Increased cortical area and thickness in the distal radius in subjects with SHOX-gene mutation.

Short-stature homeobox (SHOX) gene haploinsufficiency may cause skeletal dysplasia including Léri-Weill Dyschondrosteosis (LWD), a clinical entity characterised by the triad of low height, mesomelic disproportion and Madelung's deformity of the wrist. Bone microarchitecture and estimated strength in adult SHOX mutation carriers have not been examined. Twenty-two subjects with a SHOX mutation including 7 males and 15 females with a median age of 38.8 [21.1-52.2] years were recruited from five unrelated families. The control group consisted of 22 healthy subjects matched on age and sex. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry. Bone geometry, volumetric density, microarchitecture and finite element estimated (FEA) bone strength were measured using high-resolution peripheral quantitative computed tomography (HR-pQCT). A full region of interest (ROI) image analysis and height-matched ROI analyses adjusting for differences in body height between the two groups were performed. Areal BMD and T-scores showed no significant differences between cases and controls. Total radius area was smaller in cases than controls (207 [176-263] vs. 273 [226-298] mm, p<0.01). Radius cortical bone area (74 ± 20 vs. 58 ± 17 mm(2), p=0.01) and thickness (1.16 ± 0.30 vs. 0.84 ± 0.26 mm, p<0.01) as well as total density (428 ± 99 vs. 328 ± 72 mg/cm(3), p<0.01) were higher in SHOX mutation carriers compared to controls. Radius trabecular bone area (119 [103-192] vs. 202 [168-247] mm(2), p<0.01) and trabecular number (1.61 [1.46-2.07] vs. 1.89 [1.73-2.08] mm(-1), p=0.01) were smaller in SHOX mutation carriers. Tibia trabecular thickness was lower in cases (0.067 ± 0.012 vs. 0.076 ± 0.012 mm, p=0.01). These results remained significant after adjustment for differences in body height and when restricting analyses to females. There were no differences in BMD, radius and tibia cortical porosity or FEA failure load between groups. A segment of cortical bone defect was identified in the distal radius adjacent to ulna in five unrelated SHOX mutation carriers. Subjects with a SHOX mutation presented with a different bone geometry in radius and tibia while there were no differences in BMD or failure load compared to controls, suggesting that mutations in SHOX gene may have an impact on bone microarchitecture albeit not bone strength.

Frederiksen AL ，Hansen S ，Brixen K ，Frost M ... -  《-》

Compromised trabecular microarchitecture and lower finite element estimates of radius and tibia bone strength in adults with turner syndrome: a cross-sectional study using high-resolution-pQCT.

Although bone mass appear ample for bone size in Turner syndrome (TS), epidemiological studies have reported an increased risk of fracture in TS. We used high-resolution peripheral quantitative computed tomography (HR-pQCT) to measure standard morphological parameters of bone geometry and microarchitecture, as well as estimated bone strength by finite element analysis (FEA) to assess bone characteristics beyond bone mineral density (BMD) that possibly contribute to the increased risk of fracture. Thirty-two TS patients (median age 35, range 20-61 years) and 32 healthy control subjects (median age 36, range 19-58 years) matched with the TS participants with respect to age and body-mass index were studied. A full region of interest (ROI) image analysis and a height-matched ROI analysis adjusting for differences in body height between groups were performed. Mean bone cross-sectional area was lower in TS patients in radius (-15%) and tibia (-13%) (both p < 0.01) whereas cortical thickness was higher in TS patients in radius (18%, p < 0.01) but not in tibia compared to controls. Cortical porosity was lower in TS patients at both sites (-32% in radius, -36% in tibia, both p < 0.0001). Trabecular integrity was compromised in TS patients with lower bone volume per tissue volume (BV/TV) (-27% in radius, -22% in tibia, both p < 0.0001), trabecular number (-27% in radius, -12% in tibia, both p < 0.05), and higher trabecular spacing (54% in radius, 23% in tibia, both p < 0.01). In the height-matched ROI analysis, differences remained significant apart from total area at both sites, cortical thickness in radius, and trabecular number in tibia. FEA estimated failure load was lower in TS patients in both radius (-11%) and tibia (-16%) (both p < 0.01) and remained significantly lower in the height-matched ROI analysis. Conclusively, TS patients had compromised trabecular microarchitecture and lower bone strength at both skeletal sites, which may partly account for the increased risk of fracture observed in these patients.

Hansen S ，Brixen K ，Gravholt CH 《-》

Bone geometry and volumetric bone density at the radius in patients with isolated SHOX deficiency.

The short stature homeobox-containing gene (SHOX) plays an important role in bone development and growth. We aimed to assess bone geometry and volumetric bone mineral density at the radius in patients with isolated SHOX deficiency and to relate these bone parameters to the severity of disproportion between the upper and the lower body segment. 17 patients with isolated SHOX deficiency (median age 12.3 yrs, range 6.7-37.2, 12 children and 5 adults) were examined by peripheral quantitative CT (pQCT) at the non-dominant forearm. Results were expressed as Z-scores using published reference data. Linear regression analyses were performed to describe associations between pQCT parameters and the severity of disproportion expressed as sitting height to standing subischial leg height ratio. Trabecular volumetric bone mineral density (vBMD) at the distal radius was normal, whereas cortical vBMD was decreased (mean Z-scores 0.34±1.5, n.s., and -2.2±2.2, p<0.001, respectively). Total bone cross-sectional area was enlarged at the diaphysis (2.1±1.2, p<0.001), while cortical bone cross-sectional area was normal (-0.51±1.4, n.s.). Consequently, cortical thickness was decreased (-1.2±1.3, p<0.01). The polar strength-strain index as a surrogate of long bone strength was normal (0.40±1.4, n.s.). We found no associations between pQCT parameters and the severity of disproportion. Patients with isolated SHOX deficiency are characterized by decreased cortical vBMD and cortical thickness and enlarged diaphysis. As similar changes have been described in girls with Turner syndrome, these findings suggest that haploinsufficiency of SHOX could cause characteristic skeletal anomalies at the radius.

Soucek O ，Lebl J ，Zapletalova J ，Novotna D ，Plasilova I ，Kolouskova S ，Zemkova D ，Rocek M ，Hlavka Z ，Hirschfeldova K ，Sumnik Z ... -  《-》

Bone microarchitecture and strength of the radius and tibia in a reference population of young adults: an HR-pQCT study.

Burt LA ，Macdonald HM ，Hanley DA ，Boyd SK ... -  《-》

Bone Geometry, Volumetric Density, Microarchitecture, and Estimated Bone Strength Assessed by HR-pQCT in Adult Patients With Type 1 Diabetes Mellitus.

The primary goal of this cross-sectional in vivo study was to assess peripheral bone microarchitecture, bone strength, and bone remodeling in adult type 1 diabetes (T1D) patients with and without diabetic microvascular disease (MVD+ and MVD-, respectively) and to compare them with age-, gender-, and height-matched healthy control subjects (CoMVD+ and CoMVD-, respectively). The secondary goal was to assess differences in MVD- and MVD+ patients. Fifty-five patients with T1DM (MVD+ group: n = 29) were recruited from the Funen Diabetes Database. Dual-energy X-ray absorptiometry (DXA), high-resolution peripheral quantitative computed tomography (HR-pQCT) of the ultradistal radius and tibia, and biochemical markers of bone turnover were performed in all participants. There were no significant differences in HR-pQCT parameters between MVD- and CoMVD- subjects. In contrast, MVD+ patients had larger total and trabecular bone areas (p = 0.04 and p = 0.02, respectively), lower total, trabecular, and cortical volumetric bone mineral density (vBMD) (p < 0.01, p < 0.04, and p < 0.02, respectively), and thinner cortex (p = 0.03) at the radius, and lower total and trabecular vBMD (p = 0.01 and p = 0.02, respectively) at the tibia in comparison to CoMVD+. MVD+ patients also exhibited lower total and trabecular vBMD (radius p = 0.01, tibia p < 0.01), trabecular thickness (radius p = 0.01), estimated bone strength, and greater trabecular separation (radius p = 0.01, tibia p < 0.01) and network inhomogeneity (radius p = 0.01, tibia p < 0.01) in comparison to MVD- patients. These differences remained significant after adjustment for age, body mass index, gender, disease duration, and glycemic control (average glycated hemoglobin over the previous 3 years). Although biochemical markers of bone turnover were significantly lower in MVD+ and MVD- groups in comparison to controls, they were similar between the MVD+ and MVD- groups. The results of our study suggest that the presence of MVD was associated with deficits in cortical and trabecular bone vBMD and microarchitecture that could partly explain the excess skeletal fragility observed in these patients.

Shanbhogue VV ，Hansen S ，Frost M ，Jørgensen NR ，Hermann AP ，Henriksen JE ，Brixen K ... -  《-》