Efficacy of Denosumab for Osteoporosis in Three Female Patients with Osteogenesis Imperfecta
Efficacy of Denosumab for Osteoporosis in Three Female Patients with Osteogenesis Imperfecta
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DOI：
10.1620/tjem.242.115
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发表时间：
2017-06-01
影响因子：
2.2
通讯作者：
Kato, Hiroyuki
中科院分区：
文献类型：
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作者：
Uehara, Masashi;Nakamura, Yukio;Kato, Hiroyuki
骨生成障碍（01）是一种遗传性骨病，由于I型胶原蛋白的产生受损而导致骨折。近年来，狄诺塞单抗（一种抗核因子kB受体激活剂配体（RANKL）的人源单克隆抗体）已被广泛用作骨质疏松症的抗骨质疏松剂。本研究研究了01例骨质疏松病例，以检查地舒单抗对骨脆性的影响。这是一项回顾性连续病例系列，包括3例年龄分别为42岁、40岁和14岁的女性患者。1例患者在编码I型胶原α 1链的COL 1A 1基因中携带点突变（c.G769A），导致氨基酸取代（p.G257R）。相比之下，在另外两名患者（母亲和女儿）的01应答基因的分析区域中未发现突变。这3例患者每6个月接受一次地舒单抗皮下注射。所有患者在治疗前和治疗期间接受双能X线骨密度仪测量腰椎1-4脊柱（L-BMD）和双侧髋关节（H-BMD）的骨密度（BMD）。在治疗前、治疗2 - 4个月、治疗6个月、治疗12个月、治疗18个月和治疗24个月时评估BMD和实验室数据。Denosumab治疗期间未观察到骨折或严重副作用，如低钙血症。地舒单抗可增加L-BMD和H-BMD。24个月时，L-BMD和H-BMD的平均百分比变化分别为14.7%和15.1%。总之，01例患者在地舒单抗给药2年期间未发生骨脆性骨折。因此，地舒单抗是01例患者的良好治疗选择。
Osteogenesis imperfecta (01) is an inherited bone disorder that causes fractures due to impaired production of collagen type I. In recent years, denosumab, a human monoclonal antibody against receptor activator of nuclear factor kB ligand (RANKL), has become widely used as an anti-osteoclastic agent for osteoporosis. This study investigated osteoporotic cases of 01 to examine effects of denosumab on bone fragility. This was a retrospective, consecutive case series that included 3 female patients aged 42, 40, and 14 years, respectively. One patient carries a point mutation (c.G769A) in the COL1A1 gene, encoding collagen type I alpha 1 chain, which causes an amino-acid substitution (p.G257R). By contrast, no mutation was found in the analyzed regions of the 01 responsive genes in another two patients (mother and daughter). These three patients underwent subcutaneous injection of denosumab every 6 months. All patients underwent dual-energy X-ray absorptiometry for bone mineral density (BMD) measurement of the lumbar 1-4 spine (L-BMD) and bilateral hips (H-BMD) before and during treatment. BMD and laboratory data were evaluated before, between 2 and 4 months, and at 6, 12, 18, and 24 months of therapy. No fractures or severe side effects, such as hypocalcemia, were observed during denosumab treatment. Both L-BMD and H-BMD were increased by denosumab. At 24 months, the mean percentage changes in L-BMD and H-BMD were 14.7% and 15.1%, respectively. In conclusion, no bone fragility fractures occurred during 2 years of denosumab administration in 01 patients. Denosumab therefore is a good therapeutic option in the 01 patients.