Effect of parathyroid hormone

Hypocalcemia results from altered effects of parathyroid hormone and vitamin D on the bone, gut, and kidney. The primary causes are postoperative hypoparathyroidism and vitamin D deficiency. 

Black DM, Greenspan SL, Ensrud KE, Palermo L, McGowan JA, Lang TF, et al. (2003) The effects of parathyroid hormone and alendronate alone or in combination in postmenopausal osteoporosis. N Engl J Med 349 1207-1215... 

We have tested the hypothesis that insulin inhibits the stimulatory effect of parathyroid hormone (PTH) on calcium reabsorption in the distal nephron. PTH is known to enhance calcium transport in renal cells, probably by stimulation of adenylate cyclase and subsequent increases in 3 5 cyclic AMP productoin. Since insulin had been observed to inhibit PTH-stimulated increases in kidney cyclic AMP levels in vitro (24) we investigated whether insulin-mediated hypercalciuria was dependent on the presence of PTH in vivo. 

Neer RM et al. Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med 2001 344 1434-1441. 

Estrogens have a number of important metabolic and cardiovascular effects. They seem to be partially responsible for maintenance of the normal structure and function of the skin and blood vessels in women. Estrogens also decrease the rate of resorption of bone by promoting the apoptosis of osteoclasts and by antagonizing the osteoclastogenic and pro-osteoclastic effects of parathyroid hormone and interleukin-... 

Finkelstein JS et al The effects of parathyroid hormone, alendronate, or both in men with osteoporosis. N Engl J Med 2003 349 1216. [PMID 14500805]... 

Rodan, S. G., Rodan, G. A. The effect of parathyroid hormone and thyreocalcitonin on the accumulation of cyclic adenosine 3 ,5 -monophosphate in freshly isolated bone cells. J. Biol. Chem. 249, 3068 (1974)... 

Tolna, S. Effects of parathyroid hormone on bone acid hydrolases in tissue culture. Canad. J. Physiol. Pharmacol. 46, 261 (1968)... 

Reviews of parathyroid hormone have suggested that it is generally well tolerated (4,5,6). The adverse effects of parathyroid hormone that have been reported in clinical trials are mild and include transient bone pain, nausea, dizziness and local irritation at the injection site (7). Hypercalcemia, which is common, is usually mild and asymptomatic. Adverse effects, including hypercalcemia, appear to be dose related in the therapeutic range. 

The rate of osteosarcoma in animal and human trials of parathyroid hormone has been reviewed (20,6). Rats treated with parathyroid hormone for 2 years had a high dose-dependent rate of osteosarcoma, up to 48% in animals given 75 micrograms/kg human trials were therefore interrupted (21). However, the anabolic effect of parathyroid hormone is much greater and occurs much earlier in rats than in humans, possibly because of fundamental differences in bone biology moreover, osteosarcoma has never been associated with primary, secondary, or tertiary hyperparathyroidism in humans (20). There has been no evidence of osteosarcoma in several hundred patients involved in parathyroid hormone clinical trials lasting up to 3 years, after 5 years minimum follow-up (20). 

Alendronate significantly reduced the anabolic effect of parathyroid hormone when the two were used in combination, both in postmenopausal women (22) and in men (23). It seems likely that this interaction will also apply to other bisphosphonates, although the mechanism has not been determined. 

Neer RM, Arnaud CD, Zanchetta JR, Prince R, Gaich GA, Reginster JY, Hodsman AB, Eriksen EF, Ish-Shalom S, Genant HK, Wang O, Mitlak BH. Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med 2001 344(19) 1434-41. 

Lindsay R, Nieves J, Formica C, Henneman E, Woelfert L, Shen V, Dempster D, Cosman F. Randomised controlled study of effect of parathyroid hormone on vertebral-bone mass and fracture incidence among postmenopausal women on oestrogen with osteoporosis. Lancet 1997 350(9077) 550-5. 

Miyakoshi N. Effects of parathyroid hormone on cancellous bone mass and structure in osteoporosis. Curr Pharm Des. 2004 10 2615-2627. 

Osterloh JD (1991) Observations on the effect of parathyroid hormone on environmental blood lead concentrations in humans. Environ Res, 54 8 16. 

Know the effects of parathyroid hormone, calcitonin, and vitamin D in controlling calcium and phosphate metabolism. Know what controls the levels of such hormones in the bloodstream. 

Schaefer L, Malchow M, Schaefer RM et al. (1996) Effects of parathyroid hormone on renal tubular proteinases. Miner Electrolyte Metabol 22 182-186 Shimizu T, Hata S, Kuroda T et al. (1999) Different roles of two types of endothelin receptors in partial ablation-induced chronic renal failure in rats. Eur J Pharmacol 381 39-49 Stockelman MG, Lorenz JN, Smith FN et al. (1998) Chronic renal failure in a mouse model of human adenine phos-phoribosyltransferase deficiency. Am J Physiol 275 Renal Physiol 44 F154-F163... 

Sox4 a member of the SOX (SRY-related HMG-box) family of transcription factors involved in the regulation of embryonic development and in the determination of the cell fate. The encoded protein may act as a transcriptional regulator after forming a protein complex with other proteins, such as syndecan binding protein (syntenin). The protein may also function in the apoptosis pathway leading to cell death as well as to tumorigenesis and may mediate downstream effects of parathyroid hormone (PTH) and PTH-related protein (PTHrP) in bone development. 

Three effects of parathyroid hormone The presence of parathyroid hormone in the plasma is required for the maintenance of 1-hydroxylase activity in the kidney. The increase in PTH levels induces an increase in the activity of the hydroxylase, resulting in an increase in the production of l,25-(OH)D3 and an increase m the plasma levels of l,25-(OH)D3. In addition, PTH works in tandem with 1,25-(0H)2D3 in stimulating the osteoclasts to dissolve bones and in increasing the efficiency of calcium resorption by the kidneys. Both PTH and l,25-(OH)2D3 are required for these latter two effects. PTH is not required for the effect of the vitamin on the intestines. 

Effect of parathyroid hormone 1. increase bone resorption. 

Estrogen inhibits the bone-mobilizing effect of parathyroid hormone (PTH) by a direct effect on the osteoblasts (Chapter 37). 

Hypocalcemia is the result of alterations in the effect of parathyroid hormone and vitamin D on the bone, gut, and kidney (see Fig. 49-9). The primary causes of hypocalcemia are postoperative hypoparathyroidism and vitamin D deficiency. Other causes include magnesium deficiency, thyroid surgery, medications, hypoalbuminemia, blood transfusions, peripheral blood progenitor cell harvesting, tumor lysis syndrome, and mutations in the calcium-sensing receptor. " Parathyroid hormone concentrations are elevated in conditions of hypocalcemia, with the exception of hypoparathyroidism and hypomagnesemia (Fig. 49-11). ... 

Adverse effects of oral calcium and vitamin D supplementation include hypercalcemia and hypercalciuria, especially in the hy-poparathyroid patient, in whom the renal calcium-sparing effect of parathyroid hormone is absent. Hypercalciuria may increase the risk of calcium stone formation and nephrolithiasis in susceptible patients. One maneuver to help prevent calcium stones is to maintain the calcinm at a low normal concentration. Monitoring 24-hour urine collections for total calcium concentrations (goal <300 mg/24 h) may also minimize the occurrence of hypercalciuria. The addition of thiazide dinretics for patients at risk for stone formation may result in a reduc-tionof both urinary calcium excretion and vitamin D requirements." ... 

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