Review Question - QID 210166

Parathyroid hormone (PTH) is a hormone which is produced by chief cells in the parathyroid gland. Teriparatide is a recombinant protein form of PTH and is the only available anabolic agent in the United States.

PTH stimulates bone formation and resorption and can increase or decrease bone mass, depending on the mode of administration. Teriparatide or PTH (1-34), comprises the first 34 amino acids of the hormone and produces its chief biologic effects. Continuous infusions which will result in a persistent elevation of serum PTH concentration will lead to greater bone resorption and hypercalcemia compared to daily injections. Daily injections lead to only transient increases of PTH which may stimulate bone formation. Intermittent administration increases the number of osteoblasts, activation of pre-existing osteoblasts, increased differentiation of lining cells to become osteoblasts, and reduced osteoblast apoptosis.

Neer et al. performed a study to determine the effect of PTH for the treatment of postmenopausal women with prior vertebral fractures. They randomly assigned 1637 postmenopausal women with prior vertebral fractures to receive 20 or 40 µg of PTH (1-34) or placebo administered daily. They performed serial measurements of bone mass by dual-energy x-ray absorptiometry. They found new vertebral fractures in 14% of the placebo group compared to 5% in the treatment group. Compared with placebo, PTH increased bone mineral density by 9-13%. They conclude that treatment with PTH (1-34) decreases the risk of vertebral fractures and increases bone mineral density.

Deal wrote a review on the use of intermittent human PTH in the treatment of osteoporosis. He reports that biosynthetic human PTH (1-34) is also known as teriparatide. Its bioavailability is approximately 95% after subcutaneous administration and maximum serum levels are achieved after approximately 30 minutes. It is metabolized in the liver and kidney and no clinically important interactions with other drugs have been found. He reports that in a rat toxicology study in which PTH was administered in high doses of an extended period of time, osteosarcoma was seen. None of the patients in clinical trials have developed osteosarcoma, however.

Incorrect Answers:
Answer 1: A protein that is produced by osteocytes and is encoded by the SOST gene describes sclerostin. Sclerostin decreases bone mass by inhibiting the Wnt pathway.
Answer 3: A competitive partial agonist of the estrogen receptor describes raloxifene. Raloxifene slows bone resorption and is not anabolic.
Answer 4: A polypeptide hormone produced by parafollicular cells describes calcitonin. Calcitonin is produced by the thyroid and binds membrane receptors on osteoclasts to inhibit resorption. It is not anabolic.
Answer 5: A drug which contains a P-C-P backbone describes a bisphosphonate. Bisphosphonates inhibit osteoclast resorption and are not anabolic.