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Targeting the Osteoblast for Prevention and Treatment of Bone Diseases

  • Chapter
Bone Formation

Part of the book series: Topics in Bone Biology ((TBB,volume 1))

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Abstract

The central role the osteoblast plays in bone formation, and particularly in bone formation/ resorption coupling, provides a rationale for modulation of osteoblast differentiation and function and constitutes a viable approach for prevention and treatment of a variety of bone diseases. Osteoblastic cells are endowed with a multitude of plasma membrane and nuclear receptors so that they are prime targets for the bone actions of calcium-regulating hormones, such as parathyroid hormone (PTH) [119] and 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3), of steroid and thyroid hormones (e.g. [52]), growth factors and cytokines [60], or of such diverse local mediators as prostaglandins (PG) [115] or extracellular calcium [138]. They do not, however, possess receptors for calcitonin. In addition, the beneficial effects on bone health of some xenobiotics like fluoride or bisphosphonates are mediated at least in part through the osteoblast. The positive effect of physical activity on bone formation is also transduced through modulation of osteoblast functions.

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References

  1. Adinoff AD, Hollister JR (1983) Steroid-induced fractures and bone loss in patients with asthma. N Engl J Med 309: 265–8.

    PubMed  CAS  Google Scholar 

  2. Anderson FH, Francis RM, Peaston RT, Waste11 HJ (1997) Androgen supplementation in eugonadal men with osteoporosis: effects of six months’ treatment on markers of bone formation and resorption. J Bone Miner Res 12: 472–8.

    PubMed  CAS  Google Scholar 

  3. Arts J, Kuiper GG, Janssen JM, Gustafsson JA, Löwik CW, Pols HA, et al. (1997) Differential expression of estrogen receptors alpha and beta mRNA during differentiation of human osteoblast SV-HFO cells. Endocrinology 138: 5067–70.

    PubMed  CAS  Google Scholar 

  4. Aukee S, Alhava EM, Karjalainen P (1975) Bone mineral after partial gastrectomy II. Scand J Gastroenterol 10: 165–9.

    PubMed  CAS  Google Scholar 

  5. Barden HS, Mazess RB, Chesney RW, Rose PG, Chun R (1982) Bone status of children receiving anticonvulsant therapy. Metab Bone Dis Relat Res 4: 43–7.

    PubMed  CAS  Google Scholar 

  6. Barrett-Connor E (1989) The RDA for calcium in the elderly: too little, too late. Calcif Tissue Int 44: 303–7.

    PubMed  CAS  Google Scholar 

  7. Basso N, Heersche JNM (2002) Characteristics of in vitro osteoblastic cell loading models. Bone 30: 347–51.

    PubMed  CAS  Google Scholar 

  8. Bauer W, Aub JC, Albright F (1929) Studies of calcium and phosphorus metabolism. V. Study on the bone trabeculae as a readily available reserve supply of calcium. J Exp Med 49: 145–62.

    Google Scholar 

  9. Bekker PJ, Holloway D, Nakanishi A, Arrighi M, Leese PT, Dunstan CR (2001) The effect of a single dose of osteoprotegerin in postmenopausal women. J Bone Miner Res 16: 348–60.

    PubMed  CAS  Google Scholar 

  10. Bellido T, Jilka RL, Boyce BF, Girasole G, Broxmeyer H, Dalrymple SA, et al. (1995) Regulation of interleukin-6, osteoclastogenesis, and bone mass by androgens. The role of the androgen receptor. J Clin Invest 95: 886–2895.

    Google Scholar 

  11. Bellows CG, Aubin JE, Heersche JNM (1988) Fluoride stimulates expression of osteoprogenitors in fetal rat calvaria cells in vitro. J Bone Miner Res 3 (Suppl): 425.

    Google Scholar 

  12. Benford HL, Frith JC, Auriola S, Mönkkönen J, Rogers MJ (1999) Farnesol and geranylgeraniol prevent activation of caspases by aminobisphosphonates: biochemical evidence for two distinct pharmacological classes of bisphosphonate drugs. Mol Pharmacol 56: 131–40.

    PubMed  CAS  Google Scholar 

  13. Bex M, Abs R, Maiter D, Beckers A, Lamberigts G, Bouillon R (2002) The effects of growth hormone replacement therapy on bone metabolism in adult-onset growth hormone deficiency: a 2-year open randomized controlled multicenter trial. J Bone Miner Res 17: 1081–94.

    PubMed  CAS  Google Scholar 

  14. Bord S, Beavan S, Ireland D, Horner A, Compston JE (2001) Mechanisms by which high-dose estrogen therapy produces anabolic skeletal effects in postmenopausal women: role of locally produced growth factors. Bone 29: 216–22.

    PubMed  CAS  Google Scholar 

  15. Bourdel A, Mahoudeau JA, Guadyier-Souquières G, Leymarie P, Sabatier JP. Loyau G (1989) Étude de la fonction gonadique au cours de l’ostéoporose masculine en apparence primitive. Presse Medicale 34:1691–4.

    Google Scholar 

  16. Braidman IP, Hainey L, Batra G, Selby PL, Saunders PT, Hoyland JA (2001) Localization of estrogen receptor beta protein expression in adult human bone. J Bone Miner Res 16: 214–20.

    PubMed  CAS  Google Scholar 

  17. Breuil V, Cosman F, Stein L, Horbert W, Nieves J, Shen V, et al. (1998) Human osteoclast formation and activity in vitro: effects of alendronate. J Bone Miner Res 13: 1721–9.

    PubMed  CAS  Google Scholar 

  18. Bronner F (1994) Calcium and osteoporosis. Am J Clin Nutr 60: 831–6.

    PubMed  CAS  Google Scholar 

  19. Brosch S, Gruber R, Schuster L, Pietschmann P, Peterlik M (2000) Regulation of the generation of osteoclasts from precursor cells by steroid hormones in vitro. Bone 27: 741.

    Google Scholar 

  20. Burr DB, Robling AG, Turner CH (2002) Effects of bio-mechanical stress on bones in animals. Bone 30: 781–6.

    PubMed  Google Scholar 

  21. Canalis E (1984) Effect of cortisol on periosteal and nonperiosteal collagen and DNA synthesis in cultured rat calvariae. Calcif Tissue Int 36: 158–66.

    PubMed  CAS  Google Scholar 

  22. Caniggia A, Nuti R, Lorè F, Vattimo A (1981) Pathophysiology of the adverse effects of glucoactive corticosteroids on calcium metabolism in man. J Steroid Biochem 15: 153–61.

    PubMed  CAS  Google Scholar 

  23. Caplan AI, Elyaderani M, Mochizuki Y, Wakitani S, Goldberg VM (1997) Principles of cartilage repair and regeneration. Clin Orthop 342: 254–69.

    PubMed  Google Scholar 

  24. Caverzasio J, Palmer G, Bonjour JP (1998) Fluoride: mode of action. Bone 22: 585–9.

    PubMed  CAS  Google Scholar 

  25. Chapuy MC, Arlot ME, Duboeuf F, Brun J, Crouzet B, Arnaud S, et al. (1992) Vitamin D and calcium to prevent hip fractures in elderly women. N Engl J Med 327: 1637–42.

    PubMed  CAS  Google Scholar 

  26. Cheng MZ, Rawlinson SCF, Pitisillides AA, Zaman G, Mohan S, Baylink DJ, et al. (2002) Human osteoblasts’ proliferative responses to strain and 173-estradiol are mediated by the estrogen receptor and the receptor for insulin-like growth factor I. J Bone Miner Res 17: 593–602.

    PubMed  CAS  Google Scholar 

  27. Cosman F, Nieves J, Horton J, Shen V, Lindsay R (1994) Effects of estrogen on response to edetic acid infusion in postmenopausal osteoporotic women. J Clin Endocrinol Metab 78: 939–43.

    PubMed  CAS  Google Scholar 

  28. Coxon FP, Helfrich MH, van’t Hof R, Sebti S, Ralston SH, Hamilton A, et al. (2000) Protein geranylation is required for osteoclast formation, function, and survival: inhibition by bisphosphonates and GGTI-298. J Bone Miner Res 15: 1467–76.

    PubMed  CAS  Google Scholar 

  29. Crilly RG, Horsman A, Marshall DH, Nordin BE (1977) Post-menopausal and corticosteroid-induced osteoporosis. Front Horm Res 5: 53–75.

    PubMed  CAS  Google Scholar 

  30. Cumming RG, Nevitt MC (1997) Calcium for prevention of osteoporotic fractures in postmenopausal women. J Bone Miner Res 12: 1321–9.

    PubMed  CAS  Google Scholar 

  31. Cummings SR, Black DM, Thompson DE, Applegate WB, Barrett-Connor E, Musliner TA, et al. (1998) Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures. JAMA 280: 2077–82.

    PubMed  CAS  Google Scholar 

  32. Daniel M, Martin AD, Drinkwater DT (1992) Cigarette smoking, steroid hormones, and bone mineral density in young women. Calcif Tissue Int 50: 300–5.

    PubMed  CAS  Google Scholar 

  33. Dawson-Hughes B (1991) Calcium supplementation and bone loss: a review of controlled clinical trials. Am J Clin Nutr 54: 274–80.

    Google Scholar 

  34. Degerblad M, Elgindy N, Hall K, Sjoberg HE, Thoren M (1992) Potent effect of recombinant growth hormone on bone mineral density and body composition in adults with panhypopituitarism. Acta Endocrinol 126: 387–93.

    PubMed  CAS  Google Scholar 

  35. Delmas PD, Bjarnason NH, Mitlak BH, Ravoux AC, Shah AS, Huster WJ, et al. (1997) Effects of raloxifene on bone mineral density, serum cholesterol concentrations, and uterine endometrium in postmenopausal women. N Engl J Med 337: 1641–7.

    PubMed  CAS  Google Scholar 

  36. Dempster DW, Cosman F, Kurland ES, Zhou H, Nieves J, Woelfert L, et al. (2001) Effects of daily treatment with parathyroid hormone on bone microarchitecture and turnover in patients with osteoporosis: a paired biopsy study. J Bone Miner Res 16: 1846–53.

    PubMed  CAS  Google Scholar 

  37. Dobnig H, Turner RT (1995) Evidence that intermittent treatment with parathyroid hormone increases bone formation in adult rats by activation of bone lining cells. Endocrinology 136: 3632–8.

    PubMed  CAS  Google Scholar 

  38. Elders PJ, Lips P, Netelenbos JC, van-Ginkel FC, Khoe E, van-der-Vijgh WJ, et al (1994) Long-term effect of calcium supplementation on bone loss in peri-menopausal women. J Bone Miner Res 9: 963–70.

    PubMed  CAS  Google Scholar 

  39. Eriksen EF, Mosekilde L, Melsen F (1985) Trabecular bone remodeling and bone balance in hyperthyroidism. Bone 6: 421–8.

    PubMed  CAS  Google Scholar 

  40. Eriksen EF, Colvard DS, Berg NJ, Graham ML, Mann KG, Spelsberg TC, et al. (1988) Evidence of estrogen receptors in normal human osteoblast-like cells. Science 241: 84–6.

    PubMed  CAS  Google Scholar 

  41. Erlebacher A, Filvaroff EH, Gitelman SE, Derynck R (1995) Toward a molecular understanding of skeletal development. Cell 80: 371–8.

    PubMed  CAS  Google Scholar 

  42. Ernst M, Schmid C, Froesch ER (1988) Enhanced osteoblast proliferation and collagen gene expression by estradiol. Proc Natl Acad Sci 85: 2307–10.

    PubMed  CAS  Google Scholar 

  43. Ettinger B, Black DM, Mitlak BH, Knickerbocker RK, Nickelsen T, Genant HK, et al. (1999) Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation ( MORE ). JAMA 282: 637–45.

    Google Scholar 

  44. Farley JR, Wergedal JE, Baylink DJ (1983) Fluoride directly stimulates proliferation and alkaline phosphatase activity of bone-forming cells. Science 222: 330–2.

    PubMed  CAS  Google Scholar 

  45. Finkelstein JS, Klibanski A, Neer RM, Greenspan SL, Rosenthal DI, Crowley WF (1987) Osteoporosis in men with idiopathic hypogonadotropic hypogonadism. Ann Intern Med 106: 354–61.

    PubMed  CAS  Google Scholar 

  46. Flanagan B, Nichols G (1964) Metabolic studies of human bone in vitro. II. Changes in hyperparathyroidism. J Clin Invest 44: 1795–801.

    Google Scholar 

  47. Fucik RF, Kukreja SC, Hargis GK, Bowser EN, Henderson WJ, Williams GA (1975) Effect of glucocorticoids on function of the parathyroid glands in man. J Clin Endocrinol Metab 40: 152–5.

    PubMed  CAS  Google Scholar 

  48. Gennari C, Agnusdei D, Nardi P, Civitelli R (1990) Estrogen preserves a normal intestinal responsiveness to 1,25-dihydroxyvitamin D3 in oophorectomized women. J Clin Endocrinol Metab 71: 1288–93.

    PubMed  CAS  Google Scholar 

  49. Gillberg P, Johansson AG, Ljunghall S (1999) Decreased estradiol levels and free androgen index and elevated sex hormone-binding globulin levels in male idiopathic osteoporosis. Calcif Tissue Int 64: 209–13.

    PubMed  CAS  Google Scholar 

  50. Glantschnig H, Varga F, Rumpler M, Klaushofer K (1996) Prostacyclin (PGI2): a potential mediator of c-fos expression induced by hydrostatic pressure in osteoblastic cells. Eur J Clin Invest 26: 544–8.

    PubMed  CAS  Google Scholar 

  51. Greendale GA, Edelstein S, Barrett-Connor E (1997) Endogenous sex steroids and bone mineral density in older women and men: the Rancho Bernardo Study. J Bone Miner Res 12: 1833–43.

    PubMed  CAS  Google Scholar 

  52. Gruber R, Czerwenka K, Wolf F, Ho GM, Willheim M, Peterlik M (1999) Expression of the vitamin D receptor, of estrogen and thyroid hormone receptor a-and (3-isoforms, and of the androgen receptor in cultures of native mouse bone marrow and of stromal/osteoblastic cells. Bone 24: 465–73.

    PubMed  CAS  Google Scholar 

  53. Gruber R, Nothegger G, Ho GM, Willheim M, Peterlik M (2000) Differential stimulation by PGE2 and calcemic hormones of IL-6 in stromal/osteoblastic cells. Biochem Biophys Res Comm 270: 1080–5.

    PubMed  CAS  Google Scholar 

  54. Harris SA, Tau KR, Turner RT, Spelsberg TC (1996) Estrogens and progestins. In: Bilezikian JP, Raisz LG, Rodan GA (eds) Principles of Bone Biology. Academic Press, San Diego, pp 507–20.

    Google Scholar 

  55. Heaney RP, Gallagher JC, Johnston CC, Neer R, Parfitt AM, Chir B, et al. (1982) Calcium nutrition and bone health in the elderly. Am J Clin Nutr 36: 986–1013.

    PubMed  CAS  Google Scholar 

  56. Hesch RD, Brabant G, Rittinghaus EF, Atkinson MJ, Harms H (1988) Pulsatile secretion of parathyroid hormone and its action on a type I and type II PTH receptor: a hypothesis for understanding osteoporosis. Calcif Tissue Int 42: 341–4.

    PubMed  CAS  Google Scholar 

  57. Hesch RD, Busch U, Prokop M, Delling G, Rittinghaus EF (1989) Increase of vertebral density by combination therapy with pulsatile 1–38hPTH and sequential addition of calcitonin nasal spray in osteoporotic patients. Calcif Tissue Int 44: 176–80.

    PubMed  CAS  Google Scholar 

  58. Hofbauer LC, Khosla S, Dunstan CR, Lacey DL, Spelsberg TC, Riggs BL (1999) Estrogen stimulates gene expression and protein production of osteoprotegerin in human osteoblastic cells. Endocrinology 140: 4367–70.

    PubMed  CAS  Google Scholar 

  59. Hofbauer LC, Khosla S, Dunstan CR, Lacey DL, Boyle WJ, Riggs BL (2000) The roles of osteoprotegerin and osteoprotegerin ligand in the paracrine regulation of bone resorption. J Bone Miner Res 15: 2–12.

    PubMed  CAS  Google Scholar 

  60. Horowitz MC, Lorenzo JA (2002) In: Bilezikian JP. In: Raisz LG, Rodan GA (eds) Principles of Bone Biology. Academic Press, New York, pp 961–77.

    Google Scholar 

  61. Howard GA, Bottemiller BL, Turner RT, Rader JI, Baylink DJ (1981) Parathyroid hormone stimulates bone formation and resorption in organ culture: Evidence for a coupling mechanism. Proc Natl Acad Sci 78: 23204–8.

    Google Scholar 

  62. Hruska KA (1997) Renal osteodystrophy. Bailliere’s Clin Endocrinol Metab 11: 165–94.

    PubMed  CAS  Google Scholar 

  63. Hughes DE, Dai A, Tiffee JC, Li HH, Mundy GR, Boyce BF (1996) Estrogen promotes apoptosis of murine osteoclasts mediated by TGF-ß. Nat Med 2: 1132–6.

    PubMed  CAS  Google Scholar 

  64. Jassal SK, Barrett-Connor E, Edelstein SL (1995) Low bioavailable testosterone levels predict future height loss in postmenopausal women. J Bone Miner Res 10: 650–4.

    PubMed  CAS  Google Scholar 

  65. Jagger CJ, Chow JWM, Chambers TJ (1996) Estrogen suppresses activation but enhances formation of osteogenic response to mechanical stimulation in rat bone. J Clin Invest 98: 2351–7.

    PubMed  CAS  Google Scholar 

  66. Kalu DN, Doyle FH, Pennock J, Foster GV (1970) Parathyroid hormone and experimental osteosclerosis. Lancet 1363–6

    Google Scholar 

  67. Kanatani M, Sugimoto T, Fukase M, Fujita T (1991) Effect of elevated extracellular calcium on the proliferation of osteoblastic MC3T3-E 1 cells: its direct and indirect effects via monocytes. Biochem Biophys Res Commun 181: 1425–30.

    PubMed  CAS  Google Scholar 

  68. Karsenty G (1999) The genetic transformation of bone biology. Genes Dev 13: 3037–51.

    PubMed  CAS  Google Scholar 

  69. Kasperk CH, Wakley GK, Hierl T, Ziegler R (1997) Gonadal and adrenal androgens are potent regulators of human bone cell metabolism in vitro. J Bone Miner Res 12: 464–71.

    PubMed  CAS  Google Scholar 

  70. Kassem M, Okazaki R, DeLeon D, Harris SA, Robinson JA, Spelsberg TC, et al. (1996) Potential mechanism of estrogen-mediated decrease in bone formation: estrogen increases production of inhibitory insulin-like growth factor-binding protein-4. Proc Assoc Am Phys 108: 155–64.

    PubMed  CAS  Google Scholar 

  71. Katzenellenbogen BS, Montano MM, Ediger TR, Sun J, Ekena K, Lazennec G, et al. (2000) Estrogen receptors: selective ligands, partners, and distinctive pharmacology. Rec Progr Horm Res 55: 163–94.

    PubMed  CAS  Google Scholar 

  72. Khosla S, Melton LJ III, Atkinson EJ, O’Fallon WM, Klee GG, Riggs B (1998) Relationship of serum sex steroid levels and bone turnover markers with bone mineral

    Google Scholar 

  73. density in men and women: a key role for bioavailable estrogen. J Clin Endocrinol Metab 83:2266–2274.

    Google Scholar 

  74. Kim YH, Kim GS, Jeong-Hwa B (2002) Inhibitory action of bisphosphonates on bone resorption does not involve the regulation of RANKL and OPG expression. Exp Mol Med 34: 145–51.

    PubMed  CAS  Google Scholar 

  75. Klaushofer K, Varga F, Glantschnig H, Fratzl-Zelman N, Czerwenka E, Leis HJ, et al. (1995) The regulatory role of thyroid hormones in bone cell growth and differentiation. J Nutr 125: 1996–2003.

    Google Scholar 

  76. Klein-Nulend J, van der Plas A, Semeins CM, Ajubi NE, Frangos JA, Nijweide PT, et al. (1995) Sensitivity of osteocytes to biomechanical stress in vitro. FASEB J 9: 441–5.

    PubMed  CAS  Google Scholar 

  77. Komm BS, Terpening CM, Benz DJ, Graeme KA, Gallegos A, Korc M, et al. (1988) Estrogen binding, receptor mRNA, and biologic response in osteoblastlike osteosarcoma cells. Science 241: 81–4.

    PubMed  CAS  Google Scholar 

  78. Kuiper GGJM, Enmark E, Pelto-Huikko M, Nilsson S, Gustafsson JA (1996) Cloning of a novel receptor expressed in rat prostate and ovary. Proc Natl Acad Sci 93: 5925–30.

    PubMed  CAS  Google Scholar 

  79. Kuiper GGJM, Lemmen JG, Carlsson B, Corton JC, Safe SH, van der Saag PT, et al. (1998) Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor P. Endocrinology 139: 4252–63.

    PubMed  CAS  Google Scholar 

  80. Latennec G, Bresson D, Lucas A, Chauveau C, Vignon F (2001) ERI3 inhibits proliferation and invasion of breast cancer cells. Endocrinology 142: 4120–30.

    Google Scholar 

  81. Lau KH, Farley JR, Freeman TK, Baylink DJ (1989) A proposed mechanism of the mitogenic action of fluoride on bone cells: inhibition of the activity of an osteoblastic acid phosphatase. Metabolism 38: 858–68.

    PubMed  CAS  Google Scholar 

  82. Leis HJ, Zach D, Huber E, Ziermann L, Gleispach H, Windischhofer W (1994) Extracellular Cat+ sensing by the osteoblast-like cell line, MC3T3-El. Cell Calcium 15: 447–56.

    PubMed  CAS  Google Scholar 

  83. Liberman UA, Weiss SR, Bröll J, Minne HW, Quan H, Bell NH, et al. (1995) Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. N Engl J Med 333: 1437.

    PubMed  CAS  Google Scholar 

  84. Lin SC, Yamate T, Taguchi Y, Borba VZ, Girasole G, O’Brien CA, et al. (1997) Regulation of the gp80 and gp130 subunits of the IL-6 receptor by sex steroids in the murine bone marrow. J Clin Invest 100: 1980–90.

    PubMed  CAS  Google Scholar 

  85. Lukert BP, Carey M, McCarty B, Tiemann S, Goodnight L, Helm M, et al. (1987) Influence of nutritional factors on calcium-regulating hormones and bone loss. Calcif Tissue Int 40: 119–25.

    PubMed  CAS  Google Scholar 

  86. Maggiolini M, Bonofoglio D, Marsico D, Panno ML, Cenni B, Picard D, et al. (2001) Estrogen receptor a mediates the proliferative but not the cytotoxic dose-dependent effects of two major phytoestrogens on human breast cancer cells. Mol Pharmacol 60: 595–602.

    PubMed  CAS  Google Scholar 

  87. Manolagas SC, Jilka RL (1995) Bone marrow, cytokines, and bone remodeling. Emerging insights into the pathophysiology of osteoporosis. N Engl J Med 332: 305–11.

    Google Scholar 

  88. Manolagas SC (1999) Cell number versus cell vigor–what really matters to a regenerating skeleton? Endocrinology 140: 4377–81.

    PubMed  CAS  Google Scholar 

  89. Manolagas SC (2000) Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis. Endocr Rev 21: 115–37.

    PubMed  CAS  Google Scholar 

  90. McKane WR, Khosla S, Burritt MF, Kao PC, Wilson DM, Ory SJ, et al. (1995) Mechanism of renal conservation with estrogen replacement therapy in women in early

    Google Scholar 

  91. postmenopause - a clinical research center study. J Clin Endocrinol Metab 80:3458–64.

    Google Scholar 

  92. Murphy S, Khaw K, Cassidy A, Compston JE (1993) Sex hormones and bone mineral density in elderly men. Bone Miner 20: 133–40.

    PubMed  CAS  Google Scholar 

  93. Neer RM, Arnaud CD, Zanchetta JR, Prince R, Gaich GA, Reginster JY, et al. (2001) Effect of parathyroid hormone (1–34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med 344: 1434–41.

    PubMed  CAS  Google Scholar 

  94. Nishikawa M, Yamamoto M, Murakami T, Akatsu T, Kugai N, Nagata N (1998) A third-generation bisphosphonate, YM175, inhibits osteoclast formation in murine cocultures by inhibiting proliferation of precursor cells via supporting cell-dependent mechanisms. J Bone Miner Res 13: 986–95.

    PubMed  CAS  Google Scholar 

  95. Nordin BEC, Need AG, Morris HA, Horowitz M, Robertson WG (1991) Evidence for a renal calcium leak in postmenopausal women. J Clin Endocrinol Metab 72: 401–7.

    PubMed  CAS  Google Scholar 

  96. Owen TA, Aronow MS, Barone LM, Bettencourt B, Stein GS, Lian JB (1991) Pleiotropic effects of vitamin D on osteoblast gene expression are related to the proliferative and differentiated state of the bone cell phenotype: dependency upon basal levels of gene expression, duration of exposure, and bone matrix competency in normal rat osteoblast cultures. Endocrinology 128: 1496–504.

    PubMed  CAS  Google Scholar 

  97. Paech K, Webb P, Kuiper GGJM, Nilsson S, Gustafsson JA, Kushner PJ, et al. (1997) Differential ligand activation of estrogen receptors ERa and ER(3 at AP1 sites. Science 277: 1508–10.

    PubMed  CAS  Google Scholar 

  98. Pak CY, Zerwekh JE, Antich P (1995) Anabolic effects of fluoride on bone. Trends Endocrinol Metab 6: 229–34.

    PubMed  CAS  Google Scholar 

  99. Pak CY, Sakhaee K, Adams-Huet B, Piziak V, Peterson RD, Poindexter JR (1995) Treatment of postmenopausal osteoporosis with slow-release sodium fluoride. Final report of a randomized controlled trial, Ann Intern Med 123: 401–408.

    Google Scholar 

  100. Parfitt AM (2000) The mechanism of coupling: a role for vasculature. Bone 26: 319–23.

    PubMed  CAS  Google Scholar 

  101. Pietschmann P, Kudlacek S, Grisar J, Spitzauer S, Woloszczuk W, Willvonseder R, et al. (2001) Bone turnover markers and sex hormones in men with idiopathic osteoporosis. Eur J Clin Invest 31: 444–51.

    PubMed  CAS  Google Scholar 

  102. Pike AC, Brzozowski AM, Hubbard RE (2000) A structural biologist’s view of the oestrogen receptor. J Steroid Biochem Mol Biol 74: 261–8.

    PubMed  CAS  Google Scholar 

  103. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, et al. (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284: 143–7.

    PubMed  CAS  Google Scholar 

  104. Praet JP, Peretz A, Rozenberg S, Famaey JP, Bourdoux P (1992) Risk of osteoporosis in men with chronic bronchitis. Osteoporos Int 2: 257–61.

    PubMed  CAS  Google Scholar 

  105. Quarles LD, Hartle JEII, Siddhanti SR, Guo R, Hinson TK (1997) A distinct cation-sensing mechanism in MC3T3–E1 osteoblasts functionally related to the calcium receptor. J Bone Miner Res 12: 393–402.

    PubMed  CAS  Google Scholar 

  106. Recker R, Hinders S, Davies KM, Heaney RP, Stegmar MR, Lappe JM, et al. (1996) Correcting calcium nutritional deficiency prevents spine fractures in elderly women. J Bone Miner Res 11: 1961–6.

    PubMed  CAS  Google Scholar 

  107. Reed BY, Zerwekh JE, Antich PP, Pak CY (1993) Fluoride-stimulated [3H]thymidine uptake in a human osteoblastic osteosarcoma cell line is dependent on transforming growth factor beta. J Bone Miner Res 8: 19–25.

    PubMed  CAS  Google Scholar 

  108. Reginster JY, Meurmans L, Zegels B, Rovati LC, Minne HW, Giacovelli G, et al. (1998) The effect of sodium monofluorophosphate plus calcium on vertebral fracture rate in postmenopausal women with moderate osteoporosis. A randomized, controlled trial. Ann Intern Med 129: 1–8.

    Google Scholar 

  109. Resch H, Pietschmann P, Bernecker P (1992) The influence of partial gastrectomy ( Billroth II) on biochemical parameters of bone metabolism and bone density. Clin Invest 70: 426–9.

    Google Scholar 

  110. Riggs BL, Spelsberg TC (1993) Estrogen action on bone cells: the osteoblasts. In: Christiansen C, Riis B (eds) Proceedings of the Fourth International Symposium on Osteoporosis and Consensus Development Conference. Hong Kong, pp 386–8.

    Google Scholar 

  111. Riggs BL, Spelsberg TC (1996) Mechanism of estrogen action on bone cells. In: Papapoulos SE, Lips P, Pols HAP, Johnston CC, Delmas PD (eds) Osteoporosis 1996. Elsevier, Amsterdam, pp 241–50.

    Google Scholar 

  112. Riggs BL, Khosla S, Melton LJ III (1998) A unitary model for involutional osteoporosis: estrogen deficiency causes both type I and type II osteoporosis in postmenopausal women and contributes to bone loss in aging men. J Bone Miner Res 13: 763–73.

    PubMed  CAS  Google Scholar 

  113. Ringe JD, Dorst A, Kipshoven C, Rovati LC, Setnikar I (1998) Avoidance of vertebral fractures in men with idiopathic osteoporosis by a three year therapy with calcium and low-dose intermittent monofluorophosphate. Osteoporos Int 8: 47–52.

    PubMed  CAS  Google Scholar 

  114. Roelofsen J, Klein-Nulend J, Burger E (1995) Mechanical stimulation by intermittent hydrostatic compression promotes bone-specific gene expression in vitro. J Biomech 28: 1493–503.

    PubMed  CAS  Google Scholar 

  115. Ruedin P, Rizzoli R, Slosman D, Leski M, Bonjour JP (1994) Effects of oral calcitriol on bone mineral density in patients with end-stage renal failure. Kidney Int 45: 245–52.

    PubMed  CAS  Google Scholar 

  116. Sahni M, Guenther HL, Fleisch H, Collin P, Martin TJ (1993) Bisphosphonates act on bone resorption through the mediation of osteoblasts. J Clin Invest 91: 2004–11.

    PubMed  CAS  Google Scholar 

  117. Sarrazin P, Bkaily G, Hache R, Patry C, Dumais R, Rocha FA, et al. (2001) Characterization of the prostaglandin receptors in human osteoblasts in culture. Prostaglandins Leukot Essent Fatty Acids 64: 203–10.

    PubMed  CAS  Google Scholar 

  118. Schiller C, Gruber R, Redlich K, Ho GM, Katzgraber F, Willheim W, et al. (1997) 1713-estradiol antagonizes Effects of la,25-dihydroxyvitamin D3 on interleukin-6 production and osteoclast-like cell formation in mouse bone marrow primary cultures. Endocrinology 138: 4567–71.

    Google Scholar 

  119. Schiller C, Gruber R, Ho GM, Redlich K, Gober H-J, Katzgraber F, et al. (1998) Interaction of triiodothyronine with la,25-dihydroxyvitamin D3 on interleukin-6dependent osteoclast-like cell formation in mouse bone marrow cell cultures. Bone 22: 341–6.

    PubMed  CAS  Google Scholar 

  120. Schmidt IU, Dobnig H, Turner RT (1995) Intermittent parathyroid hormone treatment increases osteoblast number, steady state messenger ribonucleic acid levels for osteocalcin, and bone formation in tibial metaphysis of hypophysectomized female rats. Endocrinology 136: 5127–34.

    PubMed  CAS  Google Scholar 

  121. Segre GV (1996) Receptors for parathyroid hormone and parathyroid hormone-related protein. In: Bilezikian JP, Raisz LG, Rodan GA (eds) Principles of Bone Biology. Academic Press, San Diego, pp 347–62.

    Google Scholar 

  122. Sims NA, Dupont S, Krust A, Clement-Lacroix P, Minet D, Resche-Rigon M, et al. (2002) Deletion of estrogen receptors reveals a regulatory role for estrogen receptor-3 in bone remodeling in females but not in males. Bone 30: 18–25.

    PubMed  CAS  Google Scholar 

  123. Slemenda CW, Longcope C, Zhou L, Hui SL, Peacock M, Johnston CC (1997) Sex steroids and bone mass in older men. J Clin Invest 100: 1755–1759.

    PubMed  CAS  Google Scholar 

  124. Spencer H, Kramer L (1986) Factors contributing to osteoporosis. J Nutr 116: 316–9.

    PubMed  CAS  Google Scholar 

  125. Stein GS, Lian JB, Owen TA (1990) Relationship of cell growth to the regulation of tissue-specific gene expression during osteoblast differentiation. FASEB J 4: 3111–23.

    PubMed  CAS  Google Scholar 

  126. Stepan JJ, Lachmann M, Zverina J, Pacovsky V, Baylink DJ (1989) Castrated men exhibit bone loss: effect of calcitonin treatment on biochemical indices of bone remodeling. J Clin Endocrinol Metab 69: 523–7.

    PubMed  CAS  Google Scholar 

  127. Stepan J, Limanova Z (1992) Biochemical assessment of bone loss in patients on long-term thyroid hormone treatment. Bone Miner 17: 377–88.

    PubMed  CAS  Google Scholar 

  128. Stiegler C, Dimai HP, Stepan V, Lipp R, Warnkross B, Obermayer-Pietsch B, et al. (1995) Wachstumshormontherapie bei Erwachsenen: Effekte auf Knochenstoffwechsel and Knochendichte. Osteologie 4: 99–104.

    Google Scholar 

  129. Suda T, Takahashi N, Martin TJ (1992) Modulation of osteoclast differentiation. Endocr Rev 13: 66–80.

    PubMed  CAS  Google Scholar 

  130. Suda T, Udagawa N, Takahashi N (1996) Cells of bone: osteoclast generation. In: Bilezikian JB, Raiz LG, Rodan GA (eds) Principles of Bone Biology. Academic Press, San Diego, pp 87–102.

    Google Scholar 

  131. Suda T, Takahashi N, Udagawa N, Jimi E, Gillespie MT, Martin TJ (1999) Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families. Endocr Rev 20: 345–57.

    PubMed  CAS  Google Scholar 

  132. Takata S, Yasui N (2001) Disuse osteoporosis. J Med Invest 48: 147–56.

    PubMed  CAS  Google Scholar 

  133. Tilyard MW, Spears GF, Thomson J, Dovey S (1992) Treatment of postmenopausal osteoporosis with calcitriol or calcium. N Engl J Med 326: 357–62.

    PubMed  CAS  Google Scholar 

  134. Turner RT, Wakley GK, Hannon KS, Bell NH (1987) Tamoxifen prevents the skeletal effects of ovarian hormone deficiency in rats. J Bone Miner Res 2: 449–56.

    PubMed  CAS  Google Scholar 

  135. Varga F, Rumpler M, Klaushofer K (1994) Thyroid hormones increase insulin-like growth factor mRNA levels in the clonal osteoblastic cell line MC3T3-El. FEBS Lett 345: 67–70.

    PubMed  CAS  Google Scholar 

  136. Varga F, Rumpler M, Luegmayr E, Fratzl-Zelman N, Glantschnig H, Klaushofer K (1997) Triiodothyronine, a regulator of osteoblastic differentiation: depression of histone H4, attenuation of c-fos/c-jun, and induction of osteocalcin expression. Calcif Tissue Int 61: 404–11.

    PubMed  CAS  Google Scholar 

  137. Viereck V, Emons G, Lauck V, Frosch KH, Blaschke S, Grundker C, et al. (2002) Bisphosphonates pamidronate and zolendronic acid stimulate osteoprotegerin production by primary human osteoblasts. Biochem Biophys Res Comm 291: 680–6.

    PubMed  CAS  Google Scholar 

  138. Vitté C, Fleisch H, Guenther HL (1996) Bisphosphonates induce osteoblasts to secrete an inhibitor of osteoclastmediated resorption. Endocrinology 137: 2324–33.

    PubMed  Google Scholar 

  139. Wright CDP, Garrahan NJ, Stanton M, Gazet JC, Mansell RE, Compston JE (1994) Effect of long-term tamoxifen therapy on cancellous bone remodeling and structure in women with breast cancer. J Bone Miner Res 9: 153–9.

    PubMed  CAS  Google Scholar 

  140. Yamaguchi T, Kifor O, Chattopadhyay N, Brown EM (1998) Expression of extracellular calcium (Ca2+)osensing receptor in the clonal osteoblast-like cell lines, UMR-106 and SAOS-2. Biochem Biophys Res Commun 243: 753–7.

    PubMed  CAS  Google Scholar 

  141. Yamaguchi T, Chattopadhyay N, Kifor 0, Butters RR, Sugimoto T, Brown EM (1998) Mouse osteoblastic cell line (MC3T3–E1) expresses extracellular calcium (Ca2+)0-sensing receptor and its agonists stimulate chemotaxis and proliferation of MC3T3–E1 cells. J Bone Miner Res 13: 1530–8.

    PubMed  CAS  Google Scholar 

  142. Zaman G, Cheng MZ, Jessop HL, White R, Lanyon LE (2000) Mechanical strain activates estrogen response elements in bone cells. Bone 27: 233–9.

    PubMed  CAS  Google Scholar 

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  1. Meinrad Peterlik
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This article is dedicated to Felix Bronner, PhD, Professor Emeritus of Biostructure and Function at the University of Connecticut at Farmington, on the occasion of his 80th birthday, to recognize his being a long-time mentor and friend to many scientists working in the field of bone and mineral metabolism.

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Peterlik, M. (2004). Targeting the Osteoblast for Prevention and Treatment of Bone Diseases. In: Bone Formation. Topics in Bone Biology, vol 1. Springer, London. https://doi.org/10.1007/978-1-4471-3777-1_8

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  • DOI: https://doi.org/10.1007/978-1-4471-3777-1_8

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