Teriparatide Treatment in Adult Patients with Osteogenesis Imperfecta Type I
Teriparatide Treatment in Adult Patients with Osteogenesis Imperfecta Type I
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特立帕肽治疗 I 型成骨不全症成人患者
DOI：
10.1007/s00223-013-9770-2
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发表时间：
2013-11-01
影响因子：
4.2
通讯作者：
Adami, Silvano
中科院分区：
文献类型：
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作者：
Gatti, Davide;Rossini, Maurizio;Adami, Silvano
成骨不全症（OI）是一种遗传性疾病，其特征是骨量低、骨脆性增加、身材矮小和骨骼畸形。这项研究的重点是 I 型成骨不全症，这是该疾病最温和的形式。双磷酸盐代表了成骨不全患者的普遍治疗标准。特立帕肽 (TPD) 是一种具有骨合成代谢作用的 PTH 类似物，已被批准用于骨质疏松症的治疗。 13 名患有 I 型 OI 的绝经后女性接受奈立膦酸盐治疗至少 2 年，并且在治疗期间发生新的椎骨骨折，接受 TPD 治疗 18 个月。腰椎骨矿物质密度 (BMD) 在 18 个月内显着增加，达到 3.5% (p = 0.001)，而髋部 BMD 没有显着变化。治疗期间骨形成和骨吸收的血清标志物显着增加。还测量了 Wnt 抑制剂血清 dickkopf-1 (DKK1) 和硬化蛋白。在 TPD 治疗期间，血清硬化蛋白水平无显着增加，而血清 DKK1 逐渐显着升高。在 I 型 OI 患者中，TPD 治疗与骨形成标志物的显着反应相关。这表明成骨细胞对 TPD 有正常反应。然而，观察到的 BMD 增加略低于在相同滞后时间内接受 TPD 治疗的绝经后或老年骨质疏松症患者的 BMD 增加。我们的结果开启了开发 TPD 来治疗成人 I 型 OI 的可能性，但特别是在缺乏对照组的情况下，需要进行适当设计的对照研究。
Osteogenesis imperfecta (OI) is a hereditary disease characterized by low bone mass, increased bone fragility, short stature, and skeletal deformities. This study focuses on OI type I, the mildest form of the disease. Bisphosphonates represent the prevailing standard of care in patients with OI. Teriparatide (TPD) is a PTH analog with bone-anabolic actions which has been approved for osteoporosis treatment. Thirteen postmenopausal women with type I OI who had been on treatment with neridronate for at least 2 years and who incurred new vertebral fracture during treatment were treated with TPD for 18 months. Bone mineral density (BMD) increased significantly over 18 months up to 3.5 % at the lumbar spine (p = 0.001), while no significant changes were noted in hip BMD. Serum markers of bone formation and of bone resorption increased significantly during the treatment. The Wnt inhibitors serum dickkopf-1 (DKK1) and sclerostin were also measured. A nonsignificant increase was seen in serum sclerostin levels, while serum DKK1 rose gradually and significantly during TPD treatment. In patients affected by type I OI, TPD treatment is associated with a remarkable response in markers of bone formation. This suggests a normal osteoblastic response to TPD. However, the observed increases in BMD were somewhat lower than those in postmenopausal or senile osteoporosis treated with TPD for the same lag time. Our results open the possibility to develop TPD for the treatment of adult type I OI, but particularly for the lack of a control group, a properly designed controlled study is warranted.