Fracture outcomes following intravenous pamidronate initiation in children with osteogenesis imperfecta: a multicenter retrospective cohort study from Bucharest, Romania
4 affiliations
- 1Department of Pediatrics, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
- 2Department of Pediatrics, Emergency Hospital for Children “Grigore Alexandrescu”, Bucharest, Romania
- 3Department of Pediatric Orthopedics, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
- 4Department of Pediatric Orthopedics, Emergency Hospital for Children “Grigore Alexandrescu”, Bucharest, Romania
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.
Related
- Evaluation of the nutritional and digestive impact of irradiation in nasopharyngeal cancers: the French multicenter retrospective DRAKAR study
- Development and evaluation of a nurse-administered triage questionnaire for ophthalmic emergencies during on-call hours: A multicenter retrospective study
- Risk factors analysis and validation of early treatment non-response in children with primary ITP: a multicenter retrospective cohort study
- Outcomes, prognostic factors, and the role of intracranial pressure monitoring in severe community-acquired bacterial meningitis: a multicenter retrospective cohort study
- Anti-Drug Antibodies in Patients with Fabry Disease Treated with Agalsidase-Alpha or -Beta: A Retrospective Italian Multicenter Study
BibTeX
@article{dinulescu2026fracture,
title = {{Fracture outcomes following intravenous pamidronate initiation in children with osteogenesis imperfecta: a multicenter retrospective cohort study from Bucharest, Romania}},
author = {Alexandru Dinulescu and Mara-Elena Stăiculescu and Irina Dijmărescu and Mirela-Luminița Pavelescu and Daniela Păcurar and Alexandru Ulici},
journal = {Frontiers in Pediatrics},
year = {2026},
month = oct,
doi = {10.3389/fped.2026.1973795},
url = {https://doi.org/10.3389/fped.2026.1973795},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Fracture outcomes following intravenous pamidronate initiation in children with osteogenesis imperfecta: a multicenter retrospective cohort study from Bucharest, Romania
AU - Alexandru Dinulescu
AU - Mara-Elena Stăiculescu
AU - Irina Dijmărescu
AU - Mirela-Luminița Pavelescu
AU - Daniela Păcurar
AU - Alexandru Ulici
PY - 2026
DA - 2026/10/21
JO - Frontiers in Pediatrics
DO - 10.3389/fped.2026.1973795
UR - https://doi.org/10.3389/fped.2026.1973795
AB - 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.
SN - 2296-2360
ER -