Table 1.

Therapies for Treating Vascular Calcification Under Investigation.

Treatment	Mechanism of Action	Proposed Effect on Vascular Calcification	Evidence	References
Osteoporosis Therapies for Treating Vascular Calcification
Bisphosphonates	Inhibitor of osteoclast formation & survival; calcium phosphate crystal poison	Reduces release of Ca2+ and blocks hydroxyapatite nucleation and growth	Human Trials - Slowed vascular calcification with some bisphosphonates; resolution of calciphylaxis	[26–30]
Denosumab	Binds RANKL & inhibits binding to RANK	Reduces release of Ca2+; blocks RANKL mediated SMC calcification	Animal Studies - Reduced vascular calcification in mouse model of glucocorticoid-induced calcification	[18, 21, 31]
Osteoprotegerin	Binds RANKL & inhibits binding to RANK	Reduces release of Ca2+; blocks RANKL mediated SMC calcification	Animal Studies - Prevented mineralization of atherosclerotic lesions in LDLR −/− mice	[16, 32, 33]
Teriparatide	Stimulates bone formation	Increases levels of circulating osteopontin, an inhibitor of calcification	Animal Studies - Decreased valve calcification in a diabetic LDLR −/− mice	[34, 35]
Chronic Kidney Disease Therapies for Treating Vascular calcification
Phosphate Binder	Bind to dietary phosphate & prevent absorption by digestive system	Reduces serum levels of phosphate to help slow mineralization of soft tissue	Human Trials - Phosphate binders without Ca may slow progression of vascular calcification	[36, 37]
Vitamin D Receptor Agonists	Treat secondary hyperparathyroidism and Vitamin D deficiency associated with CKD	Increases levels of osteopontin and klotho, preventing calcification	Human Trials - Survival benefit with VDRA therapy	[38, 39]
Calcimimetics	Bind to calcium-sensing receptors to treat secondary hyperparathyroidism	Lowers circulating calcium levels	Human Trials - Randomized study found calcimimetics slowed progression of calcification	[40, 41]
Vitamin K	CKD patients often deficient for vitamin K, a cofactor in various metabolic pathways	Increases activation of circulating MGP, an inhibitor of calcification	Human Trials - Supplementation increased levels of active MGP	[42–44]
Sodium Thiosulfate	A vasodilator, antioxidant, and a calcium chelator	Improves local circulation, and reduces inflammation and calcification	Human Trials - Established treatment for calciphylaxis; possible treatment for other forms of vascular calcification	[45–47]
Cardiovascular Disease Therapies for Treating Vascular calcification
Endothelin Receptor Antagonists	Blocks endothelin receptor signaling and reduces blood pressure	Reduced blood pressure may result in decreased calcification	Animal Studies - Vascular calcification halted or reversed in mouse models	[48, 49]
Statins	HMG CoA reductase inhibitors; Reduce cholesterol production by liver	Prevents lipid deposition on heart valves and reduce inflammation	Human Trials–Benefit for valve calcification not seen in randomized controlled studies	[50, 51]
Experimental Therapies for Treating Vascular calcification
EDTA Chelation Therapy	Binds free calcium	Lowers serum calcium levels to reduce calcification	Human Trials - Small pilot suggested benefit to less than half of patients	[52]
Metabolic Acidosis	Side-effect of certain diseases; decreased pH of bodily fluids	Dissolution of mineral in calcified vessels	Animal Studies - Prevented vascular calcification in uremic rat model	[53, 54]
Autologous Osteoclasts	Main mineral-resorbing cells in the body	Resorb abnormal mineral in vascular calcification	Animal Studies–Limited calcification of elastin implanted subdermally in rats	[55, 56]