Primary hyperparathyroidism: pathophysiology and impact on bone

Abstract

Primary hyperparathyroidism has been associated with bone loss, especially at cortical skeletal sites. Results from studies evaluating the mineral density of cancellous bone have been more difficult to interpret. Most densitometry studies support the concept that the parathyroid hormone appears to be catabolic at cortical sites and may have anabolic effects at cancellous bone sites. Studies completed to date, however, have been limited by design, definitions of fracture and inadequate control groups. Primary hyperparathyroidism is now increasingly being detected during the asymptomatic phase. The need for parathyroidectomy has been questioned in such patients because there may be no disease progression in the absence of surgery. Medical management of primary hyperparathyroidism has to date been limited to estrogen replacement therapy in postmenopausal women. Identification of the calcium receptor has improved our understanding of calcium homeostasis, and significant reductions in calcium receptor levels have been detected in parathyroid adenomas. Thus, a new class of therapeutics may include the calcimimetic agents. Bisphosphonates are also currently being evaluated with regard to their impact on fracture prevention and their beneficial effects on bone mineral density.

Fig. 1: Calcium homeostasis with regulation of serum calcium levels via feedback inhibition through the calcium receptor. ECF = extracellular, Ca = calcium, PTH = parathyroid hormone. Photo by: Christine Kenney

Fig. 2: Schematic illustration of calcium binding to the calcium receptor at the parathyroid cell and inhibiting PTH secretion. Photo by: Christine Kenney

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