EQUILIBRIUM AND DISEQUILIBRIUM HYPER-CALCEMIA NEW LIGHT ON AN OLD CONCEPT

In many patients with primary hyperparathyroidism (HPT) the plasma calcium does not change with time; although the mean value is elevated, the degree of random fluctuation about the mean is normal. Furthermore, bone resorption and turnover may be high, normal or low and external balance negative, zero or positive. These characteristics define equilibrium hypercalcemia. This is contrasted with disequilibrium hypercalcemia, in which the plasma calcium rises progressively with time, bone resorption is always increased and calcium balance always negative. Equilibrium hypercalcemia is a disturbance of the calcium homeostatic system in bone which regulates plasma calcium, and disequilibrium hypercalcemia is a disturbance of the remodelling system which regulates bone turnover and balance. The homeostatic system is based on the blood-bone equilibrium at quiescent bone surfaces. These are the site of large bidirectional fluxes of calcium demonstrated by autoradiography, and are covered by a layer of flat cells which separate the bone from the bone marrow. This biologic equilibrium must be reconciled with the chemical disequilibrium dictated by the physical chemistry of bone mineral. In whatever way this is accomplished, the system permits hypercalcemia to be maintained indefinitely without continued net loss of calcium from bone provided that tubular reabsorption of calcium is also increased. The remodelling system carries out the turnover of bone in anatomically discrete units in which resorption is coupled to subsequent formation. In pathologic bone resorption or in severe hyperparathyroidism this coupling is broken and a large disparity between total body resorption and formation overloads the ECF with calcium. However, severe hypercalcemia occurs only if there is also some limitation of the capacity of the kidney to excrete calcium, most commonly due to a combination of reduced GFR and increased tubular reabsorption of calcium consequent to sodium depletion. Several vicious circles are then initiated such that hypercalcemia which is dependent on a combination of increased net bone resorption and decreased capacity to excrete calcium is intrinsically unstable. A third type of hypercalcemia has some of the characteristics of the first two types described ; it is associated with increased calcium absorption and positive calcium balance and occurs especially in vitamin D intoxication. All three types occur in primary hyperparathyroidism and all three are frequently associated with increased tubular reabsorption of calcium. Their characteristics and the differences between them can only be explained in terms of the separation between the homeostatic and remodelling systems in bone. © 1979.