Severe osteogenesis imperfecta: new therapeutic options?

Aminobisphosphonates offer promise, while bone marrow transplants remain experimental

Research in osteogenesis imperfecta (the brittle bone syndrome) has contributed exciting new chapters in bone biology, but little advance in treatment (International Conference on Osteogenesis Imperfecta, Montreal 1999).1 Specialised rehabilitation and timely appropriate surgery remain the therapeutic cornerstones. Calcitonin (to reduce bone resorption) and sodium fluoride (to increase formation) are ineffective. Two new approaches using the aminobisphosphonates and stromal cell transplantation now deserve our critical attention. 2 3

In osteogenesis imperfecta causal mutations in the genes for type I collagen explain the skeletal fragility, but the clinical range is wide and the relation between genotype and phenotype complex. Thus in type I osteogenesis imperfecta a non-functional allele for type I collagen halves collagen synthesis and causes mild bone disease. In contrast, in severe osteogenesis imperfecta—types II, III, and IV—mutations replace the essential helical glycine with larger amino acids; this wrecks collagen helix formation, produces unstable molecules, and dramatically reduces the amount of normal collagen. These changes may be lethal, as in type II osteogenesis imperfecta. Type …