Musculoskeletal abnormalities in a large international cohort of boys with 49,XXXXY.

49,XXXXY is the rarest X and Y chromosomal variation, with an incidence of 1 in 80,000-100,000 live male births and has been associated with numerous musculoskeletal abnormalities. Data was collected from an international cohort of boys with 49,XXXXY over 10 years. Children were evaluated by a multidisciplinary team consisting of a pediatric orthopedist, a neurogeneticist, a neurodevelopmentalist, and two physical therapists. Increased rates of torticollis (32.4%), hamstring tightness (42%), radioulnar synostosis (67.6%), pes planus (65.2%), and other foot abnormalities (86.9%) were observed. Several anomalies increased with age, specifically hamstring tightness, kyphosis, and scoliosis. The elucidation of the orthopedic profile of this population is necessary in order to provide healthcare providers with current medical information. This research further supports the necessity for the comprehensive multidisciplinary treatment of boys with 49,XXXXY.

Mid- and Long-Term Outcome After Arthroscopically Assisted Transosseous Triangular Fibrocartilage Complex Refixation-Good to Excellent Results in Spite of Some Loss of Stability of the Distal Radioulnar Joint.

PURPOSE: To evaluate mid- and long-term outcomes after arthroscopically-assisted transosseous reattachment of the triangular fibrocartilage complex (TFCC) and to analyze the association of distal radioulnar joint (DRUJ) stability with the clinical outcome. METHODS: Patients treated with an arthroscopically-assisted transosseous reattachment of the deep layer of the TFCC between 2000 and 2009 and a minimum follow-up of 12 months at mid-term and 4 years at long-term follow-up were retrospectively reviewed. Mayo Modified Wrist Score (MMWS); Disabilities of the Arm, Shoulder and Hand (DASH) score; pain visual analogue scale (VAS); grip strength and stability of the DRUJ were assessed at 2 follow-up clinical examinations. At the last follow-up, the Patient-Rated Wrist Evaluation score was additionally recorded. RESULTS: Thirty patients with a mean age of 29 (±13) years were included. Most of the patients were female (70%, n = 21). The mid-term evaluation took place at a median of 30 months (range, 12-83 months). The assessed scores showed statistically significant clinical improvement (MMWS, P < .001; DASH score P < .001; VAS P < .001). Stability assessment showed a stable DRUJ in 23 (76.7%) patients. At a median of 106 months (range 52-215 months), the long-term clinical assessment was performed. The evaluated scores demonstrated persisting significant improvement (MMWS P < .001; DASH score P < .001; VAS P < .001). Stability assessment showed a stable DRUJ in 19 patients (63.3%). DRUJ instability did not correlate with clinical outcome. No permanent surgery-related complications occurred. CONCLUSION: Arthroscopically-assisted transosseous reattachment of the deep fibers of radioulnar ligaments leads to excellent and good clinical results in mid- and long-term follow-up. In 95.5% of the analyzed patients, the measured improvement in the DASH score exceeded the in literature reported minimal clinically important difference of 13.5. Loss of DRUJ stability during follow-up was not associated with deterioration of clinical parameters and patient satisfaction. LEVEL OF EVIDENCE: Level IV, retrospective case series.

Bone Health Following Bariatric Surgery: An Update.

Obesity rates are increasing rapidly, and bariatric surgery is currently the most effective tool for weight loss. Recently, bariatric surgery induced bone loss has gained attention. Such detrimental effect on bone is multifactorial and causes may include nutrient deficiencies, gut and gonadal hormonal changes, mechanical unloading, loss of lean mass, increased bone marrow fat, and increased risk of fall. This review describes the available evidence on bone loss and fracture risk following bariatric surgery and summarizes the guidelines on the topic. Increased bone resorption starts early postsurgery, and bone markers peak at 1-2 yr. Across studies, the drop in areal bone mineral density is inconsistent at the lumbar spine, while a 2%-5% drop at 6 mo and a 6%-10.5% at 9-12 mo are observed at the total hip. Conversely, studies using quantitative CT showed a 6%-7% decrease in volumetric bone mineral density at the lumbar spine at 6-12 mo postsurgery. These studies also report significant bone loss at the radius and tibia, in addition to alteration in bone microarchitecture. Fracture risk increases 2 yr after surgery, more so following malabsorptive procedures. Fractures were reported at axial, weight bearing sites and at appendicular sites. The available evidence is very heterogeneous, and mostly derived from studies on Roux-en-y gastric bypass in premenopausal women. Data on restrictive procedures is scarce. Our findings suggest that the early postoperative phase represents the "golden window" to intervene and promote bone health. More research is needed to determine the effect of different bariatric procedures on bone, to identify optimal interventions to prevent bone loss and to characterize high risk individuals who should be targeted.

Effect of ulnar angulation and soft tissue sectioning on radial head stability in anterior Monteggia injuries: an in vitro biomechanical study.

BACKGROUND: Radial head instability continues to be a challenge in the management of anterior Monteggia injuries; however, there is a paucity of literature on the factors that contribute to this instability. The aim of this biomechanical investigation was to examine the effects of ulnar angulation and soft tissue insufficiency on radial head stability in anterior Monteggia injuries. METHODS: Six cadaveric arms were mounted in an elbow motion simulator. Radial head translation was measured during simulated active elbow flexion with the forearm supinated. After testing the elbows in the intact state, the ulna was osteotomized and tested at 0°, 10°, 20°, and 30° of extension angulation. To examine the effect of soft tissue insufficiency, the anterior radiocapitellar joint capsule, annular ligament, quadrate ligament, and the proximal and middle interosseous membrane (IOM) were sequentially sectioned. RESULTS: There was a significant increase in anterior radial head translation with greater ulnar extension angulation. Sequential soft tissue sectioning also significantly increased anterior radial head translation. There was no increase in radial head translation with isolated sectioning of the anterior radiocapitellar joint capsule. Additional sectioning of the annular ligament and quadrate ligament slightly increased anterior radial head translation but did not reach statistical significance. Subsequent sectioning of the proximal and middle IOM resulted in significant increases in anterior radial head translation. CONCLUSION: Our study demonstrates that progressive ulnar extension angulation results in an incremental increase in anterior radial head translation in anterior Monteggia injuries. Moreover, increasing magnitudes of soft tissue disruption result in greater anterior radial head instability.

Growth Disturbance Following Intra-articular Distal Radius Fractures in the Skeletally Immature Patient.

INTRODUCTION: The purpose of this study was to characterize the incidence of growth disturbance following intra-articular distal radius fractures in skeletally immature patients and to assess early radiographic and functional outcomes. METHODS: A retrospective investigation of pediatric patients with intra-articular distal radius fractures between 1997 and 2012 at a single institution was performed. Pathologic fractures and fractures in patients with closed physes were excluded. In total, 28 patients (24 males, 4 females), with a mean age of 13.8 years and mean follow-up of 31.7 months, met inclusion criteria. Fractures were categorized according to the Salter-Harris classification, and all radiographs were assessed for evidence of physeal disturbance. Information regarding treatment and early clinical results were obtained from a medical record review. Functional outcomes using the Disabilities of the Arm, Shoulder, and Hand (DASH) and Modified Mayo Wrist Score (MMWS) were collected. Fisher exact test was used to compare the incidence of physeal arrest in the study population to previously published rates of physeal arrest in extra-articular fractures involving the distal radius. Because the data were not parametrically distributed, the Mann-Whitney-Wilcoxon test was used to compare those who did and did not develop physeal arrest. RESULTS: Of the 28 patients, 9 (32%) sustained Salter-Harris III fractures and 19 (68%) sustained Salter-Harris IV fractures. Growth disturbance occurred in 12 (43%) patients, comprised of 3 Salter-Harris III fractures and 9 Salter-Harris IV fractures; 7 of these patients underwent surgical intervention to address deformity. All 4 children age 10 years or younger had growth arrests that underwent subsequent procedures for a skeletal rebalancing of the wrist. No significant differences in DASH or MMWS were seen in the short term between patients who did or did not have physeal arrest. CONCLUSIONS: Intra-articular distal radius fractures in skeletally immature patients have a considerably higher rate of physeal growth arrest than extra-articular physeal fractures. Following acute management aimed at restoring and preserving anatomic physeal and articular alignment, follow-up radiographs should be obtained to evaluate for physeal arrest in skeletally immature children. Patients and families should be counseled regarding the high rate of growth disturbance and the potential need for deformity correction in the future, particularly in younger children. LEVEL OF EVIDENCE: IV-case series.

Correlation between radiographic findings and clinical failure in monopolar radial head replacement.

INTRODUCTION: The purpose of this study is to analyze the mid-term outcomes of a modular monopolar type of radial head arthroplasty in the treatment of complex fractures associated with acute elbow joint instability. We postulated that radiographic changes are related to the development of clinical complications. MATERIALS AND METHODS: We evaluated at last follow-up 26 radial head arthroplasties in 26 consecutive patients who were followed for at least one and a half year. All patients had suffered radial head fractures (Mason III) in the context of unstable elbow injuries. Definitive treatment of the radial fracture was performed with modular and monopolar prosthesis which was inserted as a press fit. All patients were evaluated preoperatively and postoperatively. The evaluation included a clinical examination and a protocolized imaging study (standard X-Rays and CT) of the elbow. We analyzed the incidence of: heterotopic ossifications, secondary radiocapitellar joint osteoarthritis, hardware loosening, hardware disengagement, and joint infection. Diagnosis of clinical failure of the implant was defined as the time to the second surgery due to major complications related to the prosthesis, such as persistent lateral side pain or elbow stiffness and any kind of implant instability or dislocation. RESULTS: The implant-specific reoperation rate was 15% (four reoperations). The need for the second surgery was statistically associated with heterotopic ossifications, radiocapitellar osteoarthritis and cortical resorption around radial neck (p = 0.054, p = 0.033, and p = 0.019, respectively), being periprosthetic osteolysis the most likely factor related to failure, and radial pain the main symptom leading to surgical revision. CONCLUSIONS: Our study shows a positive association between radiographic findings and patient symptoms for postoperative complications after radial head arthroplasty. Failed radial head replacements may lead to reoperation mainly due to pain, and this can be distinguished from other causes of pain in elbow region based on its radial location. Radiological loosening was prevalent in this group of failed replacement.

Abaloparatide effect on forearm bone mineral density and wrist fracture risk in postmenopausal women with osteoporosis.

PURPOSE: Wrist fractures are common, contribute significantly to morbidity in women with postmenopausal osteoporosis, and occur predominantly at the ultradistal radius, a site rich in trabecular bone. This exploratory analysis of the phase 3 ACTIVE study evaluated effects of abaloparatide versus placebo and teriparatide on forearm bone mineral density (BMD) and risk of wrist fracture. METHODS: Forearm BMD was measured by dual energy X-ray absorptiometry in a subset of 982 women from ACTIVE, evenly distributed across the three treatment groups. Wrist fractures were ascertained in the total cohort (N = 2463). RESULTS: After 18 months, ultradistal radius BMD changes from baseline were 2.25 percentage points greater for abaloparatide compared with placebo (95% confidence interval (CI) 1.38, 3.12, p < 0.001) and 1.54 percentage points greater for abaloparatide compared with teriparatide (95% CI 0.64, 2.45, p < 0.001). At 18 months, 1/3 radius BMD losses (versus baseline) were similar for abaloparatide compared with placebo (-0.42; 95% CI -1.03, 0.20; p = 0.19) but losses with teriparatide exceeded those of placebo (-1.66%; 95% CI -2.27, -1.06; p < 0.001). The decline with abaloparatide was less than that seen with teriparatide (group difference 1.22%; 95% CI 0.57, 1.87; p < 0.001). The radius BMD findings, at both ultradistal and 1/3 sites, are consistent with the numerically lower incidence of wrist fractures observed in women treated with abaloparatide compared with teriparatide (HR = 0.43; 95% CI 0.18, 1.03; p = 0.052) and placebo (HR = 0.49, 95% CI 0.20, 1.19, p = 0.11). CONCLUSIONS: Compared with teriparatide, abaloparatide increased BMD at the ultradistal radius (primarily trabecular bone) and decreased BMD to a lesser extent at the 1/3 radius (primarily cortical bone), likely contributing to the numerically lower wrist fracture incidence observed with abaloparatide.

Disrupted radial and tibial microarchitecture in patients with monoclonal gammopathy of undetermined significance.

Patients with monoclonal gammopathy of undetermined significance (MGUS) had abnormalities in volumetric BMD (vBMD), microarchitecture, and stiffness at both the radius and tibia by high-resolution peripheral quantitative CT compared to matched controls. This is the first report demonstrating that patients with MGUS have microarchitectural deficits at multiple skeletal sites. INTRODUCTION: Fracture risk is elevated in patients with monoclonal gammopathy of undetermined significance (MGUS). However, the pathogenesis of bone disease in these patients is poorly understood. Prior work using high-resolution peripheral CT (HRpQCT) demonstrated abnormal microarchitecture at the radius, with predominantly cortical abnormalities. We hypothesized that patients with MGUS have abnormal microarchitecture at both radius and tibia compared to controls, reflecting global skeletal effects of the disease. METHODS: This case-control study enrolled 36 subjects; patients with MGUS (n = 12) were matched 1:2 by age, sex, and race to controls (n = 24). Areal BMD (aBMD) was measured by DXA, vBMD, and microarchitecture by HRpQCT, and whole bone stiffness by finite element analysis. Serum was drawn for markers of bone metabolism and inflammation. RESULTS: By DXA, MGUS patients had lower aBMD at the lumbar spine, femoral neck, and 1/3 radius. Markers of bone metabolism and inflammation did not differ. By HRpQCT at the radius, MGUS patients had lower total, trabecular and cortical density, lower trabecular number, and greater trabecular separation and heterogeneity. At the tibia, MGUS patients had lower total and trabecular density, lower trabecular number, greater separation and heterogeneity, and lower whole bone stiffness. CONCLUSIONS: Patients with MGUS had lower vBMD, cortical, and trabecular abnormalities at the radius compared to matched controls. At the tibia, trabecular abnormalities predominated. These results suggest that in addition to previously described cortical deficits, deterioration of trabecular bone may contribute to a generalized skeletal fragility in patients with MGUS.

Validation of distal radius failure load predictions by homogenized- and micro-finite element analyses based on second-generation high-resolution peripheral quantitative CT images.

This study developed a well-standardized and reproducible approach for micro-finite element (mFE) and homogenized-FE (hFE) analyses that can accurately predict the distal radius failure load using either mFE or hFE models when using the approaches and parameters developed in this study. INTRODUCTION: Micro-FE analyses based on high-resolution peripheral quantitative CT (HR-pQCT) images are frequently used to predict distal radius failure load. With the introduction of a second-generation HR-pQCT device, however, the default modelling approach no longer provides accurate results. The aim of this study was to develop a well-standardized and reproducible approach for mFE and hFE analyses that can provide precise and accurate results for distal radius failure load predictions based on second-generation HR-pQCT images. METHODS: Second-generation HR-pQCT was used to scan the distal 20-mm section of 22 cadaver radii. The sections were excised and mechanically tested afterwards. For these sections, mFE and hFE models were made that were used to identify required material parameters by comparing predicted and measured results. Using these parameters, the models were cropped to represent the 10-mm region recommended for clinical studies to test their performance for failure load prediction. RESULTS: After identification of material parameters, the measured failure load of the 20-mm segments was in good agreement with the results of mFE models (R2 = 0.969, slope = 1.035) and hFE models (R2 = 0.966, slope = 0.890). When the models were restricted to the clinical region, mFE still accurately predicted the measured failure load (R2 = 0.955, slope = 1.021), while hFE predictions were precise but tended to overpredict the failure load (R2 = 0.952, slope = 0.780). CONCLUSIONS: It was concluded that it is possible to accurately predict the distal radius failure load using either mFE or hFE models when using the approaches and parameters developed in this study.

The association between prevalent vertebral fractures and bone quality of the distal radius and distal tibia as measured with HR-pQCT in postmenopausal women with a recent non-vertebral fracture at the Fracture Liaison Service.

We evaluated the association between prevalent vertebral fractures and bone micro-architecture and strength measured using HR-pQCT in postmenopausal women with a recent non-vertebral fracture visiting the Fracture Liaison Service. The presence and severity of prevalent vertebral fracture reflect generalized bone deterioration. INTRODUCTION: We evaluated the association between prevalent vertebral fractures (VFs) and bone micro-architecture and strength measured using HR-pQCT in postmenopausal women visiting the Fracture Liaison Service. METHODS: In this cross-sectional study in women aged 50-90 with a recent non-vertebral fracture (NVF), VFs were identified on lateral spine images by dual-energy X-ray absorptiometry. Bone micro-architecture and strength were measured at the non-dominant distal radius and distal tibia using HR-pQCT. Linear regression analyses were used to estimate the association between prevalent VFs and HR-pQCT parameters. RESULTS: We included 338 women of whom 74 (21.9%) women had at least one prevalent VF. After adjustment for femoral neck aBMD (FN aBMD) and other parameters, women with at least one prevalent vertebral fracture had significantly lower total and trabecular vBMD and trabecular number (ß - 16.7, - 11.8, and - 7.8 in the radius and - 21.4, - 16.6, and - 7.2 in the tibia, respectively), higher trabecular separation at the radius and tibia (ß 9.0 and 9.3, respectively), and lower cortical thickness and calculated ultimate failure load and compressive bone strength at the tibia (ß - 5.9, - 0.6, and - 10.9, respectively) as compared with those without prevalent VFs. Furthermore, more severe prevalent VFs were associated with even lower total and trabecular vBMD and lower ultimate failure load and compressive stiffness at the radius and tibia, and lower trabecular number and higher trabecular separation at the radius. CONCLUSION: This study indicates that the presence and severity of prevalent VFs reflect generalized bone deterioration in women with a recent NVF, independently of FN aBMD.

Long-term denosumab treatment restores cortical bone loss and reduces fracture risk at the forearm and humerus: analyses from the FREEDOM Extension cross-over group.

Upper limb fractures (including wrist, forearm, and humerus) represent a significant burden among postmenopausal women with osteoporosis. Up to 7 years of treatment with denosumab resulted in an increase in bone mineral density and decrease in fractures in upper limb sites. INTRODUCTION: Upper limb (wrist, forearm, and humerus) fractures are a significant burden in osteoporosis, associated with significant morbidity and mortality. Denosumab, a monoclonal antibody against RANK ligand, increases bone mineral density (BMD) and decreases vertebral, nonvertebral, and hip fractures. Here, we evaluated the long-term effect of denosumab treatment on upper limb fracture risk and BMD. METHODS: In the FREEDOM trial, subjects were randomized 1:1 to receive every-6-month denosumab 60 mg or placebo subcutaneously for 3 years, after which all subjects could receive denosumab for up to 7 years (Extension). Among placebo subjects who completed FREEDOM and enrolled in the Extension, wrist, forearm, humerus, and upper limb fracture rates and rate ratios between different time periods (FREEDOM years 1-3, Extension years 1-3, and Extension years 4-7) were computed. BMD at the ultradistal radius, 1/3 radius, and total radius was analyzed in a subset of subjects in a BMD substudy. RESULTS: This analysis included 2207 subjects (116 in the BMD substudy). Fracture rates decreased over the 7-year Extension; fracture rate ratios between Extension years 4-7 (denosumab) and FREEDOM years 1-3 (placebo) reduced significantly for the wrist (0.57), forearm (0.57), humerus (0.42), and upper limb (0.52; p < 0.05 for all). Percentage increase in BMD from Extension baseline at the ultradistal radius, 1/3 radius, and total radius was significant by Extension year 7 (p < 0.05 for all). CONCLUSIONS: Long-term treatment with denosumab decreases upper limb fracture risk and increases forearm BMD, suggesting beneficial effects on both cortical and trabecular bone accruing over time.

Distal radius and tibia bone microarchitecture impairment in female patients with diffuse systemic sclerosis.

Radius and tibia bone microarchitecture, analyzed through a high-resolution peripheral quantitative computed tomography, were significantly impaired in female patients with diffuse systemic sclerosis compared with healthy controls. Acroosteolysis, quality of life-grip strength, hand disability, and disease duration were significantly associated with this bone deterioration. INTRODUCTION: The effect of diffuse systemic sclerosis (dSSc) on the bone is not completely understood. The objective of this study was to analyze the volumetric bone mineral density (vBMD), microarchitecture, and biomechanical parameters at the distal radius and tibia using high-resolution peripheral quantitative computed tomography (HR-pQCT, XtremeCT) in female patients with dSSc and identify clinical and laboratory variables associated with these parameters. METHODS: Thirty-eight women with dSSc and 76 healthy controls were submitted to HR-pQCT at the distal radius and tibia. Clinical and laboratory findings, bone mineral density(BMD), nailfold capillaroscopy (NC), total passive range of motion(ROM), and quality of life (health assessment questionnaire-HAQ) were associated with HR-pQCT (Scanco Medical AG, Brüttisellen, Switzerland) parameters. Multiple linear regression models adjusted for clinical and laboratory variables, ROM and HAQ, were performed. RESULTS: Density, microarchitecture, and biomechanical parameters at the distal radius and tibia were significantly impaired in dSSc patients compared with healthy controls (p < 0.001). Multiple linear regression models showed that lower trabecular density (Tb.vBMD) (radius R2 = 0.561, p = 0.002; and tibia R2 = 0.533, p = 0.005), and lower trabecular number (Tb.N) (tibia R2 = 0.533, p = 0.005) were significantly associated with acroosteolysis. Higher trabecular separation (Tb.Sp) was associated with disease duration and higher HAQ-grip strength (radius R2 = 0.489, p = 0.013), while cortical density (Ct.vBMD) was associated with ROM (radius R2 = 0.294, p = 0.002). CONCLUSION: Bone microarchitecture in patients with dSSc, analyzed through HR-pQCT, showed impairment of trabecular and cortical bone at distal radius and tibia. Variables associated with hand involvement (acroosteolysis, quality of life-grip strength, and ROM) and disease duration may be considered prognostic factors of this bone impairment.

High FGF23 levels are associated with impaired trabecular bone microarchitecture in patients with osteoporosis.

This cross-sectional study examined the associations between c-terminal FGF23 levels, laboratory markers of bone metabolism and bone microarchitecture in 82 patients with osteoporosis. Higher FGF23 levels were associated with impaired trabecular but not cortical bone microarchitecture, and this was confirmed after adjusting for confounding variables such as age or BMI. INTRODUCTION: Fibroblast growth factor 23 (FGF23) is an endocrine hormone-regulating phosphate and vitamin D metabolism. While its mode of action is well understood in diseases such as hereditary forms of rickets or tumor-induced osteomalacia, the interpretation of FGF23 levels in patients with osteoporosis with regard to bone microarchitecture is less clear. METHODS: C-terminal FGF23 levels and bone turnover markers were assessed in 82 patients with osteoporosis (i.e., DXA T-score ≤ - 2.5 at the lumbar spine or total hip). Bone microarchitecture was measured by high-resolution peripheral quantitative computed tomography (HR-pQCT) at the distal radius and tibia. Data were analyzed in a cross-sectional design using correlation and regression models. RESULTS: We found a significant negative logarithmic correlation between FGF23 levels and trabecular but not cortical bone microarchitecture at both skeletal sites. Furthermore, using a multiple linear regression model, we confirmed FGF23 as a predictor for reduced trabecular parameters even when adjusting for confounding factors such as age, BMI, phosphate, bone-specific alkaline phosphatase, vitamin D3, and PTH. CONCLUSIONS: Taken together, high FGF23 levels are associated with impaired trabecular bone microarchitecture in osteoporosis patients, and this association seems to occur after adjustment of confounding variables including phosphate and vitamin D. Future longitudinal studies are now needed to validate our findings and investigate FGF23 in relation to fracture risk.

Associations between radius low-frequency axial ultrasound velocity and bone fragility in elderly men and women.

An exploratory study in elderly women and men from the Geneva Retirees Cohort indicates that low-frequency quantitative ultrasound measurement at the radius captures aBMD, bone size, and cortical tissue mineral density and might be used for screening purposes prior to DXA to evaluate fracture risk. INTRODUCTION: The contribution of distal radius bone mineral density (BMD) and cortical microstructure to fracture risk has recently been demonstrated. In this exploratory study, we investigated whether low-frequency quantitative ultrasound measurement at the distal radius may capture the peripheral determinants of bone fragility assessed with dual-energy X-ray absorptiometry (DXA) and high-resolution peripheral quantitative computed tomography (HR-pQCT). METHODS: Low-frequency velocity (VLF) was measured at the radius using OsCare Sono®, a portable axial transmission ultrasonometer, in 271 community-dwelling postmenopausal women and men (age 71.5 ± 1.4 years) from the Geneva Retirees Cohort. Cortical (Ct) and trabecular (Tb) volumetric (v) BMD and microstructure at the distal radius were assessed by HR-pQCT, in addition to areal (a) BMD by DXA, at the same time point. RESULTS: VLF was highly correlated with aBMD at the distal third radius (r = 0.72, p < 0.001). For microstructure parameters, the highest correlation was observed with cortical area (r = 0.59, p < 0.001). VLF also captured bone geometry (total area) and cortical tissue mineral density independently of aBMD. In models adjusted for age and sex, VLF was significantly associated with prevalent low-trauma fractures [OR 95%CI for one SD decrease of VLF 1.50 (1.05, 2.14), p = 0.024], with discrimination performance comparable to femoral neck or distal radius aBMD. CONCLUSION: Measurement of VLF at the radius captures aBMD, bone size, and cortical tissue mineral density and might be used for screening purposes prior to DXA to evaluate fracture risk.

Comparison of three plain radiography methods for evaluating proximal humerus bone strength in women.

BACKGROUND: We assessed the correlation between three methods for measuring cortical thickness of the humerus on a plain radiograph and bone mineral density measured by dual-energy X-ray absorptiometry in order to establish a simple bone strength evaluation method in patients at risk of proximal humerus fragility fracture. METHODS: In this retrospective study, 1732 patients underwent screening of the distal third radius, proximal femur, and lumbar spine by dual-energy X-ray absorptiometry. We identified 224 patients who also underwent anteroposterior shoulder radiography. Patients with fractures or who had undergone surgery in the region of interest were excluded. The study consisted of 80 women with a mean age of 76 years (range: 39-94 years). Cortical thickness, cortical index, and deltoid tuberosity index were determined to assess the proximal humerus. Correlation between bone mineral density measured by dual-energy X-ray absorptiometry and cortical thickness determined using these three methods was examined. We defined the osteoporosis group as patients satisfying both the World Health Organization criteria and the diagnostic criteria for primary osteoporosis (2012 revision) and compared values between the osteoporotic and non-osteoporotic groups. RESULTS: BMD correlated positively with cortical thickness, cortical index, and deltoid tuberosity index values, but the strength of correlation differed. These values were significantly lower in the osteoporotic group than in the non-osteoporotic group. Receiver operating characteristic curve analysis revealed that only the distal third radius had an area under the curve of 0.7 or more for all methods. CONCLUSIONS: All three methods yielded values that correlated with the dual-energy X-ray absorptiometry bone mineral density measured at the distal third radius, the proximal femur, and the lumbar spine. The correlation coefficient in the radius was high and differed significantly from those of weight-bearing bones (proximal femur, lumbar spine).

The relationship between maternal and child bone density in Nigerian children with and without nutritional rickets.

We found a positive relationship between bone density in Nigerian children with and without rickets and that of their mothers. After treatment, children with rickets had greater bone density than children without rickets, indicating that children genetically programmed to have greater bone density may have a higher risk of rickets. INTRODUCTION: To determine the relationship between bone density in children with and without rickets and that of their mothers METHODS: Using an unmatched case-control design, forearm areal bone mineral density (aBMD) was measured in 52 and 135 Nigerian children with and without rickets and their mothers, respectively. We performed multivariate linear regression analyses to assess the relationship between maternal and child aBMD Z-scores. RESULTS: Forearm aBMD Z-scores in children were associated with maternal aBMD Z-scores at metaphyseal (effect estimate 0.23; 95% CI 0.08 to 0.37) and diaphyseal (effect estimate 0.16; 0.01 to 0.30) sites, after adjustment for rickets in the child, child's age and sex, height-for-age Z-score, and weight-for-age Z-score. In the adjusted model, rickets was inversely associated with child's aBMD Z-score at the diaphyseal site only (- 0.45, - 0.65 to - 0.24). The positive relationship between maternal and child aBMD Z-scores was marginally greater in children with rickets (slope 0.56, r = 0.47) than without rickets (slope 0.19, r = 0.20) at the diaphyseal site only (P = 0.06 for interaction) but not at the metaphyseal site (slopes 0.35 and 0.30, respectively, P = 0.48). After treatment with calcium for 6 months, metaphyseal aBMD Z-scores were greater in children with treated rickets (effect estimate 0.26; 95% CI 0.02 to 0.49) than in those without rickets. CONCLUSION: In Nigerian children with and without rickets, forearm aBMD Z-scores were positively associated with maternal aBMD Z-scores. Active rickets in the child marginally modified the relationship at the diaphyseal site only. After treatment, children with rickets had greater metaphyseal aBMD Z-scores than children without rickets.

The association between diabetes status, HbA1c, diabetes duration, microvascular disease, and bone quality of the distal radius and tibia as measured with high-resolution peripheral quantitative computed tomography-The Maastricht Study.

In this small cross-sectional study of predominantly well-treated participants with relatively short-term type 2 diabetes duration, HbA1c > 7% (53 mmol/mol) was associated with lower cortical density and thickness and higher cortical porosity at the distal radius, lower trabecular thickness at the distal tibia, and higher trabecular number at both sites. INTRODUCTION: To examine the association between diabetes status and volumetric bone mineral density (vBMD), bone microarchitecture and strength of the distal radius and tibia as assessed with HR-pQCT. Additionally-in participants with type 2 diabetes (T2DM), to examine the association between HbA1c, diabetes duration, and microvascular disease (MVD) and bone parameters. METHODS: Cross-sectional data from 410 (radius) and 198 (tibia) participants of The Maastricht Study (mean age 58 year, 51% female). Diabetes status (normal glucose metabolism, prediabetes, or T2DM) was based on an oral glucose tolerance test and medication history. RESULTS: After full adjustment, prediabetes and T2DM were not associated with vBMD, bone microarchitecture, and strength of the radius and tibia, except for lower trabecular number (Tb.N) of the tibia (- 4%) in prediabetes and smaller cross-sectional area of the tibia (- 7%) in T2DM. In T2DM, HbA1c > 7% was associated with lower cortical vBMD (- 5%), cortical thickness (- 16%), higher cortical porosity (+ 20%) and Tb.N (+ 9%) of the radius, and higher Tb.N (+ 9%) and lower trabecular thickness (- 13%) of the tibia. Diabetes duration > 5 years was associated with higher Tb.N (+ 6%) of the radius. The presence of MVD was not associated with any bone parameters. CONCLUSIONS: In this study with predominantly well-treated T2DM participants with relatively short-term diabetes duration, inadequate blood glucose control was negatively associated with cortical bone measures of the radius. In contrast, trabecular number was increased at both sites. Studies of larger sample size are warranted for more detailed investigations of bone density and bone quality in patients with T2DM.

Type 2 diabetes is associated with higher trabecular bone density but lower cortical bone density: the Vietnam Osteoporosis Study.

It is not clear why type 2 diabetes (T2D) has an increased risk of fracture despite higher areal bone mineral density. This study showed that compared with controls, T2D patients had higher trabecular bone density but lower cortical bone density, resulting in a lower bone strength. INTRODUCTION: To define the association between type 2 diabetes and bone architecture and measures of bone strength. METHODS: The study was part of the Vietnam Osteoporosis Study, in which 1115 women and 614 men aged ≥ 30 were randomly recruited from Ho Chi Minh City. HbA1c levels were measured with analyzers ADAMS™ A1c HA-8160 (Arkray, Kyoto, Japan). The diagnosis of T2D was made if HbA1c was ≥ 6.5%. Trabecular and cortical volumetric bone density (vBMD) was measured in the forearm and leg by a pQCT XCT2000 (Stratec, Germany). Polar stress strain index (pSSI) was derived from the pQCT measurements. Difference in bone parameters between T2D and non-diabetic individuals was assessed by the number of standard deviations (effect size [ES]) by the propensity score analysis. RESULTS: The prevalence of T2D was ~ 8%. The results of propensity score matching for age, sex, and body mass index in 137 pairs of diabetic and non-diabetic individuals showed that T2D patients had significantly higher distal radius trabecular vBMD (ES 0.26; 95% CI, 0.02 to 0.50), but lower cortical vBMD (ES - 0.22; - 0.46 to 0.00) and reduced pSSI (ES - 0.23; - 0.47 to - 0.02) compared with non-diabetic individuals. Multiple linear regression analysis based on the entire sample confirmed the results of the propensity score analysis. CONCLUSION: Compared with non-diabetic individuals, patients with T2D have greater trabecular but lower cortical vBMD which leads to lower bone strength.

Characterization of trabecular bone microstructure in premenopausal women with distal radius fractures.

Individual trabecular segmentation was utilized to identify differences in trabecular bone structure in premenopausal women with wrist fractures and non-fracture controls. Fracture subjects had reduced trabecular plate volume, number, thickness, and connectivity. Identifying altered trabecular microarchitecture in young women offers opportunities for counseling and lifestyle modifications to reduce fracture risk. INTRODUCTION: Premenopausal women with distal radius fractures (DRF) have worse trabecular bone microarchitecture than non-fracture controls (CONT), yet the characteristics of their trabecular bone structure are unknown. METHODS: Premenopausal women with DRF (n = 40) and CONT (n = 80) were recruited. Primary outcome variables included trabecular structure at the distal radius and tibia, assessed by volumetric decomposition of individual trabecular plates and rods from high-resolution peripheral quantitative CT images. Trabecular morphology included plate and rod number, volume, thickness, and connectivity. Areal bone mineral density (aBMD) of the femoral neck (FN aBMD), and ultradistal radius (UDR aBMD) were measured by DXA. RESULTS: Trabecular morphology differed between DRF and CONT at the radius and tibia (OR per SD decline 1.58-2.7). At the radius, associations remained significant when adjusting for age and FN aBMD (ORs = 1.76-3.26) and age and UDR aBMD (ORs = 1.72-3.97). Plate volume fraction, number and axially aligned trabeculae remained associated with DRF after adjustment for trabecular density (ORs = 2.55-2.85). Area under the curve (AUC) for discriminating DRF was 0.74 for the proportion of axially aligned trabeculae, compared with 0.60 for FN aBMD, 0.65 for UDR aBMD, and 0.69 for trabecular density. Plate number, plate-plate junction, and axial bone volume fraction remained associated with DRF at the tibia (ORs = 2.14-2.77) after adjusting for age, FN aBMD, or UDR aBMD. AUCP.P.Junc.D was 0.72 versus 0.61 for FNaBMD, 0.66 for UDRaBMD, and 0.70 for trabecular density. CONCLUSION: Premenopausal women with DRF have lower trabecular plate volume, number, thickness, and connectivity than CONT. Identification of young women with altered microarchitecture offers opportunities for lifestyle modifications to reduce fracture risk.

Abnormal microarchitecture and stiffness in postmenopausal women using chronic inhaled glucocorticoids.

Postmenopausal (PM) women using inhaled glucocorticoids (IGCs) had substantial abnormalities in volumetric BMD (vBMD), microarchitecture, and stiffness using high resolution peripheral computed tomography (HRpQCT) compared to age- and race-matched controls. Abnormalities were most severe at the radius. These preliminary results suggest that there may be major, heretofore unrecognized, skeletal deficits in PM women using IGCs. INTRODUCTION: While oral glucocorticoids are well recognized to have destructive skeletal effects, less is known about the effects of IGCs. The detrimental skeletal effects of IGCs may be greatest in PM women, in whom they compound negative effects of estrogen loss and aging. The goal of this study was to evaluate microarchitecture and stiffness in PM women using chronic IGCs. METHODS: This case-control study compared PM women using IGCs for ≥ 6 months (n = 20) and controls matched for age and race/ethnicity (n = 60). Skeletal parameters assessed included areal BMD (aBMD) by DXA, trabecular and cortical vBMD and microarchitecture by HRpQCT of the radius and tibia, and whole bone stiffness by finite element analysis. RESULTS: By DXA, mean values in both groups were in the osteopenic range; hip aBMD was lower in IGC users (P < 0.04). By HRpQCT, IGC users had lower total, cortical, and trabecular vBMD at both radius and tibia (all P < 0.05). IGC users had lower cortical thickness, lower trabecular number, greater trabecular separation and heterogeneity at the radius (all P < 0.03), and greater heterogeneity at the tibia (P < 0.04). Whole bone stiffness was lower in IGC users at radius (P < 0.03) and tended to be lower at the tibia (P = 0.09). CONCLUSIONS: PM women using IGCs had substantial abnormalities in vBMD, microarchitecture, and stiffness compared to controls. These abnormalities were most severe at the radius. These preliminary results suggest that there may be major, heretofore unrecognized, skeletal deficits in PM women using IGCs.