Decreased fracture rate, pharmacogenetics and BMD response in 79 Swedish children with osteogenesis imperfecta types I, III and IV treated with Pamidronate

被引：34

作者：

Lindahl, K. ^{[1
]}

Kindmark, A. ^{[1
,2
]}

Rubin, C. -J. ^{[3
]}

Malmgren, B. ^{[4
]}

Grigelioniene, G. ^{[5
,6
]}

Soderhall, S. ^{[7
,8
]}

Ljunggren, O. ^{[1
]}

Astrom, E. ^{[7
,8
]}

机构：

[1] Uppsala Univ, Dept Med Sci, Uppsala, Sweden

[2] Univ Uppsala Hosp, Dept Med Sci, Sci Life Lab, Uppsala, Sweden

[3] Uppsala Univ, Dept Med Biochem & Microbiol, Uppsala, Sweden

[4] Karolinska Inst, Dept Dent Med, Div Pediat Dent, Stockholm, Sweden

[5] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden

[6] Karolinska Univ Hosp Stockholm, Dept Clin Genet, Stockholm, Sweden

[7] Karolinska Univ Hosp, Neuropediat Unit, Stockholm, Sweden

[8] Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden

来源：

BONE | 2016年 / 87卷

基金：

瑞典研究理事会;

关键词：

Osteogenesis imperfecta; Bisphosphonate; Fracture; Pharmacogenetics; Mutation; Collagen type I; GENOTYPE-PHENOTYPE CORRELATIONS; INTRAVENOUS PAMIDRONATE; HELICAL DOMAIN; BONE TURNOVER; MUTATIONS; ADOLESCENTS; COLLAGEN; BISPHOSPHONATE; EPIDEMIOLOGY; POPULATION;

D O I：

10.1016/j.bone.2016.02.015

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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. (C) 2016 Elsevier Inc. All rights reserved.

引用

页码：11 / 18

页数：8

共 45 条

[11] Homozygosity for a Missense Mutation in SERPINH1, which Encodes the Collagen Chaperone Protein HSP47, Results in Severe Recessive Osteogenesis Imperfecta [J].