A pharmaceutical composition and a method of treating, reducing or preventing vascular, cardiovascular arterial or valve calcification in a subject in need comprising administering to the subject an effective amount of an agent that prevents or reduces the expression of HDAC4, an agent that modulates the location of HDAC4, an agent that binds to HDAC4 or an inhibitor of HDAC4 or any combination thereof is provided. In some embodiments, there is provided a pharmaceutical composition comprising: an agent that prevents or reduces the expression of HDAC4, an agent that modulates the location of HDAC4, an agent that binds to HDAC4 or an inhibitor of HDAC4 or any combination thereof; an agent that prevents or reduces the expression of SIK or is an inhibitor of SIK; and/or an agent that prevents or reduces the expression of ENIGMA (Pdlim7) or is an inhibitor of ENIGMA.