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Pharmacological Therapy: Past, Present, and Future

  • Silvia Migliaccio
  • Andrea Lenzi
  • Emanuela A. Greco
Chapter

Abstract

Osteoporosis is a metabolic chronic disease characterized by a skeletal fragility leading to an increased risk of developing spontaneous and traumatic fractures and has been defined a social disease due to its high impact on mortality and morbidity, to its significant alterations of the quality of life of patients, and to its high economic impact. Pharmacological therapies lead to modulate the activity of bone target cells, to increase skeletal strength, and to reduce the risk of fractures. This chapter considers past, present, and future of pharmacological therapy of osteoporosis.

Keywords

Osteoporosis Fragility fractures Anti-resorptive drugs Anabolic drugs 

References

  1. 1.
    NIH consensus development panel on osteoporosis. Osteoporosis prevention, diagnosis and therapy. JAMA. 2001;285:785–95.Google Scholar
  2. 2.
    Kado DM, Browner WS, Palermo L, Nevitt MC, Genant HK, Cummings SR. Vertebral fractures and mortality in older women: a prospective study. Study of Osteoporotic Fractures Research Group. Arch Intern Med. 1999;159(11):1215–20.CrossRefPubMedGoogle Scholar
  3. 3.
    Gold DT. The nonskeletal consequences of osteoporotic fractures. Psychologic and social outcomes. Rheum Dis Clin N Am. 2001;27:255–62.CrossRefGoogle Scholar
  4. 4.
    Seeman E. Bone quality. Osteoporos Int. 2003;14(S5):3–7.CrossRefGoogle Scholar
  5. 5.
    Migliaccio S, Falcone S, Spera G. Bone modeling and remodeling: from biology to clinical application. Aging Clin Exp Res. 2004;3:S20–2.Google Scholar
  6. 6.
    Migliaccio S, Brama M, Spera G. The differential effects of bisphosphonates, SERMS (selective estrogen receptor modulators), and parathyroid hormone on bone remodeling in osteoporosis. Clin Interv Aging. 2007;2(1):55–64.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Boivin G, Meunier PJ. Methodological considerations in measurement of bone mineral content. Osteoporos Int. 2003;14(Suppl 5):S22–7. discussion S27–8.CrossRefPubMedGoogle Scholar
  8. 8.
    Adami S, Bertoldo F, Brandi ML, SIOMMMS, et al. Guidelines for the diagnosis, prevention and treatment of osteoporosis. Reumatismo. 2009;61(4):260–84.PubMedGoogle Scholar
  9. 9.
    Migliaccio S, Brama M, Malavolta N. Management of glucocorticoids-induced osteoporosis: role of teriparatide. Ther Clin Risk Manag. 2009;5(2):305–10.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Diez-Perez A. Bisphosphonates. Maturitas. 2002;43(Suppl):S19–26.CrossRefPubMedGoogle Scholar
  11. 11.
    Taranta A, Brama M, et al. The selective estrogen receptor modulator Raloxifene modulates osteoblast and osteoclast activity in vitro. Bone. 2002;30:365–37.CrossRefGoogle Scholar
  12. 12.
    Ettinger B, Black DM, et al. Reduction of vertebral fracture risk in post menopausal women with osteoporosis treated with raloxifene. Results from a 3-year randomized clinical trial. JAMA. 1999;282:637–45.CrossRefPubMedGoogle Scholar
  13. 13.
    Chesnut CH 3rd, Silverman S, Andriano K, Genant H, Gimona A, Harris S, et al. A randomized trial of nasal spray salmon calcitonin in postmenopausal women with established osteoporosis: the prevent recurrence of osteoporotic fractures study. PROOF Study Group. Am J Med. 2000;109(4):267–76.CrossRefPubMedGoogle Scholar
  14. 14.
    Migliaccio S, Fornari R, Greco EA, Di Luigi L, Lenzi A. New therapeutical horizons in the management of postmenopausal osteoporosis. Aging Clin Exp Res. 2013;25(Suppl 1):S117–9.CrossRefPubMedGoogle Scholar
  15. 15.
    Hodsman AB, Bauer DC, Dempster DW, Dian L, Hanley DA, Harris ST, Kendler DL, McClung MR, Miller PD, Olszynski WP, Orwoll E, Yuen CK. 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):688–703.CrossRefPubMedGoogle Scholar
  16. 16.
    Khosla S. Update on estrogens and the skeleton. J Clin Endocrinol Metab. 2010;95(8):3569–77.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Wells G, Tugwell P, Shea B, Guyatt G, Peterson J, Zytaruk N, et al. Meta-analyses of therapies for postmenopausal osteoporosis. V. Meta-analysis of the efficacy of hormone replacement therapy in treating and preventing osteoporosis in postmenopausal women. Endocr Rev. 2002;23:529–39.CrossRefPubMedGoogle Scholar
  18. 18.
    North American Menopause Society. Management of osteoporosis in postmenopausal women: 2006 position statement of the North American Menopause Society. Menopause. 2006;13:340–67.CrossRefGoogle Scholar
  19. 19.
    Johnell O, Scheele WH, Lu Y, Reginster JY, Need AG, Seeman E. Additive effects of raloxifene and alendronate on bone density and biochemical markers of bone remodeling in postmenopausal women with osteoporosis. J Clin Endocrinol Metab. 2002;87(3):985–92.CrossRefPubMedGoogle Scholar
  20. 20.
    Siris ES, Harris ST, Eastell R, Zanchetta JR, Goemaere S, Diez-Perez A, Continuing Outcomes Relevant to Evista (CORE) Investigators, et al. Skeletal effects of raloxifene after 8 years: results from the continuing outcomes relevant to Evista (CORE) study. J Bone Miner Res. 2005;20(9):1514–24.CrossRefPubMedGoogle Scholar
  21. 21.
    Barrett-Connor E, Mosca L, Collins P, Geiger MJ, Grady D, Kornitzer M, Raloxifene Use for The Heart (RUTH) Trial Investigators, et al. Effects of raloxifene on cardiovascular events and breast cancer in postmenopausal women. N Engl J Med. 2006;355(2):125–37.CrossRefPubMedGoogle Scholar
  22. 22.
    Watts NB, Diab DL. Long-term use of bisphosphonates in osteoporosis. J Clin Endocrinol Metab. 2010;95(4):1555–65.CrossRefPubMedGoogle Scholar
  23. 23.
    Schnitzer T, Bone HG, Crepaldi G, Adami S, McClung M, Kiel D, et al. Therapeutic equivalence of alendronate 70 mg once-weekly and alendronate 10 mg daily in the treatment of osteoporosis. Alendronate Once-Weekly Study Group. Aging (Milano). 2000;12(1):1–12.Google Scholar
  24. 24.
    Black DM, Cummings SR, Karpf DB, Cauley JA, Thompson DE, Nevitt MC, et al. Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Fracture Intervention Trial Research Group. Lancet. 1996;348(9041):1535–41.CrossRefPubMedGoogle Scholar
  25. 25.
    Cummings SR, Black DM, Thompson DE, Applegate WB, Barrett-Connor E, Musliner TA, et al. Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial. JAMA. 1998;280(24):2077–82.CrossRefPubMedGoogle Scholar
  26. 26.
    Pols HA, Felsenberg D, Hanley DA, Stepán J, Muñoz-Torres M, Wilkin TJ, et al. Multinational, placebo-controlled, randomized trial of the effects of alendronate on bone density and fracture risk in postmenopausal women with low bone mass: results of the FOSIT study. Fosamax International Trial Study Group. Osteoporos Int. 1999;9(5):461–8.CrossRefPubMedGoogle Scholar
  27. 27.
    Black DM, Schwartz AV, Ensrud KE, Cauley JA, Levis S, Quandt SA, Cummings SR, FLEX Research Group, et al. Effects of continuing or stopping alendronate after 5 years of treatment: the Fracture Intervention Trial Long-term Extension (FLEX): a randomized trial. JAMA. 2006;296(24):2927–38.CrossRefPubMedGoogle Scholar
  28. 28.
    Reginster J, Minne HW, Sorensen OH, Hooper M, Roux C, Brandi ML, et al. Randomized trial of the effects of risedronate on vertebral fractures in women with established postmenopausal osteoporosis. Vertebral Efficacy with Risedronate Therapy (VERT) Study Group. Osteoporos Int. 2000;11(1):83–91.CrossRefPubMedGoogle Scholar
  29. 29.
    McClung MR, Geusens P, Miller PD, Zippel H, Bensen WG, Roux C, Hip Intervention Program Study Group, et al. Effect of risedronate on the risk of hip fracture in elderly women. Hip Intervention Program Study Group. N Engl J Med. 2001;344(5):333–40.CrossRefPubMedGoogle Scholar
  30. 30.
    Chesnut IIICH, Skag A, Christiansen C, Recker R, Stakkestad JA, Hoiseth A, Oral Ibandronate Osteoporosis Vertebral Fracture Trial in North America and Europe (BONE), et al. Effects of oral ibandronate administered daily or intermittently on fracture risk in postmenopausal osteoporosis. J Bone Miner Res. 2004;19(8):1241–9.CrossRefPubMedGoogle Scholar
  31. 31.
    Miller PD, McClung MR, Macovei L, Stakkestad JA, Luckey M, Bonvoisin B, et al. Monthly oral ibandronate therapy in postmenopausal osteoporosis: 1-year results from the MOBILE study. J Bone Miner Res. 2005;20(8):1315–22.CrossRefPubMedGoogle Scholar
  32. 32.
    Delmas PD, Adami S, Strugala C, Stakkestad JA, Reginster JY, Felsenberg D, et al. Intravenous ibandronate injections in postmenopausal women with osteoporosis: one-year results from the dosing intravenous administration study. Arthritis Rheum. 2006;54(6):1838–46.CrossRefPubMedGoogle Scholar
  33. 33.
    Black DM, Delmas PD, Eastell R, Reid IR, Boonen S, Cauley JA, HORIZON Pivotal Fracture Trial, et al. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med. 2007;356(18):1809–22.CrossRefPubMedGoogle Scholar
  34. 34.
    Lyles KW, Colón-Emeric CS, Magaziner JS, Adachi JD, Pieper CF, Mautalen C, HORIZON Recurrent Fracture Trial, et al. Zoledronic acid in reducing clinical fracture and mortality after hip fracture. N Engl J Med. 2007;357:1799–809.CrossRefPubMedGoogle Scholar
  35. 35.
    Black DM, Reid IR, Boonen S, Bucci-Rechtweg C, Cauley JA, Cosman F, et al. The effect of 3 versus 6 years of zoledronic acid treatment of osteoporosis: a randomized extension to the HORIZON-Pivotal Fracture Trial (PFT). J Bone Miner Res. 2012;27(2):243–54.CrossRefPubMedGoogle Scholar
  36. 36.
    Boonen S, Ferrari S, Miller PD, Eriksen EF, Sambrook PN, Compston J, et al. Postmenopausal osteoporosis treatment with antiresorptives: effects of discontinuation or long-term continuation on bone turnover and fracture risk--a perspective. J Bone Miner Res. 2012;27(5):963–74.CrossRefPubMedGoogle Scholar
  37. 37.
    Rizzoli R, Reginster JY, Boonen S, Bréart G, Diez-Perez A, Felsenberg D, et al. Adverse reactions and drug-drug interactions in the management of women with postmenopausal osteoporosis. Calcif Tissue Int. 2011;89(2):91–104.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Daroszewska A. Prevention and treatment of osteoporosis in women: an update. Obstet Gynaecol Reprod Med. 2012;22(6):162–9.CrossRefGoogle Scholar
  39. 39.
    Cummings SR, San Martin J, McClung MR, Siris ES, Eastell R, Reid IR, FREEDOM Trial, et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 2009;361(8):756–65.CrossRefPubMedGoogle Scholar
  40. 40.
    Bone HG, Chapurlat R, Brandi ML, Brown JP, Czerwinski E, Krieg MA, et al. The effect of three or six years of denosumab exposure in women with postmenopausal osteoporosis: results from the FREEDOM extension. J Clin Endocrinol Metab. 2013;98(11):4483–92.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Bone HG, Bolognese MA, Yuen CK, Kendler DL, Miller PD, Yang YC, et al. Effects of denosumab treatment and discontinuation on bone mineral density and bone turnover markers in postmenopausal women with low bone mass. J Clin Endocrinol Metab. 2011;96(4):972–80.CrossRefPubMedGoogle Scholar
  42. 42.
    Neer RM, Arnaud CD, Zanchetta JR, Prince R, Gaich GA, Reginster JY, 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):1434–41.CrossRefPubMedGoogle Scholar
  43. 43.
    Black DM, Greenspan SL, Ensrud KE, Palermo L, McGowan JA, Lang TF, PaTH Study Investigators, et al. The effects of parathyroid hormone and alendronate alone or in combination in postmenopausal osteoporosis. N Engl J Med. 2003;349(13):1207–15.CrossRefPubMedGoogle Scholar
  44. 44.
    Meunier PJ, Roux C, Seeman E, Ortolani S, Badurski JE, Spector TD, 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):459–68.CrossRefPubMedGoogle Scholar
  45. 45.
    Reginster JY, Seeman E, De Vernejoul MC, Adami S, Compston J, Phenekos C, 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):2816–22.CrossRefPubMedGoogle Scholar
  46. 46.
    Reginster JY, Kaufman JM, Goemaere S, Devogelaer JP, Benhamou CL, Felsenberg D, et al. Maintenance of antifracture efficacy over 10 years with strontium ranelate in postmenopausal osteoporosis. Osteoporos Int. 2012;23(3):1115–22.CrossRefPubMedGoogle Scholar
  47. 47.
    Nielsen SP, Slosman D, Sørensen OH, Basse-Cathalinat B, De Cassin P, Roux C, et al. Influence of strontium on bone mineral density and bone mineral content measurements by dual X-ray absorptiometry. J Clin Densitom. 1999;2(4):371–9.CrossRefPubMedGoogle Scholar
  48. 48.
    Langdahl B, Binkley N, Bone H, Gilchrist N, Resch H, Rodriguez Portales J, et al. Odanacatib in the treatment of postmenopausal women with low bone mineral density: five years of continued therapy in a phase 2 study. J Bone Miner Res. 2012;27(11):2251–8.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Silvia Migliaccio
    • 1
  • Andrea Lenzi
    • 2
  • Emanuela A. Greco
    • 2
  1. 1.Department of Movement, Human and Health Sciences, Unit of EndocrinologyUniversity “Foro Italico” of RomeRomeItaly
  2. 2.Department of Experimental Medicine, Section of Medical Pathophysiology, Endocrinology and NutritionUniversity “Sapienza” of RomeRomeItaly

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