Bone characteristics of autosomal dominant hypophosphatemic rickets patients.

Autosomal dominant hypophosphatemic rickets (ADHR) is a rare disease caused by activating mutations in fibroblast growth factor 23 (FGF23) gene. With FGF23 activation, ADHR is a good model to explore the effects of FGF23 on skeletal development and mineralization. However, the bone microarchitecture of ADHR patients is poorly investigated. This study aims to illustrate the bone properties of ADHR patients and clarify the effect of FGF23 on load bearing and non-load bearing bone. Bone microarchitectures of 11 ADHR subjects and sex- and age-matched healthy controls were analyzed by HR-pQCT. The effect of FGF23 mutations on load bearing and non-load bearing bone was explored by comparison of bone microarchitecture in distal radius and distal tibia. The BMD, bone microarchitecture and bone strength were compared between 7 ADHR patients and 7 age- and sex-matched XLH patients. Among 11 subjects with FGF23 mutations, 10 patients presented with obvious symptoms, five of which had received 1-3 years of iron supplement, neutral phosphate, and calcitriol treatments. The symptomatic patients presented with low bone density and fractures in X rays, with decreased Z score of aBMD (L1-L4: -1.3 ± 1.4, femoral neck: -2.1 ± 1.8, total hip: -1.85 ± 1.6). Compared with controls, HR-pQCT analysis of 5 untreated ADHR patients showed increased total area (+61.6 %, p = 0.03) and cortical perimeter (+17.2 %, p = 0.03) in distal radius. No significant differences were found in other parameters in distal radius. In distal tibia, the patients presented obvious defects in cancellous bone, with decreased trabecular vBMD (-62.9 %, p = 0.003), trabecular BV/TV (-48.7 %, p = 0.003) and trabecular number (-42.2 %, p = 0.001). The trabecular separation (+113.3 %, p = 0.007) and trabecular network inhomogeneity (+226.7 %, p = 0.001) were accordingly increased. In addition to another 5 treated patients, the bone microarchitecture changes revealed similar pattern, but the increase of total area and cortical perimeter in distal radius was no longer statistically significant. The non-symptomatic ADHR patient demonstrated slightly decreased total vBMD, trabecular vBMD and trabecular BV/TV in distal tibia. The changing pattern of bone geometry and microarchitecture of ADHR patients were similar to XLH patients but showed less deficit and stronger bone strength. ADHR patients presented increased total area and cortical perimeter in distal radius, and obvious defect in cancellous bone in distal tibia. FGF23 have impairment effect on trabecular bone especially in weight bearing site.

Liu C ，Ni X ，Zhao Z ，Qi W ，Jiang Y ，Li M ，Wang O ，Xing X ，Xia W ... -  《-》

Evaluation of bone mineral density and microarchitectural parameters by DXA and HR-pQCT in 37 children and adults with X-linked hypophosphatemic rickets.

Colares Neto GP ，Pereira RM ，Alvarenga JC ，Takayama L ，Funari MF ，Martin RM ... -  《-》

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 ... -  《-》

Bone microstructure evaluated by TBS and HR-pQCT in Chinese adults with X-linked hypophosphatemia.

X-linked hypophosphatemia (XLH) is the most common form of heritable hypophosphatemic rickets. Although generalized mineralization defects have been observed, elevated areal bone mineral density (aBMD) in the lumbar spine measured by dual-energy X-ray absorptiometry (DXA) has also been found in XLH. In contrast, high-resolution peripheral quantitative computed tomography (HR-pQCT) revealed lower volumetric BMD (vBMD) and damaged bone microstructure in the peripheral bone in XLH. Trabecular bone score (TBS), which can assess the trabecular microstructure in the lumbar spine, has not been explored in XLH. This study aimed to explore TBS and its correlations with biochemical indices and HR-pQCT parameters in adult XLH patients. A total of 66 patients with XLH (26 men and 40 women) aged 29.6 ± 9.6 years and 66 age- and sex-matched healthy controls were included. Z score of lumbar spine aBMD was relatively high [2.0 (0.6, 3.7)], with normal TBS (1.475 ± 0.129) in the XLH patients. HR-pQCT revealed larger total and trabecular area in the peripheral bone in the XLH group compared with the control group. In addition, lower trabecular and cortical vBMD, lower trabecular number with greater separation, and lower bone strength at both the radius and tibia were found in the XLH group compared with the control group. Smaller cortical area, lower thickness and higher porosity in the XLH group compared with controls were only found at the radius. TBS was not associated with any biochemical indices, while better HR-pQCT parameters correlated with higher serum phosphate and lower ALP levels. TBS was positively related with aBMD but not HR-pQCT parameters. In conclusion, adult patients with XLH had high bone mass and normal TBS in the lumbar spine but compromised microarchitecture and bone strength in the peripheral bone. This finding indicated a site-specific effect of the disease on the skeleton in the XLH patients.

Ni X ，Guan W ，Pang Q ，Jin C ，Gong Y ，Liu W ，Wang O ，Li M ，Xing X ，Yu W ，Jiang Y ，Xia W ... -  《-》

Evaluation of bone density and microarchitecture in adult patients with X-linked hypophosphatemic rickets: A pilot longitudinal study.

Funck-Brentano T ，Vanjak A ，Ostertag A ，Nethander M ，Fernandez S ，Collet C ，Hans D ，van Rietbergen B ，Cohen-Solal M ... -  《-》