Influence of the parathyroid glands on bone metabolism

Bone is a classic target tissue for parathyroid hormone (PTH), whose calciotropic effect is mediated largely via catabolic actions on this tissue. Paradoxically, PTH also exerts anabolic actions, with intermittent injections of PTH or its amino-terminal fragments causing an increase in bone formation and bone mass, actions that form the basis for the use of PTH in the treatment of osteoporosis. Besides vitamin D, PTH is the only other known bone anabolic agent. High-affinity PTH receptors (PTH-1R) have been detected on osteoblasts and osteoclasts (albeit in lower numbers). Bone turnover, which includes activation of osteoclasts and osteoblasts, appears to be best reflected not by absolute concentrations of PTH (which can vary based on the assay and antibody used) but by a balance of circulating full-length PTH-(1-84) and amino-terminally truncated C-PTH fragments. When PTH-(1-84) is predominant, bone turnover is promoted. Among PTH fragments, PTH-(7-84) appears to be the most potent antagonist of PTH-(1-84). The mechanisms involved in these effects are unclear although mediation via unique C-terminal receptors has been suggested. We propose that, within the range of total PTH (100-1000 pg mL^-1), the ratio of PTH-(1-84)/C-PTH fragment is a valuable tool for diagnosis of bone turnover. Data indicate that at PTH levels < 100-150 pg mL^-1 and > 1000 pg mL^-1, the ratio looses its predictive power. Assay type, patient characteristics (race, underlying renal disease) and treatment attributes (vitamin D, corticosteroids, phosphate binders) have an impact on the PTH ratio, and care should be used in interpreting assay results and making subsequent treatment decisions.