Distal phalangeal bone erosions observed by HR-pQCT in patients with psoriatic onycholysis.

OBJECTIVES: PsA prevalence among skin psoriasis is ∼30%. Nail psoriasis, especially onycholysis, is present in >70% of PsA and the risk of developing PsA is more than doubled in patients with nail involvement. We hypothesized that onycholysis may be associated with early bone erosions of the DIP joint without harbouring PsA symptoms. METHODS: We compared tendon thickness, assessed by US, and bone erosions, assessed by high-resolution peripheral quantitative CT, of the DIP joint in patients with psoriatic onycholysis without PsA (ONY) with those in patients with cutaneous psoriasis only (PSO). We used patients with PsA as reference (PsA group), and healthy age-matched controls (CTRL). Differences between groups were assessed by analysis of variance tests followed by post hoc analysis using the Scheffe method. RESULTS: Mean (s.e.m.) age of the 87 participants (61% males) was 45.2 (1.3) years. The mean extensor tendon thickness was significantly larger in ONY than in PSO patients. In the PsA group, 68% of patients exhibited erosions of three different shapes: V-, Omega- and U-shape. Association with erosions was greater in the ONY group than in the PSO group (frequency: 57 vs 14%; P < 0.001; mean number of erosions: 1.10 (0.35) vs 0.03 (0.03); P < 0.001). CONCLUSION: Onycholysis was associated with significant enthesopathy and bone erosions in our cohort. These data support the pathogenic role of enthesopathy in PsA. Onycholysis may be considered as a surrogate marker of severity in psoriasis. TRIAL REGISTRATION: ClinicalTrails.gov, https://clinicaltrials.gov, NCT02813720.

Local and global microarchitecture is associated with different features of bone biomechanics.

PURPOSE: Beside areal bone mineral density (aBMD), evaluation of fragility fracture risk mostly relies on global microarchitecture. However, microarchitecture is not a uniform network. Therefore, this study aimed to compare local structural weakness to global microarchitecture on whole vertebral bodies and to evaluate how local and global microarchitecture was associated with bone biomechanics. METHODS: From 21 human L3 vertebrae, aBMD was measured using absorptiometry. Parameters of global microarchitecture were measured using HR-pQCT: trabecular bone volume fraction (Tb.BV/TVglobal), trabecular number, structure model index and connectivity density (Conn.D). Local minimal values of aBMD and Tb.BV/TV were identified in the total (Tt) or trabecular (Tb) area of each vertebral body. "Two dimensional (2D) local structural weakness" was defined as Tt.BMDmin, Tt.BV/TVmin and Tb.BV/TVmin. Mechanical testing was performed in 3 phases: 1/ initial compression until mild vertebral fracture, 2/ unloaded relaxation, and 3/ second compression until failure. RESULTS: Initial and post-fracture mechanics were significantly correlated with bone mass, global and local microarchitecture. Tt.BMDmin, Tt.BV/TVmin, Tb.BV/TVmin, and initial and post-fracture mechanics remained significantly correlated after adjustment for aBMD or Tb.BV/TVglobal (p < 0.001 to 0.038). The combination of the most relevant parameter of bone mass, global and local microarchitecture associated with failure load and stiffness demonstrated that global microarchitecture explained initial and post-fracture stiffness, while local structural weakness explained initial and post-fracture failure load (p < 0.001). CONCLUSION: Local and global microarchitecture was associated with different features of vertebral bone biomechanics, with global microarchitecture controlling stiffness and 2D local structural weakness controlling strength. Therefore, determining both localized low density and impaired global microarchitecture could have major impact on vertebral fracture risk prediction.

Consensus approach for 3D joint space width of metacarpophalangeal joints of rheumatoid arthritis patients using high-resolution peripheral quantitative computed tomography.

BACKGROUND: Joint space assessment for rheumatoid arthritis (RA) by ordinal conventional radiographic scales is susceptible to floor and ceiling effects. High-resolution peripheral quantitative computed tomography (HR-pQCT) provides superior resolution, and may detect earlier changes. The goal of this work was to compare existing 3D methods to calculate joint space width (JSW) metrics in human metacarpophalangeal (MCP) joints with HR-pQCT and reach consensus for future studies. Using the consensus method, we established reproducibility with repositioning as well as feasibility for use in second-generation HR-pQCT scanners. METHODS: Three published JSW methods were compared using datasets from individuals with RA from three research centers. A SPECTRA consensus method was developed to take advantage of strengths of the individual methods. Using the SPECTRA method, reproducibility after repositioning was tested and agreement between scanner generations was also established. RESULTS: When comparing existing JSW methods, excellent agreement was shown for JSW minimum and mean (ICC 0.987-0.996) but not maximum and volume (ICC 0.000-0.897). Differences were identified as variations in volume definitions and algorithmic differences that generated high sensitivity to boundary conditions. The SPECTRA consensus method reduced this sensitivity, demonstrating good scan-rescan reliability (ICC >0.911) except for minimum JSW (ICC 0.656). There was strong agreement between results from first- and second-generation HR-pQCT (ICC >0.833). CONCLUSIONS: The SPECTRA consensus method combines unique strengths of three independently-developed algorithms and leverages underlying software updates to provide a mature analysis to measure 3D JSW. This method is robust with respect to repositioning and scanner generations, suggesting its suitability for detecting change.

Prediction of Fractures in Men Using Bone Microarchitectural Parameters Assessed by High-Resolution Peripheral Quantitative Computed Tomography-The Prospective STRAMBO Study.

Areal bone mineral density (aBMD) poorly identifies men at high fracture risk. Our aim was to assess prediction of fractures in men by bone microarchitectural measures. At baseline, 825 men aged 60 to 87 years had the assessment of bone microarchitecture at distal radius and distal tibia by high-resolution peripheral QCT (HR-pQCT; XtremeCT-I, Scanco Medical, Brüttisellen, Switzerland). Bone strength was estimated by micro-finite element analysis. During the prospective 8-year follow-up, 105 men sustained fractures (59 vertebral fractures in 49 men and 70 nonvertebral fractures in 68 men). After adjustment for age, body mass index (BMI), prior falls, and fractures, most HR-pQCT measures at both skeletal sites predicted fractures. After further adjustment for aBMD, low distal radius trabecular number (Tb.N) was most strongly associated with higher fracture risk (hazard ratio [HR] = 1.63 per SD, 95% confidence interval [CI] 1.31-2.03, p < 0.001). In similar models, low Tb.N was associated with higher risk of major osteoporotic fracture (HR = 1.80 per SD, p < 0.001), vertebral fracture (HR = 1.78 per SD, p < 0.01) and nonvertebral fracture (HR = 1.46 per SD, p < 0.01). In comparison with the reference model (age, BMI, falls, fractures, aBMD), the adjustment for distal radius Tb.N increased the estimated fracture probability in men who sustained fractures versus those who did not have ones (difference = 4.1%, 95% CI 1.9-6.3%, p < 0.001). However, the adjustment for distal radius Tb.N did not increase the area under the curve (AUC, p = 0.37). Similar results were found for distal radius trabecular separation (Tb.Sp) and connectivity density (Conn. D). They were predictive of all fracture types and increased the estimated fracture risk, but not AUC, in men who had incident fractures. Thus, poor distal radius trabecular microarchitecture is predictive of fracture after adjustment for age, BMI, falls, fractures, and aBMD. Although distal radius Tb.N, Conn. D, and Tb.Sp improve the discrimination between men who will or who will not have fracture, they do not provide clinically relevant improvement of fracture prediction in older men. © 2018 American Society for Bone and Mineral Research.

Least-detectable and age-related local in vivo bone remodelling assessed by time-lapse HR-pQCT.

We previously developed an image analysis approach for the determination of local sites of bone remodelling using time-lapse in vivo HR-pQCT. The involved image filtering for removing noise was chosen rather aggressively, and also removed some effects of the bone remodelling. In this paper, we quantify these filtering settings using ex vivo reproducibility HR-pQCT images, and determine the least-detectable bone remodelling using in vivo reproducibility HR-pQCT images, as well as testing whether the approach is capable of capturing age-related bone remodelling by use of in vivo long-term HR-pQCT images. We found that a threshold value of 225 mg HA/cm3 for the filtering led to acceptable results with falsely determined bone remodelling of less than 0.5%, and that the least-detectable bone formation and bone resorption are 2.0 ± 1.0% and 2.2 ± 0.7% respectively. We also found that age-related local bone remodelling can be captured satisfactorily in postmenopausal women. The latter revealed new insights into the effect of ageing on bone remodelling, and showed that bone remodelling seems to take place through a few small formation packets and many large resorption volumes leading to a net bone loss. We conclude that local in vivo bone remodelling can be successfully assessed with time-lapse in vivo HR-pQCT capable of assessing age-related changes in bone remodelling.

Longitudinal Bone Mineralization Assessment in Children Treated With Long-Term Parenteral Nutrition for Severe Intestinal Failure.

BACKGROUND: Metabolic bone disease is common in children receiving home parenteral nutrition (HPN) for intestinal failure (IF). Long-term evolution of bone mass in pediatric IF is poorly documented. The aims of this study were (1) to determine the prevalence of low bone mass (LBM) in children receiving HPN for IF, (2) to evaluate the evolution of total bone mineral content (TBMC) during HPN with dual-energy x-ray absorptiometry (DXA), and (3) to identify related factors. METHODS: All children referred in our HPN center from 2004 to 2014 were eligible. Inclusion criteria were HPN dependence due to noninflammatory IF, at least 2 TBMC assessments, and HPN duration of at least 2 years at last DXA. TBMC was expressed in z score for ideal weight for height (WFH). LBM was defined by a TBMC WFH z score ≤-2 standard deviations (SD). RESULTS: A total of 175 DXAs for 31 children were performed, mean of 5.6 ± 2.9 assessments per child. The median time between first and last DXA recorded was 6.2 years (0.7-16.6). At the first DXA, 14 children (45%) had a LBM. TBMC increased by +0.1 ± 0.04 SD per year of HPN (P = .012). The risk of LBM decreased with an odds ratio of 0.9 per year of HPN (95% confidence interval, 0.92-0.99; P = .018). Lean mass z score and calcium parenteral intakes were related to the TBMC improvement. CONCLUSION: LBM is common in pediatric IF, but bone status could improve during HPN in these children.

The Relationship Between Body Composition and Bone Quality Measured with HR-pQCT in Peritoneal Dialysis Patients.

BACKGROUND: Bone is known to be impaired in chronic kidney disease and dialysis patients. Recent studies have shown that body composition (fat mass and lean mass) may impact bone health. Some of these effects may be related to mediators that are secreted by adipose tissue. METHODS: The aim of this study was to evaluate the association between body composition (dual x-ray absorptiometry [DEXA]) and adipokines (leptin, adiponectin), with bone density and microarchitecture assessed with high-resolution peripheral quantitative computed tomography (HR-pQCT) in chronic peritoneal dialysis (PD) patients in a single-center prospective study. RESULTS: Twenty-three patients with a median age of 61 years and body mass index (BMI) of 27 kg/m2 were recruited. On univariate analysis, age was negatively associated with total volumetric bone mineral density (vBMD) (r = -0.75, p < 0.01), cortical vBMD (r = -0.85, p < 0.01), and cortical thickness (r = -0.71, p < 0.01). There was a negative association between leptin and cortical thickness (r = -0.48, p = 0.021). Fat mass (FM) was negatively correlated with cortical thickness (r = -0.52, p = 0.012). No association was found between bone parameters and dialysis duration, serum insulin, intact parathyroid hormone, osteocalcin, and adiponectin. The short dialysis vintage could in part explain the lack of correlation with bone parameters. In multivariate analysis, FM was significantly and negatively correlated with total vBMD, cortical and trabecular thickness. CONCLUSIONS: These data suggest that FM is negatively associated with bone quality in PD patients, supporting a relation between body composition and bone that is independent from other dialysis-associated complications. The relative contribution of the different fat deposits (visceral versus subcutaneous) needs to be assessed in future studies.

Similarities in trabecular hypertrophy with site-specific differences in cortical morphology between men and women with type 2 diabetes mellitus.

The goal of our study was to investigate interactions between sex and type 2 diabetes mellitus (T2DM) with regard to morphology of the peripheral skeleton. We recruited 85 subjects (mean age, 57±11.4 years): women with and without T2DM (n = 17; n = 16); and men with and without T2DM (n = 26; n = 26). All patients underwent high-resolution, peripheral, quantitative, computed tomography (HR-pQCT) imaging of the ultradistal radius (UR) and tibia (UT). Local bone geometry, bone mineral density (BMD), and bone microarchitecture were obtained by quantitative analysis of HR-pQCT images. To reduce the amount of data and avoid multi-collinearity, we performed a factor-analysis of HR-pQCT parameters. Based on factor weight, trabecular BMD, trabecular number, cortical thickness, cortical BMD, and total area were chosen for post-hoc analyses. At the radius and tibia, diabetic men and women exhibited trabecular hypertrophy, with a significant positive main effect of T2DM on trabecular number. At the radius, cortical thickness was higher in diabetic subjects (+20.1%, p = 0.003). Interestingly, there was a statistical trend that suggested attenuation of tibial cortical hypertrophy in diabetic men (cortical thickness, pinteraction = 0.052). Moreover, we found an expected sexual dichotomy, with higher trabecular BMD, Tb.N, cortical BMD, Ct.Th, and total area in men than in women (p≤ 0.003) at both measurement sites. Our results suggest that skeletal hypertrophy associated with T2DM is present in men and women, but appears attenuated at the tibial cortex in men.

Bone Microarchitecture Assessed by HR-pQCT as Predictor of Fracture Risk in Postmenopausal Women: The OFELY Study.

Several cross-sectional studies have shown that impairment of bone microarchitecture contributes to skeletal fragility. The aim of this study was to prospectively investigate the prediction of fracture (Fx) by bone microarchitecture assessed by high-resolution peripheral computed tomography (HR- pQCT) in postmenopausal women. We measured microarchitecture at the distal radius and tibia with HR-pQCT in the OFELY study, in addition to areal BMD with dual-energy X-ray absorptiometry (DXA) in 589 women, mean ± SD age 68 ± 9 years. During a median [IQ] 9.4 [1.0] years of follow-up, 135 women sustained an incident fragility Fx, including 81 women with a major osteoporotic Fx (MOP Fx). After adjustment for age, women who sustained Fx had significantly lower total and trabecular volumetric densities (vBMD) at both sites, cortical parameters (area and thickness at the radius, vBMD at the tibia), trabecular number (Tb.N), connectivity density (Conn.D), stiffness, and estimated failure load at both sites, compared with control women. After adjustment for age, current smoking, falls, prior Fx, use of osteoporosis-related drugs, and total hip BMD, each quartile decrease of several baseline values of bone microarchitecture at the radius was associated with significant change of the risk of Fx (HR of 1.39 for Tb.BMD [p = 0.001], 1.32 for Tb.N [p = 0.01], 0.76 for Tb.Sp.SD [p = 0.01], 1.49 [p = 0.01] for Conn.D, and 1.27 for stiffness [p = 0.02]). At the tibia, the association remained significant for stiffness and failure load in the multivariate model for all fragility Fx and for Tt.BMD, stiffness, and failure load for MOP Fx. We conclude that impairment of bone microarchitecture-essentially in the trabecular compartment of the radius-predict the occurrence of incident fracture in postmenopausal women. This assessment may play an important role in identifying women at high risk of fracture who could not be adequately detected by BMD measurement alone, to benefit from a therapeutic intervention. © 2017 American Society for Bone and Mineral Research.

Definition for Rheumatoid Arthritis Erosions Imaged with High Resolution Peripheral Quantitative Computed Tomography and Interreader Reliability for Detection and Measurement.

OBJECTIVE: High-resolution peripheral quantitative computed tomography (HR-pQCT) sensitively detects erosions in rheumatoid arthritis (RA); however, nonpathological cortical bone disruptions are potentially misclassified as erosive. Our objectives were to set and test a definition for pathologic cortical bone disruptions in RA and to standardize reference landmarks for measuring erosion size. METHODS: HR-pQCT images of metacarpophalangeal joints of RA and control subjects were used in an iterative process to achieve consensus on the definition and reference landmarks. Independent readers (n = 11) applied the definition to score 58 joints and measure pathologic erosions in 2 perpendicular multiplanar reformations for their maximum width and depth. Interreader reliability for erosion detection and variability in measurements between readers [root mean square coefficient of variation (RMSCV), intraclass correlation (ICC)] were calculated. RESULTS: Pathologic erosions were defined as cortical breaks extending over a minimum of 2 consecutive slices in perpendicular planes, with underlying trabecular bone loss and a nonlinear shape. Interreader agreement for classifying pathologic erosions was 90.2%, whereas variability for width and depth erosion assessment was observed (RMSCV perpendicular width 12.3%, axial width 20.6%, perpendicular depth 24.0%, axial depth 22.2%; ICC perpendicular width 0.206, axial width 0.665, axial depth 0.871, perpendicular depth 0.783). Mean erosion width was 1.84 mm (range 0.16-8.90) and mean depth was 1.86 mm (range 0.30-8.00). CONCLUSION: We propose a new definition for erosions visualized with HR-pQCT imaging. Interreader reliability for erosion detection is good, but further refinement of selection of landmarks for erosion size measurement, or automated volumetric methods, will be pursued.

In Vivo High-Resolution Trabecular Microstructure of Kienböck Lunate before and after Radial Shortening: A Case Report.

We report a patient with stage IIIB Kienböck disease treated with radial shortening where preoperative and sequential postoperative imaging were done using in vivo high-resolution peripheral quantitative micro-computed tomography (micro-CT) scan. Sequential in vivo micro-CT scan analysis of a target zone of the Kienböck lunate of this patient demonstrated early signs of lunate remodeling (bone trabecular densification) at 5-month follow-up suggesting an ongoing healing process. These early remodeling micro-CT scan signs were confirmed at 5 years' follow-up as well.

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

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

Voxel size dependency, reproducibility and sensitivity of an in vivo bone loading estimation algorithm.

A bone loading estimation algorithm was previously developed that provides in vivo loading conditions required for in vivo bone remodelling simulations. The algorithm derives a bone's loading history from its microstructure as assessed by high-resolution (HR) computed tomography (CT). This reverse engineering approach showed accurate and realistic results based on micro-CT and HR-peripheral quantitative CT images. However, its voxel size dependency, reproducibility and sensitivity still need to be investigated, which is the purpose of this study. Voxel size dependency was tested on cadaveric distal radii with micro-CT images scanned at 25 µm and downscaled to 50, 61, 75, 82, 100, 125 and 150 µm. Reproducibility was calculated with repeated in vitro as well as in vivo HR-pQCT measurements at 82 µm. Sensitivity was defined using HR-pQCT images from women with fracture versus non-fracture, and low versus high bone volume fraction, expecting similar and different loading histories, respectively. Our results indicate that the algorithm is voxel size independent within an average (maximum) error of 8.2% (32.9%) at 61 µm, but that the dependency increases considerably at voxel sizes bigger than 82 µm. In vitro and in vivo reproducibility are up to 4.5% and 10.2%, respectively, which is comparable to other in vitro studies and slightly higher than in other in vivo studies. Subjects with different bone volume fraction were clearly distinguished but not subjects with and without fracture. This is in agreement with bone adapting to customary loading but not to fall loads. We conclude that the in vivo bone loading estimation algorithm provides reproducible, sensitive and fairly voxel size independent results at up to 82 µm, but that smaller voxel sizes would be advantageous.

Age-related changes in bone strength from HR-pQCT derived microarchitectural parameters with an emphasis on the role of cortical porosity.

The high resolution peripheral computed tomography (HR-pQCT) technique has seen recent developments with regard to the assessment of cortical porosity. In this study, we investigated the role of cortical porosity on bone strength in a large cohort of women. The distal radius and distal tibia were scanned by HR-pQCT. We assessed bone strength by estimating the failure load by microfinite element analysis (µFEA), with isotropic and homogeneous material properties. We built a multivariate model to predict it, using a few microarchitecture variables including cortical porosity. Among 857 Caucasian women analyzed with µFEA, we found that cortical and trabecular properties, along with the failure load, impaired slightly with advancing age in premenopausal women, the correlations with age being modest, with |rage| ranging from 0.14 to 0.38. After the onset of the menopause, those relationships with age were stronger for most parameters at both sites, with |rage| ranging from 0.10 to 0.64, notably for cortical porosity and failure load, which were markedly deteriorated with increasing age. Our multivariate model using microarchitecture parameters revealed that cortical porosity played a significant role in bone strength prediction, with semipartial r(2)=0.22 only at the tibia in postmenopausal women. In conclusion, in our large cohort of women, we observed a small decline of bone strength at the tibia before the onset of menopause. We also found an age-related increase of cortical porosity at both scanned sites in premenopausal women. In postmenopausal women, the relatively high increase of cortical porosity accounted for the decline in bone strength only at the tibia.

A Meta-Analysis of Trabecular Bone Score in Fracture Risk Prediction and Its Relationship to FRAX.

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 meta-analysis 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 = 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. © 2015 American Society for Bone and Mineral Research.

Noninvasive Assessment of Skeletal Microstructure and Estimated Bone Strength in Hypoparathyroidism.

In hypoparathyroidism, areal bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) is above average, and skeletal indices by bone biopsy are abnormal. We used high-resolution peripheral quantitative computed tomography (HRpQCT) and finite element analyses (FEA) to further investigate skeletal microstructure and estimated bone strength. We studied 60 hypoparathyroid subjects on conventional therapy using DXA, HRpQCT, and FEA of the distal radius and tibia compared with normative controls from the Canadian Multicentre Osteoporosis Study. In hypoparathyroid women and men, areal BMD was above average at the lumbar spine and hip sites by DXA; radial BMD was also above average in hypoparathyroid women. Using HRpQCT, cortical volumetric BMD was increased in the hypoparathyroid cohort compared with controls at both the radius and tibia. Cortical porosity was reduced at both sites in pre- and postmenopausal women and at the tibia in young men with a downward trend at the radius in men. At the tibia, trabecular number was increased in premenopausal women and men and trabecular thickness was lower in women. Ultimate stress and failure load at both sites for the hypoparathyroid subjects were similar to controls. Using a linear regression model, at both radius and tibia, each increment in age decreased ultimate stress and failure load, whereas each increment in duration of hypoparathyroidism increased these same indices. These results provide additional evidence for the critical role of parathyroid hormone in regulating skeletal microstructure. Longer disease duration may mitigate the adverse effects of age on estimated bone strength in hypoparathyroidism.

Fracture Risk Prediction by Non-BMD DXA Measures: the 2015 ISCD Official Positions Part 2: Trabecular Bone Score.

Bone mineral density (BMD) as measured by dual-energy X-ray absorptiometry (DXA) is the gold standard for the diagnosis and management of osteoporosis. However, BMD explains only 60%-80% of bone strength, and a number of skeletal features other than BMD contribute to bone strength and fracture risk. Advanced imaging modalities can assess some of these skeletal features, but compared to standard DXA, these techniques have higher costs and limited accessibility. A major challenge, therefore, has been to incorporate in clinical practice a readily available, noninvasive technology that permits improvement in fracture-risk prediction beyond that provided by the combination of standard DXA measurements and clinical risk factors. To this end, trabecular bone score (TBS), a gray-level textural index derived from the lumbar spine DXA image, has been investigated. The purpose of this International Society for Clinical Densitometry task force was to review the evidence and develop recommendations on how to incorporate TBS in clinical practice. Clinical applications of TBS for fracture risk assessment, treatment initiation, monitoring of treatment, and use of TBS in special conditions related to greater fracture risk, were addressed. We present the official positions approved by an expert panel following careful review of the recommendations and evidence presented by the TBS task force.

Bone remodelling in humans is load-driven but not lazy.

During bone remodelling, bone cells are thought to add and remove tissue at sites with high and low loading, respectively. To predict remodelling, it was proposed that bone is removed below and added above certain thresholds of tissue loading and within these thresholds, called a 'lazy zone', no net change in bone mass occurs. Animal experiments linking mechanical loading with changes in bone density or microstructure support load-adaptive bone remodelling, while in humans the evidence for this relationship at the micro-scale is still lacking. Using new high-resolution CT imaging techniques and computational methods, we quantify microstructural changes and physiological tissue loading in humans. Here, we show that bone remodelling sites in healthy postmenopausal women strongly correlate with tissue loading following a linear relationship without a 'lazy zone' providing unbiased evidence for load-driven remodelling in humans. This suggests that human and animal bones both react to loading induced remodelling in a similar fashion.

Current issues in the presentation of asymptomatic primary hyperparathyroidism: proceedings of the Fourth International Workshop.

OBJECTIVE: This report summarizes data on traditional and nontraditional manifestations of primary hyperparathyroidism (PHPT) that have been published since the last International Workshop on PHPT. PARTICIPANTS: This subgroup was constituted by the Steering Committee to address key questions related to the presentation of PHPT. Consensus was established at a closed meeting of the Expert Panel that followed. EVIDENCE: Data from the 5-year period between 2008 and 2013 were presented and discussed to determine whether they support changes in recommendations for surgery or nonsurgical follow-up. CONSENSUS PROCESS: Questions were developed by the International Task Force on PHPT. A comprehensive literature search for relevant studies was undertaken. After extensive review and discussion, the subgroup came to agreement on what changes in the recommendations for surgery or nonsurgical follow-up of asymptomatic PHPT should be made to the Expert Panel. CONCLUSIONS: 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.