Treatments in Endocrinology

, Volume 5, Issue 6, pp 347–358 | Cite as

Anabolic Agents for Osteoporosis

What is Their Likely Place in Therapy?
  • Monica Girotra
  • Mishaela R
  • John P
Current Opinion

Abstract

Antiresorptive agents for osteoporosis are a cornerstone of therapy, but anabolic drugs have recently widened our therapeutic options. By directly stimulating bone formation, anabolic agents reduce fracture incidence by improving other bone qualities in addition to increasing bone mass. Teriparatide (human parathyroid hormone[1–34]) has clearly emerged as a major approach for selected patients with osteoporosis. Teriparatide increases bone mineral density and bone turnover, improves bone microarchitecture, and changes bone size. The incidence of vertebral and non-vertebral fractures is reduced. Teriparatide is approved in many countries throughout the world for the treatment of both postmenopausal women and men with osteoporosis who are at high risk for fracture. Another anabolic agent, strontium ranelate, may both promote bone formation and inhibit bone resorption. Clinical trials support the use of strontium ranelate as a treatment for postmenopausal osteoporosis and have shown that strontium ranelate reduces the frequency of vertebral and non-vertebral fractures. Other potential anabolic therapies for osteoporosis, including other forms of parathyroid hormone, growth hormone, and insulin-like growth factor-I, have been examined, although less data are currently available on these approaches.

References

  1. 1.
    Rosen CJ. Clinical practice: postmenopausal osteoporosis. N Engl J Med 2005; 353(6): 595–603PubMedCrossRefGoogle Scholar
  2. 2.
    Hauselmann HJ, Rizzoli R. A comprehensive review of treatments for postmenopausal osteoporosis. Osteoporos Int 2003; 14(1): 2–12PubMedCrossRefGoogle Scholar
  3. 3.
    Lindsay R, Cosman F. The pharmacology of estrogens in osteoporosis. In: Bilezikian JP, Raisz LG, Rodan GA, editors. Principles of bone biology. San Diego (CA): Academic Press, 1996: 1063–8Google Scholar
  4. 4.
    Fleisch H. Bisphosphonates: mechanisms of action and clinical use. In: Bilezikian JP, Raisz LG, Rodan GA, editors. Principles of bone biology. San Diego (CA): Academic Press, 1996: 1037–52Google Scholar
  5. 5.
    Rubin M, Bilezikian J. The anabolic effects of parathyroid hormone therapy. Clin Geriatr Med 2002; 19: 415–32CrossRefGoogle Scholar
  6. 6.
    Hodsman AB, Bauer DC, Dempster D, et al. Parathyroid hormone and teriparatide for the treatment of osteoporosis: a review of the evidence and suggested guidelines for its use. Endocr Rev 2005; 26(5): 688–703PubMedCrossRefGoogle Scholar
  7. 7.
    Albright F, Aub JC, Bauer W. Hyperparathyroidism: a common and polymorphic condition as illustrated by seventeen proven cases from one clinic. JAMA 1934; 102: 1276–87CrossRefGoogle Scholar
  8. 8.
    Albright F, Reifenstein EC. The parathyroid glands and metabolic bone disease. Baltimore (MD): Williams & Wilkins, 1948Google Scholar
  9. 9.
    Dempster DW, Parisien M, Silverberg SJ, et al. On the mechanism of cancellous bone preservation in postmenopausal women with mild primary hyperparathyroidism. J Clin Endocrinol Metab 1999; 84(5): 1562–6PubMedCrossRefGoogle Scholar
  10. 10.
    Neer RM, Arnaud CD, Zanchetta JR, 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(19): 1434–41PubMedCrossRefGoogle Scholar
  11. 11.
    Dempster DH, Zhou F, Cosman J, et al. PTH treatment directly stimulates bone formation in cancellous and cortical bone in humans [abstract]. 23rd Annual Meeting of the ASBMR; 2001 Oct 12–16; Phoenix (AZ): 1171Google Scholar
  12. 12.
    Jiang Y, Zhao JJ, Mitlak BH, et al. Recombinant human parathyroid hormone (1–34) [teriparatide] improves both cortical and cancellous bone structure. J Bone Miner Res 2003; 18(11): 1932–41PubMedCrossRefGoogle Scholar
  13. 13.
    Recker R, Bare S, Miller M, et al. Treatment of osteoporotic women with parathyroid hormone 1–84 for 18 months improves cancellous bone formation and structure; a bone biopsy study [abstract]. Bone Min Res 2004; 19Suppl. 1: S97Google Scholar
  14. 14.
    Burr DB, Hirano T, Turner CH, et al. Intermittently administered human parathyroid hormone (1–34) treatment increases intracortical bone turnover and porosity without reducing bone strength in the humerus of ovariectomized cynomolgus monkeys. J Bone Miner Res 2001; 16(1): 157–65PubMedCrossRefGoogle Scholar
  15. 15.
    Parfitt AM. Parathyroid hormone and periosteal bone expansion. J Bone Miner Res 2002; 17(10): 1741–3PubMedCrossRefGoogle Scholar
  16. 16.
    Turner RT, Wakley GK, Hannon KS. Differential effects of androgens on cortical bone histomorphometry in gonadectomized male and female rats. J Orthop Res 1990; 8(4): 612–7PubMedCrossRefGoogle Scholar
  17. 17.
    Zanchetta JR, Bogado CE, Ferretti JL, et al. Effects of teriparatide [recombinant human parathyroid hormone (1–34)] on cortical bone in postmenopausal women with osteoporosis. J Bone Miner Res 2003; 18(3): 539–43PubMedCrossRefGoogle Scholar
  18. 18.
    Lindsay R, Silverman SL, Cooper C, et al. Risk of new vertebral fracture in the year following a fracture. JAMA 2001; 285(3): 320–3PubMedCrossRefGoogle Scholar
  19. 19.
    Kanis JA, Borgstrom C, De Laet H, et al. Assessment of fracture risk. Osteoporosis Int 2005; 16(6): 581–9CrossRefGoogle Scholar
  20. 20.
    Body JJ, Gaich GA, Scheele WH, et al. A randomized double-blind trial to compare the efficacy of teriparatide [recombinant human parathyroid hormone (1–34)] with alendronate in postmenopausal women with osteoporosis. J Clin Endocrinol Metab 2002; 87(10): 4528–35PubMedCrossRefGoogle Scholar
  21. 21.
    Gallagher JC, Genant HK, Crans GG, et al. Teriparatide reduces the fracture risk associated with increasing number and severity of osteoporotic fractures. J Clin Endocrinol Metab 2005; 90(3): 1583–7PubMedCrossRefGoogle Scholar
  22. 22.
    Marcus R, Wang O, Satterwhite J, et al. The skeletal response to teriparatide is largely independent of age, initial bone mineral density, and prevalent vertebral fractures in postmenopausal women with osteoporosis. J Bone Miner Res 2003; 18(1): 18–23PubMedCrossRefGoogle Scholar
  23. 23.
    Chen P, Miller PD, Delmas PD, et al. Change in bone mineral density (BMD) and fracture risk reduction in teriparatide-treated women with osteoporosis. 27th Annual Meeting of the American Society for Bone and Mineral Research; 2005 Sep 23–27; Nashville (TN)Google Scholar
  24. 24.
    Delmas PD, Licata AA, Reginster JY, et al. Fracture risk reduction during treatment with teriparatide is independent of pretreatment bone turnover. Bone 2006; 39(2): 237–43PubMedCrossRefGoogle Scholar
  25. 25.
    Delmas P, Licata A, Crans G, et al. Fracture risk reduction during treatment with teriparatide is independent of pretreatment bone turnover [abstract]. J Bone Miner Res 2004; 19 Suppl. 1: 1170Google Scholar
  26. 26.
    Prince R, Sipos A, Hossain A, et al. Sustained nonvertebral fragility fracture risk reduction after discontinuation of teriparatide treatment. J Bone Miner Res 2005; 20(9): 1507–13PubMedCrossRefGoogle Scholar
  27. 27.
    Kurland ES, Cosman F, McMahon DJ, et al. Parathyroid hormone as a therapy for idiopathic osteoporosis in men: effects on bone mineral density and bone markers. J Clin Endocrinol Metab 2000; 85(9): 3069–76PubMedCrossRefGoogle Scholar
  28. 28.
    Orwoll ES, Scheele WH, Paul S, et al. The effect of teriparatide [human parathyroid hormone (1–34)] therapy on bone density in men with osteoporosis. J Bone Miner Res 2003; 18(1): 9–17PubMedCrossRefGoogle Scholar
  29. 29.
    Kaufman JM, Orwoll E, Goemaere S, et al. Teriparatide effects on vertebral fractures and bone mineral density in men with osteoporosis: treatment and discontinuation of therapy. Osteoporos Int 2005 May; 16(5): 510–6PubMedCrossRefGoogle Scholar
  30. 30.
    Hodsman AB, Hanley DA, Ettinger MP, et al. Efficacy and safety of human parathyroid hormone(1–84) in increasing bone mineral density in postmenopausal osteoporosis. J Clin Endocrinol Metab 2003; 88(11): 5212–20PubMedCrossRefGoogle Scholar
  31. 31.
    Fox J, Miller MA, Recker RR, et al. Treatment of postmenopausal osteoporotic women with parathyroid hormone 1–84 for 18 months increases cancellous bone formation and improves cancellous architecture: a study of iliac crest biopsies using histomorphometry and micro computed tomography. J Musculoskelet Neuronal Interact 2005; 5(4): 356–7PubMedGoogle Scholar
  32. 32.
    Ettinger M, Greenspan S, Marriott TB, et al. atPTH(1–84) prevents first vertebral fracture in postmenopausal women with osteoporosis: results from the TOP study [abstract no. L17]. American College of Rheumatology Annual Scientific Meeting; 2005 Oct 17–21; San Antonio (TX)Google Scholar
  33. 33.
    Cosman F, Nieves J, Woelfert L, et al. Parathyroid hormone added to established hormone therapy: effects on vertebral fracture and maintenance of bone mass after parathyroid hormone withdrawal. J Bone Miner Res 2001; 16(5): 925–31PubMedCrossRefGoogle Scholar
  34. 34.
    Roe E, Sanchez S, del Puerto G, et al. Parathyroid hormone 1–34 (hPTH 1–34) and estrogen produce dramatic bone density increases in postmenopausal osteoporosis: results from a placebo-controlled randomized trial [abstract]. J Bone Miner Res 1999; 14Suppl. 1: S137Google Scholar
  35. 35.
    Ettinger B, San Martin J, Crans G, et al. Differential effects of teriparatide on BMD after treatment with raloxifene or alendronate. J Bone Miner Res 2004; 19(5): 745–51PubMedCrossRefGoogle Scholar
  36. 36.
    Cosman F, Nieves J, Woelfert L, et al. Alendronate does not block the anabolic effect of PTH in postmenopausal osteoporotic women. J Bone Miner Res 1998; 13(6): 1051–5PubMedCrossRefGoogle Scholar
  37. 37.
    Cosman F, Nieves J, Luckey M, et al. Daily vs cyclic PTH combined with alendronate vs alendronate alone for treatment of osteoporosis [abstract]. Bone Miner 2003; 18: S32Google Scholar
  38. 38.
    Cosman F, Nieves M, Zion L, et al. Daily and cyclic parathyroid hormone in women receiving alendronate. N Engl Med 2005; 353(6): 566–75CrossRefGoogle Scholar
  39. 39.
    Rubin MR, Bilezikian JP. Clinical review 151: the role of parathyroid hormone in the pathogenesis of glucocorticoid-induced osteoporosis: a re-examination of the evidence. J Clin Endocrinol Metab 2002; 87(9): 4033–41PubMedCrossRefGoogle Scholar
  40. 40.
    Lane NE, Sanchez S, Modin GW, et al. Parathyroid hormone treatment can reverse corticosteroid-induced osteoporosis: results of a randomized controlled clinical trial. J Clin Invest 1998; 102(8): 1627–33PubMedCrossRefGoogle Scholar
  41. 41.
    Black DM, Greenspan SL, Ensrud KE, et al. The effects of parathyroid hormone and alendronate alone or in combination in postmenopausal osteoporosis. N Engl J Med 2003; 349(13): 1207–15PubMedCrossRefGoogle Scholar
  42. 42.
    Finkelstein JS, Hayes A, Hunzelman JL, et al. The effects of parathyroid hormone, alendronate, or both in men with osteoporosis. N Engl J Med 2003; 349(13): 1216–26PubMedCrossRefGoogle Scholar
  43. 43.
    Deal C, Omizo M, Schwartz EN, et al. Combination teriparatide and raloxifene therapy for postmenopausal osteoporosis: results from a 6-month double-blind placebo-controlled trial. J Bone Miner Res 2005; 20(11): 1905–11PubMedCrossRefGoogle Scholar
  44. 44.
    Onyia J. Gene array analysis of the bone effects of raloxifene and alendronate show that alendronate strongly inhibits the expression of bone formation marker genes [abstract]. J Bone Miner Res 2002; 17Suppl. 1: S157Google Scholar
  45. 45.
    Misof BM, Roschger P, Cosman F, et al. Effects of intermittent parathyroid hormone administration on bone mineralization density in iliac crest biopsies from patients with osteoporosis: a paired study before and after treatment. J Clin Endocrinol Metab 2003; 88(3): 1150–6PubMedCrossRefGoogle Scholar
  46. 46.
    Lindsay R, Scheele WH, Neer R, et al. Sustained vertebral fracture risk reduction after withdrawal of teriparatide in postmenopausal women with osteoporosis. Arch Intern Med 2004; 164(18): 2024–30PubMedCrossRefGoogle Scholar
  47. 47.
    Lindsay R, Scheele WH, Clancy AD, et al. atReduction in nonvertebral fragility fractures and increase in spinal bone density is maintained 31 months after discontinuation of recombinant human parathyroid hormone(1–34) in postmenopausal women with osteoporosis [abstract]. 84th Annual Meeting of the Endocrine Society; 2002 Jun 19–22; San Francisco (CA): OR35-6Google Scholar
  48. 48.
    Lindsay R, Nieves J, Formica C, et al. 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): 550–5PubMedCrossRefGoogle Scholar
  49. 49.
    Kurland ES, Heller SL, Diamond B, et al. The importance of bisphosphonate therapy in maintaining bone mass in men after therapy with teriparatide [human parathyroid hormone(1–34)]. Osteoporos Int 2004; 15(12): 992–7PubMedCrossRefGoogle Scholar
  50. 50.
    Lane NE, Sanchez S, Modin GW, et al. Bone mass continues to increase at the hip after parathyroid hormone treatment is discontinued in glucocorticoid-induced osteoporosis: results of a randomized controlled clinical trial. J Bone Miner Res 2000; 15(5): 944–51PubMedCrossRefGoogle Scholar
  51. 51.
    Black DM, Bilezikian JP, Ensrud KE, et al. One year of alendronate after one year of parathyroid hormone (1–84) for osteoporosis. N Engl J Med 2005; 353(6): 555–65PubMedCrossRefGoogle Scholar
  52. 52.
    Neer R, Arnaud CD, Zanchetta J, et al. Recombinant human PTH [rhPTH (1–34)] reduces the risk of spine and non-spine fractures in postmenopausal osteoporosis [abstract]. 82nd Annual Meeting of the Endocrine Society; 2000 Jun 21–24; Toronto (ON)Google Scholar
  53. 53.
    Tashjian Jr AH, Gagel RF. Teriparatide [human PTH (1–34)]: 2.5 years of experience on the use and safety of the drug for the treatment of osteoporosis. J Bone Miner Res 2006; 21(3): 354–65PubMedCrossRefGoogle Scholar
  54. 54.
    Miller PD, Bilezikian JP, Deal ST, et al. Clinical use of teriparatide in the real world: initial insights. Endocr Pract 2004; 10(2): 139–48PubMedGoogle Scholar
  55. 55.
    Vahle JL, Long GG, Sandusky G, et al. Bone neoplasms in F344 rats given teriparatide [rhPTH (1–34)] are dependent on duration of treatment and dose. Toxicol Pathol 2004; 32(4): 426–38PubMedCrossRefGoogle Scholar
  56. 56.
    Wilker C, Jolette J, Smith S, et al. A no observable carcinogenic effect dose level identified in Fischer 344 rats following daily treatment with PTH(1–84) for 2 years: role of the C-terminal PTH receptor? [abstract]. J Bone Miner Res 2004; 19Suppl. 1: SA435Google Scholar
  57. 57.
    Betancourt M, Wirfel KL, Raymond AK, et al. Osteosarcoma of bone in a patient with primary hyperparathyroidism: a case report. J Bone Miner Res 2003; 18(1): 163–6PubMedCrossRefGoogle Scholar
  58. 58.
    Jimenez C, Kim W, Al Sagier F, et al. Primary hyperparathyroidism and osteosarcoma: examination of a large osteosarcoma cohort identifies unique characteristics [abstract]. J Bone Miner Res 2003; 18Suppl. 2: LB6Google Scholar
  59. 59.
    Palmer M, Adami HO, Krusemo UB, et al. Increased risk of malignant diseases after surgery for primary hyperparathyroidism: a nationwide cohort study. Am J Epidemiol 1988; 127(5): 1031–40PubMedGoogle Scholar
  60. 60.
    Smith J, Huvos AG, Chapman M, et al. Hyperparathyroidism associated with sarcoma of bone. Skeletal Radiol 1997; 26(2): 107–12PubMedCrossRefGoogle Scholar
  61. 61.
    Tashjian Jr AH, Chabner BA. Commentary on clinical safety of recombinant human parathyroid hormone 1–34 in the treatment of osteoporosis in men and postmenopausal women. J Bone Miner Res 2002; 17(7): 1151–61PubMedCrossRefGoogle Scholar
  62. 62.
    Wiig JN, Bakken TS. Hyperparathyroidism with multiple malignant tumours of bone with giant-cells: a case report. Acta Chir Scand 1971; 137(4): 391–3PubMedGoogle Scholar
  63. 63.
    Gopalakrishnan V, Hwang S, Loughre H, et al. Administration of ThPTH to humans using Macroflux transdermal technology results in the rapid delivery of biologically active PTH [abstract]. J Bone Miner Res 2004; 19Suppl. 1: M484Google Scholar
  64. 64.
    Leone-Bay A, Sato M, Paton D, et al. Oral delivery of biologically active parathyroid hormone. Pharm Res 2001; 18(7): 964–70PubMedCrossRefGoogle Scholar
  65. 65.
    Mehta NM, Gilligan JP, Stern B, et al. Biological activity of recombinant PTH analog 7841 [abstract]. J Bone Miner Metab 2002; 17Suppl. 1: SA362Google Scholar
  66. 66.
    Fraher LJ, Avram R, Watson PH, et al. Comparison of the biochemical responses to human parathyroid hormone-(1–31)NH2 and hPTH-(1–34) in healthy humans. J Clin Endocrinol Metab 1999; 84(8): 2739–43PubMedCrossRefGoogle Scholar
  67. 67.
    Horwitz MJ, Tedesco MB, Gundberg C, et al. Short-term, high-dose parathyroid hormone-related protein as a skeletal anabolic agent for the treatment of postmenopausal osteoporosis. J Clin Endocrinol Metab 2003; 88(2): 569–75PubMedCrossRefGoogle Scholar
  68. 68.
    Black DM, Rosen CJ. Parsimony with PTH: is a single weekly injection of PTH superior to a larger cumulative dose given daily? [abstract]. J Bone Miner Res 2002; 17 Suppl. 1: SA367Google Scholar
  69. 69.
    Arlot M, Meunier PJ, Boivin G, et al. Differential effects of teriparatide and alendronate on bone remodeling in postmenopausal women assessed by histomorphometric parameters. J Bone Miner Res 2005; 20(7): 1244–53PubMedCrossRefGoogle Scholar
  70. 70.
    McClung MR, San Martin J, Miller PD, et al. Opposite bone remodeling effects of teriparatide and alendronate in increasing bone mass. Arch Intern Med 2005; 165(15): 1762–8PubMedCrossRefGoogle Scholar
  71. 71.
    Heaney RP, Recker RR. Combination and sequential therapy for osteoporosis. N Engl J Med 2005; 353(6): 624–5PubMedCrossRefGoogle Scholar
  72. 72.
    Cosman F, Nieves JW, Zion M, et al. Effects of PTH rechallenge 1 year after the first PTH course in patients on long-term alendronate. 27th Annual Meeting of the American Society for Bone and Mineral Research; 2005 Sep 23–27; Nashville (TN)Google Scholar
  73. 73.
    Gowen M, Stroup GB, Dodds RA, et al. Antagonizing the parathyroid calcium receptor stimulates parathyroid hormone secretion and bone formation in osteopenic rats. J Clin Invest 2000; 105(11): 1595–604PubMedCrossRefGoogle Scholar
  74. 74.
    Marie PJ, Hott M, Modrowski D, et al. An uncoupling agent containing strontium prevents bone loss by depressing bone resorption and maintaining bone formation in estrogen-deficient rats. J Bone Miner Res 1993; 8(5): 607–15PubMedCrossRefGoogle Scholar
  75. 75.
    Hott M, Deloffre P, Tsouderos Y, et al. S12911-2 reduces bone loss induced by short-term immobilization in rats. Bone 2003; 33(1): 115–23PubMedCrossRefGoogle Scholar
  76. 76.
    Marie PJ, Ammann P, Boivin G, et al. Mechanisms of action and therapeutic potential of strontium in bone. Calcif Tissue Int 2001; 69(3): 121–9PubMedCrossRefGoogle Scholar
  77. 77.
    Brown EM. Is the calcium receptor a molecular target for the actions of strontium on bone? Osteoporos Int 2003; 14 Suppl. 3: S25–34Google Scholar
  78. 78.
    Pi M, Quarles LD. A novel cation-sensing mechanism in osteoblasts is a molecular target for strontium. J Bone Miner Res 2004; 19(5): 862–9PubMedCrossRefGoogle Scholar
  79. 79.
    Meunier PJ, Slosman DO, Delmas PD, et al. Strontium ranelate: dose-dependent effects in established postmenopausal vertebral osteoporosis: a 2-year randomized placebo controlled trial. J Clin Endocrinol Metab 2002; 87(5): 2060–6PubMedCrossRefGoogle Scholar
  80. 80.
    Meunier PJ, Roux C, Seeman E, et al. The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis. N Engl J Med 2004; 350(5): 459–68PubMedCrossRefGoogle Scholar
  81. 81.
    Reginster JY, Seeman E, De Vernejoul MC, et al. Strontium ranelate reduces the risk of nonvertebral fractures in postmenopausal women with osteoporosis: Treatment Of Peripheral Osteoporosis (TROPOS) study. J Clin Endocrinol Metab 2005; 90(5): 2816–22PubMedCrossRefGoogle Scholar
  82. 82.
    Fogelman I, Blake GM. Strontium ranelate for the treatment of osteoporosis. BMJ 2005; 330(7505): 1400–1PubMedCrossRefGoogle Scholar
  83. 83.
    Roux C, Reginster JY, Fechtenbaum J, et al. Vertebral fracture risk reduction with strontium ranelate in women with postmenopausal osteoporosis is independent of baseline risk factors. J Bone Miner Res 2006; 21(4): 536–42PubMedCrossRefGoogle Scholar
  84. 84.
    Shorr E, Carter AC. The usefulness of strontium as an adjuvant to calcium in the remineralization on skeleton in man. Bull Hosp Jt Dis Orthop Inst 1952; 13: 59–66Google Scholar
  85. 85.
    Fuleihan Gel H. Strontium ranelate: a novel therapy for osteoporosis or a permutation of the same? N Engl J Med 2004; 350(5): 504–6CrossRefGoogle Scholar
  86. 86.
    Boivin G, Deloffre P, Perrat B, et al. Strontium distribution and interactions with bone mineral in monkey iliac bone after strontium salt (S 12911) administration. J Bone Miner Res 1996; 11(9): 1302–11PubMedCrossRefGoogle Scholar
  87. 87.
    Delannoy P, Bazot D, Marie PJ. Long-term treatment with strontium ranelate increases vertebral bone mass without deleterious effect in mice. Metabolism 2002; 51(7): 906–11PubMedCrossRefGoogle Scholar
  88. 88.
    Rizzoli R. A new treatment for post-menopausal osteoporosis: strontium ranelate. J Endocrinol Invest 2005; 28(8 Suppl.): 50–7PubMedGoogle Scholar
  89. 89.
    Burlet N, Reginster JY. Strontium ranelate: the first dual acting treatment for postmenopausal osteoporosis. Clin Orthop Relat Res 2006; 443: 55–60Google Scholar
  90. 90.
    Locklin RM, Khosla S, Turner RT, et al. Mediators of the biphasic responses of bone to intermittent and continuously administered parathyroid hormone. J Cell Biochem 2003; 89(1): 180–90PubMedCrossRefGoogle Scholar
  91. 91.
    Rudman D, Feller AG, Nagraj HS, et al. Effects of human growth hormone in men over 60 years old. N Engl J Med 1990; 323(1): 1–6PubMedCrossRefGoogle Scholar
  92. 92.
    Holloway L, Butterfield G, Hintz RL, et al. Effects of recombinant human growth hormone on metabolic indices, body composition, and bone turnover in healthy elderly women. J Clin Endocrinol Metab 1994; 79(2): 470–9PubMedCrossRefGoogle Scholar
  93. 93.
    Donahue LR, Rosen CJ. The aging skeleton. In: Rosen CJ, Glowacki J, Bilezikian JP, editors. Growth hormone/IGF-1. San Diego (CA): Academic Press, 1999: 579–Google Scholar
  94. 94.
    Ackert-Bicknell C, Rubin J, Zhu X, et al. IGF-I acts as a coupling factor for bone remodeling by regulating osteoprotegerin and RANK ligand in vitro and osteoprotogerin in vivo. 84th Annual Meeting of the Endocrine Society; 2002 Jun 19–21; San Francisco (CA): P3-366Google Scholar
  95. 95.
    Landin-Wilhelmsen K, Nilsson A, Bosaeus I, et al. Growth hormone increases bone mineral content in postmenopausal osteoporosis: a randomized placebo-controlled trial. J Bone Miner Res 2003; 18(3): 393–405PubMedCrossRefGoogle Scholar
  96. 96.
    Rosen CJ, Wuster C. Growth hormone rising: did we quit too quickly? J Bone Miner Res 2003; 18(3): 406–9PubMedCrossRefGoogle Scholar
  97. 97.
    Donahue L, Rosen CJ. IGFs and bone: the osteoporosis connection revisited. Proc Soc Exp Biol Med 1998; 219: 1–7PubMedGoogle Scholar
  98. 98.
    Hurley MM, Okada Y, Sobue T, et al. The anabolic effect of parathyroid hormone is impaired in bones of Fgf2 null mice [abstract]. J Bone Miner Metab 2002; 17 Suppl. 1: 1061Google Scholar
  99. 99.
    Sugimoto T, Nishiyama K, Kuribayashi F, et al. Serum levels of insulin-like growth factor (IGF) I, IGF-binding protein (IGFBP)-2, and IGFBP-3 in osteoporotic patients with and without spinal fractures. J Bone Miner Res 1997; 12(8): 1272–9PubMedCrossRefGoogle Scholar
  100. 100.
    Bauer DC, Rosen CJ, Cauley J, et al. Low serum IGF-1 but not IGFBP-3 predicts hip and spine fracture: the study of osteoporotic fracture [abstract]. J Bone Miner Res 1998; 23: S561Google Scholar
  101. 101.
    Ghiron LJ, Thompson JL, Holloway L, et al. Effects of recombinant insulin-like growth factor-I and growth hormone on bone turnover in elderly women. J Bone Miner Res 1995; 10(12): 1844–52PubMedCrossRefGoogle Scholar
  102. 102.
    Grinspoon S, Baum H, Lee K, et al. Effects of short-term recombinant human insulin-like growth factor I administration on bone turnover in osteopenic women with anorexia nervosa. J Clin Endocrinol Metab 1996; 81(11): 3864–70PubMedCrossRefGoogle Scholar
  103. 103.
    Geusens P, Bouillon R, Broos P. Musculoskeletal effects of rhIGF-I/IGFBP-3 in hip fracture patients: results from a double-blind, placebo controlled phase II study [abstract]. Bone 1998; 23: S157Google Scholar
  104. 104.
    Kleerekoper M. Fluoride and the skeleton. Crit Rev Clin Lab Sci 1996; 33(2): 139–61PubMedCrossRefGoogle Scholar
  105. 105.
    Kleerekoper M, Peterson EL, Nelson DA, et al. A randomized trial of sodium fluoride as a treatment for postmenopausal osteoporosis. Osteoporos Int 1991; 1(3): 155–61PubMedCrossRefGoogle Scholar
  106. 106.
    Haguenauer D, Welch V, Shea B, et al. Fluoride for the treatment of postmenopausal osteoporotic fractures: a meta-analysis. Osteoporos Int 2000; 11(9): 727–38PubMedCrossRefGoogle Scholar
  107. 107.
    Haguenauer D, Welch V, Shea B, et al. Fluoride for treating postmenopausal osteoporosis. Cochrane Database Syst Rev 2000; (4): CD002825PubMedGoogle Scholar
  108. 108.
    Cranney A, Guyatt G, Griffith L, et al. Meta-analyses of therapies for postmenopausal osteoporosis: IX. Summary of meta-analyses of therapies for postmenopausal osteoporosis. Endocr Rev 2002; 23(4): 570–8PubMedCrossRefGoogle Scholar
  109. 109.
    Brown JP, Josse RG. 2002 clinical practice guidelines for the diagnosis and management of osteoporosis in Canada. CMAJ 2002; 167(10 Suppl.): S1–34PubMedGoogle Scholar
  110. 110.
    US Department of Health and Human Services. Bone health and osteoporosis: a report of the Surgeon General [online]. Available from URL: http://www.surgeongeneral.gov/library/bonehealth/content.html[Accessed 2005 Jun 12]Google Scholar
  111. 111.
    Palmer C, Wolfe SH. Position of the American Dietetic Association: the impact of fluoride on health. J Am Diet Assoc 2005; 105(10): 1620–8PubMedCrossRefGoogle Scholar
  112. 112.
    Ott SM. Sclerostin and Wnt signaling: the pathway to bone strength. J Clin Endocrinol Metab 2005; 90(12): 6741–3PubMedCrossRefGoogle Scholar
  113. 113.
    vanBezooijen RL, ten Dijke P, Papapoulos SE, et al. SOST/sclerostin, an osteocyte-derived negative regulator of bone formation. Cytokine Growth Factor Rev 2005; 16(3): 319–27PubMedCrossRefGoogle Scholar
  114. 114.
    Gardner JC, van Bezooijen RL, Mervis B, et al. Bone mineral density in sclerosteosis; affected individuals and gene carriers. J Clin Endocrinol Metab 2005; 90(12): 6392–5PubMedCrossRefGoogle Scholar
  115. 115.
    Warmington K, Ominsky M, Bolon B, et al. Sclerostin monoclonal antibody treatment of osteoporotic rats completely reverses one year of ovariectomy-induced systemic bone loss. 27th Annual Meeting of the American Society for Bone and Mineral Research; 2005 Sep 23–27; Nashville (TN)Google Scholar
  116. 116.
    Kulkarni NH, Halladay DL, Miles RR, et al. Effects of parathyroid hormone on Wnt signaling pathway in bone. J Cell Biochem 2005; 95(6): 1178–90PubMedCrossRefGoogle Scholar
  117. 117.
    Bellido T, Ali AA, Gubrij I, et al. Chronic elevation of parathyroid hormone in mice reduces expression of sclerostin by osteocytes: a novel mechanism for hormonal control of osteoblastogenesis. Endocrinology 2005; 146(11): 4577–83PubMedCrossRefGoogle Scholar
  118. 118.
    Keller H, Kneissel M. SOST is a target gene for PTH in bone. Bone 2005; 37(2): 148–58PubMedCrossRefGoogle Scholar
  119. 119.
    Poole KE, Reeve J. Parathyroid hormone: a bone anabolic and catabolic agent. Curr Opin Pharmacol 2005; 5(6): 612–7PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2006

Authors and Affiliations

  • Monica Girotra
    • 1
  • Mishaela R
    • 1
  • John P
    • 1
    • 2
  1. 1.Department of Medicine, College of Physicians and SurgeonsColumbia UniversityNew YorkUSA
  2. 2.Columbia UniversityNew YorkUSA

Personalised recommendations