HR-pQCT appears promising to assess bone density and microarchitecture at peripheral sites in terms of reproducibility and ability to detect age- and disease-related changes.

BMD, bone microarchitecture, and bone mechanical properties assessed in vivo by finite element analysis were associated with wrist fracture in postmenopausal women.Introduction: Many fractures occur in individuals with normal BMD. Assessment of bone mechanical properties by finite element analysis (FEA) may improve identification of those at high risk for fracture. Materials and Methods: We used HR-pQCT to assess volumetric bone density, microarchitecture, and FEderived bone mechanical properties at the radius in 33 postmenopausal women with a prior history of fragility wrist fracture and 33 age-matched controls from the OFELY cohort. Radius areal BMD (aBMD) was also measured by DXA. Associations between density, microarchitecture, mechanical parameters and fracture status were evaluated by univariate logistic regression analysis and expressed as ORs (with 95% CIs) per SD change. We also conducted a principal components (PCs) analysis (PCA) to reduce the number of parameters and study their association (OR) with wrist fracture. Results: Areal and volumetric densities, cortical thickness, trabecular number, and mechanical parameters such as estimated failure load, stiffness, and the proportion of load carried by the trabecular bone at the distal and proximal sites were associated with wrist fracture (p < 0.05). The PCA revealed five independent components that jointly explained 86.2% of the total variability of bone characteristics. The first PC included FE-estimated failure load, areal and volumetric BMD, and cortical thickness, explaining 51% of the variance with an OR for wrist fracture ‫ס‬ 2.49 (95% CI, 1.32-4.72). Remaining PCs did not include any density parameters. The second PC included trabecular architecture, explaining 12% of the variance, with an OR ‫ס‬ 1.82 (95% CI, 0.94-3.52). The third PC included the proportion of the load carried by cortical versus trabecular bone, assessed by FEA, explaining 9% of the variance, and had an OR ‫ס‬ 1.61 (95% CI, 0.94-2.77). Thus, the proportion of load carried by cortical versus trabecular bone seems to be associated with wrist fracture independently of BMD and microarchitecture (included in the first and second PC, respectively). Conclusions: These results suggest that bone mechanical properties assessed by FE may provide information about skeletal fragility and fracture risk not assessed by BMD or architecture measurements alone and are therefore likely to enhance the prediction of wrist fracture risk.

ABSTRACT:We assessed the role of low aBMD and impaired architecture-assessed by an HR-pQCT system-in a case-control study of postmenopausal women with fractures. Vertebral and nonvertebral fractures are associated with low volumetric BMD and architectural alterations of trabecular and cortical bone, independent of aBMD assessed by DXA.Introduction: Alterations of bone architecture and low BMD both contribute to skeletal fragility, but the contribution of cortical and trabecular architecture, independently of areal BMD (aBMD), to the risk of fracture in postmenopausal women has not been thoroughly evaluated. We assessed the role of impaired architecture and low BMD in postmenopausal women with fractures. Materials and Methods: A matched case-control study in women from the OFELY cohort was performed after 13 years of follow-up. One hundred one women (mean, 73.7 ± 8 years) who sustained a fragility fracture during the follow-up of the study were age-matched with one control who never had a fracture. Density and architecture at the distal radius and tibia were measured with high-resolution pQCT (HR-pQCT) using an XTreme CT (Scanco Medical AG, Bassersdorf, Switzerland). aBMD at the total hip and ultradistal radius was measured by DXA. Results: There were 80 peripheral fractures in 72 women, 44 vertebral fractures in 34 women, and both types of fractures in 5 women over the 14 years of follow-up. At the distal radius, women with fractures had lower volumetric total (D tot) and trabecular (D trab) BMDs, BV/TV, cortical thickness (Cort Th), trabecular number (TbN), and trabecular thickness (TbTh) and higher trabecular separation (TbSp) and distribution of trabecular separation (TbSpSd) than controls without fractures. In a logistic model, each SD decrease of volumetric total and trabecular densities was associated with a significantly increased risk of fracture at both sites (ORs ranged from 2.00 to 2.47). After adjusting for aBMD measured by DXA at the ultradistal radius, differences between cases and controls remained significant for D trab, and there was a similar trend for TbN, TbSp, and TbSpSd, with adjusted ORs ranging from 1.32 to 1.50. At the distal tibia, before and after adjusting for total hip aBMD, differences between cases and controls remained significant for D tot, D trab, Cort Th, and TbTh, with adjusted ORs ranging from 1.80 to 2.09. Conclusions: In postmenopausal women, vertebral and nonvertebral fractures are associated with low volumetric BMD and architectural alterations of trabecular and cortical bone that can be assessed noninvasively and that are partially independent of aBMD assessed by DXA.

Trabecular bone score (TBS) is a gray-level textural index of bone microarchitecture derived from lumbar spine dual-energy X-ray absorptiometry (DXA) images. TBS is a bone mineral density (BMD)-independent predictor of fracture risk. The objective of this metaanalysis was to determine whether TBS predicted fracture risk independently of FRAX probability and to examine their combined performance by adjusting the FRAX probability for TBS. We utilized individual-level data from 17,809 men and women in 14 prospective population-based cohorts. Baseline evaluation included TBS and the FRAX risk variables, and outcomes during follow-up (mean 6.7 years) comprised major osteoporotic fractures. The association between TBS, FRAX probabilities, and the risk of fracture was examined using an extension of the Poisson regression model in each cohort and for each sex and expressed as the gradient of risk (GR; hazard ratio per 1 SD change in risk variable in direction of increased risk). FRAX probabilities were adjusted for TBS using an adjustment factor derived from an independent cohort (the Manitoba Bone Density Cohort). Overall, the GR of TBS for major osteoporotic fracture was 1.44 (95% confidence interval [CI] 1.35-1.53) when adjusted for age and time since baseline and was similar in men and women (p > 0.10). When additionally adjusted for FRAX 10-year probability of major osteoporotic fracture, TBS remained a significant, independent predictor for fracture (GR ¼ 1.32, 95% CI 1.24-1.41). The adjustment of FRAX probability for TBS resulted in a small increase in the GR (1.76, 95% CI 1.65-1.87 versus 1.70, 95% CI 1.60-1.81). A smaller change in GR for hip fracture was observed (FRAX hip fracture probability GR 2.25 vs. 2.22). TBS is a significant predictor of fracture risk independently of FRAX. The findings support the use of TBS as a potential adjustment for FRAX probability, though the impact of the adjustment remains to be determined in the context of clinical assessment guidelines.

Chronic kidney disease (CKD) patients may have high rates of bone loss and fractures, but microarchitectural and biochemical mechanisms of bone loss in CKD patients have not been fully described. In this longitudinal study of 53 patients with CKD Stages 2-5D, we used dual energy X-ray absorptiometry (DXA), high resolution peripheral quantitative computed tomography (HRpQCT) and biochemical markers of bone metabolism to elucidate effects of CKD on the skeleton. Median follow-up was 1.5 years (Range 0.9 to 4.3 years); bone changes were annualized and compared to baseline. By DXA, there were significant declines in areal bone mineral density (BMD) of the total hip and ultradistal radius: −1.3% (95% CI: −2.1 to −0.6) and −2.4% (95% CI: −4.0 to −0.9), respectively. By HRpQCT at the distal radius, there were significant declines in cortical area, density and thickness, and increases in porosity: −2.9% (95% CI −3.7 to −2.2), −1.3% (95% CI −1.6 to −0.6), −2.8% (95% CI −3.6 to −1.9), and +4.2% (95% CI 2.0 to 6.4) respectively. Radius trabecular area increased significantly: +0.4% (95% CI 0.2 to 0.6), without significant changes in trabecular density or microarchitecture. Elevated time-averaged levels of parathyroid hormone (PTH) and bone turnover markers predicted cortical deterioration. Higher levels of serum 25-hydroxyvitamin D predicted decreases in trabecular network heterogeneity. These data suggest that significant cortical loss occurs with CKD, which is mediated by hyperparathyroidism and elevated turnover. Future investigations are required to determine whether these cortical losses can be attenuated by treatments that reduce PTH levels and remodeling rates.

1) There are limited new data available on the natural history of asymptomatic PHPT. Although recognition of normocalcemic PHPT (normal serum calcium with elevated PTH concentrations; no secondary cause for hyperparathyroidism) is increasing, data on the clinical presentation and natural history of this phenotype are limited. 2) Although there are geographic differences in the predominant phenotypes of PHPT (symptomatic, asymptomatic, normocalcemic), they do not justify geography-specific management guidelines. 3) Recent data using newer, higher resolution imaging and analytic methods have revealed that in asymptomatic PHPT, both trabecular bone and cortical bone are affected. 4) Clinically silent nephrolithiasis and nephrocalcinosis can be detected by renal imaging and should be listed as a new criterion for surgery. 5) Current data do not support a cardiovascular evaluation or surgery for the purpose of improving cardiovascular markers, anatomical or functional abnormalities. 6) Some patients with mild PHPT have neuropsychological complaints and cognitive abnormalities, and some of these patients may benefit from surgical intervention. However, it is not possible at this time to predict which patients with neuropsychological complaints or cognitive issues will improve after successful parathyroid surgery.

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The intensity of bone remodeling is a critical determinant of the decay of cortical and trabecular microstructure after menopause. Denosumab suppresses remodeling more than alendronate, leading to greater gains in areal bone mineral density (aBMD). These greater gains may reflect differing effects of each drug on bone microarchitecture and strength. In a phase 2 double-blind pilot study, 247 postmenopausal women were randomized to denosumab (60mg subcutaneous 6 monthly), alendronate (70mg oral weekly), or placebo for 12 months. All received daily calcium and vitamin D. Morphologic changes were assessed using high-resolution peripheral quantitative computed tomography (HR-pQCT) at the distal radius and distal tibia and QCT at the distal radius. Denosumab decreased serum C-telopeptide more rapidly and markedly than alendronate. In the placebo arm, total, cortical, and trabecular BMD and cortical thickness decreased (−2.1% to −0.8%) at the distal radius after 12 months. Alendronate prevented the decline (−0.6% to 2.4%, p = .051 to < .001 versus placebo), whereas denosumab prevented the decline or improved these variables (0.3% to 3.4%, p < .001 versus placebo). Changes in total and cortical BMD were greater with denosumab than with alendronate (p ≤ .024). Similar changes in these parameters were observed at the tibia. The polar moment of inertia also increased more in the denosumab than alendronate or placebo groups (p < .001). Adverse events did not differ by group. These data suggest that structural decay owing to bone remodeling and progression of bone fragility may be prevented more effectively with denosumab.