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...

Full description

Saved in:
Bibliographic Details
Published inBone (New York, N.Y.) Vol. 167; p. 116602
Main Authors Liu, Chang, Ni, Xiaolin, Zhao, Zhen, Qi, Wenting, Jiang, Yan, Li, Mei, Wang, Ou, Xing, Xiaoping, Xia, Weibo
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 01.02.2023
Subjects
Online AccessGet full text
ISSN8756-3282
1873-2763
1873-2763
DOI10.1016/j.bone.2022.116602

Cover

More Information
Summary: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. •ADHR may be a useful model of FGF23 action on bone.•ADHR patients had increased total bone area and cortical perimeter using HR-pQCT of the distal radius, with more significant cancellous bone abnormality in the distal tibia.•FGF23 may impair trabecular bone structure particularly at weight bearing sites either directly or indirectly via a renal phosphate leak.•In comparison to XLH patient, alterations in bone anatomy and microarchitecture of ADHR patients was similar but less abnormal and stronger.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:8756-3282
1873-2763
1873-2763
DOI:10.1016/j.bone.2022.116602