RA with wrist deformity. © 2013 American Society for Bone and Mineral Research.     

Correlates of trabecular and cortical volumetric bone mineral density at the femoral neck and lumbar spine: The osteoporotic fractures in men study (MrOS)

The objective of this cross‐sectional analysis was to examine the correlates of trabecular and cortical volumetric bone mineral density (vBMD) in 3670 community‐dwelling men, mean age 73.6 ± 5.9 years. vBMD was measured by quantitative computed tomography (QCT) and areal BMD by dual‐energy X‐ray absorptiometry (DXA). Demographic, historical, and lifestyle information was obtained by interview, and height, weight, and neuromuscular function were determined by examination. To express the strength of the associations, percent differences (95% confidence interval) were calculated from multivariable linear regression models using the formula 100 (β × unit/mean BMD). Units for continuous variables were chosen to approximate 1 standard deviation (SD). The multivariable linear regression models predicted 15%, 21%, and 20% of the overall variance in trabecular and cortical vBMD of the femoral neck and vBMD of the lumbar spine, respectively. Diabetes was associated with a 16.5% greater trabecular vBMD at the femoral neck and 11% at the lumbar spine but less than 2% for cortical vBMD. For femoral neck trabecular vBMD, the strongest negative correlates were past smoking (?9%), fracture history (?15%), kidney stones (?7%), corticosteroids (?11%), and insulin therapy (?26%). For cortical vBMD, the strongest negative correlate was use of thyroid medication (?2.8%). The strongest negative correlates for lumbar spine trabecular vBMD were fracture history (?5%), antiandrogen use (?19%), height (?8%), and thiazoliainedione use (?22%). Bioavailable estradiol and testosterone levels were positively related and sex hormone–binding globulin was negatively related to trabecular vBMD of the spine. There was no relationship between sex hormones and femoral neck trabecular vBMD. Our conclusion is that correlates of trabecular vBMD and cortical vBMD appear to differ in older men. © 2010 American Society for Bone and Mineral Research     

Characterization of low bone mass in young patients with thalassemia by DXA, pQCT and markers of bone turnover

Previous reports using dual x-ray absorptiometry (DXA) suggest that up to 70% of adults with thalassemia major (Thal) have low bone mass. However, few studies have controlled for body size and pubertal delay, variables known to affect bone mass in this population. In this study, bone mineral content and areal density (BMC, aBMD) of the spine and whole body were assessed by DXA, and volumetric BMD and cortical geometries of the distal tibia by peripheral quantitative computed tomography (pQCT) in subjects with Thal (n = 25, 11 male, 10 to 30 years) and local controls (n=34, 15 male, 7 to 30 years). Z-scores for bone outcomes were calculated from reference data from a large sample of healthy children and young adults. Fasting blood and urine were collected, pubertal status determined by self-assessment and dietary intake and physical activity assessed by written questionnaires. Subjects with Thal were similar in age, but had lower height, weight and lean mass index Z-scores (all p < 0.001) compared to controls. DXA aBMD was significantly lower in Thal compared to controls at all sites. Adult Thal subjects (> 18 years, n = 11) had lower tibial trabecular vBMD (p = 0.03), cortical area, cortical BMC, cortical thickness, periosteal circumference and section modulus Z-scores (all p < 0.01) compared to controls. Cortical area, cortical BMC, cortical thickness, and periosteal circumference Z-scores (p = 0.02) were significantly lower in young Thal (≤ 18 years, n = 14) compared to controls. In separate multivariate models, tibial cortical area, BMC, and thickness and spine aBMD and whole body BMC Z-scores remained lower in Thal compared to controls after adjustment for gender, lean mass and/or growth deficits (all p < 0.01). Tanner stage was not predictive in these models. Osteocalcin, a marker of bone formation, was significantly reduced in Thal compared to controls after adjusting for age, puberty and whole body BMC (p=0.029). In summary, we have found evidence of skeletal deficits that cannot be dismissed as an artifact of small bone size or delayed maturity alone. Given that reduced bone density and strength are associated with increased risk of fracture, therapies focused on increasing bone formation and bone size in younger patients are worthy of further evaluation.