Calcium: More Than Bone? Implications for Clinical Practice and Theory

Serum calcium is routinely screened, but rarely scrutinized in the context of normal, physiologic functioning. This brief review strives to explore the implications of serum calcium, suggests guidelines for its interpretation, and discusses the implications of high, low, and "normocalcemia" in the clinical setting. We find that serum Ca2+ concentrations are a valuable prognostic indicator in routine metabolic workups and advocate for greater attention, on behalf of the provider, to variations in a patient's calcemic status. Variations in calcemic status are primarily tied to malignancy, impaired parathyroid hormone (PTH) secretion, defects in vitamin D synthesis, insulin-like growth factor 1 (IGF-1) fluctuation, genetic syndromes (DiGeorge syndrome) and calcium-sensing receptor (CaSR) mutation. Prognostic implications for high and low serum Ca2+ include, but are not limited to, increased thromboembolic and major adverse cardiovascular event (MACE) risk, cardiac remodeling, hypertension, cognitive decline, and insulin resistance.