title: Intravenous Bisphosphonate Therapy of Young Children With Osteogenesis Imperfecta: Skeletal Findings During Follow Up Throughout the Growing Years.
abstract: Cyclical intravenous bisphosphonate therapy is widely used to treat children with osteogenesis imperfecta (OI), but little is known about long-term treatment outcomes. We therefore reviewed 37 children with OI (OI type I, n = 1; OI type III, n = 14; and OI type IV, n = 22) who started intravenous bisphosphonate therapy before 5 years of age (median 2.2 years; range, 0.1 to 4.8 years), and who had a subsequent follow-up period of at least 10 years (median 14.8 years; range, 10.7 to 18.2 years), during which they had received intravenous bisphosphonate treatment (pamidronate or zoledronic acid) for at least 6 years. During the observation period, the mean lumbar spine areal bone mineral density Z-score increased from -6.6 (SD 3.1) to -3.0 (SD 1.8), and weight Z-score increased from -2.3 (SD 1.5) to -1.7 (SD 1.7) (p < 0.001 and p = 0.008). At the time of the last assessment, patients with OI type IV had significantly higher height Z-scores than a control group of patients matched for age, gender, and OI type who had not received bisphosphonates. Patients had a median of six femur fractures (range, 0 to 18) and five tibia fractures (range, 0 to 17) during the follow-up period. At baseline, 35% of vertebra were affected by compression fractures, whereas only 6% of vertebra appeared compressed at the last evaluation (p < 0.001), indicating vertebral reshaping during growth. Spinal fusion surgery was performed in 16 patients (43%). Among the 21 patients who did not have spinal fusion surgery, 13 had scoliosis with a curvature ranging from 10 to 56 degrees. In conclusion, long-term intravenous bisphosphonate therapy was associated with higher Z-scores for lumbar spine areal bone mineral density and vertebral reshaping, but long-bone fracture rates were still high and the majority of patients developed scoliosis.
authors.affiliation: Shriners Hospital for Children and McGill University, Montreal, Quebec, Canada.
authors.forename: Telma
authors.initials: T
authors.lastname: Palomo
authors.affiliation: Shriners Hospital for Children and McGill University, Montreal, Quebec, Canada.
authors.forename: François
authors.initials: F
authors.lastname: Fassier
authors.affiliation: Shriners Hospital for Children and McGill University, Montreal, Quebec, Canada.
authors.forename: Jean
authors.initials: J
authors.lastname: Ouellet
authors.affiliation: Shriners Hospital for Children and McGill University, Montreal, Quebec, Canada.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Sato
authors.affiliation: Shriners Hospital for Children and McGill University, Montreal, Quebec, Canada.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Montpetit
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.
authors.forename: Frank
authors.initials: F
authors.lastname: Rauch
mesh_terms: D015502:Absorptiometry, Photon; D000293:Adolescent; D000886:Anthropometry; D015519:Bone Density; D050071:Bone Density Conservation Agents / Q000008:administration & dosage*; D001842:Bone and Bones / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D024042:Collagen Type I / Q000235:genetics; D000090602:Collagen Type I, alpha 1 Chain; D003720:Densitometry; D004164:Diphosphonates / Q000008:administration & dosage*; D005260:Female; D005264:Femoral Fractures / Q000000981:diagnostic imaging; D005500:Follow-Up Studies; D050815:Fractures, Compression / Q000517:prevention & control; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage; D007223:Infant; D007262:Infusions, Intravenous; D008159:Lumbar Vertebrae / Q000187:drug effects; D008297:Male; D009154:Mutation; D010013:Osteogenesis Imperfecta / Q000188:drug therapy*; D000077268:Pamidronate; D012600:Scoliosis / Q000150:complications; D013123:Spinal Fusion; D013978:Tibial Fractures / Q000000981:diagnostic imaging; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; C000601279:COL1A2 protein, human; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid; D000077268:Pamidronate; D002118:Calcium
keywords: OSTEOGENESIS IMPERFECTA; PAMIDRONATE; ZOLEDRONIC ACID