A study is conducted to assess the effect of parathyroid hormone (PTH) on bone remodeling. Half of the study subjects receive intermittent PTH injections and the other half receive a continuous infusion of PTH. The results show that the effects on bone metabolism of intermittent PTH injections are different from those of continuous infusion. Which of the following is most likely to be the predominant bone effect with intermittent injections?

Question

A study is conducted to assess the effect of parathyroid hormone (PTH) on bone remodeling.  Half of the study subjects receive intermittent PTH injections and the other half receive a continuous infusion of PTH.  The results show that the effects on bone metabolism of intermittent PTH injections are different from those of continuous infusion.  Which of the following is most likely to be the predominant bone effect with intermittent injections?

Quizplus · Accepted Answer

Parathyroid hormone (PTH) is secreted in response to low circulating calcium levels. It has a very short half-life (<5 min) and is released in a combination continuous/tonic and pulsatile pattern (approximately two-thirds tonic secretion, one-third pulsatile). PTH supports plasma calcium levels by increasing intestinal calcium absorption, renal calcium reabsorption, and release of calcium from bone stores. Continuous high levels of PTH (ie, hyperparathyroidism) lead to excessive release of calcium from bones and increase the risk of osteoporosis. However, pulsatile PTH secretion has an anabolic effect on bone metabolism, stimulating osteoblast proliferation, decreasing osteoblast apoptosis, and inducing increased formation of new bone. Recombinant PTH analogues (eg, teriparatide) are used to treat severe osteoporosis; these analogues promote bone remodeling by inducing increased resorption of old bone while stimulating a corresponding increase in new bone production, resulting in a net increase in total bone mass (ie, positive bone balance). (Choice A) Matrix metalloproteinases (MMPs) are a family of enzymes involved in the turnover of connective tissue proteins in the extracellular matrix. Multiple MMPs are produced by osteoclasts and are involved in the breakdown of bone matrix. In general, intermittent PTH has more effect on bone formation, with minimal increase in osteoclast/MMP activity. (Choices B and C) High estrogen levels in premenopausal women delay the onset of osteoporosis by suppressing bone resorption. This effect is mediated largely by osteoprotegerin, which induces apoptosis of osteoclasts by acting as a decoy receptor to the receptor activator of nuclear factor kappa B (RANK)/RANK-ligand interaction. (Choice E) Binding of PTH to PTH receptor type 1 on osteoblasts increases (not suppresses) the expression of RANK-ligand, which subsequently interacts with RANK on osteoclast precursors to promote osteoclast differentiation and suppress osteoclast apoptosis. Educational objective: Parathyroid hormone (PTH) is released in a combination continuous/tonic and pulsatile pattern. Continuous high levels of PTH lead to excessive release of calcium from bones and increase the risk of osteoporosis; however, pulsatile secretion has an anabolic effect on bone metabolism, stimulating osteoblast proliferation and inducing increased formation of new bone. __________ References: Bone modeling and remodeling: potential as therapeutic targets for the treatment of osteoporosis. (http://www.ncbi.nlm.nih.gov/pubmed/28255336)

A Study Is Conducted to Assess the Effect of Parathyroid