Cyclical intravenous pamidronate treatment affects metaphyseal modeling in growing patients with osteogenesis imperfecta

J Bone Miner Res. 2006 Mar;21(3):374-9. doi: 10.1359/JBMR.051207. Epub 2005 Dec 19.

Abstract

This analysis of 50 growing patients with osteogenesis imperfecta revealed that 2-4 years of pamidronate treatment lead to abnormalities in the shape of the distal femoral metaphyses.

Introduction: Cyclical intravenous pamidronate therapy is of clinical benefit in children and adolescents with moderate to severe osteogenesis imperfecta (OI) but might interfere with the shaping of long bone metaphyses during growth.

Materials and methods: We evaluated the distal femur in 50 growing children with moderate to severe OI (mean age, 6.7 +/- 3.4 years; 26 girls) who had received 2-4 years of pamidronate therapy (annual dose, 9 mg/kg body weight). The mediolateral width of the distal femoral growth plate and of the metaphysis, as well as the ratio between these two measures (called metaphyseal index), were determined on lower limb radiographs.

Results: Compared with untreated OI patients who were matched for OI type and age, pamidronate-treated patients had similar growth plate width but wider metaphyses, resulting in a 26% higher metaphyseal index (p < 0.001). Apart from the effect on bone shape, each pamidronate cycle induces a transverse line in metaphyses that are adjacent to active growth plates. Analyses of these transverse lines revealed that they persist for an average time of approximately 4 years, with a range from 2 to 8 years.

Conclusions: Pamidronate interferes with the process of periosteal resorption that is normally responsible for shaping the distal femoral metaphysis. Pamidronate-induced transverse lines disappear with time, supporting the view that these lines represent horizontal trabeculae that undergo remodeling. There is no evidence at present that these treatment induced morphological changes have any clinical implications.

Publication types

  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Density Conservation Agents / administration & dosage
  • Bone Density Conservation Agents / adverse effects*
  • Bone Development / drug effects*
  • Bone Remodeling / drug effects*
  • Child
  • Child, Preschool
  • Cohort Studies
  • Diphosphonates / administration & dosage
  • Diphosphonates / adverse effects*
  • Female
  • Femur / diagnostic imaging
  • Femur / pathology
  • Humans
  • Injections, Intravenous
  • Male
  • Osteogenesis Imperfecta / diagnostic imaging
  • Osteogenesis Imperfecta / drug therapy*
  • Osteogenesis Imperfecta / pathology
  • Pamidronate
  • Radiography

Substances

  • Bone Density Conservation Agents
  • Diphosphonates
  • Pamidronate