Clinical and Genetic Characterization of Osteogenesis Imperfecta in Japanese Patients: Outcomes of Sequential Bisphosphonate Therapy

Although novel drug development and clinical trials are ongoing, bisphosphonates remain the standard treatment of osteogenesis imperfecta (OI). This study aimed to evaluate clinical effects of bisphosphonate therapy across clinical subtypes and genetic variants of OI, and to explore treatment outcomes of sequential bisphosphonate therapy in patients with severe disease. This retrospective analysis was conducted using clinical data from patients with genetically confirmed OI. Bone mineral density (BMD), trabecular bone score (TBS), height, and fracture incidence were analyzed in patients undergoing pamidronate (PAM) treatment and in those who switched from PAM to zoledronate (ZOL). A total of 83 patients with OI were included, of whom 51 (type I: n = 36; type III: n = 9; type IV: n = 5; type V: n = 1) with a history of PAM treatment were selected for subgroup analysis. Analysis of up to 5 years of PAM treatment demonstrated a significant overall increase in BMD accompanied by a reduction in the annualized fracture rate. However, BMD improvement was significantly attenuated in patients with type III compared with those with other types (years 2–4, p < 0.001). Although BMD significantly increased in both groups following PAM initiation, the glycine-substitution group showed lower BMD than the haploinsufficiency group. Type III patients who switched from PAM to ZOL demonstrated increased BMD Z-scores and reduced fracture incidence. Switching from PAM to ZOL appears to be associated with improved outcomes in severe cases. These results suggest that clinical classification, alongside genotype information, may help inform prognosis and guide treatment strategies.