Bone geometry, volumetric density, microarchitecture, and estimated bone strength assessed by HR-pQCT in Klinefelter syndrome.

Although the expected skeletal manifestations of testosterone deficiency in Klinefelter's syndrome (KS) are osteopenia and osteoporosis, the structural basis for this is unclear. The aim of this study was to assess bone geometry, volumetric bone mineral density (vBMD), microarchitecture, and estimated bone strength using high-resolution peripheral quantitative computed tomography (HR-pQCT) in patients with KS. Thirty-one patients with KS confirmed by lymphocyte chromosome karyotyping aged 35.8 ± 8.2 years were recruited consecutively from a KS outpatient clinic and matched with respect to age and height with 31 healthy subjects aged 35.9 ± 8.2 years. Dual-energy X-ray absorptiometry (DXA) and HR-pQCT were performed in all participants, and blood samples were analyzed for hormonal status and bone biomarkers in KS patients. Twenty-one KS patients were on long-term testosterone-replacement therapy. In weight-adjusted models, HR-pQCT revealed a significantly lower cortical area (p < 0.01), total and trabecular vBMD (p = 0.02 and p = 0.04), trabecular bone volume fraction (p = 0.04), trabecular number (p = 0.05), and estimates of bone strength, whereas trabecular spacing was higher (p = 0.03) at the tibia in KS patients. In addition, cortical thickness was significantly reduced, both at the radius and tibia (both p < 0.01). There were no significant differences in indices of bone structure, estimated bone strength, or bone biomarkers in KS patients with and without testosterone therapy. This study showed that KS patients had lower total vBMD and a compromised trabecular compartment with a reduced trabecular density and bone volume fraction at the tibia. The compromised trabecular network integrity attributable to a lower trabecular number with relative preservation of trabecular thickness is similar to the picture found in women with aging. KS patients also displayed a reduced cortical area and thickness at the tibia, which in combination with the trabecular deficits, compromised estimated bone strength at this site.

Shanbhogue VV ，Hansen S ，Jørgensen NR ，Brixen K ，Gravholt CH ... -  《-》

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 ... -  《-》

Bone geometry, volumetric density, microarchitecture, and estimated bone strength assessed by HR-pQCT in adult patients with hypophosphatemic rickets.

Hypophosphatemic rickets (HR) is characterized by a generalized mineralization defect. Although densitometric studies have found the patients to have an elevated bone mineral density (BMD), data on bone geometry and microstructure are scarce. The aim of this cross-sectional in vivo study was to assess bone geometry, volumetric BMD (vBMD), microarchitecture, and estimated bone strength in adult patients with HR using high-resolution peripheral quantitative computed tomography (HR-pQCT). Twenty-nine patients (aged 19 to 79 years; 21 female, 8 male patients), 26 of whom had genetically proven X-linked HR, were matched with respect to age and sex with 29 healthy subjects. Eleven patients were currently receiving therapy with calcitriol and phosphate for a median duration of 29.1 years (12.0 to 43.0 years). Because of the disproportionate short stature in HR, the region of interest in HR-pQCT images at the distal radius and tibia were placed in a constant proportion to the entire length of the bone in both patients and healthy volunteers. In age- and weight-adjusted models, HR patients had significantly higher total bone cross-sectional areas (radius 36%, tibia 20%; both p < 0.001) with significantly higher trabecular bone areas (radius 49%, tibia 14%; both p < 0.001) compared with controls. In addition, HR patients had lower total vBMD (radius -20%, tibia -14%; both p < 0.01), cortical vBMD (radius -5%, p < 0.001), trabecular number (radius -13%, tibia -14%; both p < 0.01), and cortical thickness (radius -19%; p < 0.01) compared with controls, whereas trabecular spacing (radius 18%, tibia 23%; p < 0.01) and trabecular network inhomogeneity (radius 29%, tibia 40%; both p < 0.01) were higher. Estimated bone strength was similar between the groups. In conclusion, in patients with HR, the negative impact of lower vBMD and trabecular number on bone strength seems to be compensated by an increase in bone diameter, resulting in HR patients having normal estimates of bone strength. © 2014 American Society for Bone and Mineral Research.

Shanbhogue VV ，Hansen S ，Folkestad L ，Brixen K ，Beck-Nielsen SS ... -  《-》

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 《-》

Compromised Volumetric Bone Density and Microarchitecture in Men With Congenital Hypogonadotropic Hypogonadism.

Men with congenital hypogonadotropic hypogonadism (CHH) and Kallmann syndrome (KS) have both low circulating testosterone and estradiol levels. Whether bone structure is affected remains unknown. To characterize bone geometry, volumetric density and microarchitecture in CHH/KS. This cross-sectional study, conducted at a single French tertiary academic medical center, included 51 genotyped CHH/KS patients and 40 healthy volunteers. Among CHH/KS men, 98% had received testosterone and/or combined gonadotropins. High-resolution peripheral quantitative computed tomography (HR-pQCT), dual-energy x-ray absorptiometry (DXA), and measurement of serum bone markers were used to determine volumetric bone mineral density (vBMD) and cortical and trabecular microarchitecture. CHH and controls did not differ for age, body mass index, and levels of vitamin D and PTH. Despite long-term hormonal treatment (10.8 ± 6.8 years), DXA showed lower areal bone mineral density (aBMD) in CHH/KS at lumbar spine, total hip, femoral neck, and distal radius. Consistent with persistently higher serum bone markers, HR-pQCT revealed lower cortical and trabecular vBMD as well as cortical thickness at the tibia and the radius. CHH/KS men had altered trabecular microarchitecture with a predominant decrease of trabecular thickness. Moreover, CHH/KS men exhibited lower cortical bone area, whereas total and trabecular areas were higher only at the tibia. Earlier treatment onset (before age 19 years) conferred a significant advantage for trabecular bone volume/tissue volume and trabecular vBMD at the tibia. Both vBMD and bone microarchitecture remain impaired in CHH/KS men despite long-term hormonal treatment. Treatment initiation during adolescence is associated with enhanced trabecular outcomes, highlighting the importance of early diagnosis.

Ostertag A ，Papadakis GE ，Collet C ，Trabado S ，Maione L ，Pitteloud N ，Bouligand J ，De Vernejoul MC ，Cohen-Solal M ，Young J ... -  《-》