Clinical Characteristics and Genotype-specific Response to Zoledronic ACID in South African Children With Osteogenesis Imperfecta: A Retrospective Cohort Study

Methods: A retrospective cohort study was conducted in children aged 0-18 years with OI treated with ZA at Steve Biko Academic Hospital (SBAH) from January 2013 to June 2022.

Findings: Forty patients were included: 2 (5%) had OI type 1, 1 (2∙5%) had OI type 2, and 37 (92∙5%) had OI type 3. Among patients with OI type 3, 18 (48∙6%) were FKBP10-positive and 18 (48∙6%) were FKBP10-negative; one was untested. The male-to-female ratio was 1∙35:1. Common clinical features included blue sclera (55%), dentinogenesis imperfecta (50%) and vitamin D insufficiency (25%). Before treatment, the most common fracture sites were the femur (33∙1%), humerus (12∙2%) and ribs (10∙5%), while tibial fractures predominated during treatment (16∙4%). The median annual fracture rate for all patients decreased from 1∙6 to 1∙0 fractures/year following ZA, representing a 38% reduction (p=0∙002). FKBP10–negative patients had a higher baseline fracture rate than FKBP10-positive patients (2∙4 vs 0∙9 fractures/year). ZA significantly reduced fractures in the FKBP10-negative subgroup (2∙4 to 0∙9 fractures/year; p=0∙003), whereas no significant improvement was observed in FKBP10-positive patients (0∙9 to 1∙1 fractures/year; p=0∙906). Patients who required surgery (29/40) had a mean of 2∙9 orthopaedic procedures per patient. Overall growth velocity was 7∙56 cm/year; although FKBP10-positive patients had significantly lower growth velocity (5∙95 cm/year; p=0∙005).

Interpretation: The FKBP10 pathogenic variant is highly prevalent among SA children with OI type 3. ZA significantly reduced fracture rates overall but appeared less effective in patients with the FKBP10 pathogenic variant, suggesting genotype may influence treatment response. Larger prospective studies are needed to confirm these findings.