Evaluation of quality and bone microarchitecture alterations in osteopetrosis patients: assessed by HR-pQCT

Abstract Context Osteopetrosis (OPT) is a rare skeletal disease characterized by high bone mass that has two major inheritance patterns: autosomal dominant osteopetrosis (ADO) and autosomal recessive osteopetrosis (ARO). However, comprehensive descriptions of bone microarchitecture in OPT patients are limited. Objectives The aim of this study was to comprehensively investigate the bone microarchitecture of OPT patients, explore age-related bone alterations and describe the skeletal heterogeneity among different genotypes. Methods Nine OPT patients, including 7 ADO patients with CLCN7 mutations, 1 ARO patient with CAII mutation, and 1 ARO patient with TCIRG1 mutation, were retrospectively enrolled in this study. Clinical and biochemical examinations were performed. Bone microstructure was investigated by high-resolution peripheral quantitative computed tomography (HR-pQCT). Results Compared with age- and sex-matched healthy controls, OPT patients had greater total volumetric bone mineral density. In addition, trabecular bone was denser, with greater trabecular volumetric bone mineral density, increased trabecular number, and decreased trabecular separation. However, the cortical bone in OPT patients was weaker, characterized by increased cortical thickness and porosity. OPT patients exhibited characteristic patterns, including bone islets and uneven dense structures, on the representative reconstruction HR-pQCT images. Skeletal heterogeneity across different genotypes was observed, with looser cortical bone in one OPT patient with CAII mutation and thicker cortical bone in one OPT patient with TCIRG1 mutation. Conclusions Compared with healthy controls, OPT patients presented with denser trabecular bone, thicker but looser cortical bone, unique bone patterns and skeletal heterogeneity. These results provide new insights into bone alterations in OPT patients.