Denosumab v terapii postmenopauzální osteoporózy – lék s novým mechanismem účinku snižující riziko zlomenin a zlepšující kvalitu kosti

Číslo: 6 / 2010 (Obsah)
Rubrika: Farmakoterapeutické postupy
Obor: Osteologie
Autoři: Doc. MUDr. Pavel Horák, CSc.
MUDr. Martina Skácelová
Autoři - působiště: III. interní klinika nefrologie, revmatologie a endokrinologie LF UP a FN, Olomouc
Klíčová slova: osteoporóza, RANK ligand, denosumab
Citace: 1 Lewiecki EM. RANK ligand inhibition with denosumab for the management of osteoporosis. Expert Opin Biol Ther 2006;6:1041–50. 2 McClung MR, Lewiecki EM, Cohen SB, et al. Denosumab in postmenopausal women with low bone mineral density. N Engl J Med 2006; 354:821–31. 3 Hsu H, Lacey DL, Dunstan CR, et al. Tumor necrosis factor receptor family member RANK mediates osteoclast differentiation and activation induced by osteoprotegerin ligand. Proc Natl Acad Sci 1999;96:3540–5. 4 Fata JE, Kong YY, Li J, et al. The osteoclast differentiation factor osteoprotegerin ligand is essentials for mammary gland development. Cell 2000;103:41–50. 5 Anderson DM, Maraskovsky E, Billingsley WL, et al. A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function. Nature 1997;390:175–9. 6 Boyle WJ, Simonet WS, Laceyet DL, el al. Osteoclast differentiation and activation. Nature 2003;423:337–42. 7 Bekker PJ, Holloway DL, Rasmussen AS, et al. Single-dose placebo-controlled study of AMG 162, a fully human monoclonal antibody to RANKL, in postmenopausal women. J Bone Miner Res 2004;19:1059–66. 8 Yasuda H, Shima N, Nakagawa N, et al. Osteoclast differentiation factor is a ligand for osteoprotegerin/oscteoclastogenesis inhibitory factor and is identical to TRANCE/RANKL. Proc Natl Acad Sci 1998;95:3597–602. 9 Lacey DL, Tan HL, Lu J, et al. Osteoprotegerin ligand modulates murine osteoclast survival in vitro and in vivo. Am J Pathol 2000;157:435–48. 10 Lewiecki EM, Miller PD, McClung MR, et al. Two-year treatment with denosumab (AMG 162) in a randomized phase 2 study of postmenopausal women with low bone mineral density. J Bone Miner Res 2007;22:1832–41. 11 Miller PD, Bolognese MA, Lewiecki EM, et al. Effect of denosumab on bone density and turnover in postmenopausal women with low bone mass after long-term continued, discontinued, and restarting of therapy: a randomized blinded phase 2 clinical trial. Bone 2008;43:222–9. 12 Bone HG, Bolognese MA, Yuen CK, et al. Effects of denosumab on bone mineral density and bone turnover in postmenopausal women. J Clin Endocrinol Metab 2008;93:2149–57. 13 Brown JP, Prince RL, Deal C, et al. Comparison of the effect of denosumab and alendronate on bone mineral density and biochemical markers of bone turnover in postmenopausal women with low bone mass: A randomized, blinded, phase 3 trial. J Bone Miner Res 2009;24:153–61. 14 Kendler DL, Roux C, Benhamou CL, et al. Effects of denosumab on bone mineral density and bone turnover in postmenopausal women transitioning from alendronate therapy. J Bone Miner Res 2010;25:72–81. 15 Cummings SR, San Martin J, McClung MR, et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 2009;361:756–65. 16 Li Z, Chines AA, Meredith MP. Statistical validation of surrogate endpoints: is bone density a valid surrogate for fracture? J Musculoskelet Neuronal Interact 2004;4:64–74. 17 Cummings S, Yang Y, Vittinghoff E, et al. Increases in BMD on denosumab explain much of the reduction in fracture risk. J Bone Miner Res 2009;24(Suppl 1):56. 18 Dempster DW. Primer on the metabolic bone diseases and disorders of mineral metabolism. 6th ed. 2006:7–11. 19 Seeman E, Delmas PD. Bone quality – the material and structural basis of bone strength and fragility. N Engl J Med 2006;354:2250–61. 20 Wilson KE. Emerging trends in dual energy x-ray absorptiometry. Hologic, Inc. http://www.hologic.com/data/ W_159_09-06_%20EmergTrendinDXA.pdf 21 Beck TJ. Extending DXA beyond bone mineral density: understanding hip structure analysis. Curr Osteoporos Rep 2007;5:49–55. 22 Beck TJ, Lewiecki EM, Miller PD, et al. Effects of denosumab on the geometry of the proximal femur in postmenopausal women in comparison with alendronate. J Clin Densitometry 2008;11: 351–9. 23 Genant HK, Engelke K, Hanley DA, et al. Denosumab improves density and strength parameters as measured by QCT of the radius in postmenopausal women with low bone mineral density. Bone 2010;47:131–9. 24 Gever J. FDA questions denosumab safety in advisory meeting documents. Available at: http://www.medpagetoday.com/ ProductAlert/Prescriptions/15486, accessed November 20, 2010. 25 Lewiecki EM. Treatment of osteoporosis with denosumab. Maturitas 2010;66:182–86.

Souhrn

Denosumab je novým lékem postmenopauzální osteoporózy s novým mechanismem účinku a s potenciálem širokého využití u různých stavů spojených s vysokým kostním obratem. V rozsáhlém programu klinických studií II. a III. fáze byly zkoumány různé aspekty jeho účinku. Denosumab prokázal účinnost z pohledu redukce rizika fraktur ve studii FREEDOM. Byl rovněž srovnáván s etablovaným lékem osteoporózy alendronátem, přičemž ve všech sledovaných lokalizacích byl prokázán výraznější účinek denosumabu na zvýšení kostní denzity (BMD). Lék byl účinný rovněž u pacientek předléčených alendronátem. V subanalýzách klinických studií bylo hodnoceno působení léku na trámčitou i kortikální kost a byl prokázán příznivý vliv na oba základní typy kosti. „

Literatura

1 Lewiecki EM. RANK ligand inhibition with denosumab for the management of osteoporosis. Expert Opin Biol Ther 2006;6:1041–50. 2 McClung MR, Lewiecki EM, Cohen SB, et al. Denosumab in postmenopausal women with low bone mineral density. N Engl J Med 2006; 354:821–31. 3 Hsu H, Lacey DL, Dunstan CR, et al. Tumor necrosis factor receptor family member RANK mediates osteoclast differentiation and activation induced by osteoprotegerin ligand. Proc Natl Acad Sci 1999;96:3540–5. 4 Fata JE, Kong YY, Li J, et al. The osteoclast differentiation factor osteoprotegerin ligand is essentials for mammary gland development. Cell 2000;103:41–50. 5 Anderson DM, Maraskovsky E, Billingsley WL, et al. A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function. Nature 1997;390:175–9. 6 Boyle WJ, Simonet WS, Laceyet DL, el al. Osteoclast differentiation and activation. Nature 2003;423:337–42. 7 Bekker PJ, Holloway DL, Rasmussen AS, et al. Single-dose placebo-controlled study of AMG 162, a fully human monoclonal antibody to RANKL, in postmenopausal women. J Bone Miner Res 2004;19:1059–66. 8 Yasuda H, Shima N, Nakagawa N, et al. Osteoclast differentiation factor is a ligand for osteoprotegerin/oscteoclastogenesis inhibitory factor and is identical to TRANCE/RANKL. Proc Natl Acad Sci 1998;95:3597–602. 9 Lacey DL, Tan HL, Lu J, et al. Osteoprotegerin ligand modulates murine osteoclast survival in vitro and in vivo. Am J Pathol 2000;157:435–48.
10
Lewiecki EM, Miller PD, McClung MR, et al. Two-year treatment with denosumab (AMG 162) in a randomized phase 2 study of postmenopausal women with low bone mineral density. J Bone Miner Res 2007;22:1832–41.
11
Miller PD, Bolognese MA, Lewiecki EM, et al. Effect of denosumab on bone density and turnover in postmenopausal women with low bone mass after long-term continued, discontinued, and restarting of therapy: a randomized blinded phase 2 clinical trial. Bone 2008;43:222–9.
12
Bone HG, Bolognese MA, Yuen CK, et al. Effects of denosumab on bone mineral density and bone turnover in postmenopausal women. J Clin Endocrinol Metab 2008;93:2149–57.
13
Brown JP, Prince RL, Deal C, et al. Comparison of the effect of denosumab and alendronate on bone mineral density and biochemical markers of bone turnover in postmenopausal women with low bone mass: A randomized, blinded, phase 3 trial. J Bone Miner Res 2009;24:153–61.
14
Kendler DL, Roux C, Benhamou CL, et al. Effects of denosumab on bone mineral density and bone turnover in postmenopausal women transitioning from alendronate therapy. J Bone Miner Res 2010;25:72–81.
15
Cummings SR, San Martin J, McClung MR, et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 2009;361:756–65.
16
Li Z, Chines AA, Meredith MP. Statistical validation of surrogate endpoints: is bone density a valid surrogate for fracture? J Musculoskelet Neuronal Interact 2004;4:64–74.
17
Cummings S, Yang Y, Vittinghoff E, et al. Increases in BMD on denosumab explain much of the reduction in fracture risk. J Bone Miner Res 2009;24(Suppl 1):56.
18
Dempster DW. Primer on the metabolic bone diseases and disorders of mineral metabolism. 6th ed. 2006:7–11.
19
Seeman E, Delmas PD. Bone quality – the material and structural basis of bone strength and fragility. N Engl J Med 2006;354:2250–61.
20
Wilson KE. Emerging trends in dual energy x-ray absorptiometry. Hologic, Inc. http://www.hologic.com/data/ W_159_09-06_%20EmergTrendinDXA.pdf
21
Beck TJ. Extending DXA beyond bone mineral density: understanding hip structure analysis. Curr Osteoporos Rep 2007;5:49–55.
22
Beck TJ, Lewiecki EM, Miller PD, et al. Effects of denosumab on the geometry of the proximal femur in postmenopausal women in comparison with alendronate. J Clin Densitometry 2008;11: 351–9.
23
Genant HK, Engelke K, Hanley DA, et al. Denosumab improves density and strength parameters as measured by QCT of the radius in postmenopausal women with low bone mineral density. Bone 2010;47:131–9.
24
Gever J. FDA questions denosumab safety in advisory meeting documents. Available at: http://www.medpagetoday.com/ ProductAlert/Prescriptions/15486, accessed November 20, 2010.
25
Lewiecki EM. Treatment of osteoporosis with denosumab. Maturitas 2010;66:182–86.

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