Beneficial effect of long term intravenous bisphosphonate treatment of osteogenesis imperfecta

Abstract

Aim: To find an effective symptomatic treatment for osteogenesis imperfecta (OI). Methods: In a prospective observational study disodium pamidronate (APD) was given as monthly intravenous infusions to 28 children and adolescents (aged 0.6-18 years) with severe OI or a milder form of the disease, but with spinal compression fractures. Results: During treatment for 2-9 years, dual energy x ray absorptiometry measurements of the total body and of the lumbar spine showed a gradual increase in bone density. All bone metabolism variables in serum (alkaline phosphatase, osteocalcin, procollagen 1 C-terminal peptide, collagen 1 teleopeptide) and urine (deoxypyridinoline) indicated that there was a decrease in bone turnover. All patients experienced beneficial effects and the younger patients reported a major improvement in wellbeing, pain, and mobility without significant side effects. Vertebral remodelling was also seen. Conclusions: APD seems to be an efficient symptomatic treatment for children and adolescents with OI.

Osteogenesis imperfecta: Recent findings shed new light on this once well-understood condition

“…Attempts to use bisphosphonates as a treatment for OI were pioneered by Glorieux et al 45 An open-label trial of cyclical intravenous Pamidronate (a bisphosphonate) was reported by Glorieux et al and the effects of relatively long-term use in adults by Astrom and Soderhall 46 and Zeitlin et al 47 Falk et al 48 replicated the study of Glorieux et al in children over 22 months of age, but of note did report one child with fracture nonunion after treatment with Pamidronate. Nonunion is known to occur in individuals with OI not receiving Pamidronate and the relevance of this observation is thus not clear.…”

Cyclic Pamidronate Treatment in Two Korean Boys with Osteogenesis Imperfecta Type I Caused by COL1A1 Mutations - Case Report

“…A recent study showed that bisphosphonates can prevent osteoblast and osteocyte apoptosis, which is dependent on the expression of connexin (Cx)43 [14]. In addition, a study of intravenous pamidronate therapy for OI patients showed a gradual increase of lumbar bone density and a decrease of bone turnover [10]. As a result, bisphosphonate therapy is increasingly used for OI and other osteoporotic conditions in children; however, the most effective dosing regimen has yet to be defined.…”

“…Gene analysis showed a novel heterozygous missense mutation of COL1A1 (c.2T>G, p.Met1Arg) in the patient and his mother, which was previously reported [9]. We treated with monthly cyclic pamidronate infusion with the following protocol: 10 mg/m 2 body surface area (BSA) for 1 ~ 3 months, 20 mg/m 2 for 4 ~ 6 months, and 30 mg/m 2 after 7 month [10]. Pamidronate was intravenously infused over 4 h at concentration of less than 0.1 mg/mL in isotonic saline.…”

Osteogenesis Imperfecta: An Uncommon Association with Non-Communicating Hydrocephalus

“…Intravenous pamidronate or oral alendronate improve quality of life and inhibit bone resorption thus increasing bone mineralisation 7,8 .…”