Abstract
The homeostatic regulation of a stable systemic pH is of critical importance for mammalian survival. During metabolic acidosis (a reduction in systemic pH caused by a primary decrease in serum bicarbonate concentration), as seen in clinical disorders such as the later stages of chronic kidney disease, renal tubular acidosis, or chronic diarrhea, bone buffers the accumulated acid; however, this homeostatic function of the skeleton occurs at the expense of the bone mineral content and leads to decreased bone quality. During short-term studies to model acute metabolic acidosis, there is initial physiochemical bone mineral dissolution, releasing carbonate and phosphate proton buffers into the extracellular fluid. In addition, there is net proton influx into the mineral with release of bone sodium and potassium. During long-term studies to model chronic metabolic acidosis, there is also inhibition of osteoblast activity, resulting in reduced bone formation, and an increase in osteoclast activity, resulting in increased bone resorption and release of calcium and anionic proton buffers. These physicochemical and cell-mediated bone responses to metabolic acidosis, in addition to an acidosis-induced increased urine calcium excretion, without a corresponding increase in intestinal calcium absorption, induce a net loss of body calcium that is almost certainly derived from the mineral stores of bone.