Antagonizing the parathyroid calcium receptor stimulates parathyroid hormone secretion and bone formation in osteopenic rats

Journal of Clinical Investigation

Volumn 105, Issue 11, 2000, Pages 1595-1604

  Gowen, Maxine ^a   Stroup, George B ^a   Dodds, Robert A ^a   James, Ian E ^a   Votta, Bart J ^a   Smith, Brian R ^a   Bhatnagar, Pradip K ^a   Lago, Amparo M ^a   Callahan, James F ^a   DelMar, Eric G ^b   Miller, Michael A ^b   Nemeth, Edward F ^b   Fox, John ^b  

^a GLAXOSMITHKLINE   (United Kingdom)

^b NPS Pharmaceutical Inc   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

PARATHYROID HORMONE RECEPTOR;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BONE MASS; BONE STRENGTH; BONE TURNOVER; CALCIUM METABOLISM; CELL STIMULATION; CONTROLLED STUDY; MOLECULAR CLONING; NONHUMAN; OSSIFICATION; OSTEOPENIA; PARATHYROID CELL; PARATHYROID HORMONE RELEASE; PRIORITY JOURNAL; RAT; SECONDARY HYPERPARATHYROIDISM;

EID: 0034123554     PISSN: 00219738     EISSN: None     Source Type: Journal    
DOI: 10.1172/JCI9038     Document Type: Article

References (53)

1. Melton, L.J. 1995. Epidemiology of fractures. In Osteoporosis: etiology, diagnosis and management. 2nd edition. B.L. Riggs and L.J. Melton, III. editors. Lippincott Williams & Wilkins Publishers. Philadelphia, Pennsylvania, USA. 225-2-47.
2. Ray, N.F., Chan, J.K., Thamer, M., and Melton, L.J., III. 1997. Medical expenditures for the treatment of osteoporotic fractures in the United States in 1995: report from the National Osteoporosis Foundation. J. Bone Miner. Res. 12:24-35.
3. Dempster, D.W., Cosman, F., Parisien, M., Shen, V., and Lindsay, R. 1993. Anabolic actions of parathyroid hormone on bone. Endocr. Rev. 14:690-709.
4. Reeve, J. 1996. PTH: a future role in the management of osteoporosis? J. Bone Miner. Res. 11:440-445.
5. Li, M., and Wronski, T.J. 1995. Response of femoral neck to estrogen depletion and parathyroid hormone in aged rats. Bone. 16:551-557.
6. Jerome, C.P. 1994. Anabolic effect of high doses of human parathyroid hormone (1-38) in mature intact female rats. J. Bone Miner. Res. 9:933-942.
7. Ejersted, C., Andreassen, T.T., Hauge, E.-M., Melsen, F., and Oxlund, H. 1995. Parathyroid hormone (1-34) increases vertebral bone mass, compressive strength. and quality in old rats. Bone. 17 507-511.
8. Slovik, D.M., et al. 1986. Restoration of spinal bone in osteoporotic men by treatment with human parathyroid hormone (1-34) and 1,25-dihydroxyvitamin D. J. Bone Miner Res. 1:377-381.
9. Kurland, E.S., et al. 1998. Parathyroid hormone (PTH 1-34) increases cancellous bone mass markedly in men with idiopathic osteoporosis. Bone. 23(Suppl.):S158. (Abstr.)
10. Lindsay, R., et al. 1997. Randomised controlled study of effect of parathyroid hormone on vertebral-bone mass and fracture incidence among postmenopausal women on oestrogen with osteoporosis. Lancet. 350:550-555.
11. Hodsman, A. B., et al. 1997. A randomized controlled trial to compare the efficacy of cyclical parathyroid hormone versus cyclical parathyroid hormone and sequential calcitonin to improve bone mass in postmenopausal women with osteoporosis. J. Clin. Endocrinol. Metab. 82:620-628.
12. Lane, N.E., et al. 1998. Parathyroid hormone treatment can reverse corticosteroid-induced osteoporosis. J. Clin. Invest. 102:1627-1633.
13. Roe, E.B., et al. 1999. Parathyroid hormone 1-34(hPTH 1-34) and estrogen produce dramatic bone density increases in postmenopausal osteoporosis. Results from a placebo-controlled randomized trial. J. Bone Miner. Res 14(Suppl. 1):S137. (Abstr.)
14. Nemeth, E.F. 1996. Calcium receptors as novel drug targets. In Principles of bone biology. J.P. Bilezekian, L.G. Raisz, and G. Rodan, editors. Academic Press, San Diego, California, USA, 1019-1035.
15. 2+-sensing receptor from bovine parathyroid. Nature. 366:575-580.
16. Garnett, J.E., et al. 1995. Molecular cloning and functional expression of human parathyroid calcium receptor cDNAs. J. Biol. Chem. 270:12919-12925.
17. Brown, E.M., Pollak, M., and Hebert, S.C. 1998. The extracellular calcium-sensing receptor: its role in health and disease. Annu. Rev. Med. 49:15-29.
18. Nemeth, E.F., and Fox, J. 1999. Calcimimetic compounds a direct approach to controlling plasma levels of parathyroid hormone in hyperparathyroidism. Trends Endocrinol Meteb. 10:66-71.
19. Nemeth, E.F., et al. 1998. Calcimimetics with potent and selective activity on the parathyroid calcium receptor. Proc. Natl. Acad. Sci. USA. 95:4040-4045.
20. Silverberg, S.J., et al. 1997. Short-term inhibition of parathyroid hormone secretion by a calcium-receptor agonist in patients with primary hyperparathyroidism. N. Engl. J. Med. 337:1506-1510.
21. Antonsen, J.E., Sherrard, D.J., and Andress, D. L. 1998. A calcimimetic agent acutely suppresses parathyroid hormone levels in patients with chronic renal failure. Kidney Int. 53:223-227.
22. Fox, J., Miller, M.A., Stroup, G.B., Nemeth, E.F., and Miller, S.C. 1997. Plasma levels of parathyroid hormone that induce anabolic effects in bone of ovariectomized rats can be achieved by stimulation of endogenous hormone secretion. Bone. 21:163-169.
23. Nemeth, E.F., et al. 1998. Stimulation of parathyroid hormone secretion by a small molecule antagonist of the calcium receptor. Bone. 23:(Suppl.) 156. (Abstr.)
24. 2+ sensing receptor: a versatile regulator of diverse cellular functions. Vitam. Horm. 55:1-71.
25. Villanueva, A.R. 1988. A new Goldner's one-step trichrome stain for identification of osteoid seams, bone and cells in undecalcified, plastic embedded sections of bone. Journal of Histotechnology. 11:249-251.
26. Parfitt, A.M., et al. 1987. Bone histomorphometry: standardization of nomenclature, symbols, and units. J. Bone Miner. Res. 2:595-610.
27. James, I.E., Dodds, R.A., Olivera, D.L., Nuttall, M.E., and Gowen, M. 1996. Human osteoclastoma-derived stromal cells: correlation of the ability to form mineralized nodules in vitro with formation of bone in vivo. J. Bone Miner. Res. 11:1453-1460.
28. Beresford, J.N., et al. 1984. The effects of monocyte-conditioned medium and interleukin 1 on the synthesis of collagenous and non-collagenous proteins by mouse bone and human bone cells in vitro. Biochim. Biophys. Acta. 801:58-65.
29. Gowen, M., MacDonald, B.R., and Russell, R.G. 1988. Actions of recombinant human λ-interferon and tumor necrosis factor α on the proliferation and osteoblastic characteristics of human trabecular bone cells in vitro. Arthritis Rheum. 31:1500-1507.
30. James, I. E., et al. 1999. Development and characterization of a human in vitro resorption assay: demonstration of utility using novel antiresorptive agents. J. Bone Miner. Res. 14:1562-1569.
31. Foged, N.T., et al. 1996. Quantification of the collagenolytic activity of isolated osteoclasts by enzyme-linked immunosorbent assay. J. Bone Miner. Res. 11:226-237
32. Votta, B.J., and Bertolini, D.R. 1994 Cytokine suppressive anti-inflammatory compounds inhibit bone resorption in vitro. Bone. 15:533-538.
33. Silverberg, S.J., et al. 1995. Increased bone mineral density after parathyroidectomy in primary hyperparathyroidism. J. Clin. Endocrinol. Metab. 80:729-734.
34. Miller, M.A., Chin, J., Miller, S.C., and Fox, J. 1998. Disparate effects of mild, moderate, and severe secondary hyperparathyroidism on cancellous and cortical bone in rats with chronic renal insufficiency. Bone. 23:257-266.
35. Dobnig, H., and Turner, R.T. 1997. The effects of programmed administration of human parathyroid hormone fragment (1-34) on bone histomorphometry and serum chemistry in rats. Endocrinology. 138:4607-4612.
36. Lindsay, R., Nieves, J., Henneman, E., Shen, V., and Cosman, F. 1993. Subcutaneous administration of the amino-terminal fragment of human parathyroid hormone-(1-34): kinetics and biochemical response in estrogen ized osteoporotic patients. J. Clin. Endocrinol. Metab. 77:1535-1539.
37. Ham, A.W., Littner, B.A., Drake, T.G.H., Robertson, E.C., and Tisdall, F.F. 1940. Physiological hypertrophy of the parathyroids, its cause and its relation to rickets. Am. J. Pathol. 16:277-286.
38. Naveh-Many, T., Rahamimov, R., Livni, N., and Silver, J. 1995. Parathyroid cell proliferation in normal and chronic renal failure rats. The effects of calcium, phosphate, and vitamin D. J. Clin. Invest. 96:1786-1793.
39. Wernerson, A., Widholm, S.M., Svensson, O., and Reinholt, F.P. 1991. Parathyroid cell number and size in hypocalcemic young rats. APMIS. 99:1096-1102.
40. Mosekilde, L., Sogaard, C.H., McOsker, J.E., and Wronski, T.J. 1994. PTH has a more pronounced effect on vertebral bone mass and biomechanical competence than antiresorptive agents (estrogen and bisphosphonate)-assessed in sexually mature, ovariectomized rats. Bone. 15:401-408.
41. Sogaard, C.H., Wronski, T.J., McOsker, J.E., and Mosekilde, L. 1994. The positive effect of parathyroid hormone on femoral neck bone strength in ovariectomized rats is more pronounced than that of estrogen or bis-phosphonates. Endocrinology. 134:650-657.
42. Li, M., Mosekilde, L., Sogaard, C.H., Thomsen, J.S., and Wronski, T.J. 1995. Parathyroid hormone monotherapy and cotherapy with antiresorptive agents restore vertebral bone mass and strength in aged ovariectomized rats. Bone. 16:629-635.
43. Baumann, B.D., and Wronski, T.J. 1995. Response of cortical bone to antiresorptive agents and parathyroid hormone in aged ovariectomized rats. Bone. 16:247-253.
44. Delmas, P.D., et al. 1995. The anabolic effect of human PTH (1-34) on bone formation is blunted when bone resorption is inhibited by tiludronate: is activated resorption a prerequisite for the in vivo effect of PTH on formation in a remodeling system? Bone. 16:603-610.
45. House, M.G., et al. 1997. Expression of an extracellular calcium-sensing receptor in human and mouse bone marrow cells. J. Bone Miner. Res. 12:1959-1970.
46. o)-sensing receptor in clonal osteoblast-like cell lines, UMR-106 and SAOS-2. Biochem. Biophys. Res. Commun. 243:753-757.
47. Quarles, L.D., Hartle, J.E., II, Siddhanti, S.R., Guo, R., and Hinson, T.K. 1997. A distinct cation-sensing mechanism in MC3T3-E1 osteoblasts functionally related to the calcium receptor. J. Bone Miner. Res. 12:393-402.
48. Zaidi, M., Adebanjo, O.A., Moonga, B.S., Sun, L., and Huang, C.L.-H. 1999. Emerging insights into the role of calcium ions in osteoclast regulation. J. Bone Miner. Res. 14:669-674.
49. Steffey, M.E., and Nemeth, E.F. 1993. Extracellular calcium-sensing receptors on osteoclasts and parathyroid cells are pharmacologically distinct. J. Bone Miner. Res. 8(Suppl. 1):S385. (Abstr.)
50. Pi, M., Hinson, T.K., and Quarles, L.D. 1999. Failure to detect the extracellular calcium-sensing receptor (CasR) in human osteoblast cell lines. J. Bone Miner. Res. 14:1310-1319.
51. Kenakin, T. 1995. Agonist-receptor efficacy I: mechanisms of efficacy and receptor promiscuity. Trends Pharmacol. Sci. 16:188-192.
52. Lavigne, J.R., et al. 1998. Stimulation of calcitonin secretion by calcium receptor activators: evaluation using a new, highly-sensitive, homologous immunoradiometric assay for rat calcitonin. Endocrine. 9:293-301.
53. 2+ receptor in rats. J. Pharmacol. Exp. Ther. 290:480-486.