Bone microarchitecture is more severely affected in patients on hemodialysis than in those receiving peritoneal dialysis.

We used high-resolution quantitative computed tomography to study the microarchitecture of bone in patients with chronic kidney disease on dialysis. We compared bone characteristics in 56 maintenance hemodialysis (21 women, 14 post-menopausal) and 23 peritoneal dialysis patients (9 women, 6 post-menopausal) to 79 healthy men and women from two cohorts matched for age, body mass index, gender, and menopausal status. All underwent dual-energy X-ray absorptiometry of the spine and hip to measure areal bone mineral density, and high-resolution peripheral quantitative computed tomography of the radius and tibia to measure volumetric bone mineral density and microarchitecture. When compared to their matched healthy controls, patients receiving hemodialysis and peritoneal dialysis had a significantly lower areal bone mineral density in the hip. Hemodialysis patients had significantly lower total, cortical, and trabecular volumetric bone mineral density at both sites. Hemodialysis patients had significantly lower trabecular volumetric bone mineral density and microarchitecture at the tibia than the peritoneal dialysis patients. Overall, peritoneal dialysis patients were less affected, their cortical thickness at the distal tibia being the only significant difference versus controls. Thus, we found more severe trabecular damage at the weight-bearing tibia in hemodialysis compared to peritoneal dialysis patients, but this latter finding needs confirmation in larger cohorts.

Bone assessment in children with chronic kidney disease: data from two new bone imaging techniques in a single-center pilot study.

Bone damage in children with chronic kidney disease (CKD) is a challenge for pediatric nephrologists. Areal measurements of bone mineral density (BMD) by dual x-ray absorptiometry (DXA) have been routinely performed to assess bone mass but recent international guidelines have concluded that DXA was of less value in CKD. The aim of this study is to evaluate bone quality in CKD children using new bone imaging techniques in a pilot cross-sectional single-center study. We performed bone imaging (high-resolution peripheral quantitative computed tomography, HR-pQCT, XtremeCT, Scanco Medical AG, Switzerland), to assess compartmental volumetric BMD and trabecular microarchitecture in 22 CKD children and 19 controls. In seven younger patients (i.e., under 10 years of age), we performed bone texture analysis (BMA, D3A Medical Systems, France) in comparison to 15 healthy prepubertal controls. Among older children, CKD patients had significantly lower height and body weight without significant impairment of BMD and microarchitecture than healthy controls. In univariate analysis, there were significant correlations between cortical BMD and glomerular filtration rate (r= -0.46), age (r=0.60) and body mass index (r=0.67). In younger children, bone texture parameters were not different between patients and controls. Our results did not show significant differences between healthy controls and CKD children for compartmental bone densities and microarchitecture, but the small sample size and the heterogeneity of the CKD group require caution in the interpretation. Novel bone imaging techniques seem feasible in children, and further longitudinal studies are required to thoroughly explore long-term cardiovascular and bone consequences of phosphate-calcium metabolism deregulation during CKD.

Assessment of hand bone loss in rheumatoid arthritis by high-resolution peripheral quantitative CT.

OBJECTIVES: A new high-resolution peripheral quantitative CT (HR-pQCT) system allows for in vivo assessment of bone microarchitecture and volumetric bone mineral density (vBMD) with an 82 microm isotropic resolution. With this device, the microarchitecture impairment was evaluated in patients with rheumatoid arthritis (RA) in comparison with healthy controls and measured the erosion volume at metacarpal heads (MCPs). METHODS: In this cross-sectional study, the reproducibility was first assessed by 3 HR-pQCT exams with repositioning in 14 patients with late RA and 14 healthy subjects. Then, HR-pQCT parameters were measured in a group of 93 patients with RA and 31 healthy controls. Two RA subgroups were distinguished: early RA (disease duration < or =2 years) (n=36) and late RA (n=57) and compared them to healthy controls. RESULTS: The precision of the HR-pQCT volumetric measurements as assessed with coefficient of variation ranged from 0.7% to 1.8% in patients with late RA and from 0.6% to 1.4% in healthy subjects at MCPs. Total and trabecular vBMD and trabecular thickness were significantly decreased in patients with RA compared to healthy subjects and were significantly correlated to disease activity. The erosion volume was highly correlated to a semiquantitative assessment using the Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) scoring system applied to the HR-pQCT slices. CONCLUSIONS: This study demonstrated the good reproducibility of the HR-pQCT volumetric measurements at MCPs and confirmed the involvement of trabecular compartment in periarticular osteopoenia. Thus, HR-pQCT appears interesting to simultaneously assess differences in bone volumetric density, microarchitecture and erosions.

Assessment of bone microarchitecture in chronic kidney disease: a comparison of 2D bone texture analysis and high-resolution peripheral quantitative computed tomography at the radius and tibia.

Bone microarchitecture can be studied noninvasively using high-resolution peripheral quantitative computed tomography (HR-pQCT). However, this technique is not widely available, so more simple techniques may be useful. BMA is a new 2D high-resolution digital X-ray device, allowing for bone texture analysis with a fractal parameter (H(mean)). The aims of this study were (1) to evaluate the reproducibility of BMA at two novel sites (radius and tibia) in addition to the conventional site (calcaneus), (2) to compare the results obtained with BMA at all of those sites, and (3) to study the relationship between H(mean) and trabecular microarchitecture measured with an in vivo 3D device (HR-pQCT) at the distal tibia and radius. BMA measurements were performed at three sites (calcaneus, distal tibia, and radius) in 14 healthy volunteers to measure the short-term reproducibility and in a group of 77 patients with chronic kidney disease to compare BMA results to HR-pQCT results. The coefficient of variation of H(mean) was 1.2, 2.1, and 4.7% at the calcaneus, radius, and tibia, respectively. We found significant associations between trabecular volumetric bone mineral density and microarchitectural variables measured by HR-pQCT and H(mean) at the three sites (e.g., Pearson correlation between radial trabecular number and radial H(mean) r = 0.472, P < 0.001). This study demonstrated a significant but moderate relationship between 2D bone texture and 3D trabecular microarchitecture. BMA is a new reproducible technique with few technical constraints. Thus, it may represent an interesting tool for evaluating bone structure, in association with biological parameters and DXA.

Bone metabolism in oxalosis: a single-center study using new imaging techniques and biomarkers.

The deposition of calcium oxalate crystals in the kidney and bone is a hallmark of primary hyperoxaluria type 1 (PH1). We report here an evaluation of the bone status of 12 PH1 children based on bone biomarkers [parathyroid hormone, vitamin D, fibroblast growth factor 23 (FGF23)] and radiological assessments (skeletal age, three-dimensional high-resolution peripheral quantitative computed tomography, HR-pQCT) carried out within the framework of a cross-sectional single-center study. The controls consisted of healthy and children with chronic kidney disease already enrolled in local bone and mineral metabolism studies. The mean age (+ or - standard deviation) age of the patients was 99 (+ or - 63) months. Six children suffered from fracture. Bone maturation was accelerated in five patients, four of whom were <5 years. The combination of new imaging techniques and biomarkers highlighted new and unexplained features of PH1: advanced skeletal age in young PH1 patients, increased FGF23 levels and decreased total volumetric bone mineral density with bone microarchitecture alteration.

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.

Bone imaging and chronic kidney disease: will high-resolution peripheral tomography improve bone evaluation and therapeutic management?

Bone damage because of chronic kidney disease (CKD) represents a daily challenge for nephrologists. The impact of CKD on bone health may be immediate (serum phosphocalcic disturbances) or delayed (bone fractures and vascular calcifications). Histomorphometry remains the gold standard to evaluate bone, but it is rarely performed in clinical practice. Areal measurement of bone mineral density by dual x-ray absorptiometry is routinely performed to evaluate bone mass. However, this technique presents some limitations. In 2000, the United States National Institutes of Health defined new "quality" criteria for the diagnosis of osteoporosis in addition to decreased bone mass. Bone strength actually integrates two concepts: bone quantity and bone quality (i.e., microarchitectural organization, bone turnover, bone material properties such as mineralization, collagen traits, and microdamage) that cannot be evaluated by dual x-ray absorptiometry. New three-dimensional, noninvasive bone-imaging techniques have thus been developed, e.g., high-resolution peripheral quantitative computed tomography. High-resolution peripheral quantitative computed tomography allows evaluation of both volumetric density and microarchitecture in different compartments of bone, at the distal radius and tibia. High-resolution peripheral quantitative computed tomography may be useful in predicting fractures and assessing bone preventive or therapeutic strategies in CKD patients. It should be evaluated in long-term, longitudinal follow-ups.

Validation of calcaneus trabecular microstructure measurements by HR-pQCT.

OBJECTIVE: Assessment of calcaneus microstructure using high-resolution peripheral quantitative computed tomography (HR-pQCT) might be used to improve fracture risk predictions or to assess responses to pharmacological and physical interventions. To develop a standard clinical protocol for the calcaneus, we validated calcaneus trabecular microstructure measured by HR-pQCT against 'gold-standard' micro-CT measurements. METHODS: Ten human cadaveric feet were scanned in situ using HR-pQCT (isotropic 82µm voxel size) at 100, 150 and 200ms integration times, and at 100ms integration time following removal of the calcaneus from the foot (ex vivo). Dissected portions of these bones were scanned using micro-computed tomography (micro-CT) at an isotropic 17.4µm voxel size. HR-pQCT images were rigidly registered to those obtained with micro-CT and divided into multiple 5mm sided cubes to evaluate and compare morphometric parameters between the modalities. Standard HR-pQCT measurements (derived bone volume fraction (BV/TVd); trabecular number, Tb.N; derived trabecular thickness, Tb.Thd; derived trabecular spacing, Tb.Spd) and corresponding micro-CT voxel-based measurements (BV/TV, Tb.N, Tb.Th, Tb.Sp) were compared. RESULTS: A total of 108 regions of interest were analysed across the 10 specimens. At all integration times HR-pQCT BV/TVd was strongly correlated with micro-CT BV/TV (r2=0.95-0.98, RMSE=1%), but BV/TVd was systematically lower than that measured by micro-CT (mean bias=5%). In contrast, HR-pQCT systematically overestimated Tb.N at all integration times; of the in situ scans, 200ms yielded the lowest mean bias and the strongest correlation with micro-CT (r2=0.61, RMSE=0.15mm-1). Regional analysis revealed greater accuracy for Tb.N in the superior regions of the calcaneus at all integration times in situ (mean bias=0.44-0.85mm-1; r2=0.70-0.88, p<0.001 versus mean bias=0.63-1.46mm-1; r2≤0.08, p≥0.21 for inferior regions). Tb.Spd was underestimated by HR-pQCT compared to micro-CT, but showed similar trends with integration time and the region evaluated as Tb.N. HR-pQCT Tb.Thd was also underestimated and moderately correlated (r2=0.53-0.59) with micro-CT Tb.Th, independently from the integration time. Stronger correlations, smaller biases and error were found in the scans of the calcaneus ex vivo compared to in situ. CONCLUSION: Calcaneus trabecular BV/TVd and trabecular microstructure, particularly in the superior region of the calcaneus, can be assessed by HR-pQCT. The highest integration time examined, 200ms, compared best with micro-CT. Weaker correlations for microstructure at inferior regions, and also with lower integration times, might limit the use of the proposed protocol, which warrants further investigation in vivo.

Cortical and Trabecular Bone Microstructure Did Not Recover at Weight-Bearing Skeletal Sites and Progressively Deteriorated at Non-Weight-Bearing Sites During the Year Following International Space Station Missions.

Risk for premature osteoporosis is a major health concern in astronauts and cosmonauts; the reversibility of the bone lost at the weight-bearing bone sites is not established, although it is suspected to take longer than the mission length. The bone three-dimensional structure and strength that could be uniquely affected by weightlessness is currently unknown. Our objective is to evaluate bone mass, microarchitecture, and strength of weight-bearing and non-weight-bearing bone in 13 cosmonauts before and for 12 months after a 4-month to 6-month sojourn in the International Space Station (ISS). Standard and advanced evaluations of trabecular and cortical parameters were performed using high-resolution peripheral quantitative computed tomography. In particular, cortical analyses involved determination of the largest common volume of each successive individual scan to improve the precision of cortical porosity and density measurements. Bone resorption and formation serum markers, and markers reflecting osteocyte activity or periosteal metabolism (sclerostin, periostin) were evaluated. At the tibia, in addition to decreased bone mineral densities at cortical and trabecular compartments, a 4% decrease in cortical thickness and a 15% increase in cortical porosity were observed at landing. Cortical size and density subsequently recovered and serum periostin changes were associated with cortical recovery during the year after landing. However, tibial cortical porosity or trabecular bone failed to recover, resulting in compromised strength. The radius, preserved at landing, unexpectedly developed postflight fragility, from 3 months post-landing onward, particularly in its cortical structure. Remodeling markers, uncoupled in favor of bone resorption at landing, returned to preflight values within 6 months, then declined farther to lower than preflight values. Our findings highlight the need for specific protective measures not only during, but also after spaceflight, because of continuing uncertainties regarding skeletal recovery long after landing. © 2017 American Society for Bone and Mineral Research.

Fast estimation of Colles' fracture load of the distal section of the radius by homogenized finite element analysis based on HR-pQCT.

Fractures of the distal section of the radius (Colles' fractures) occur earlier in life than other osteoporotic fractures. Therefore, they can be interpreted as a warning signal for later, more deleterious fractures of vertebral bodies or the femoral neck. In the past decade, the advent of HR-pQCT allowed a detailed architectural analysis of the distal radius and an automated but time-consuming estimation of its strength with linear micro-finite element (µFE) analysis. Recently, a second generation of HR-pQCT scanner (XtremeCT II, SCANCO Medical, Switzerland) with a resolution beyond 61 µm became available for even more refined biomechanical investigations in vivo. This raises the question how biomechanical outcome variables compare between the original (LR) and the new (HR) scanner resolution. Accordingly, the aim of this work was to validate experimentally a patient-specific homogenized finite element (hFE) analysis of the distal section of the human radius for the fast prediction of Colles' fracture load based on the last generation HR-pQCT. Fourteen pairs of fresh frozen forearms (mean age = 77.5±9) were scanned intact using the high (61 µm) and the low (82 µm) resolution protocols that correspond to the new and original HR-pQCT systems. From each forearm, the 20mm most distal section of the radius were dissected out, scanned with µCT at 16.4 µm and tested experimentally under compression up to failure for assessment of stiffness and ultimate load. Linear and nonlinear hFE models together with linear micro finite element (µFE) models were then generated based on the µCT and HR-pQCT reconstructions to predict the aforementioned mechanical properties of 24 sections. Precision errors of the short term reproducibility of the FE analyses were measured based on the repeated scans of 12 sections. The calculated failure loads correlated strongly with those measured in the experiments: accounting for donor as a random factor, the nonlinear hFE provided a marginal coefficient of determination (Rm2) of 0.957 for the high resolution (HR) and 0.948 for the low resolution (LR) protocols, the linear hFE with Rm2 of 0.957 for the HR and 0.947 for the LR protocols. Linear µFE predictions of the ultimate load were similar with an Rm2 of 0.950 for the HR and 0.954 for the LR protocols, respectively. Nonlinear hFE strength computation led to precision errors of 2.2 and 2.3% which were higher than the ones calculated based on the linear hFE (1.6 and 1.9%) and linear µFE (1.2 and 1.6%) for the HR and LR protocols respectively. Computation of the fracture load with nonlinear hFE demanded in average 6h of CPU time which was 3 times faster than with linear µFE, while computation with linear hFE took only a few minutes. This study delivers an extensive experimental and numerical validation for the application of an accurate and fast hFE diagnostic tool to help in identifying individuals who may be at risk of an osteoporotic wrist fracture and to follow up pharmacological and other treatments in such patients.

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.

In obese postmenopausal women, bone microarchitecture and strength are not commensurate to greater body weight: the Os des Femmes de Lyon (OFELY) study.

Obesity is associated with higher areal bone density (aBMD) but its protective effect on the risk of fracture is controversial. We aimed to analyze bone microarchitecture and biomechanical properties in obese (OB) postmenopausal French women compared with normal weight (NW) women. A matched case-control study from the Os des Femmes de Lyon (OFELY) cohort was conducted in 63 OB women (body mass index [BMI] > 30, mean age 69 ± 8 years) age-matched with 126 NW women (19 ≤ BMI ≤ 25). Bone architecture was measured with high-resolution pQCT at the distal radius and tibia and bone strength was assessed by micro-finite element analysis (µFEA). aBMD, total body fat mass (FM) and lean mass (LM) were measured by dual-energy X-ray absorptiometry (DXA). aBMD was 15% higher at the total hip in OB compared with NW women. At the radius, OB had 13% and 14% higher volumetric total and trabecular bone densities, 11% higher cortical thickness, 13% greater trabecular number, and 22% lower distribution of trabecular separation compared with NW (p adjusted for height, physical activity, and medication use, <0.01 for all). Differences of a similar magnitude were found at the distal tibia. At both sites, µFEA showed significant higher values of bone strength in OB compared to controls. After normalizing values for individual body weight, we observed that all the parameters were relatively lower in OB compared to NW women. The increase of FM was fourfold greater than the increase of LM in OB. The effect of FM on bone parameters was more pronounced at the tibia compared to the non-weight-bearing site. Nevertheless, the coefficients of correlation were about one-half of those of LM for the biomechanical parameters. We conclude that higher absolute values of bone densities, cortical and trabecular architecture, and strength indices were not in proportion to the excess of BMI and particularly of FM in obese postmenopausal French women.

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

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

Higher serum osteocalcin is associated with lower abdominal aortic calcification progression and longer 10-year survival in elderly men of the MINOS cohort.

CONTEXT: Abdominal aortic calcification (AAC) is an indicator of cardiovascular risk, especially in the diseases characterized by insulin resistance such as type 2 diabetes. Osteocalcin is a bone-secreted hormone that favors insulin sensitivity and insulin secretion. OBJECTIVES: We investigated whether total serum osteocalcin level at baseline is associated with AAC progression and 10-year all-cause mortality in elderly men. DESIGN AND PARTICIPANTS: We assessed 774 men aged 51-85 years from the MINOS cohort who had osteocalcin measurement and lumbar spine radiographs at baseline. They were followed-up prospectively for 10 years. Among them, 615 patients had a follow-up radiograph at 3.5 or 7 years. MAIN OUTCOME MEASURES: Serum total osteocalcin was measured with an immunoradiometric assay on morning fasting serum collected at baseline. Kauppila's AAC score was assessed from lumbar spine radiographs. AAC progression rate was calculated as the difference between AAC on the last available radiograph and AAC at baseline divided by the follow-up time. Death status was collected over 10 years. RESULTS: In multivariate analysis, higher baseline total osteocalcin was associated with lower AAC progression rate (odds ratio = 0.74 [0.57-0.97] per 10 ng/mL variation; P = 0.029). At the 10-year follow-up, there were 599 men alive (77%), 181 dead (23%), and 2 lost to follow-up. Higher osteocalcin was associated with lower 10-year all-cause mortality (hazard ratio = 0.62 [0.44-0.86] per 10 ng/mL variation; P = 0.005). CONCLUSION: Higher baseline total osteocalcin concentrations were associated with lower AAC progression rate and lower mortality. These data suggest that osteocalcin level might be an independent indicator of cardiovascular risk and global health in elderly Caucasian men.

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

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

Assessment of hand trabecular bone texture with high resolution direct digital radiograph in rheumatoid arthritis: a case control study.

OBJECTIVES: Rheumatoid arthritis is characterized by an early inflammatory related periarticular osteopenia. A new high resolution direct digital X-ray device has been recently developed to provide bone texture analysis which is designed to assess changes in trabecular bone architecture. For the first time, we have evaluated trabecular bone texture impairment in rheumatoid arthritis patients compared to healthy controls. METHODS: In this cross-sectional study, the reproducibility was assessed by three separate digital X-rays of the right hand, with repositioning in 14 late rheumatoid arthritis patients and 14 healthy subjects. Then, trabecular bone texture of the MCP2 and MCP3 from patients enrolled in a prospective cohort of 78 rheumatoid arthritis patients was compared with that of 50 healthy subjects, using three texture parameters: Hmean, co-occurrence and run-length. RESULTS: The coefficients of variation of the high resolution direct digital X-ray measurements ranged from 0.5 to 1.8%. Only the Hmean parameter was significantly decreased in rheumatoid arthritis patients compared to healthy subjects at MCP2 (0.637±0.040 vs. 0.654±0.032, P<0.05) and at MCP3 (0.646±0.044 vs. 0.665±0.037, P<0.05). This reduction was significantly correlated to disease activity. CONCLUSIONS: This study demonstrated both the good reproducibility of the high resolution digital X-ray measurements and the trabecular bone texture impairment at MCP joints in rheumatoid arthritis patients. In addition to provide a high resolution hand radiograph, this technique may represent an interesting tool to easily quantify periarticular osteopenia with a low radiation dose.

Cross-sectional analysis of the association between fragility fractures and bone microarchitecture in older men: the STRAMBO study.

Areal bone mineral density (aBMD) measured by dual-energy X-ray absorptiometry (DXA) identifies 20% of men who will sustain fragility fractures. Thus we need better fracture predictors in men. We assessed the association between the low-trauma prevalent fractures and bone microarchitecture assessed at the distal radius and tibia by high-resolution peripheral quantitative computed tomography (HR-pQCT) in 920 men aged 50 years of older. Ninety-eight men had vertebral fractures identified on the vertebral fracture assessment software of the Hologic Discovery A device using the semiquantitative criteria, whereas 100 men reported low-trauma peripheral fractures. Men with vertebral fractures had poor bone microarchitecture. However, in the men with vertebral fractures, only cortical volumetric density (D.cort) and cortical thickness (C.Th) remained significantly lower at both the radius and tibia after adjustment for aBMD of ultradistal radius and hip, respectively. Low D.cort and C.Th were associated with higher prevalence of vertebral fractures regardless of aBMD. Severe vertebral fractures also were associated with poor trabecular microarchitecture regardless of aBMD. Men with peripheral fractures had poor bone microarchitecture. However, after adjustment for aBMD, all microarchitectural parameters became nonsignificant. In 15 men with multiple peripheral fractures, trabecular spacing and distribution remained increased after adjustment for aBMD. Thus, in men, vertebral fractures and their severity are associated with impaired cortical bone, even after adjustment for aBMD. The association between peripheral fractures and bone microarchitecture was weaker and nonsignificant after adjustment for aBMD. Thus bone microarchitecture may be a determinant of bone fragility in men, which should be investigated in prospective studies.

Comparison of 2D and 3D bone microarchitecture evaluation at the femoral neck, among postmenopausal women with hip fracture or hip osteoarthritis.

OBJECTIVES: High resolution peripheral quantitative tomography (HR-pQCT) is used more widely to assess microarchitecture, but we are lacking comparisons between HR-pQCT and histomorphometry, which is considered the gold standard. They have only been assessed on different anatomical regions. The purpose of our study was to assess the microarchitecture and the relative contribution of cortical and trabecular bone in hip fracture with this 3D imaging technique, compared with the 2D histomorphometry. MATERIAL AND METHODS: We compared the distribution of cortical and trabecular bone in the ultradistal femoral neck samples (~3mm thick) obtained after total hip replacement in 21 hip osteoarthritis (HOA, 66±8yrs) and 20 hip fracture (HF, 79±8yrs) menopausal women by a direct 3D evaluation method (HR-pQCT: XtremeCT, Scanco Medical AG) and by histomorphometry, performed and averaged on three 10µm-thick sections 800µm apart. RESULTS: Significant correlations were found between both techniques for trabecular bone volume, number, thickness, separation and cortical thickness (0.51

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.