Effectiveness of etoricoxib on bone microarchitecture in PHO patients: A 12-month longitudinal study assessed by HR-pQCT.

Abstract

Primary hypertrophic osteoarthropathy (PHO) is a rare hereditary disorder characterized by both skin and skeletal abnormalities and is classified into two subtypes: PHO autosomal recessive 1 (PHOAR1) and PHO autosomal recessive 2 (PHOAR2). Cyclooxygenase-2 (COX-2) inhibitor Etoricoxib is first-line medication for PHO which could alleviate digital clubbing and pachydermia. However, its effects on the skeletal abnormalities associated with PHO remain unclear. This study aims to comprehensively investigate changes in bone microarchitecture at the distal radius, tibia and interphalangeal bones in PHO patients after 12-month Etoricoxib treatment. A total of 20 PHO patients were enrolled, including 9 PHOAR1 patients and 11 PHOAR2 patients. Bone microstructure was investigated by high-resolution peripheral quantitative computed tomography (HR-pQCT). After 12 months' treatment, periosteosis in long bones and osteolysis at the 3rd interphalangeal joint of PHO were visually reduced. HR-pQCT parameters revealed improvements in total volumetric bone mineral density (Tot.vBMD), cortical vBMD (Ct.vBMD) at distal radius and tibia, accompanied with decreased cortical porosity. Trabecular bone showed no significant improvement. Besides, bone stiffness and failure load were significantly enhanced at radius site. In subgroup analysis, PHOAR2 patients experienced decline in trabecular number at the distal tibia, a change not observed in PHOAR1 patients. Correlation analysis revealed inverse associations between disease duration and changes in vBMD and bone strength in PHOAR2 patients, whereas no significant associations were found in PHOAR1 patients. Our findings indicated that 12 months of Etoricoxib treatment improved bone microstructure in PHO patients and highlighted differential treatment responses between different genotypes, which might optimize treatment strategies for PHO patients.