Fracture outcomes following intravenous pamidronate initiation in children with osteogenesis imperfecta: a multicenter retrospective cohort study from Bucharest, Romania
Year: 2026
Type: article
Study design: Observational Study
Abstract: Introduction Osteogenesis imperfecta (OI) is a rare inherited disorder characterized by skeletal fragility and recurrent fractures. Intravenous pamidronate is widely used in pediatric OI, but long-term real-world data from Eastern Europe remain limited. We compared fracture incidence before and after pamidronate initiation in Romanian children with OI. Methods We conducted a 20-year retrospective multicenter before-and-after cohort study in three tertiary pediatric centers in Bucharest, Romania. Fracture counts and person-years before and after treatment initiation were analyzed using negative binomial generalized estimating equations (GEE), accounting for repeated observations within patients and including log person-years as an offset. The model included treatment period, Sillence type, sex, and age at pamidronate initiation. Results Forty-nine children with OI receiving intravenous pamidronate were included. The cohort included 28 females (57.1%) and 21 males (42.9%). Median age at diagnosis was 24.5 months (IQR, 0.25–81.25), and pamidronate was initiated at a median age of 45 months (IQR, 15.5–95). Before initiation, 198 fractures occurred over 250.3 person-years, compared with 208 fractures over 359.3 person-years afterward, corresponding to incidence rates of 0.79 and 0.58 fractures per person-year, respectively. In the adjusted GEE model, fracture incidence was lower during the post-pamidronate period (IRR 0.49, 95% CI 0.35–0.68; p < 0.001). Compared with type I OI, fracture incidence was higher in type III (IRR 2.09, 95% CI 1.49–2.92; p < 0.001) and type IV (IRR 1.72, 95% CI 1.01–2.94; p = 0.048). Sex was not associated with fracture incidence. Older age at pamidronate initiation was associated with lower fracture incidence (IRR 0.992 per month, 95% CI 0.989–0.996; p < 0.001). Adjustment for corrective osteotomies with telescopic intramedullary rodding procedures did not materially change the findings. Conclusions Fracture incidence was substantially lower after pamidronate initiation, including after accounting for repeated within-patient observations and clinical characteristics. Although the observational design prevents causal attribution to pamidronate, these findings provide long-term real-world data from an Eastern European pediatric OI cohort and support prospective studies incorporating age-dependent fracture risk and time-varying exposures.
Source: Frontiers in Pediatrics
Institution: Carol Davila University of Medicine and Pharmacy
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7223158125