Hoyer-Kuhn Heike, Stark Christina, Franklin Jeremy, Schoenau Eckhard, Semler Oliver
Children's Hospital, University of Cologne, Germany.
Cologne Centre for Musculoskeletal Biomechanics, Medical Faculty, University of Cologne, Germany.
Pediatr Endocrinol Rev. 2017 Nov;15(Suppl 1):123-129. doi: 10.17458/per.vol15.2017.hsf.correlationbonemineraldensity.
Osteogenesis imperfecta (OI) is a rare hereditary skeletal disease leading to recurrent fractures, short stature and impaired mobility. The phenotype varies from mildly affected patients to perinatal lethal forms. In most cases an impaired collagen production due to mutations in COL1A1 or COL1A2 cause this hereditary bone fragility syndrome with an autosomal dominant inheritance. Currently an interdisciplinary therapeutic approach with antiresorptive drugs, physiotherapy and surgical procedures is the state of the art therapy. The effect of such a therapy is evaluated by measuring different surrogate parameters like areal bone mineral density or by using different mobility tests or questionnaires. Up till now the impact of these parameters on quality of life of the patients is not evaluated. Currently pharmacological strategies are based on antiresorptive treatment with bisphosphonates. In this trial we investigated the effect of an antiresorptive therapy with the monoclonal antibody denosumab decreasing the activity of osteoclasts. Denosumab was administered subcutaneously in a dose of 1mg/kg body weight in 10 children with OI (5-10 years of age) every 12 weeks for 48 weeks. Areal bone mineral density, mobility, pain scores and quality of life were measured. The results showed a good effect of the treatment on bone mineral density but this improvement showed no correlation to pain and quality of life. In conclusion further trials have to define parameters to assess interventions which influence activities of daily life of the patients. An interdisciplinary approach including physicians, basic researchers and patient organisation is needed to focus research on topics improving quality of life of patients with severe skeletal diseases.
成骨不全症（OI）是一种罕见的遗传性骨骼疾病，可导致反复骨折、身材矮小和行动能力受损。其表型从轻度受影响的患者到围产期致死型不等。在大多数情况下，由于COL1A1或COL1A2基因发生突变导致胶原蛋白生成受损，从而引发这种具有常染色体显性遗传的遗传性骨脆性综合征。目前，采用抗吸收药物、物理治疗和外科手术的多学科治疗方法是最先进的治疗手段。通过测量不同的替代参数（如骨面积密度）或使用不同的行动能力测试或问卷来评估这种治疗的效果。到目前为止，尚未评估这些参数对患者生活质量的影响。目前的药物治疗策略基于使用双膦酸盐进行抗吸收治疗。在本试验中，我们研究了用单克隆抗体地诺单抗进行抗吸收治疗降低破骨细胞活性的效果。对10名年龄在5至10岁的成骨不全症儿童，每12周皮下注射一次剂量为1mg/kg体重的地诺单抗，持续48周。测量了骨面积密度、行动能力、疼痛评分和生活质量。结果显示该治疗对骨密度有良好效果，但这种改善与疼痛和生活质量无关。总之，进一步的试验必须确定评估影响患者日常生活活动的干预措施的参数。需要一种包括医生、基础研究人员和患者组织的多学科方法，将研究重点放在改善严重骨骼疾病患者生活质量的课题上。
