COMBINED THERAPIES OF OSTEOPOROSIS: BISPHOSPHONATES AND THE D-HORMONE ANALOGS


Cite item

Full Text

Abstract

The article considers new potentials for prevention of vertebral and nonvertebral fractures, which are mainly attributable to postmenopausal and glucocorticoid-induced osteoporosis. In this context, the combination of bisphosphonates (BP, especially alendronate) and D-hormone analogs is of considerable interest. The theoretical basis of the complementary actions of alendronate and D-hormone analogs is discussed; data on the effects of BP and D-hormone analog on the falls, bone mineral density and fracture risk in various forms of osteoporosis are presented. The data on the safety of this combination are considered. It is emphasized that the combined use of active vitamin D metabolites with BP (for example, alfacalcidol with alendronate) demonstrates greater efficacy compared with monotherapy because of the different mechanisms of action, complementing each other (complementary or synergistic effect), that makes this combination valuable alternative for the treatment of osteoporosis.

References

  1. Youm T, Koval KJ, Kummer FJ, et al. Do all hip fractures result from a fall? Am J Orthop 1999;28:190-94.
  2. Van Staa TP, Leufkens HGM, Abenhaim L, et al. Use of oral corticosteroids and risk of fractures. J Bone Miner Res 2000;15:993-1000.
  3. Nevitt MC, Cummings SR, Stone KL, et al. Risk factors for a first-incident radiographic vertebral fracture in women > 65 years of age: The study of osteoporotic fractures. J Bone Miner Res 2005;201:131-40.
  4. McClung MR, Geusens P, Miller PD, et al. Effect of risedronate on the risk of hip fracture in elderly women. N Engl J Med 2001;344:333-40.
  5. Wu-Wong JR, Tian J, Goltzman D. Vitamin D analogs as therapeutic agents: a clinical study update. Curr Opin Invest Drugs 2004;5:320-26.
  6. Kanis JA. Vitamin D analogs: from renal bone disease to osteoporosis. Kidney Int 1999;73:77-81.
  7. Richy F, Ethgen O, Bruyere O, et al. Efficacy of alphacalcidol and calcitriol in primary and corticos-teroid-induced osteoporosis: a meta-analysis of their effects on bone mineral density and fracture rate. Osteoporos Int 2004;15:301-10.
  8. Richy F, Schacht E, Bruyere O, er al. Vitamin D analogs versus native Vitamin D in preventing bone loss and osteoporosis-related fractures: A comparative meta-analysis. Calcif Tissue Int 2005;76:176486.
  9. Uebelhart D, Frey D, Frey-Rindova P, et al. Therapy of osteoporosis: bisphosphonates, SERMs, teriparatide and strontium. Z Rheumatol 2003;62:512-17.
  10. Boonen S, Body JJ, Boutsen Y, et al. Evidence-based guidelines for the treatment of postmenopausal osteoporosis: a consensus document of the Belgian Bone Club. Osteoporos Int 2005;16:239-54.
  11. Breuil V, Cosman F, Stein L, et al. Human osteoclast formation and activity in vitiv: effects of alendronate. J Bone Miner Res 1998;13:1721-29.
  12. Sato M, Grasser W. Effects of bisphosphonates on isolated rat osteoclasts as examined by reflected light microscopy. J Bone Miner Res 1990;5:31-40.
  13. Fleisch H. Bisphosphonates: mechanisms of action. Endocr Rev 1998;19:80-100.
  14. Russell RG, Rogers MJ. Bisphosphonates: from the laboratory to the clinic and back again. Bone 1999;25:97-106.
  15. Shiraishi A, Takeda S, Masaki T, et al. Alfacalcidol inhibits bone resorption and stimulates formation in an ovariec-tomized rat model of osteoporosis: distinct action from estrogen. J Bone Miner Res 2000;15:770-74.
  16. Shibata T, Shiraishi A, Sato T, et al. Vitamin D hormone inhibits osteoclastogenesis in vivo by decreasing the pool of osteoclast precursors in bone marrow. J Bone Miner Res 2002;17:622-29.
  17. Chavassieux PM, Allot ME, Reda C, et al. Histomorphometric assessment of the long-term effects of alendronate on bone quality and remodeling in patients with osteoporosis. J Clin Invest 1997;100:1475-80.
  18. Boivin GY, Chavassieux PM, Santora AC, et al. Alendronate increases bone strength by increasing the mean degree of mineralization of bone tissue in osteoporotic women. Bone 2000;27:687-94.
  19. Schacht E. Rationale for treatment of involutional osteoporosis in women and for prevention and treatment of corticosteroid-induced osteoporosis with alfa-calcidol. Calcif Tissue Int 1999;65:317-27.
  20. DeLuca HF, Cantorna MT. Vitamin D. Its Role and uses in immunology. FASEB J 2001;15:2579-85.
  21. Inanir A, Ozoran K, Tutkak H, et al. The effects of calcitriol therapy on serum interleukin-1, interleukin-6 and tumour necrosis factor-alpha concentrations in postmenopausal patients with osteoporosis. J Int Med Res 2004;32:570-82.
  22. Scharla SH, Schacht E, Lempert UG. AJfacalcidoI versus plain Vitamin D in inflammation induced bone loss. J Rheumatol 2005;32:26-32.
  23. Dambacher MA, David G, Kneer W, et al. Praktische OrthopSdie - Osteoporose. In: Hedtmann A, G6tte S (Hrg). Steinkopff-Verlag, Darmstadt 2000:49-56.
  24. Iwamoto J, Takeda T, Sato Y, et al. Comparison of the effect of alendronate on lumbar bone mineral density and bone turnover in men and postmenopausal women with osteoporosis. Clin Rheumatol 2007;26:161-67.
  25. Greenspan SL, Resnick NM, Parker RA. Early changes in biochemical markers of bone turnover are associated with long-term changes in bone mineral density in elderly women on alendronate, hormone replacement therapy, or combination therapy: a three-year, double-blind, placebo-controlled, randomized clinical trial. J Clin Endocrinol Metab 2005;90:2762-67.
  26. Ikeda K, Ogata E. The effect of Vitamin D on osteoblasts and osteoclasts. Curr Opin Orthop 1999;10:339-43.
  27. Shiraishi A, Higashi S, Ohkawa H, et al. The advantage of alfacalcidol over Vitamin D in the treatment of osteoporosis. Calcif Tissue Int 1999;65:311-16.
  28. Reszka AA, Pun S, Rodan GA, et al. Bone anabolic effects of l,25(OH)2 Vitamin D3 are detected only in the presence of a powerful antiresorp-tive. J Bone Miner Res 2004;19:S483.
  29. Erben RG, Mosekilde L, Thomsen JS, et al. Prevention of bone loss in ovariectomized rats by combined treatment with risedronate and la, 25-dihydroxyvitamin D3. J Bone Miner Res 2002;17:1498-511.
  30. Ito M, Azuma Y, Takagi H, et al. Curative effect of combined treatment with alendronate and la-Hydroxyvitamin D3 on bone loss by ovariectomy in aged rats. Jpn J Pharmacol 2002;89:255-66.
  31. Dambacher MA, Schacht E, Scharla SH, et al. Optimierung der osteoporosetherapie-kombination von alfacalcidol und alendronate. J Miner Stoffwechs 2003;10:17-20.
  32. Dukas L, Bischoff HA, Lindpaintner LS, et al. Alfacalcidol reduces the number of fallers in a community-dwelling elderly population with a minimum calcium intake of more Geriatr Soc 2004;52:230-36.
  33. Gallagher JC. The effects of calcitriol on falls and fractures and physical performance tests. J Steroid Biochem Mol Biol 2004;89-90:497-501.
  34. Dukas L, Schacht E, Mazor Z, et al. Treatment with alfacalcidol in elderly people significantly decreases the high risk of falls associated with a low creatinine clearance of < 65 ml/min. Osteoporos Int 2005;16:198-203.
  35. Schacht E, Richy F, Reginster J-Y. The therapeutic effects of alfacalcidol on bone strength, muscle metabolism and prevention of falls and fractures. J Musculoskelet Neuronal Interact 2005;5:273-84.
  36. Uusi-Rasi K, Kannus P, Cheng S, et al. Effect of alendronate and exercise on bone and physical performance of postmenopausal women: a randomized controlled trial. Bone 2003;33:132-43.
  37. Delmas PD, Vergnaud P, Arlot ME, et al. The anabolic effect of human PTH (1-34) on bone formation is blunted when bone resorption is inhibited by the bisphosphonate tilu-dronate - is activated resorption a prerequisite for the in vivo effect of PTH on formation in a remodeling system? Bone 1995;16:603-10.
  38. Fisher JE, Rogers MJ, Halasy JM, et al. Alendronate mechanism of action: geranylgeraniol, an intermediate in the mevalonate pathway, prevents inhibition of osteoclast formation, bone resorption, and kinase activation in vitro. Proc Natl Acad Sci USA 1999;96:133-38.
  39. Kanis JA, Gluer CC. An update on the diagnosis and assessment of osteoporosis with densitometry. Committee of Scientific Advisors, Internationa. Osteoporosis Foundation. Osteoporos Int 2000;11:192-202.
  40. Kaptoge S, Benevolenskaya LI, Bhalla AK, et al. Low BMD is less predictive than reported falls for future limb fractures in women across Europe: results from the European Prospective Osteoporosis Study. Bone 2005;36:387-98.
  41. Runge M, Schacht E. Multifactorial pathogenesis of falls as a basis for multifactorial interventions. J Musculoskelet Neuronal Interact 2005;5:127-34.
  42. Bischoff HA, Borchers M, Gudat F, et al. In situ detection of 1,25-dihydroxyvitamin D3 receptor in human skeletal muscle tissue. Histochem 2001;33:19-24.
  43. Boland R. Role of Vitamin D in skeletal muscle function. Endocr Rev 1986;784:434-48.
  44. Endo I, Inoue D, Mitsui T, et al. Deletion of Vitamin D receptor gene in mice results in abnormal skeletal muscle development with deregulated expression of myoregulatory transcription factors. Endocrinology 2003;144:5138-44.
  45. Bischoff-Ferrari HA, Borchers M, Gudat F, et al. Vitamin D receptor expression in human muscle tissue decreases with age. J Bone Miner Res 2004;19:265-69.
  46. Bischoff HA, Stahelin HB, Urscheier N, et al. Muscle strength in the elderly: its relation to Vitamin D metabolites. Arch Phys Med Rehabil 1999;80:54-58.
  47. Dukas L, Schacht E, Bischoff HA. Better functional mobility in community-dwelling elderly is related to D-hormone serum levels and to a daily calcium intake. J Nutr Health Aging 2005;9:347-51.
  48. Verhaar HJJ, Samson MM, Jansen PAF, et al. Muscle strength, functional mobility and Vitamin D in older women. Aging Clin Exp Res 2000;12:455-60.
  49. Frediani В, Allegri A, Bisogno S, et al. Effects of combined treatment with calcitriol plus alendronate on bone mass and bone turnover in postmenopausal osteoporosis. Two years of continuous treatment. Clin Drug Invest 1998;15:235-44.
  50. Ringe JD, Farahmand P, Schacht E, et al. Superiority of a combined treatment of Alendronate and Alfacalcidol compared to the combination of Alendronate and plain Vitamin D or Alfacalcidol alone in established postmenopausal or male osteoporosis (AAC-Trial). Rheumatol Int 2007;27:425-39.
  51. Greiwe JS, Cheng B, Rubin DC, et al. Resistance exercise decreases skeletal muscle tumor necrosis factor a in frail elderly humans. FASEB J 2001;15:475-82.
  52. Saag KG, Emkey R, Schnitzel TJ, et al. Alendronate for the prevention and treatment of glucocorti-coid-induoed osteoporosis. N Engl J Med 1998;339:292-99.
  53. Adachi JD, Saag KG, Delmas PD, et al. Two-year effects of alendronate on bone mineral density and vertebral fracture in patients receiving glucocorticoids: a randomized, double-blind, placebo-controlled extension trial (Osteoporosis and Bone). Arthritis Rheum 2001;44:202-11.
  54. Reginster JY, Kuntz D, Verdickt W, et al. Prophylactic use of alfacalcidol in corticosteroid-induced osteoporosis. Osteoporos Int 1999;9:75-81.
  55. Lakatos P, Nagy Z, Kiss L, et al. Prevention of corticosteroid-induced osteoporosis by alfacalcidol. Z Rheumatol 2000;59:48-52.
  56. Ringe JD, Dorst A, Faber H, et al. Superiority of alfacalcidol over plain Vitamin D in the treatment of glucocorticoid-induced osteoporosis. Rheumatol Int 2004;24:63-70.
  57. de Nijs RNJ, Jacobs JWG, Algra A, et al. Prevention and treatment of glucocorticoid-induced osteoporosis with active Vitamin D3 analogues: a review with meta-analysis of randomized controlled trials including organ transplantation studies. Osteoporos Int 2004;15:589-602.
  58. Ebert R, Jovanovic M, Ulmer M, et al. Downregulation by nuclear factor kB of human 25-hydroxyvitamin D3 la-hydroxylase promoter. Mol Endocrinol 2004;18:2440-50.
  59. Oelzner P, Muller A, Deschner F, et al. Relationship between disease activity and serum levels of Vitamin D metabolites and PTH in rheumatoid arthritis. Calcif Tissue Int 1998;62:193-98.
  60. Godschalk M, Levy RJ, Downs RW. Glucocorticoids decrease Vitamin D receptor numbers and gene expression in human osteosarcoma cells. J Bone Miner Res 1992;7:21-27.
  61. Wiese RJ, Uhland-Smith A, Ross TK, et al. Up-regulation of the Vitamin D receptor in response to 1,25-dihydroxyvitamin D3 results from ligand-induced stabilization. J Biol Chem 1992;267:20082-86.
  62. Mathieu C, Adorini L. The coming of age of 1,25-dihy-droxyvitamin D3 analogs as immunomodulatory agents. Trends Mol Med 2002;8:174-79.
  63. Lempert UG, Minne HW, Albrecht B, et al. 1,25-dihydroxyvitamin D3 prevents the decrease of bone mineral appositional rate in rats with inflammation-mediated osteopenia (IMO). Bone Miner 1989;7:149-58.
  64. Frediani B, Allegri A, Storri L, et al. Alendronate plus calcitriol: a combined treatment in corticosteroid induced osteoporosis. Osteoporos Int 1999;9:10-11.
  65. Miya К, Morimoto S, Fukuo K, et al. Cognitive function and calcium related factors in elderly female subjects. Nippon Ronen Igakkai Zasshi 1991;28:34-39.
  66. Latham NK, Anderson CS, Lee A, et al. A randomized, controlled trial of quadriceps resistance exercise and Vitamin D in frail older people: The frailty interventions trial in elderly subjects (FITNESS). J Am Geriatr Soc 2003;51:291-99.
  67. Smith H, Anderson F, Raphael H, et al. Effect of annual intramuscular Vitamin D supplementation on fracture risk: population-based, randomised, double-blind, placebo-controlled trial. Osteoporos Int 2004;15:S8.
  68. Porthouse J, Cockayne S, King C, et al. Randomised controlled trial of calcium and supplementation with cholecalciferol (Vitamin D3) for prevention of fractures in primary care. BMJ 2005;330:1003-06.
  69. The RECORD Trial Group. Oral Vitamin D3 and calcium for secondary prevention of low-trauma fractures in elderly people (Randomised Evaluation of Calcium Or Vitamin D, RECORD): a randomised placebo-controlled trial. Lancet 2005;365:1621-28.
  70. Van Etten E, Branisteanu DD, Overbergh L, et al. Combination of a 1,25-dihy-droxyvitamin D3 analog and a bisphosphonate prevents experimental autoimmune encephalomyelitis and preserves bone. Bone 2003; 32:397-404.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2011 Bionika Media

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies