Parathyroid hormone is a potent systemic stimulator of osteoclastic bone resorption. Osteoclasts, however, lack receptors for parathyroid hormone. Osteoblasts express receptors for parathyroid hormone and control the initiation of bone resorption. In response to parathyroid hormone, osteoblasts contract and leave exposed bone surfaces on which the osteoclasts can attach. The activated osteoblasts secrete or activate collagenases that remove a thin layer of normal, unmineralized fibers from the bone spicules so that the osteoclast can attach to a fully mineralized surface.
Osteoclasts are unable to resorb unmineralized matrix.
In addition, osteoblasts release cytokines that attract and stimulate inactive osteoclasts within the local environment. Calcitonin is a systemic inhibitor of osteoclasts. Osteoclasts have receptors for calcitonin and respond by involution of their brush border and detaching from the bone surface. The role of phosphorous is not fully understood. High plasma phosphate depresses ionized calcium and thereby stimulates the release of parathyroid hormone.