title: Scoliosis in osteogenesis imperfecta caused by COL1A1/COL1A2 mutations - genotype-phenotype correlations and effect of bisphosphonate treatment.
abstract: Bisphosphonates are widely used to treat children with osteogenesis imperfecta (OI), a bone fragility disorder that is most often caused by mutations in COL1A1 or COL1A2. However, it is unclear whether this treatment decreases the risk of developing scoliosis. We retrospectively evaluated spine radiographs and charts of 437 patients (227 female) with OI caused by mutations in COL1A1 or COL1A2 and compared the relationship between scoliosis, genotype and bisphosphonate treatment history. At the last follow-up (mean age 11.9 [SD: 5.9] years), 242 (55%) patients had scoliosis. The prevalence of scoliosis was highest in OI type III (89%), followed by OI type IV (61%) and OI type I (36%). Moderate to severe scoliosis (Cobb angle ≥25°) was rare in individuals with COL1A1 haploinsufficiency mutations but was present in about two fifth of patients with triple helical glycine substitutions or C-propeptide mutations. During the first 2 to 4years of bisphosphonate therapy, patients with OI type III had lower Cobb angle progression rates than before bisphosphonate treatment, whereas in OI types I and IV bisphosphonate treatment was not associated with a change in Cobb angle progression rates. At skeletal maturity, the prevalence of scoliosis (Cobb angle >10°) was similar in patients who had started bisphosphonate treatment early in life (before 5.0years of age) and in patients who had started therapy later (after the age of 10.0years) or had never received bisphosphonate therapy. Bisphosphonate treatment decreased progression rate of scoliosis in OI type III but there was no evidence of a positive effect on scoliosis in OI types I and IV. The prevalence of scoliosis at maturity was not influenced by the bisphosphonate treatment history in any OI type.
authors.affiliation: Shriners Hospital for Children and McGill University, Montreal, Quebec, Canada; Department of Joint Surgery and Sports Medicine, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Sato
authors.affiliation: Shriners Hospital for Children and McGill University, Montreal, Quebec, Canada.
authors.forename: Jean
authors.initials: J
authors.lastname: Ouellet
authors.affiliation: Department of Joint Surgery and Sports Medicine, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Muneta
authors.affiliation: Shriners Hospital for Children and McGill University, Montreal, Quebec, Canada.
authors.forename: Francis H
authors.initials: FH
authors.lastname: Glorieux
authors.affiliation: Shriners Hospital for Children and McGill University, Montreal, Quebec, Canada. Electronic address: frauch@shriners.mcgill.ca.
authors.forename: Frank
authors.initials: F
authors.lastname: Rauch
mesh_terms: D002648:Child; D024042:Collagen Type I / Q000235:genetics*; D000090602:Collagen Type I, alpha 1 Chain; D004164:Diphosphonates / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D010013:Osteogenesis Imperfecta / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D015995:Prevalence; D012600:Scoliosis / Q000150:complications / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics*
chemical_list: C000601279:COL1A2 protein, human; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D004164:Diphosphonates
keywords: Collagen Type I; Osteogenesis imperfecta; Pamidronate; Scoliosis; Zoledronic acid