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Parathyroid hormone/parathyroid hormone-related protein analogs for osteoporosis

Clifford J Rosen, MD
Section Editor
Marc K Drezner, MD
Deputy Editor
Jean E Mulder, MD


The majority of osteoporosis medications (eg, bisphosphonates, denosumab, raloxifene, and estrogen) are antiresorptive agents that slow bone turnover, decrease bone resorption, and enhance bone mineral density (BMD), as more mineral is gradually deposited in older remodeling units. In contrast, parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP) analogs belong to a different class of anti-osteoporosis drugs called "anabolic" agents. There are fundamental differences in the mode of action of and skeletal response to PTH and PTHrP analogs compared with antiresorptive drugs [1].

This topic will review the use of PTH and PTHrP analogs as a therapy for osteoporosis. PTH physiology and other treatments for osteoporosis are reviewed in detail elsewhere. (See "Parathyroid hormone secretion and action" and "Overview of the management of osteoporosis in postmenopausal women" and "Treatment of osteoporosis in men".)


In contrast to antiresorptive agents (eg, bisphosphonates, denosumab, raloxifene, and estrogen), PTH and PTHrP analogs stimulate bone formation and activate bone remodeling. Increases in bone formation occur more quickly than bone resorption, leading to an increase in lumbar bone mineral density (BMD) that is greater in the first two years of treatment than any antiresorptive agent.

PTH – Parathyroid hormone (PTH) is an 84-amino acid polypeptide secreted by the parathyroid glands in response to relatively small changes in serum calcium (figure 1). PTH is one of the three key hormones modulating calcium and phosphate homeostasis; the other two are calcitriol (1,25-dihydroxyvitamin D) and fibroblast growth factor 23 (FGF23). Through its actions to stimulate 1,25-dihydroxyvitamin D production, renal tubular calcium reabsorption, and bone resorption, PTH is responsible for maintaining serum ionized calcium concentrations within a narrow range. (See "Parathyroid hormone secretion and action".)

PTHrP – Parathyroid hormone-related protein (PTHrP) is produced in a wide variety of tissues and has diverse functions. It shares some of the actions of PTH, including stimulation of renal tubular calcium reabsorption and bone resorption, but it has minimal effect on intestinal calcium absorption, the latter due to weak stimulation of 1,25 dihydroxyvitamin D production. PTHrP also regulates cellular proliferation and is an important component of fetal calcium regulation, placental calcium transfer, and lactation [2,3]. PTHrP is produced by some cancers and is the primary cause of humeral hypercalcemia of malignancy. (See "Hypercalcemia of malignancy: Mechanisms", section on 'PTH-related protein'.)


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Literature review current through: Jul 2017. | This topic last updated: Jul 28, 2017.
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