title: The effects of intravenous pamidronate on the bone tissue of children and adolescents with osteogenesis imperfecta.
abstract: Cyclical pamidronate infusions increase bone mass in children suffering from osteogenesis imperfecta. The histological basis for these effects remains unknown. Therefore, we compared parameters of iliac bone histomorphometry from 45 patients before and after 2.4 +/- 0.6 years of pamidronate treatment (age at the time of the first biopsy, 1.4-17.5 years; 23 girls). Although biopsy size did not change significantly (P = 0.30), cortical width increased by 88%. Cancellous bone volume increased by 46%. This was due to a higher trabecular number, whereas trabecular thickness remained stable. Bone surface-based indicators of cancellous bone remodeling decreased by 26-75%. There was no evidence for a mineralization defect in any of the patients. These results suggest that, in the growing skeleton, pamidronate has a twofold effect. In remodeling, bone resorption and formation are coupled and consequently both processes are inhibited. However, osteoclasts and osteoblasts are active on different surfaces (and are thus uncoupled) during modeling of cortical bone. Therefore resorption is selectively targeted, and continuing bone formation can increase cortical width.
authors.affiliation: Genetics Unit, Shriners Hospital for Children, and McGill University, Montréal, Québec, Canada. frauch@shriners.mcgill.ca
authors.forename: Frank
authors.initials: F
authors.lastname: Rauch
authors.forename: Rose
authors.initials: R
authors.lastname: Travers
authors.forename: Horacio
authors.initials: H
authors.lastname: Plotkin
authors.forename: Francis H
authors.initials: FH
authors.lastname: Glorieux
mesh_terms: D000293:Adolescent; D015519:Bone Density / Q000187:drug effects; D001846:Bone Development / Q000187:drug effects; D016723:Bone Remodeling / Q000187:drug effects; D001862:Bone Resorption / Q000517:prevention & control; D001842:Bone and Bones / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D024042:Collagen Type I / Q000235:genetics; D004164:Diphosphonates / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D010013:Osteogenesis Imperfecta / Q000188:drug therapy* / Q000503:physiopathology; D000077268:Pamidronate
chemical_list: D024042:Collagen Type I; D004164:Diphosphonates; D000077268:Pamidronate