Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing, China.
Department of Endocrinology, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
Front Endocrinol (Lausanne). 2022 Sep 26;13:901925. doi: 10.3389/fendo.2022.901925. eCollection 2022.
This study aimed to investigate the skeletal outcomes of patients with osteogenesis imperfecta (OI) who received bisphosphonate (BP) treatment and entered drug holiday after achieving an age- and sex-specific bone mineral density (BMD) reference.
Patients with OI receiving BP treatment were enrolled when they entered drug holidays of BPs. The skeletal outcomes were evaluated in detail during the drug holiday, including BMD, X-ray of the bone, bone fracture incidence, and bone turnover biomarkers. The pathogenic mutations of OI were identified by next-generation sequencing and confirmed by Sanger sequencing.
A total of 149 OI patients (127 juveniles and 22 adults) who entered drug holidays after nearly 4 years of BP treatment were included. Areal BMD at the lumbar spine increased from 0.934 ± 0.151 to 0.990 ± 0.142 g/cm and was stable in the second (1.029 ± 0.176 g/cm) and third years (1.023 ± 0.174 g/cm) of BP drug holidays, and BMD at the femoral neck, trochanter, and total hip had no significant change, but it was gradually inferior to that of the same-gender juveniles in the second and third years of the drug holiday. BMD at the lumbar spine and proximal hip did not change and was inferior to that of the same-gender adults. The average time of fractures fluctuated from 0.18 to 0.08 per year in juveniles, while only one adult suffered from a fracture during BP drug holidays. Bone turnover markers were in the normal range, except for a mildly high level of β-carboxy-terminal cross-linked telopeptide of type 1 collagen in the juvenile group. A total of 17 (11.4%) patients received BP retreatment because of bone loss during the drug holiday. OI type III and type IV and mutation were correlated to a longer duration of BP treatment to enter drug holidays (all < 0.05). Old age at initial treatment (OR, 1.056) and OI type III (OR, 10.880) were correlated to a higher risk of BP retreatment.
OI patients will undergo nearly 4 years of BP treatment to achieve drug holidays. During the 3 years of the drug holiday, the patients' BMD is stable, and fracture incidence does not increase significantly. Patients are more inclined to need retreatment during drug holidays owing to the late start of BP treatment and more severe OI phenotypes.
本研究旨在探讨达到年龄和性别特异性骨密度（BMD）参考值后接受双膦酸盐（BP）治疗并进入药物假期的成骨不全症（OI）患者的骨骼结局。
当 OI 患者接受 BP 治疗进入药物假期时，将其纳入研究。在药物假期期间详细评估骨骼结局，包括 BMD、骨 X 射线、骨折发生率和骨转换生物标志物。通过下一代测序确定 OI 的致病突变，并通过 Sanger 测序进行确认。
共纳入 149 例接受 BP 治疗近 4 年后进入药物假期的 OI 患者（127 例青少年和 22 例成人）。腰椎的面积 BMD 从 0.934 ± 0.151 增加到 0.990 ± 0.142 g/cm，在药物假期的第二年（1.029 ± 0.176 g/cm）和第三年（1.023 ± 0.174 g/cm）保持稳定，股骨颈、转子间和总髋部的 BMD 没有明显变化，但在药物假期的第二年和第三年逐渐低于同性别青少年的水平。腰椎和近端髋部的 BMD 没有变化，且低于同性别成人的水平。青少年骨折的平均时间从 0.18 年波动至 0.08 年/年，而只有 1 例成人在 BP 药物假期期间发生骨折。骨转换标志物均在正常范围内，仅青少年组β-羧基端交联型 1 型胶原肽水平轻度升高。共有 17 例（11.4%）患者因药物假期期间发生骨丢失而接受 BP 重新治疗。OI 类型 III 和 IV 以及突变与更长的 BP 治疗时间以进入药物假期相关（均<0.05）。初始治疗时年龄较大（OR，1.056）和 OI 类型 III（OR，10.880）与 BP 重新治疗的风险较高相关。
OI 患者将接受近 4 年的 BP 治疗以达到药物假期。在药物假期的 3 年期间，患者的 BMD 稳定，骨折发生率没有显著增加。由于 BP 治疗开始较晚和 OI 表型更严重，患者在药物假期期间更倾向于需要重新治疗。
