Department of Cell Biology and Anatomy, University of Turku, Kiinamyllynkatu 10, 20520, Turku, Finland.
Calcif Tissue Int. 2014 Jun;94(6):608-12. doi: 10.1007/s00223-013-9835-2. Epub 2014 Jan 4.
This is the first prospective follow-up study to describe the effects of oral alendronate medication on neurofibromatosis 1 (NF1)-related osteoporosis. NF1 is a neurocutaneous skeletal syndrome associated with increased fracture risk and high frequency of osteopenia and osteoporosis. Alendronate is a bisphosphonate drug which inhibits the function of bone-resorbing osteoclasts, ultimately leading to an increase in bone mineral density (BMD) and reduction in fracture risk. However, in vitro studies have shown that NF1 osteoclasts display insensitivity to apoptotic signals caused by bisphosphonates. Our aim was to monitor the effects of alendronate medication in patients with NF1. Five men and one woman, aged 28-76 years, with NF1-related osteoporosis were enrolled to the study. Study participants did not have other conditions and were not taking any medication known to affect bone. The medication included a weekly dose of 70 mg alendronate and a daily 20 μg vitamin D supplementation. After 23 months of follow-up, BMD was increased in five out of six patients, but the increase was not statistically significant. Serum levels of the bone turnover markers CTX and PINP were reduced, suggesting slower bone remodeling, as expected. An unexpected result was that serum levels of the osteoclast activity marker TRAP5b did not change during the follow-up. One new stress fracture of the tibia was documented during the alendronate therapy. Even though the study group was small, the findings of the current study (one new fracture and one patient with decreased BMD) call for a larger study to assess the efficacy of bisphosphonates in NF1-related osteoporosis.
这是第一项前瞻性随访研究，旨在描述口服阿仑膦酸盐治疗对神经纤维瘤病 1 型（NF1）相关骨质疏松症的影响。NF1 是一种神经皮肤骨骼综合征，与骨折风险增加、骨量减少和骨质疏松症发生率高有关。阿仑膦酸盐是一种双膦酸盐药物，可抑制破骨细胞的功能，最终导致骨密度（BMD）增加和骨折风险降低。然而，体外研究表明，NF1 破骨细胞对双膦酸盐引起的凋亡信号不敏感。我们的目的是监测 NF1 患者接受阿仑膦酸盐治疗的效果。共纳入 5 名男性和 1 名女性，年龄 28-76 岁，患有 NF1 相关骨质疏松症。研究参与者没有其他疾病，也没有服用任何已知会影响骨骼的药物。治疗方案包括每周 70mg 阿仑膦酸盐和每日 20μg 维生素 D 补充剂。经过 23 个月的随访，6 名患者中有 5 名的 BMD 增加，但增加不具有统计学意义。骨转换标志物 CTX 和 PINP 的血清水平降低，表明骨重塑速度减缓，这符合预期。出乎意料的是，破骨细胞活性标志物 TRAP5b 的血清水平在随访期间没有变化。在接受阿仑膦酸盐治疗期间，有 1 例新发生胫骨应力性骨折。尽管研究组规模较小，但本研究的结果（1 例新发骨折和 1 例 BMD 降低的患者）表明需要更大规模的研究来评估双膦酸盐在 NF1 相关骨质疏松症中的疗效。
