Milovanovic Petar, Savic Ivana, Popovic Ana, Grajic Mirko
Center of Bone Biology, Institute of Anatomy, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
Institute of Pathology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
Clin Rheumatol. 2025 Mar;44(3):869-886. doi: 10.1007/s10067-025-07335-w. Epub 2025 Jan 24.
Ectopic calcifications occur in tendons, ligaments, entheses, muscles, and fasciae, and are often associated with pain and inflammation. In clinical settings, these calcifications are commonly treated by physical therapy and/or surgical interventions. However, there is not enough understanding of pharmacological treatments as primary cures, supportive therapy to physical or surgical treatment, or even preventive measures to avoid or diminish the development of ectopic calcifications. Here, we summarize preclinical and clinical evidence for pharmacological candidates for treatment/prevention of ectopic calcification in the context of painful syndromes in the musculoskeletal field. Specifically, we discuss the potential mechanisms of nonsteroidal anti-inflammatory drugs, corticosteroids, H2-receptor blockers, bisphosphonates, minocycline, biologics, ACTH analogues, colchicine, calcium channel blockers, vitamins K2 and D, magnesium, zinc, curcumin, and phytates. Given that ectopic calcification is sometimes paradoxically associated with reduced bone mineralization, it appears particularly reasonable to employ strategies that can both inhibit ectopic calcification and promote bone mineralization, such as bisphosphonates and the combination of vitamin K2 and vitamin D, along with other supplements such as magnesium and zinc. Future studies need to test whether differential therapeutic approaches are needed in different phases of the disease and whether different mechanisms of ectopic calcification require different therapeutic strategies. A precondition for such approaches is further clinical and/or imaging delineation and differentiation of various types and phases of calcific diseases. Finally, it is essential to ensure that anti-calcification effects of new treatment strategies do not harm bone formation and skeletal mineralization.
异位钙化发生于肌腱、韧带、附着点、肌肉和筋膜，常伴有疼痛和炎症。在临床环境中，这些钙化通常通过物理治疗和/或手术干预进行治疗。然而，对于将药物治疗作为主要治疗方法、作为物理或手术治疗的支持性疗法，甚至作为避免或减少异位钙化发生的预防措施，我们的了解还不够。在此，我们总结了在肌肉骨骼领域疼痛综合征背景下，用于治疗/预防异位钙化的候选药物的临床前和临床证据。具体而言，我们讨论了非甾体抗炎药、皮质类固醇、H2受体阻滞剂、双膦酸盐、米诺环素、生物制剂、促肾上腺皮质激素类似物、秋水仙碱、钙通道阻滞剂、维生素K2和D、镁、锌、姜黄素和植酸盐的潜在作用机制。鉴于异位钙化有时与骨矿化减少存在矛盾关联，采用既能抑制异位钙化又能促进骨矿化的策略似乎尤为合理，如双膦酸盐以及维生素K2和维生素D的组合，还有镁和锌等其他补充剂。未来的研究需要测试在疾病的不同阶段是否需要不同的治疗方法，以及异位钙化的不同机制是否需要不同的治疗策略。此类方法的一个前提是对钙化疾病的各种类型和阶段进行进一步的临床和/或影像学描述及区分。最后，必须确保新治疗策略的抗钙化作用不会损害骨形成和骨骼矿化。
