The concentration of free calcium in plasma is set by the extracellular action of noncollagenous proteins and hydroxyapatite

The late Wm. F. Neuman frequently included the following statement in his speeches: “Plasma calcium is undersaturated in respect to itself, but supersaturated in respect to bone”. As a physical chemist he knew that if plasma or extracellular fluid came in direct contact with bone surfaces plasma calcium level should fall to the saturated solubility of hydroxyapatite. How could the condition given in the quote exist? He answered this question by laboratory experiments but unfortunately died before he could explain it scientifically. In the current perspective article we feel that we cannot only explain Neuman’s riddle but also use the answer to describe a revised premise for extracellular control of calcium concentrations in body fluids. The answer lies in the solubility of hydroxyapatite. A simple contact of bone mineral surface with body fluids should lead to a calcium concentration in plasma too low to support life. The evolutionary process prevented this by adding one or more noncollagenous proteins at the surface of hydroxyapatite. These proteins elevated the saturated solubility of the crystal latticework sufficiently to provide a calcium concentration that would sustain life. This report explains the solubility process in as much detail as our scientific information will permit and also includes the role of parathyroid hormone in the process. We hope that serious study of our article will permit acceptance of our premise for calcium control and induce further study that should demonstrate its importance in all aspects of bone metabolism.