title: Long-bone changes after pamidronate discontinuation in children and adolescents with osteogenesis imperfecta.
abstract: Cyclical intravenous pamidronate is a widely used symptomatic therapy in moderate to severe osteogenesis imperfecta (OI). The effects of treatment discontinuation on long bone development have not been characterized. In this observational study we used peripheral quantitative computed tomography to assess the radius at the distal metaphysis and at the diaphysis in 23 young OI patients (11 female) who had received pamidronate for at least 3 years. Measurements were performed twice, at the time of treatment discontinuation (when the age of the patients ranged from 5.9 to 21.3 years) and at an average of 1.9 years (range 1.5 to 2.4 years) later. At the time of pamidronate discontinuation, all but one of the patients who were below 15 years of age (n=14) had a positive age- and sex-specific z-score for bone mineral content (BMC) at the metaphysis, resulting in a mean z-score of +2.0 (SD=1.0) for this subgroup. In contrast, patients aged 15 years or older (n=9) had an average metaphyseal BMC z-score of -1.5 (SD=1.5). After pamidronate discontinuation, metaphyseal BMC z-score decreased by an average of 2.4 (SD=2.0) in the whole group. The change in BMC z-score was growth-dependent, as BMC z-scores decreased by about 2 or more in all patients in whom distal radius growth plates were open when pamidronate was discontinued. In contrast, none of the 11 patients with closed distal radius growth plates experienced a decrease in metaphyseal BMC z-score by more than 2. At the diaphysis, the average BMC z-score was low at the time of the last pamidronate infusion [z-score -1.7 (SD=1.4)]. After pamidronate discontinuation, the average diaphyseal BMC z-score decreased by only 0.3 (SD=0.4). In summary, this study shows that the effect of pamidronate discontinuation is much larger at the radial metaphysis than at the diaphysis and is dependent on growth. Metaphyseal bone tissue added by longitudinal growth after treatment discontinuation has a lower density than tissue created during treatment. It is possible that this produces zones of localized bone fragility after pamidronate treatment is stopped in growing children.
authors.affiliation: Genetics Unit, Shriners Hospital for Children and McGill University, 1529 Cedar Avenue, Montréal, Québec, Canada H3G 1A6. frauch@shriners.mcgill.ca
authors.forename: Frank
authors.initials: F
authors.lastname: Rauch
authors.forename: Sylvie
authors.initials: S
authors.lastname: Cornibert
authors.forename: Moira
authors.initials: M
authors.lastname: Cheung
authors.forename: Francis H
authors.initials: FH
authors.lastname: Glorieux
mesh_terms: D000293:Adolescent; D000328:Adult; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001846:Bone Development / Q000187:drug effects*; D002648:Child; D002675:Child, Preschool; D004164:Diphosphonates / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D008297:Male; D010013:Osteogenesis Imperfecta / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000077268:Pamidronate; D011884:Radius / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014057:Tomography, X-Ray Computed
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D000077268:Pamidronate