Scoliosis in osteogenesis imperfecta caused by COL1A1/COL1A2 mutations - genotype-phenotype correlations and effect of bisphosphonate treatment
Scoliosis in osteogenesis imperfecta caused by COL1A1/COL1A2 mutations - genotype-phenotype correlations and effect of bisphosphonate treatment
复制标题
DOI：
10.1016/j.bone.2016.02.018
复制
发表时间：
2016-05-01
期刊：
影响因子：
4.1
通讯作者：
Rauch, Frank
中科院分区：
文献类型：
--
作者：
Sato, Atsuko;Ouellet, Jean;Rauch, Frank
双膦酸盐广泛用于治疗儿童成骨不全（OD，一种骨脆性疾病，最常见的是由COL 1A 1或COLIA 2突变引起的。然而，目前尚不清楚这种治疗是否会降低患脊柱侧凸的风险。我们回顾性评估了437例（227名女性）由COL 1A 1或COLIA 2突变引起的01患者的脊柱X线片和图表，并比较了脊柱侧凸、基因型和双膦酸盐治疗史之间的关系。末次随访时（平均年龄11.9 [SD：5.9]岁），242例（55%）患者患有脊柱侧凸。01 III型脊柱侧凸患病率最高（89%），其次是01 IV型（61%）和01 I型（36%）。中度至重度脊柱侧凸（Cobb角25）在COL 1A 1单倍不足突变的个体中很少见，但在三螺旋甘氨酸取代或C-前肽突变的患者中约有五分之二存在。在双膦酸盐治疗的前2 - 4年，01 III型患者的Cobb角进展率低于双膦酸盐治疗前，而01 I型和IV型双膦酸盐治疗与Cobb角进展率的变化无关。在骨骼成熟时，在生命早期（5岁之前）开始双膦酸盐治疗的患者和在生命后期（10岁之后）开始治疗或从未接受过双膦酸盐治疗的患者中，脊柱侧凸（Cobb角>10）的患病率相似。双膦酸盐治疗降低了01 III型脊柱侧凸的进展率，但没有证据表明对01 I型和IV型脊柱侧凸有积极影响。在任何01类型中，成熟期脊柱侧凸的患病率不受双膦酸盐治疗史的影响。(C)2016 Elsevier Inc. All rights reserved.
Bisphosphonates are widely used to treat children with osteogenesis imperfecta (OD, a bone fragility disorder that is most often caused by mutations in COL1A1 or COLIA2. 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 01 caused by mutations in COL1A1 or COLIA2 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 01 type III (89%), followed by 01 type IV (61%) and 01 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 4 years of bisphosphonate therapy, patients with 01 type III had lower Cobb angle progression rates than before bisphosphonate treatment, whereas in 01 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 5.0 years of age) and in patients who had started therapy later (after the age of 10.0 years) or had never received bisphosphonate therapy. Bisphosphonate treatment decreased progression rate of scoliosis in 01 type III but there was no evidence of a positive effect on scoliosis in 01 types I and IV. The prevalence of scoliosis at maturity was not influenced by the bisphosphonate treatment history in any 01 type. (C) 2016 Elsevier Inc. All rights reserved.