Ectopic calcifications in the musculoskeletal field: the basis for preventive and curative pharmacological strategies

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.