Division of Endocrinology, Metabolism, and Lipids, Department of Medicine, Emory University School of Medicine, 101 Woodruff Circle, WMRB 1027, Atlanta, GA, 30232, USA.
Curr Osteoporos Rep. 2021 Jun;19(3):358-367. doi: 10.1007/s11914-021-00673-z. Epub 2021 Apr 14.
Fibrodysplasia ossificans progressiva (FOP) is a debilitating rare disease known for episodic endochondral heterotopic ossification (HO) caused by gain-of-function mutations in ACVR1/ALK2. However, disease severity varies among patients with identical mutations suggesting disease-modifying factors, including diet, may have therapeutic implications. The roles of vitamin D in calcium metabolism and chondrogenesis are known, but its effects on BMP signaling and chondrogenesis are less studied. This review attempts to assess the possibility of vitamin D's effects in FOP by exploring relevant intersections of VD with mechanisms of FOP flares.
In vitro and in vivo studies suggest vitamin D suppresses inflammation, while clinical studies suggest that vitamin D protects against arteriosclerosis and inversely correlates with non-genetic intramuscular HO. However, the enhancement of chondrogenesis, BMP signaling, and possibly Activin A expression by vitamin D may be more relevant in FOP. There appears to be little potential for vitamin D to reduce HO in FOP, but testing the potential for excess vitamin D to promote HO may be warranted.
成骨不全性骨纤维发育异常（FOP）是一种使人衰弱的罕见疾病，其特征是由于 ACVR1/ALK2 功能获得性突变而导致间歇性软骨内异位骨化（HO）。然而，具有相同突变的患者的疾病严重程度存在差异，这表明包括饮食在内的疾病修饰因素可能具有治疗意义。维生素 D 在钙代谢和软骨生成中的作用是已知的，但它对 BMP 信号传导和软骨生成的影响研究较少。本综述通过探讨 VD 与 FOP 发作机制的相关交叉点，试图评估维生素 D 在 FOP 中的作用的可能性。
体外和体内研究表明维生素 D 可抑制炎症，而临床研究表明维生素 D 可预防动脉硬化，并且与非遗传性肌内 HO 呈负相关。然而，维生素 D 增强软骨生成、BMP 信号传导，并且可能增强 Activin A 表达在 FOP 中可能更为相关。维生素 D 似乎不太可能减少 FOP 中的 HO，但测试过量维生素 D 促进 HO 的潜力可能是合理的。
