Evaluation of a Modified Pamidronate Protocol for the Treatment of Osteogenesis Imperfecta

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.

Low Dose of Bisphosphonate Enhances Sclerostin Antibody-Induced Trabecular Bone Mass Gains in Brtl/+ Osteogenesis Imperfecta Mouse Model

“…Through their high affinity for calcium ions, these potent inhibitors of bone resorption strongly bind to hydroxyapatite bone surfaces where they can later be internalized by osteoclasts to interrupt the resorption process . Several controlled clinical trials have established the beneficial effects of treating pediatric OI with BP, including decreased bone turnover and increased bone mineral density, particularly at sites of trabecular bone . During endochondral growth, primary trabeculae are remodeled and converted to secondary spongiosa, and extended BP treatment interrupts this process, thus retaining calcified cartilage and increasing metaphyseal mass.…”

“…(4) Several controlled clinical trials have established the beneficial effects of treating pediatric OI with BP, including decreased bone turnover and increased bone mineral density, particularly at sites of trabecular bone. (5)(6)(7)(8)(9)(10)(11) During endochondral growth, primary trabeculae are remodeled and converted to secondary spongiosa, and extended BP treatment interrupts this process, thus retaining calcified cartilage and increasing metaphyseal mass. In support of these studies, we and others have shown that with BP treatment, significant improvements in trabecular number, but not trabecular thickness are realized.…”

Bisphosphonates in Langerhans Cell Histiocytosis: An International Retrospective Case Series

“…Pamidronate is the only bisphosphonate that is most widely used in children for various bone conditions with a well-established safety profile. 22 , 23 Similarly, the safety and efficacy of zoledronate has been extensively reviewed in adults, and especially found to be effective in decreasing the risk of skeletal-related events secondary to breast cancer such as pathological fractures, spinal cord compressions and hypercalcemia. 24 Although there are few reports demonstrating the role and safety of alendronate in certain skeletal conditions such as avascular necrosis and osteoporosis, large-scale prospective studies evaluating its safety profile and efficacy is still lacking.…”

Bifosfonati e disfunzione renale

“…14 Il profilo di sicurezza del pamidronato somministrato per via ev è stato descritto in uno studio di Palomo e colleghi nel 2015. 15 Gli autori hanno proposto una modifica al protocollo standard per l’osteogenesi imperfecta in una popolazione pediatrica. La somministrazione di pamidronato ev ha seguito il seguente schema: 2 mg/kg in 2 h ogni 4 mesi per un anno.…”

“…La somministrazione di pamidronato ev ha seguito il seguente schema: 2 mg/kg in 2 h ogni 4 mesi per un anno. 15 Già noto per il trattamento delle metastasi ossee e del mieloma, l’acido zoledronico è stato studiato per la terapia dell’osteoporosi, alla dose di 5 mg ev una volta all’anno. Le credenziali di efficacia del farmaco sono molto buone, anche se è stata segnalata tossicità cardiaca (episodi di fibrillazione atriale) e renale (insufficienza renale acuta reversibile).…”