Advertisement

The Ideal Drug for the Treatment of Osteoporosis

  • David Hosking

Abstract

The ideal drug for osteoporosis would be one which replaced lost bone and restored its disorganized micro-architecture so that fracture risk was reduced to that of the normal population. It would be free of side effects and sufficiently inexpensive for widespread use. Its beneficial effects on bone would persist for a significant time once therapy was withdrawn, opening the way to intermittent courses of treatment. It should be effective when given by a variety of routes to improve patient acceptance and maintain compliance. Such a drug is not available but several of the currently available compounds fulfill some (but not all) of the requirements and point the way to the future optimization of therapy. There have also been several important recent advances in our understanding of the cell biology of bone which may also lead to the development of better treatment.

Keywords

Bone Mineral Density Vertebral Fracture Postmenopausal Osteoporosis Lumbar Spine Bone Mineral Density Ideal Drug 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Consensus Development Conference: diagnosis, prophylaxis and treatment of osteoporosis. Am J Med 1993;94:646–50.Google Scholar
  2. 2.
    Riggs BL, Hodgson SF, O’Fallon WM et al. Effect of fluoride treatment on fracture rate in postmenopausal women with osteoporosis. N Engl J Med 1990; 22: 802–9.CrossRefGoogle Scholar
  3. 3.
    Eiken P, Kolthoff N, Pors Nielsen S. Effects of 10 years’ hormone replacement therapy on bone mineral content in postmenopausal women. Bone 1996; 19: 1915–35.CrossRefGoogle Scholar
  4. 4.
    Storm T, Killerup G, Thamsborg G, Genant HK, Sorensen OH. Five years of clinical experience with intermittent cyclical etidronate for postmenopausal osteoporosis. J Rheumatol 1996; 23: 1560–4.PubMedGoogle Scholar
  5. 5.
    Devogelaer JP, Broil H, Correa-Potter R et al. Oral alendronate induced progressive increases in bone mass of the spine, hip and total body over 3 years in postmenopausal women with osteoporosis. Bone 1996; 18: 141–50.PubMedCrossRefGoogle Scholar
  6. 6.
    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: 550–5.PubMedCrossRefGoogle Scholar
  7. 7.
    Mosekilde L, Eriksen EF, Charles P. Hypercalcaemia of malignancy: pathophysiology, diagnosis and treatment. Crit Rev Oncol Haematol 1991; 11: 1–27.CrossRefGoogle Scholar
  8. 8.
    Meunier PJ, Bolvin G. Bone mineral density reflects bone mass but also the degree of mineralisation of bone: therapeutic implications. Bone 1997; 21: 373–7.PubMedCrossRefGoogle Scholar
  9. 9.
    Chestnut CH, McClung MR, Ensrud KE et al. Alendronate treatment of the postmenopausal osteoporotic woman: effect of multiple dosages on bone mass and bone remodelling. Am J Med 1995; 99: 44–152.Google Scholar
  10. 10.
    Garnero P, Shih WJ, Gineyts E, Karpf DB, Delmas PD. Comparison of new biochemical markers of bone turnover in late postmenopausal osteoporotic women in response to alendronate treatment. J Clin Endocrinol Metab 1994; 79: 1693–700.PubMedCrossRefGoogle Scholar
  11. 11.
    Fleisch H. New bisphosphonates in osteoporosis. Osteoporos Int Suppl 1993; 2: S15–22.CrossRefGoogle Scholar
  12. 12.
    Ravn P, Bidstrup M, Wasnich RD et al. Alendronate and estrogen-progestin prevent bone loss in healthy postmenopausal women: 4 year results from the Early Postmenopausal Intervention Cohort (EPIC) study, a randomised clinical trial. Ann Intern Med 1999; 131: 935–42.PubMedGoogle Scholar
  13. 13.
    Christiansen C, Christensen MS, Transbol I. Bone mass after withdrawal of oestrogen replacement. Lancet 1981 May 9;i:1053–4.Google Scholar
  14. 14.
    Delmas PD, Bjarnason NH, Mitlak BH et al. Effects of raloxifene on bone mineral density, serum cholesterol concentrations, and uterine endometrium in postmenopausal women. N Engl J Med 1997; 337: 1641–7.PubMedCrossRefGoogle Scholar
  15. 15.
    Liberman UA, Weiss SR, Broil J et al. Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. N Engl J Med 1995; 333: 1437–43.PubMedCrossRefGoogle Scholar
  16. 16.
    Chestnut CH 3rd, Silverman S, Andriano K, 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: 267–76.CrossRefGoogle Scholar
  17. 17.
    Khairi MRA, Altman RD, DeRosa GP, Zimmermann J, Schenk RK, Johnston CC. Sodium etidronate in the treatment of Paget’s disease of bone. Ann Intern Med 1977; 87: 656–63.PubMedGoogle Scholar
  18. 18.
    Balena R, Toolan BC, Shea M et al. The effect of 2-year treatment with the aminobisphosphonate alendronate on bone metabolism, bone histomorphometry and bone strength in ovariectomised non human primates. J Clin Invest 1993; 92: 2577–86.PubMedCrossRefGoogle Scholar
  19. 19.
    Reid IR, Nicholson GC, Weinstein RS et al. Biochemical and radiologic improvement in Paget’s disease of bone treated with alendronate: A randomized, placebo-controlled trial. Am J Med 1996; 171: 341–8.CrossRefGoogle Scholar
  20. 20.
    Storm T, Thamsborg G, Steiniche T, Genant HK, Sorensen OH. Effect of intermittent cyclical etidronate therapy on bone mass and fracture rate in women with postmenopausal osteoporosis. N Engl J Med 1990; 322: 1265–1271.PubMedCrossRefGoogle Scholar
  21. 21.
    Harris ST, Watts NB, Genant HK et al. Effects of risedronate treatment on vertebral and non-vertebral fractures in women with postmenopausal osteoporosis. JAMA 1999; 282: 1344–52.PubMedCrossRefGoogle Scholar
  22. 22.
    Marshall D, Johnell O, Wedel H. Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. BMJ 1996; 312: 1254–9.PubMedCrossRefGoogle Scholar
  23. 23.
    Barrett-Connor E. The economic and human cost of osteoporotic fracture. Am J Med 1995; 98 (Suppl 2A): 3S - 8S.PubMedCrossRefGoogle Scholar
  24. 24.
    Ettinger B, Black DM, Mitlak B et al. Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: Results from a 3-year randomized clinical trial. JAMA 1999; 282: 637–45.PubMedCrossRefGoogle Scholar
  25. 25.
    Ringe JD, Kippshoven C, Coster A, Umbach R. Therapy of established postmenopausal osteoporosis with monofluorophosphate plus calcium: dose-related effects on bone density and fracture rate. Osteoporos Int 1999; 9: 171–8.PubMedCrossRefGoogle Scholar
  26. 26.
    Adami S, Braga V, Squaranti R, Rossinin M, Gatti D, Zamberlan N. Bone measurements in asymptomatic primary hyperparathyroidism. Bone 1998; 22: 565–70.PubMedCrossRefGoogle Scholar
  27. 27.
    Black DM, Cummings SR, Karpf DB et al. Randomised trial of effects of alendronate on risk of fracture in women with existing vertebral fractures. Lancet 1996; 348: 1535–41.PubMedCrossRefGoogle Scholar
  28. 28.
    Reid IR, Ames RW, Evans MC, Gamble D, Sharpe SJ. Long-term effects of calcium supplementation on bone loss and fractures in post-menopausal women: a randomized controlled trial. Am J Med 1995; 98: 331–5.PubMedCrossRefGoogle Scholar
  29. 29.
    Dawson-Hughes B, Harris SS, Krall EA, Dallal GE. Effect of calcium and Vitamin D supplementation on bone density in men and women 65 years of age or older. N Engl J Med 1997; 337: 670–6.PubMedCrossRefGoogle Scholar
  30. 30.
    Tilyard MW, Spears GFS, Thomson J, Dovey S. Treatment of postmenopausal osteoporosis with calcitriol or calcium N Engl J Med 1992; 326: 357–62.PubMedGoogle Scholar
  31. 31.
    De Groen PC, Lubbe DF, Hirsch LJ et al. Esophagitis associated with the use of alendronate. N Engl J Med 1996; 335: 1016–21.PubMedCrossRefGoogle Scholar
  32. 32.
    Kumbar V, Green S, Stack G, Berry M, Jin JR, Chambon P. Functional domains of the human estrogen receptor. Cell 1987; 51: 941–51.CrossRefGoogle Scholar
  33. 33.
    Colditz GA, Hankinson Se, Hunter DJ et al. The use of estrogens and progestins and the risk of breast cancer in postmenopausal women. N Engl J Med 1995; 332: 1589–93.PubMedCrossRefGoogle Scholar
  34. 34.
    Sambrook P, Birmingham J, Kelly P et al. Prevention of corticosteroid osteoporosis. A comparison of calcium, calcitriol, and calcitonin. N Engl J Med 1993; 328: 1747–52.PubMedCrossRefGoogle Scholar
  35. 35.
    Tan AU, Levine BS, Mazess RB et al. Effective suppression of parathyroid hormone by 1 alphahydroxy-vitamin D2 in haemodialysis patients with moderate to severe secondary hyperparathyroidism. Kidney Int 1997; 51: 317–23.PubMedCrossRefGoogle Scholar
  36. 36.
    Aaron JE, Francis RM, Peacock M, Makins NB. Contrasting micro-anatomy of idiopathic and corticosteroid induced osteoporosis. Clin Orthop 1989; 243: 294–305.PubMedGoogle Scholar
  37. 37.
    Adachi JD, Bensen WG, Brown J et al. Intermittent etidronate therapy to prevent corticosteroid induced osteoporosis. N Engl J Med 1997; 337: 382–7.PubMedCrossRefGoogle Scholar
  38. 38.
    Saag K, Emkey R, Schnitzer TJ et al. Alendronate for the prevention and treatment of glucocorticoid-induced osteoporosis. N Engl J Med 1998; 339: 292–9.PubMedCrossRefGoogle Scholar
  39. 39.
    Herd RJM, Balena R, Blake GM, Ryan PJ, Fogelman I. The prevention of early postmenopausal bone loss by cyclical etidronate therapy: a 2-year, double blind, placebo controlled study. Am J Med 1997; 103: 92–9.PubMedCrossRefGoogle Scholar
  40. 40.
    Anderson FH, Francis RM, Bishop DJ, Rawlings D. Effect of intermittent cyclical disodium etidronate on bone mineral density in men with vertebral fractures. Age Ageing 1997; 156: 359–65.CrossRefGoogle Scholar
  41. 41.
    Jilka RL. Cytokines, bone remodelling and estrogen deficiency: a 1998 update. Bone 1998; 23: 75–81.PubMedCrossRefGoogle Scholar
  42. 42.
    Jilka RJ, Weinstein RS, Bellido T, Roberson P, Parfitt AM, Manolagas SC. Increased bone formation by prevention of osteoblast apoptosis with parathyroid hormone. J Clin Invest 1999; 104: 439–46.PubMedCrossRefGoogle Scholar
  43. 43.
    Harris ST, Watts NB, Jackson RD et al. Four year study of intermittent cyclical Etidronate treatment of post-menopausal osteoporosis; three years of blinded therapy followed by one year of open therapy. Am J Med 1993; 95: 557–67.PubMedCrossRefGoogle Scholar
  44. 44.
    Hosking DJ, Chilvers CED, Christiansen C et al. Prevention of bone loss with Alendronate in postmenopausal women under 60 years of age. N Engl J Med 1998; 338: 485–92.PubMedCrossRefGoogle Scholar
  45. 45.
    Seeman E, Delmas PD. Reconstructing the skeleton with intermittent parathyroid hormone. Trends Endocrinol Metab. 2001; 12: 281–3.PubMedCrossRefGoogle Scholar
  46. 46.
    Dempster DW, Cosman F, Kurland ES et al. Effects of daily treatment with parathyroid hormone on bone microarchitecture and turnover in patients with osteoporosis a paired biopsy study. J Bone Miner Res. 2001; 16: 1846–53.PubMedCrossRefGoogle Scholar
  47. 47.
    Zhou H, Shen V, Dempster DW, Lindsay R. Continuous parathyroid hormone and estrogen administration increases vertebral cancellous bone volume and cortical width in the estrogen-deficient rat. J Bone Miner Res. 2001; 16: 1300–7PubMedCrossRefGoogle Scholar
  48. 48.
    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: 1434–41.CrossRefGoogle Scholar
  49. 49.
    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: 925–31.PubMedCrossRefGoogle Scholar
  50. 50.
    Rittmaster RS, Bolognese M, Ettinger MP, et al. Enhancement of bone mass in osteoporotic women with parathyroid hormone followed by alendronate. J Clin Endocrinol Metab. 2000; 85: 2129–34.PubMedCrossRefGoogle Scholar
  51. 51.
    Samnegârd E, Akhter MP, and Recker RR. Maintenance of vertebral body bone mass and strength created by human parathyroid hormone treatment in ovariectomized rats. Bone 2001: 28: 414–422.PubMedCrossRefGoogle Scholar
  52. 52.
    Samnegârd E, Iwaniec UT, Cullen DM, Kimmel DB, and Recker RR. Maintenance of cortical bone in human parathyroid hormone(1–84)-treated ovariectomized rats. Bone 2001: 28: 251–260.PubMedCrossRefGoogle Scholar
  53. 53.
    Iwaniec UT, Samnegârd E, Cullen DM, and Kimmel DB. Maintenance of cancellous bone in ovariectomized, human parathyroid hormone [hPTH(1–84)]-treated rats by estrogen, risedronate, or reduced hPTH, Bone 2001: 29: 352–360.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag London 2002

Authors and Affiliations

  • David Hosking

There are no affiliations available

Personalised recommendations