Bone characteristics of autosomal dominant hypophosphatemic rickets patients

Liu, Chang; Ni, Xiaolin; Zhao, Zhen; Qi, Wenting; Jiang, Yan; Li, Mei; Wang, Ou; Xing, Xiaoping; Xia, Weibo

Affiliations

¹Department of Endocrinology, NHC Key Laboratory of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China

²Department of Endocrinology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, China

³Department of Geriatrics, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China

Abstract and keywords

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Autosomal dominant hypophosphatemic rickets; FGF23; HR-pQCT; Bone microarchitecture

Links

DOI: 10.1016/j.bone.2022.116602

PubMed: 36347435

WoS: 000890579000006

History

Received: 2022-05-15

Revised: 2022-10-10

Accepted: 2022-10-31

Online: 2022-11-5

Cited Works (4)

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