Endocrine Abstracts

JOINT1411

Introduction: PLS3-associated X-linked early-onset osteoporosis (EOOP) is a rare condition that was first described in 2013. Consistent with the X-linked inheritance, males are more severely affected, although varying degrees of severity have also been documented for females. The function of PLS3 and the effects of pathogenic PLS3 variants are poorly understood. The aim of this retrospective analysis was to describe the clinical features of patients with EOOP due to variants in PLS3 in comparison to patients diagnosed with Osteogenesis imperfecta type I.

Materials and methods: We retrospectively collected clinical data from patients diagnosed with EOOP who carry (likely) pathogenic genetic variants in the PLS3 gene. The data were collected at the specialized outpatient clinic of the National Bone Board at the University Medical Center Hamburg-Eppendorf and include fracture history, treatment history, laboratory parameters, HR-pQCT and DXA data, as well as muscle function tests (Chair Rising Test, grip strength).

Results: Patients with variants in the PLS3 gene had an increased number of fractures, low Z-scores and severely reduced microstructural parameters, with men being more affected than women. Compared with OI type I patients, there were no statistically significant differences in fracture frequency, but women with pathogenic variants in the PLS3 gene had significantly higher Z-scores on DXA scans. In men with causative PLS3 variants, HR-pQCT measurements showed a significant reduction in structural parameters compared to OI type I, especially in the cortical compartment. There were no significant differences regarding relevant laboratory parameters.

Discussion: The results of this study highlight the specific influence of pathogenic PLS3 variants on the clinical presentation and bone structure of affected patients. In particular, the significantly reduced cortical thickness on HR-pQCT measurements in affected men suggests specific effects of the PLS3 variants. These microstructural deficits may play a central role in the clinical presentation of patients with PLS3-associated X-linked early-onset osteoporosis. However, larger studies are needed to further elucidate the pathogenesis of this rare condition.