Evaluation of a Modified Pamidronate Protocol for the Treatment of Osteogenesis Imperfecta
Telma Palomo1,2, Maria C Andrade3, Barbara S E Peters4
1Bone and Mineral Unit, Division of Endocrinology, Universidade Federal de São Paulo, São Paulo, Brazil. telmapalomo@yahoo.com.br.
Insights
A modified pamidronate infusion protocol for pediatric osteogenesis imperfecta (OI) shows renal safety and comparable bone density improvements to the standard protocol. This simpler regimen offers a potentially effective alternative for OI treatment.
Area of Science:
- Pediatric Nephrology
- Pediatric Endocrinology
- Bone Metabolism
Background:
- Intravenous pamidronate is a standard treatment for pediatric osteogenesis imperfecta (OI).
- The established protocol involves daily infusions over 3 days every 4 months.
- Evaluating alternative, simpler administration protocols is crucial for patient care.
Purpose of the Study:
- To assess the renal safety and bone mineral density effects of a modified, simplified intravenous pamidronate protocol in children with OI.
- To compare the outcomes of the modified protocol with the standard protocol.
Main Methods:
- A prospective evaluation of 18 pediatric patients with OI (types I, III, IV) receiving a modified pamidronate protocol (2 mg/kg in a single 2-hour infusion every 4 months) for 12 months.
- Comparison with 18 historical controls treated with the standard protocol (1 mg/kg/day for 3 days every 4 months).
- Assessment of serum creatinine for renal safety and bone mineral density (BMD) Z-scores at the lumbar spine.
Main Results:
- The modified protocol demonstrated mild, transient increases in serum creatinine during infusions, with levels returning to baseline by study end.
- Serum creatinine levels remained stable from baseline to 12 months in the modified protocol group (0.40 vs. 0.41 mg/dl, P = 0.79).
- Both protocols showed similar improvements in lumbar spine BMD Z-scores over 12 months, with the modified protocol increasing scores from -2.7 to -1.8 (P = 0.68 for group difference).
Conclusions:
- The modified intravenous pamidronate protocol is safe regarding renal function in children with OI.
- The simplified protocol appears to yield comparable bone mineral density improvements to the standard protocol.
- Further long-term studies are warranted to confirm anti-fracture efficacy of the modified protocol.
Abstract:
Intravenous pamidronate is widely used to treat children with osteogenesis imperfecta (OI). In a well-studied protocol ('standard protocol'), pamidronate is given at a daily dose of 1 mg per kg body weight over 4 h on 3 successive days; infusion cycles are repeated every 4 months. Here, we evaluated renal safety of a simpler protocol for intravenous pamidronate infusions (2 mg per kg body weight given in a single infusion over 2 h, repeated every 4 months; 'modified protocol'). Results of 18 patients with OI types I, III, or IV treated with the modified protocol for 12 months were compared to 18 historic controls, treated with standard protocol. In the modified protocol, mild transient post-infusion increases in serum creatinine were found during each infusion but after 12 months serum creatinine remained similar from baseline [0.40 mg/dl (SD: 0.13)] to the end of the study [0.41 mg/dl (SD: 0.11)] (P = 0.79). The two protocols led to similar changes in serum creatinine during the first pamidronate infusion [modified protocol: +2% (SD: 21%); standard protocol: -3% (SD: 8%); P = 0.32]. Areal lumbar spine bone mineral density Z-scores increased from -2.7 (SD: 1.5) to -1.8 (SD: 1.4) with the modified protocol, and from -4.1 (SD: 1.4) to -3.1 (SD: 1.1) with standard protocol (P = 0.68 for group differences in bone density Z-score changes). The modified pamidronate protocol is safe and may have similar effects on bone density as the standard pamidronate protocol. More studies are needed with longer follow-up to prove anti-fracture efficacy.
