medigraphic.com
Federación Mexicana de Ginecología y Obstetricia, A.C.

2013, Number 03

<< Back Next >>

Ginecol Obstet Mex 2013; 81 (03)

Inhibition of RANK-L in the pathophysiology of osteoporosis. Clinical evidences of its use

Neyro JL, Cancelo MJ, Palacios S

Language: Spanish
References: 33
Page: 146-157
PDF size: 1226.24 Kb.


ABSTRACT

The increase bone turnover is the most important fact at the physiopathology of postmenopausal osteoporosis. At the molecular level it is the increase of the RANK-L the principal mediator who allows the osteoclasts formation, survival and development of them. Multiple models have been in use in preclinical investigations for evaluating the effects of the inhibition of the RANKL, between which it is included on OPG’s over-expression in mice and transgenic mouse and by means of other models that include the treatment with recombinant OPG. The results of these studies show that RANKL’s inhibition improves the DMO as well as the geometry and resistance of the bone. Several references clinical trials have investigated the potential of denosumab as antiresorptive drug for the prevention and treatment of bone disease. It is a monoclonal antibody, the first fully human, which were recently published results of randomized clinical trials to eight years for increasing BMD in different locations and five years for the prevention of vertebral and hip fractures. We review the fundamentals of the mechanism of inhibition of RANK-L and the results of several clinical trials of Denosumab


REFERENCES

  1. Crockett JC, Mellis DJ, Scott DI, Helfrich MH. New knowledge on critical osteoclast formation and activation pathways from study of rare genetic diseases of osteoclasts: focus on the RANK/RANKL axis. Osteoporos Int 2011;22:1-20.

  2. Lewiecki EM. Denosumab update. Curr Opin Rheumatol 2009;21.

  3. Neyro JL, Cano A, Palacios S. Regulación del metabolismo óseo a través del sistema RANK-RANKL-OPG. Rev Osteoporos Metab Miner 2011;3:105-112. Disponible en http://www. revistadeosteoporosisymetabolismomineral.com/articulo.php ?ano=2011&volumen=3&numero=2&paginicio=105&pagfin=1 12&idnumero=120110302. Última consulta 18.02.12

  4. Prolia®. Ficha técnica (denosumab). Laboratorios Amgen SA. Disponible en http://www.amgen.com/medpro/products_prolia. html. Última consulta 18.02.12

  5. Nakashima T, Hayashi M, Fukunaga T, Kurata K, Oh-hora M, et al. Evidence for osteocyte regulation of bone homeostasis through RANKL expression. Nature America, 2011. Published online at http://www.nature.com/naturemedicine/. Última consulta 19.02.12.

  6. Kearns AE, Khosla S, Kostenuik PJ. Receptor activator of nuclear factor kappaB ligand and osteoprotegerin regulation of bone remodeling in health and disease. Endocr Rev 2008;29:155-192.

  7. Boyce BF, Xing L. Functions of RANKL/RANK/OPG in bone modeling and remodeling. Arch Biochem Biophys 2008;473:139-146.

  8. Boyle WJ, Simonet WS, Lacey DL. Osteoclast differentiation and activation. Nature 2003; 423:337-342.

  9. Takahashi N, Maeda K, Ishihara A, Uehara S, Kobayashi Y. Regulatory mechanism of osteoclastogenesis by RANKL and Wnt signals. Front Biosci 2011;16:21-30.

  10. Kostenuik PJ. Osteoprotegerin and RANKL regulate bone resorption, density, geometry and strength. Curr Opin Pharmacol 2005;5(6):618-625.

  11. Vega D, Maalouf NM, Sakhaee K. The role of receptor activator of nuclear factor-kappaB (RANK)/RANK ligand/ osteoprotegerin: clinical implications. J Clin Endocrinol Metab 2007;92:4514-4521.

  12. Fiter J, Nolla JM. Fisiopatología: remodelado óseo en el anciano. En: Osteoporosis. Guía de buena práctica clínica en geriatría. Osteoporosis. 2004. Sociedad Española de Geriatría y Gerontología. Ed: Mesa MP, Guañabens N. 21-34. Disponible en: Fiter J, Nolla JM. Fisiopatología: remodelado óseo en el anciano. En: Osteoporosis. Guía de buena práctica clínica en geriatría. Osteoporosis. 2004. Sociedad Española de Geriatría y Gerontología. Ed: Mesa MP, Guañabens N. 21-34. Disponible en: http://www.scribd.com/doc/6696048/Gui-a-Osteoporosis.

  13. Geusens P. Emerging treatments for postmenopausal osteoporosis - focus on denosumab. Clin Interv Aging 2009;4:241-250.

  14. Tanos T, Brisken C. High hopes for RANKL: will the mouse model live up to its promise? Breast Cancer Res 2011;13:302.

  15. González-Suárez E. RANKL inhibition: a promising novel strategy for breast cancer treatment. Clin Transl Oncol 2011;13:222-228.

  16. González-Suarez E, Jacob AP, Jones J, Miller R, Roudier- Meyer MP, et al. RANK ligand mediates progestin-induced mammary epithelial proliferation and carcinogenesis. Nature 2010;468:103-107. Epub 2010 Sep 29.

  17. Hock JM. Anabolic Actions of PTH in the skeletons of animals. J Musculoskel Neuron Interact 2001;2:33-47.

  18. Ma YL, Cain RL, Halladay DL, Yang X, Zeng Q, et al. Catabolic Effects of continuous human PTH (1-38) in vivo is associated with sustained stimulation of RANKL and inhibition of osteoportegein and gene-associated bone formation. Endocrinology 2001;142:4047-4054.

  19. Onyia JE, Helvering LM, Glebert L, Wei T, Huang S, et al. Molecular profile of catabolic versus anabolic treatment regimens of parathyroid hormone (PTH) in rat bone: An analysis by DNA microarry. J Cell Biochem 2005;95:403-418.

  20. Ominsky MS, Li C, Li X, Tan HL, Lee E, et al Inhibition of sclerostin by monoclonal antibody enhances bone healing and improves bone density and strength of non-fractured bones. J. Bone Miner Res 2010 Dec. DOI: 10.1002/jbmr.307. Disponible en http://onlinelibrary.wiley.com/doi/10.1002/jbmr.307. Última consulta 19.02.12.

  21. Disponible en http://www. c l i n i c a l t r i a l s . g o v / c t 2 / results?term=denosumab. Última consulta 19.02.12

  22. McClung MR, Lewiecki EM, Cohen SB, Bolognese MA, Woodson GC, et al. Denosumab in postmenopausal women with low bone mineral density. N Engl J Med 2006;354:821-831.

  23. Bone HG, Bolognese MA, Yuen CK, Kendler DL, Wang H, et al. Effects of denosumab on bone mineral density and bone turnover in postmenopausal women. J Clin Endocrinol Metab 2008;93:2149-2157.

  24. Brown JP, Prince RL, Deal C, Recker RR, Kiel DP, et al. Comparison of the effect of denosumab and alendronate on BMD and biochemical markers of bone turnover in postmenopausal women with low bone mass: a randomized, blinded, phase 3 trial. J Bone Miner Res 2009;24:153-161.

  25. Kendler DL, Roux C, Benhamou CL, Brown JP, Lillestol M, et al. Effects of Denosumab on Bone Mineral Density and Bone Turnover in Postmenopausal Women Transitioning from Alendronate Therapy. J Bone Miner Res 2009 Jul 13. [Epub ahead of print] PMID: 19594293.

  26. Kendler DL, Bessette L, Hill CD, Gold DT, Horne R, et al. Preference and satisfaction with a 6-month subcutaneous injection versus a weekly tablet for treatment of low bone mass. Osteoporos Int. 2009 Aug 6. [Epub ahead of print] PMID: 19657689.

  27. Cummings SR, San Martin J, McClung MR, Siris ES, Eastell R, et al. FREEDOM Trial. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 2009;361:756-765.

  28. Neyro JL, Palacios S, Cano A. Perfil de acción de Denosumab en el tratamiento de la osteoporosis. Rev Osteoporos Metab Miner 2011;4:183-188. Disponible en http://www.revistadeosteoporosisymetabolismomineral. com/articulo.php?ano=2011 &volumen=3&numero=4&paginicio=183&pagfin=188&idnum ero=120110304. Última consulta 18.02.12.

  29. Papapoulos S, Chapurlat R, Libanati C, Brandi M, Brown J, et al. Five years of denosumab exposure in women with postmenopausal osteoporosis: Results from the first two years of the FREEDOM extension. JBMR 2012;27:694-701.

  30. McClung M, Lewiecki EM, Bolognese MA, Peacock M, Weinstein R, Ding B, Geller ML, Grauer A, Wagman RB, Miller P. Effects of Denosumab on Bone Mineral Density and Biochemical Markers of Bone Turnover: 8-Year Results of a Phase 2 Clinical Trial. ASBMR 2011 Annual Meeting. September 16-20, 2011. San Diego, California, USA.

  31. Fosamax® (Alendronato). Ficha técnica Laboratorios Merck Sharp & Dohme Ltd Disponible en http://www.msd.es/productos/ fichas-tecnicas/ft_fosamax_70_es.pdf. Última consulta 19.02.12.

  32. Brown JP, Prince RL, Deal C, et al. Comparison of the effect of denosumab and alendronate on BMD and biochemical markers of bone turnover in postmenopausal women with low bone mass: a randomized, blinded, phase 3 trial. J Bone Miner Res. 2009; 24:153-161. Disponible en: http://delivery. sheridan.com/downloads/mobile/JBMR_152185_CP.exe. Última consulta 19.02.12.

  33. 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. Disponible en: http://delivery. sheridan.com/downloads/mobile/JBMR_162485_CP.exe. Última consulta 19.02.12.




2020     |     www.medigraphic.com