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Decreased fracture rate, pharmacogenetics and BMD response in 79 Swedish children with osteogenesis imperfecta types I, III and IV treated with Pamidronate
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism. Uppsala University, Science for Life Laboratory, SciLifeLab.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
Karolinska Inst, Dept Dent Med, Div Pediat Dent, Stockholm, Sweden..
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2016 (English)In: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 87, 11-18 p.Article in journal (Refereed) PublishedText
Abstract [en]

Background: Osteogenesis imperfecta (OI) is an inherited heterogeneous bone fragility disorder, usually caused by collagen I mutations. It is well established that bisphosphonate treatment increases lumbar spine (LS) bone mineral density (BMD), as well as improves vertebral geometry in severe 01; however, fracture reduction has been difficult to prove, pharmacogenetic studies are scarce, and it is not known at which age, or severity of disease, treatment should be initiated.

Materials and methods: COL1A1 and COL1A2 were analyzed in 79 children with OI (type I n = 33, type III n = 25 and type IV n = 21) treated with Pamidronate. Data on LS BMD, height, and radiologically confirmed non vertebral and vertebral fractures were collected prior to, and at several time points during treatment.

Results: An increase in LS BMD Z-score was observed for all types of OI, and a negative correlation to A LS BMD was observed for both age and LS BMD Z-score at treatment initiation. Supine height Z-scores were not affected by Pamidronate treatment, The fracture rate was reduced for all OI types at all time points during treatment (overall p < 0.0003, < 0.0001 and 0.0003 for all 01 types 1, III and IV respectively). The reduced fracture rate was maintained for types I and IV, while an additional decrease was observed over time for type III. The fracture rate was reduced also in individuals with continued low BMD after >4 yrs Pamidronate. Twice as many boys as girls with 01 type I were treated with Pamidronate, and the fracture rate the year prior treatment was 2.2 times higher for boys (p = 0.0236). Greater Delta LS BMD, but smaller Delta fracture numbers were observed on Pamidronate for helical glycine mutations in COL1A1 vs. COL1A2. Vertebral compression fractures did not progress in any individual during treatment; however, they did not improve in 9%, and these individuals were all >11 years of age at treatment initiation. (p < 0.0001).

Conclusion: Pamidronate treatment in children with all types of 01 increased LS BMD, decreased fracture rate, and improved vertebral compression fractures. Fracture reduction was prompt and maintained during treatment, irrespective of age at treatment initiation and collagen I mutation type.

Place, publisher, year, edition, pages
2016. Vol. 87, 11-18 p.
Keyword [en]
Osteogenesis imperfecta, Bisphosphonate, Fracture, Pharmacogenetics, Mutation, Collagen type I
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-298060DOI: 10.1016/j.bone.2016.02.015ISI: 000376055100002PubMedID: 26957348OAI: oai:DiVA.org:uu-298060DiVA: diva2:944912

Funding: We thank all of the individuals with 01 who participated in this study. Furthermore, we thank Anna-Lena Johansson, Elin Carlsson and Catharina Kumlien and Anna Hammarsjo for skillful technical assistance. Funding was received from the Swedish research council, the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet; by grants from Crown-Princess Lovisa, Axel Tiellmans Minnesfond, Samariten, Sallskapet Barnavard and Promobilia, Norrbacka Eugenia, Promobilia, RBU and Sunnerdahls foundations.

Available from: 2016-06-30 Created: 2016-06-29 Last updated: 2016-06-30Bibliographically approved

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Lindahl, KatarinaKindmark, AndreasRubin, Carl-JohanLjunggren, Östen
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Endocrinology and mineral metabolismScience for Life Laboratory, SciLifeLabDepartment of Medical Biochemistry and Microbiology
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