Endocrine Abstracts

JOINT2645

Background: Osteogenesis imperfecta type VI (OI-VI), caused by biallelic SERPINF1 mutations disrupting pigment epithelium-derived factor (PEDF) production, is a rare autosomal recessive skeletal disorder. Despite its distinct clinical profile, long-term therapeutic outcomes and genotype-phenotype relationships remain poorly characterized.

Methods: This retrospective cohort study analyzed 36 pediatric OI-VI patients from 33 families (median follow-up: 11. 5 years). Genetic testing identified SERPINF1 variants, while clinical evaluations included bone mineral density (DXA), spinal radiographs, biochemical profiling (PEDF, β-CTX, P1NP, calcium, phosphate, 25-OH-VD), and treatment responses to bisphosphonates or denosumab with calcium/vitamin D supplementation.

Results: Thirty-eight SERPINF1 variants (25 copy-number variations, 13 single-nucleotide variants) were identified, with recurrent pathogenic mutations c. 907C>T (p. Arg303Ter), c. 271_279dup (p. Ala91_Ser93dup), and c. 79G>T (p. Glu27Ter). Key clinical features included severe growth impairment (mean height Z-score: −2. 9), early-onset fractures (mean age: 1. 37 years), dentinogenesis imperfecta (82. 3%), blue sclerae (71. 4%), and vertebral compression fractures (51. 7%). Serum PEDF levels were universally deficient (mean: 0. 0017 μg/mL). All patients required surgical interventions (mean: 3. 79 procedures) combined with pharmacotherapy: 18 received bisphosphonates, and 18 switched to denosumab (11 after bisphosphonates). Hypercalcemia occurred in 5 denosumab-treated patients (mean onset age: 3. 6 years). Fracture frequency decreased post-treatment, though detailed analyses of spinal deformity progression and biomarker trends are ongoing.

Conclusions: This study delineates the genotypic spectrum and phenotypic severity of OI-VI, emphasizing early fracture onset and multisystem involvement. While bisphosphonates and denosumab reduce fracture burden, denosumab-associated hypercalcemia in young children warrants cautious monitoring. Longitudinal data on spinal remodeling and bone turnover dynamics will further clarify therapeutic efficacy, guiding optimized management strategies for this ultrarare OI subtype.