Age‐ and gender‐related differences in the geometric properties and biomechanical significance of intracortical porosity in the distal radius and tibia

Cortical bone contributes the majority of overall bone mass and bears the bulk of axial loads in the peripheral skeleton. Bone metabolic disorders often are manifested by cortical microstructural changes via osteonal remodeling and endocortical trabecularization. The goal of this study was to characterize intracortical porosity in a cross‐sectional patient cohort using novel quantitative computational methods applied to high‐resolution peripheral quantitative computed tomography (HR‐pQCT) images of the distal radius and tibia. The distal radius and tibia of 151 subjects (57 male, 94 female; 47 ± 16 years of age, range 20 to 78 years) were imaged using HR‐pQCT. Intracortical porosity (Ct.Po) was calculated as the pore volume normalized by the sum of the pore and cortical bone volume. Micro–finite element analysis (µFE) was used to simulate 1% uniaxial compression for two scenarios per data set: (1) the original structure and (2) the structure with intracortical porosity artificially occluded. Differential biomechanical indices for stiffness (ΔK), modulus (ΔE), failure load (ΔF), and cortical load fraction (ΔCt.LF) were calculated as the difference between original and occluded values. Regression analysis revealed that cortical porosity, as depicted by HR‐pQCT, exhibited moderate but significant age‐related dependence for both male and female cohorts (radius ρ = 0.7; tibia ρ = 0.5; p < .001). In contrast, standard cortical metrics (Ct.Th, Ct.Ar, and Ct.vBMD) were more weakly correlated or not significantly correlated with age in this population. Furthermore, differential µFE analysis revealed that the biomechanical deficit (ΔK) associated with cortical porosity was significantly higher for postmenopausal women than for premenopausal women (p < .001). Finally, porosity‐related measures provided the only significant decade‐wise discrimination in the radius for females in their fifties versus females in their sixties (p < .01). Several important conclusions can be drawn from these results. Age‐related differences in cortical porosity, as detected by HR‐pQCT, are more pronounced than differences in standard cortical metrics. The biomechanical significance of these structural differences increases with age for men and women and provides discriminatory information for menopause‐related bone quality effects. © 2010 American Society for Bone and Mineral Research     

Cross‐sectional Versus Longitudinal Change in a Prospective HR‐pQCT Study

Longitudinal studies assessing age‐related changes using high‐resolution peripheral quantitative computed tomography (HR‐pQCT) provide novel insight compared with cross‐sectional analyses. The purpose of this cohort study was 1) to determine individuals’ change in HR‐pQCT parameters over 5 years relative to least significant change (LSC), and 2) to evaluate if predicted rate of change from cross‐sectional data is comparable to actual change from longitudinal investigation. A cohort of 466 (162 male, 304 female) participants completed two HR‐pQCT scans with 5 years between assessments. After image registration, standard and cortical morphological analyses were conducted. Rate of bone microarchitectural change was compared between cross‐sectional models and actual change calculated from longitudinal analyses. At the young end of the life span, we observed gains in total bone density of +0.2% to +2.9% per year, whereas the older participants (aged >50 years) lost total bone density at a rate of –0.3% to –1.3% per year. Declines in total bone density begin at age 40 years in females and 60 years in males, and significant adaptation was found at both ends of the age spectrum with respect to the LSC. Models predicting rate of change from cross‐sectional data were similar to the actual change reported in this longitudinal study for total density and cortical thickness at the radius and cortical density at the tibia, but we found that changes in comparison to our 5‐year longitudinal results were often overestimated from cross‐sectional data. Studies aimed at observing age‐related changes in a normative cohort, especially in a follow‐up period of less than 5 years, are better to focus on the tibia rather than the radius because of the increased sensitivity to change at the tibia. © 2017 American Society for Bone and Mineral Research.     

Bone microstructure at the distal tibia provides a strength advantage to males in late puberty: An HR‐pQCT study

Bone is a complex structure with many levels of organization. Advanced imaging tools such as high‐resolution (HR) peripheral quantitative computed tomography (pQCT) provide the opportunity to investigate how components of bone microstructure differ between the sexes and across developmental periods. The aim of this study was to quantify the age‐ and sex‐related differences in bone microstructure and bone strength in adolescent males and females. We used HR‐pQCT (XtremeCT, Scanco Medical, Geneva, Switzerland) to assess total bone area (ToA), total bone density (ToD), trabecular bone density (TrD), cortical bone density (CoD), cortical thickness (Cort.Th), trabecular bone volume (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), trabecular spacing standard deviation (Tb.Sp SD), and bone strength index (BSI, mg²/mm⁴) at the distal tibia in 133 females and 146 males (15 to 20 years of age). We used a general linear model to determine differences by age‐ and sex‐group and age × sex interactions (p < 0.05). Across age categories, ToD, CoD, Cort.Th, and BSI were significantly lower at 15 and 16 years compared with 17 to 18 and 19 to 20 years in males and females. There were no differences in ToA, TrD, and BV/TV across age for either sex. Between sexes, males had significantly greater ToA, TrD, Cort.Th, BV/TV, Tb.N, and BSI compared with females; CoD and Tb.Sp SD were significantly greater for females in every age category. Males' larger and denser bones confer a bone‐strength advantage from a young age compared with females. These structural differences could represent bones that are less able to withstand loads in compression in females. © 2010 American Society for Bone and Mineral Research     

High‐resolution peripheral quantitative computed tomography can assess microstructural and mechanical properties of human distal tibial bone

High‐resolution peripheral quantitative computed tomography (HR‐pQCT) is a newly developed in vivo clinical imaging modality. It can assess the 3D microstructure of cortical and trabecular bone at the distal radius and tibia and is suitable as an input for microstructural finite element (µFE) analysis to evaluate bone's mechanical competence. In order for microstructural and image‐based µFE analyses to become standard clinical tools, validation with a current gold standard, namely, high‐resolution micro‐computed tomography (µCT), is required. Microstructural measurements of 19 human cadaveric distal tibiae were performed for the registered HR‐pQCT and µCT images, respectively. Next, whole bone stiffness, trabecular bone stiffness, and elastic moduli of cubic subvolumes of trabecular bone in both HR‐pQCT and µCT images were determined by µFE analysis. The standard HR‐pQCT patient protocol measurements, derived bone volume fraction (BV/TV^d), trabecular number (Tb.N*), trabecular thickness (Tb.Th), trabecular spacing (Tb.Sp), and cortical thickness (Ct.Th), as well as the voxel‐based direct measurements, BV/TV, Tb.N*, Tb.Th*, Tb.Sp*, Ct.Th, bone surface‐to‐volume ratio (BS/BV), structure model index (SMI), and connectivity density (Conn.D), correlated well with their respective gold standards, and both contributed to µFE‐predicted mechanical properties in either single or multiple linear regressions. The mechanical measurements, although overestimated by HR‐pQCT, correlated highly with their gold standards. Moreover, elastic moduli of cubic subvolumes of trabecular bone predicted whole bone or trabecular bone stiffness in distal tibia. We conclude that microstructural measurements and mechanical parameters of distal tibia can be efficiently derived from HR‐pQCT images and provide additional information regarding bone fragility. © 2010 American Society for Bone and Mineral Research     

Sex Differences and Growth‐Related Adaptations in Bone Microarchitecture,Geometry, Density,and Strength From Childhood to Early Adulthood: A Mixed Longitudinal HR‐pQCT Study

Sex differences in bone strength and fracture risk are well documented. However, we know little about bone strength accrual during growth and adaptations in bone microstructure, density, and geometry that accompany gains in bone strength. Thus, our objectives were to (1) describe growth related adaptations in bone microarchitecture, geometry, density, and strength at the distal tibia and radius in boys and girls; and (2) compare differences in adaptations in bone microarchitecture, geometry, density, and strength between boys and girls. We used HR‐pQCT at the distal tibia (8% site) and radius (7% site) in 184 boys and 209 girls (9 to 20 years old at baseline). We aligned boys and girls on a common maturational landmark (age at peak height velocity [APHV]) and fit a mixed effects model to these longitudinal data. Importantly, boys showed 28% to 63% greater estimated bone strength across 12 years of longitudinal growth. Boys showed 28% to 80% more porous cortices compared with girls at both sites across all biological ages, except at the radius at 9 years post‐APHV. However, cortical density was similar between boys and girls at all ages at both sites, except at 9 years post‐APHV at the tibia when girls’ values were 2% greater than boys’. Boys showed 13% to 48% greater cortical and total bone area across growth. Load‐to‐strength ratio was 26% to 27% lower in boys at all ages, indicating lower risk of distal forearm fracture compared with girls. Contrary to previous HR‐pQCT studies that did not align boys and girls at the same biological age, we did not observe sex differences in Ct.BMD. Boys’ superior bone size and strength compared with girls may confer them a protective advantage. However, boys’ consistently more porous cortices may contribute to their higher fracture incidence during adolescence. Large prospective studies using HR‐pQCT that target boys and girls who have sustained a fracture are needed to verify this. © 2016 American Society for Bone and Mineral Research.     

Effects on bone geometry,density, and microarchitecture in the distal radius but not the tibia in women with primary hyperparathyroidism: A case‐control study using HR‐pQCT

Patients with primary hyperparathyroidism (PHPT) have continuously elevated parathyroid hormone (PTH) and consequently increased bone turnover with negative effects on cortical (Ct) bone with preservation of trabecular (Tb) bone. High‐resolution peripheral quantitative computed tomography (HR‐pQCT) is a new technique for in vivo assessment of geometry, volumetric density, and microarchitecture at the radius and tibia. In this study we aimed to evaluate bone status in women with PHPT compared with controls using HR‐pQCT. The distal radius and tibia of 54 women—27 patients with PHPT (median age 60, range 44–75 years) and 27 randomly recruited age‐matched healthy controls (median age 60, range 44–76 years)—were imaged using HR‐pQCT along with areal bone mineral density (aBMD) by dual‐energy X‐ray absorptiomentry (DXA) of the ultradistal forearm, femoral neck, and spine (L1–L4). Groups were comparable regarding age, height, and weight. In the radius, patients had reduced Ct area (Ct.Ar) (p = .008), Ct thickness (Ct.th) (p = .01) along with reduced total (p = .002), Ct (p = .02), and Tb (p = .02) volumetric density and reduced Tb number (Tb.N) (p = .04) and increased Tb spacing (Tb.sp) (p = .05). Ct porosity did not differ. In the tibia, no differences in HR‐pQCT parameters were found. Moreover, patients had lower ultradistal forearm (p = .005), spine (p = .04), and femoral neck (p = 0.04) aBMD compared with controls. In conclusion, a negative bone effect of continuously elevated PTH with alteration of HR‐pQCT assessed geometry, volumetric density, and both trabecular and cortical microarchitecture in radius but not tibia was found along with reduced aBMD by DXA at all sites in female patients with PHPT. © 2010 American Society for Bone and Mineral Research     

Individual trabeculae segmentation (ITS)–based morphological analysis of high‐resolution peripheral quantitative computed tomography images detects abnormal trabecular plate and rod microarchitecture in premenopausal women with idiopathic osteoporosis

Idiopathic osteoporosis (IOP) in premenopausal women is a poorly understood entity in which otherwise healthy women have low‐trauma fracture or very low bone mineral density (BMD). In this study, we applied individual trabeculae segmentation (ITS)–based morphological analysis to high‐resolution peripheral quantitative computed tomography (HR‐pQCT) images of the distal radius and distal tibia to gain greater insight into skeletal microarchitecture in premenopausal women with IOP. HR‐pQCT scans were performed for 26 normal control individuals and 31 women with IOP. A cubic subvolume was extracted from the trabecular bone compartment and subjected to ITS‐based analysis. Three Young's moduli and three shear moduli were calculated by micro–finite element (µFE) analysis. ITS‐based morphological analysis of HR‐pQCT images detected significantly decreased trabecular plate and rod bone volume fraction and number, decreased axial bone volume fraction in the longitudinal axis, increased rod length, and decreased rod‐to‐rod, plate‐to‐rod, and plate‐to‐plate junction densities at the distal radius and distal tibia in women with IOP. However, trabecular plate and rod thickness did not differ. A more rod‐like trabecular microstructure was found in the distal radius, but not in the distal tibia. Most ITS measurements contributed significantly to the elastic moduli of trabecular bone independent of bone volume fraction (BV/TV). At a fixed BV/TV, plate‐like trabeculae contributed positively to the mechanical properties of trabecular bone. The results suggest that ITS‐based morphological analysis of HR‐pQCT images is a sensitive and promising clinical tool for the investigation of trabecular bone microstructure in human studies of osteoporosis. © 2010 American Society for Bone and Mineral Research     

A comparison of bone quality at the distal radius between Asian and white adolescents and young adults: An HR‐pQCT study

Paradoxically, Asians have lower areal bone mineral density (aBMD), but their rates of hip and wrist fractures are lower than whites. Therefore, we used high‐resolution pQCT (HR‐pQCT) to determine whether differences in bone macrostructure and microstructure, BMD, and bone strength at the distal radius were apparent in Asian (n = 91, 53 males, 38 females, [mean ± SD] 17.3 ± 1.5 years) and white (n = 89, 46 males, 43 females, 18.1 ± 1.8 years) adolescents and young adults. HR‐pQCT outcomes included total BMD (Tt.BMD), trabecular bone volume fraction (BV/TV), and trabecular number (Tb.N), thickness (Tb.Th), and separation (Tb.Sp). We used an automated segmentation algorithm to determine total bone area (Tt.Ar), and cortical BMD (Ct.BMD), porosity (Ct.Po), and thickness (Ct.Th), and we applied finite element (FE) analysis to HR‐pQCT scans to estimate bone strength. We fit sex‐specific multivariable regression models to compare bone outcomes between Asians and whites, adjusting for age, age at menarche (girls), lean mass, ulnar length, dietary calcium intake, and physical activity. In males, after adjusting for covariates, Asians had 11% greater Tt.BMD, 8% greater Ct.BMD, and 25% lower Ct.Po than whites (p < 0.05). Also, Asians had 9% smaller Tt.Ar and 27% greater Ct.Th (p < 0.01). In females, Asians had smaller Tt.Ar than whites (16%, p < 0.001), but this difference was not significant after adjusting for covariates. Asian females had 5% greater Ct.BMD, 12% greater Ct.Th, and 11% lower Tb.Sp than whites after adjusting for covariates (p < 0.05). Estimated bone strength did not differ between Asian and white males or females. Our study supports the notion of compensatory elements of bone structure that sustain bone strength; smaller bones as observed between those of Asian origin compared with white origin have, on average, more dense, less porous, and thicker cortices. Longitudinal studies are needed to determine whether ethnic differences in bone structure exist in childhood, persist into old age, and whether they influence fracture risk.     

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.     

Finite element analysis performed on radius and tibia HR‐pQCT images and fragility fractures at all sites in men

Few studies have investigated bone microarchitecture and biomechanical properties in men. This study assessed in vivo both aspects in a population of 185 men (aged 71 ± 10 years) with prevalent fragility fractures, compared to 185 controls matched for age, height, and weight, from the Structure of the Aging Men's Bones (STRAMBO) cohort. In this case‐control study, areal BMD (aBMD) was measured by DXA, bone microarchitecture was assessed by high resolution (HR)‐pQCT, and finite element (µFE) analysis was based on HR‐pQCT images of distal radius and tibia. A principal component (PC) analysis (PCA) was used to study the association of synthetic PCs with fracture by computing their odds ratio (OR [95%CI]) per SD change. Specific associations with vertebral fracture (n = 100), and nonvertebral fracture (n = 85) were also computed. At both sites, areal and volumetric BMD, cortical thickness and trabecular number, separation, and distribution were significantly worse in cases than in controls, with differences ranging from ?6% to 15%. µFE‐derived stiffness and failure load were 8% to 9% lower in fractures (p < .01). No difference in load distribution was found between the two groups. After adjustment for aBMD, only differences of µFE‐derived stresses, stiffness, and failure load at the tibia remained significant (p < .05). PCA resulted in defining 4 independent PCs, explaining 83% of the total variability of bone characteristics. Nonvertebral fractures were associated with PC1, reflecting bone quantity and strength at the radius (tibia) with OR = 1.64 [1.27–2.12] (2.21 [1.60–3.04]), and with PC2, defined by trabecular microarchitecture, with OR = 1.27 [1.00–1.61]. Severe vertebral fractures were associated with PC1, with OR = 1.56 [1.16–2.09] (2.21 [1.59–3.07]), and with PC2, with OR = 1.55 [1.17–2.06] (1.45 [1.06–1.98]). In conclusion, microarchitecture and biomechanical properties derived from µFE were associated with all types of fractures in men, showing that radius and tibia mechanical properties were relatively representative of distant bone site properties. © 2011 American Society for Bone and Mineral Research.     

Centile Curves for Bone Densitometry Measurements in Healthy Males and Females Ages 5–22 Yr

Normative pediatric bone measurement data are necessary for defining osteopenia in children and for identifying factors associated with normal bone growth. The LMS statistical method is used to produce centile curves plotting a growth characteristic as a function of age. The purpose of this study was to provide centile curves of bone measurements using peripheral quantitative computed tomography (pQCT) and dual X-ray absorptiometry (DXA) in 231 (107 male) healthy individuals ages 5 22 yr using the LMS method. pQCT (Norland XCT 2000; Norland, Ft. Atkinson, WI) was used to image a single slice at the 20% distal tibia. Periosteal circumference, endosteal circumference, and cortical density measurements were used to obtain centile curves. Whole-body DXA (Hologic QDR 4500; Hologic, Bedford, MA) was obtained and scans were analyzed using adult whole-body software for total body bone mineral content (BMC) and total body bone area. pQCT measurements showed prepubertal expansion of the tibia that plateaued in females at age 14 and continued in males until age 18. Tibia cortical density increased during the age of puberty more gradually in females than in males. DXA measurement curves showed that total body BMC and total body bone area plateaued in females at approximately age 15, whereas male curves of the same measurements showed a continued increase.     

In Vivo Determination of Bone Structure in Postmenopausal Women: A Comparison of HR‐pQCT and High‐Field MR Imaging

Bone structural measures obtained by two noninvasive imaging tools—3T MRI and HR‐pQCT—were compared. Significant but moderate correlations and 2‐ to 4‐fold discrepancies in parameter values were detected, suggesting that differences in acquisition and analysis must be considered when interpreting data from these imaging modalities. Introduction : High‐field MRI and high resolution (HR)‐pQCT are currently being used in longitudinal bone structure studies. Substantial differences in acquisition and analysis between these modalities may influence the quantitative data produced and could potentially influence clinical decisions based on their results. Our goal was to compare trabecular and cortical bone structural measures obtained in vivo by 3T MRI and HR‐pQCT. Materials and Methods : Postmenopausal osteopenic women (n = 52) were recruited for this study. HR‐pQCT imaging of the radius and tibia was performed using the XtremeCT scanner, with a voxel size of 82 × 82 × 82 μm³. MR imaging was performed on a 3T Signa scanner using SSFP imaging sequences, with a pixel size of 156 × 156 μm² and slice thickness of 500 μm. Structure parameters were calculated using standard HR‐pQCT and MRI analysis techniques. Relationships between measures derived from HR‐pQCT, MRI, and DXA were studied. Results : Significant correlations between HR‐pQCT and MRI parameters were found (p < 0.0001) and were strongest for Tb.N (r² = 0.52), Ct.Th (r² = 0.59), and site‐specific Tb.Sp (r² = 0.54–0.60). MRI and HR‐pQCT provided statistically different values of structure parameters (p < 0.0001), with BV/TV and Tb.Th exhibiting the largest discrepancies (MR/HR‐pQCT = 3–4). Although differences in the Tb.N values were statistically significant, the mean differences were on the order of our reproducibility measurements. Systematic differences between MRI and HR‐pQCT analysis procedures leading to discrepancies in cortical thickness values were observed, with MRI values consistently higher. Minimal correlations were found between MRI or HR‐pQCT parameters and DXA BMD or T‐score, except between HR‐pQCT measures at the radius and the ultradistal radius T‐scores, where moderate correlations were found (r² = 0.19–0.58). Conclusions : This study provides unique insight into two emerging noninvasive tools for bone structure evaluation. Our findings highlight the significant influence of analysis technique on results of in vivo assessment and underscore the importance of accounting for these differences when interpreting results from these modalities.     

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.     

Diabetes and Deficits in Cortical Bone Density,Microarchitecture, and Bone Size: Framingham HR‐pQCT Study

Older adults with type 2 diabetes (T2D) tend to have normal or greater areal bone mineral density (aBMD), as measured by DXA, than those who do not have diabetes (non‐T2D). Yet risk of fracture is higher in T2D, including 40% to 50% increased hip fracture risk. We used HR‐pQCT to investigate structural mechanisms underlying skeletal fragility in T2D. We compared cortical and trabecular bone microarchitecture, density, bone area, and strength in T2D and non‐T2D. In secondary analyses we evaluated whether associations between T2D and bone measures differed according to prior fracture, sex, and obesity. Participants included 1069 members of the Framingham Study, who attended examinations in 2005 to 2008 and underwent HR‐pQCT scanning in 2012 to 2015. Mean age was 64 ± 8 years (range, 40 to 87 years), and 12% (n = 129) had T2D. After adjustment for age, sex, weight, and height, T2D had lower cortical volumetric BMD (vBMD) (p < 0.01), higher cortical porosity (p = 0.02), and smaller cross‐sectional area (p = 0.04) at the tibia, but not radius. Trabecular indices were similar or more favorable in T2D than non‐T2D. Associations between T2D and bone measures did not differ according to sex or obesity status (all interaction p > 0.05); however, associations did differ in those with a prior fracture and those with no history of fracture. Specifically, cortical vBMD at the tibia and cortical thickness at the radius were lower in T2D than non‐T2D, but only among those individuals with a prior fracture. Cortical porosity at the radius was higher in T2D than non‐T2D, but only among those who did not have a prior fracture. Findings from this large, community‐based study of older adults suggest that modest deterioration in cortical bone and reductions in bone area may characterize diabetic bone disease in older adults. Evaluation of these deficits as predictors of fracture in T2D is needed to develop prevention strategies in this rapidly increasing population of older adults. © 2017 American Society for Bone and Mineral Research.     

Parathyroidectomy improves bone geometry and microarchitecture in female patients with primary hyperparathyroidism: a one-year prospective controlled study using high-resolution peripheral quantitative computed tomography

Following parathyroidectomy (PTX), bone mineral density (BMD) increases in patients with primary hyperparathyroidism (PHPT), yet information is scarce concerning changes in bone structure and strength following normalization of parathyroid hormone levels postsurgery. In this 1‐year prospective controlled study, high‐resolution peripheral quantitative computed tomography (HR‐pQCT) was used to evaluate changes in bone geometry, volumetric BMD (vBMD), microarchitecture, and estimated strength in female patients with PHPT before and 1 year after PTX, compared to healthy controls. Twenty‐seven women successfully treated with PTX (median age 62 years; range, 44–75 years) and 31 controls (median age 63 years; range, 40–76 years) recruited by random sampling from the general population were studied using HR‐pQCT of the distal radius and tibia as well as with dual‐energy X‐ray absorptiometry (DXA) of the forearm, spine, and hip. The two groups were comparable with respect to age, height, weight, and menopausal status. In both radius and tibia, cortical (Ct.) vBMD and Ct. thickness increased or were maintained in patients and decreased in controls (p < 0.01). Radius cancellous bone architecture was improved in patients through increased trabecular number and decreased trabecular spacing compared with changes in controls (p < 0.05). No significant cancellous bone changes were observed in tibia. Estimated bone failure load by finite element modeling increased in patients in radius but declined in controls (p < 0.001). Similar, albeit borderline significant changes in estimated failure load were found in tibia (p = 0.06). This study showed that females with PHPT had improvements in cortical bone geometry and increases in cortical and trabecular vBMD in both radius and tibia along with improvements in cancellous bone architecture and estimated strength in radius 1 year after PTX, reversing or attenuating age‐related changes observed in controls. © 2012 American Society for Bone and Mineral Research.     

Age‐ and Sex‐Dependent Changes of Intra‐articular Cortical and Trabecular Bone Structure and the Effects of Rheumatoid Arthritis

The objective of this cross‐sectional study was to define normal sex‐ and age‐dependent values of intra‐articular bone mass and microstructures in the metacarpal heads of healthy individuals by high‐resolution peripheral quantitative computed tomography (HR‐pQCT) and test the effect of rheumatoid arthritis (RA) on these parameters. Human cadaveric metacarpal heads were used to exactly define intra‐articular bone. Healthy individuals of different sex and age categories and RA patients with similar age and sex distribution received HR‐pQCT scans of the second metacarpal head and the radius. Total, cortical, and trabecular bone densities as well as microstructural parameters were compared between 1) the different ages and sexes in healthy individuals; 2) between metacarpal heads and the radius; and 3) between healthy individuals and RA patients. The cadaveric study allowed exact definition of the intra‐articular (intracapsular) bone margins. These data were applied in measuring intra‐articular and radial bone parameters in 214 women and men (108 healthy individuals, 106 RA patients). Correlations between intra‐articular and radial bone parameters were good (r = 0.51 to 0.62, p < 0.001). In contrast to radial bone, intra‐articular bone remained stable until age 60 years (between 297 and 312 mg HA/cm³) but decreased significantly (p < 0.001) in women thereafter (237.5 ± 44.3) with loss of both cortical and trabecular bone. Similarly, RA patients showed significant (p < 0.001) loss of intra‐articular total (263.0 ± 44.8), trabecular (171.2 ± 35.6), and cortical bone (610.2 ± 62.0) compared with sex‐ and age‐adjusted controls. Standard sex‐ and age‐dependent values for physiological intra‐articular bone were defined. Postmenopausal state and RA led to significant decrease of intra‐articular bone. © 2016 American Society for Bone and Mineral Research.     

Bone Geometry,Volumetric Density,Microarchitecture, and Estimated Bone Strength Assessed by HR‐pQCT in Klinefelter Syndrome

Although the expected skeletal manifestations of testosterone deficiency in Klinefelter's syndrome (KS) are osteopenia and osteoporosis, the structural basis for this is unclear. The aim of this study was to assess bone geometry, volumetric bone mineral density (vBMD), microarchitecture, and estimated bone strength using high‐resolution peripheral quantitative computed tomography (HR‐pQCT) in patients with KS. Thirty‐one patients with KS confirmed by lymphocyte chromosome karyotyping aged 35.8 ± 8.2 years were recruited consecutively from a KS outpatient clinic and matched with respect to age and height with 31 healthy subjects aged 35.9 ± 8.2 years. Dual‐energy X‐ray absorptiometry (DXA) and HR‐pQCT were performed in all participants, and blood samples were analyzed for hormonal status and bone biomarkers in KS patients. Twenty‐one KS patients were on long‐term testosterone‐replacement therapy. In weight‐adjusted models, HR‐pQCT revealed a significantly lower cortical area (p < 0.01), total and trabecular vBMD (p = 0.02 and p = 0.04), trabecular bone volume fraction (p = 0.04), trabecular number (p = 0.05), and estimates of bone strength, whereas trabecular spacing was higher (p = 0.03) at the tibia in KS patients. In addition, cortical thickness was significantly reduced, both at the radius and tibia (both p < 0.01). There were no significant differences in indices of bone structure, estimated bone strength, or bone biomarkers in KS patients with and without testosterone therapy. This study showed that KS patients had lower total vBMD and a compromised trabecular compartment with a reduced trabecular density and bone volume fraction at the tibia. The compromised trabecular network integrity attributable to a lower trabecular number with relative preservation of trabecular thickness is similar to the picture found in women with aging. KS patients also displayed a reduced cortical area and thickness at the tibia, which in combination with the trabecular deficits, compromised estimated bone strength at this site. © 2014 American Society for Bone and Mineral Research.     

Physical Activity,Sedentary Time,and Bone Strength From Childhood to Early Adulthood: A Mixed Longitudinal HR‐pQCT study

Bone strength is influenced by bone geometry, density, and bone microarchitecture, which adapt to increased mechanical loads during growth. Physical activity (PA) is essential for optimal bone strength accrual; however, less is known about how sedentary time influences bone strength and its determinants. Thus, our aim was to investigate the prospective associations between PA, sedentary time, and bone strength and its determinants during adolescence. We used HR‐pQCT at distal tibia (8% site) and radius (7% site) in 173 girls and 136 boys (aged 9 to 20 years at baseline). We conducted a maximum of four annual measurements at the tibia (n = 785 observations) and radius (n = 582 observations). We assessed moderate‐to‐vigorous PA (MVPA) and sedentary time with accelerometers (ActiGraph GT1M). We aligned participants on maturity (years from age at peak height velocity) and fit a mixed‐effects model adjusting for maturity, sex, ethnicity, leg muscle power, lean mass, limb length, dietary calcium, and MVPA in sedentary time models. MVPA was a positive independent predictor of bone strength (failure load [F.Load]) and bone volume fraction (BV/TV) at the tibia and radius, total area (Tt.Ar) and cortical porosity (Ct.Po) at the tibia, and negative predictor of load‐to‐strength ratio at the radius. Sedentary time was a negative independent predictor of Tt.Ar at both sites and Ct.Po at the tibia and a positive predictor of cortical thickness (Ct.Th), trabecular thickness (Tb.Th), and cortical bone mineral density (Ct.BMD) at the tibia. Bone parameters demonstrated maturity‐specific associations with MVPA and sedentary time, whereby associations were strongest during early and mid‐puberty. Our findings support the importance of PA for bone strength accrual and its determinants across adolescent growth and provide new evidence of a detrimental association of sedentary time with bone geometry but positive associations with microarchitecture. This study highlights maturity‐specific relationships of bone strength and its determinants with loading and unloading. Future studies should evaluate the dose‐response relationship and whether associations persist into adulthood. © 2017 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.     

Differences in Macro‐ and Microarchitecture of the Appendicular Skeleton in Young Chinese and White Women

To identify the racial differences in macro‐ and microstructure of the distal radius and tibia that may account for the lower fracture rates in Asians than whites, we studied 61 healthy premenopausal Chinese and 111 white women 18–45 yr of age using high‐resolution pQCT (HR‐pQCT). The Chinese were shorter and leaner. Distal radius total cross‐sectional area (CSA) was 14.3% smaller in Chinese because of an 18.0% smaller trabecular area (p < 0.001). Cortical thickness was 8.8% greater in the Chinese, but cortical area was no different. Total volumetric BMD (vBMD) was 10.3% higher in the Chinese because of the 8.8% higher cortical thickness and 2.8% greater cortical density (all p < 0.01). Trabecular vBMD and bone volume/tissue volume (BV/TV) did not differ by race because trabeculae were 7.0% fewer but 10.8% thicker in Chinese than whites (both p < 0.01). Similar results were found at the distal tibia. Lower fracture risk in Chinese women may be partly caused by thicker cortices and trabeculae in a smaller bone‐more bone within the bone than in whites.