Prolia Mechanism of Action | Osteoporosis | Amgen

PROLIA® HAS A UNIQUE MECHANISM OF ACTION THAT WORKS ON BOTH CORTICAL AND TRABECULAR BONE1,2

Prolia® is a fully human monoclonal IgG2 antibody against RANKL. Prolia® is a therapy that mimics osteoprotegerin, the body’s natural bone protection mechanism, to inhibit osteoclast formation, function and survival.2,3
Prolia® blocks RANKL thereby preventing its binding with the RANK receptor on the surface of osteoclasts and their precursor cells. The inhibition prevents the osteoclasts maturing or even reaching the bone surface.2,4 By preventing RANKL/RANK interaction, Prolia® decreases both cortical and trabecular bone resorption.2,5
The reversible mode of action of Prolia® means it should not be stopped without considering an alternative anti-resorptive therapy.11
Bisphosphonates preferentially bind to trabecular bone, which is more accessible and metabolically active than cortical bone. Bisphosphonates tend to integrate into the bone matrix.2,12
Prolia® acts on both cortical and trabecular bone to improve bone strength and is not incorporated into the bone matrix.1-3

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Mechanism of Action
Schematic representation of the proposed quantitative computed tomography changes in bone compartments according to Prolia® or placebo treatment.1
Adapted from McClung MR, et al. 2013.1

References:
IgG2: immunoglobulin G2; RANK(L): receptor activator of nuclear factor kappa-B (ligand).
  1. McClung MR, et al. J Clin Densitom. 2013;16:250–6.
  2. Baron R, et al. Bone. 2011;48:677–92.
  3. Prolia® (denosumab) Summary of Product Characteristics. Amgen. Last revised February 2020.
  4. Boyle WJ, et al. Nature. 2003;423:337–42.
  5. Bolognese MA, et al. J Clin Densitom. 2013;16:147–53.
  6. Dempster DW. Primer on the metabolic bone diseases and disorders of mineral metabolism. 6th ed. Washington, DC: American Society for Bone and Mineral Research; 2006;7–11.
  7. Bishop NJ, Russell G. Chapter 53 – Bisphosphonates. In: Shapiro JR, Byers PH, Glorieux FH, Sponseller PD (eds). Osteogenesis Imperfecta. London: Academic Press; 2014:495–500.
  8. Allen MR. Expert Opin Drug Metab Toxicol. 2008;4:1371–8.
  9. Seeman E, et al. J Bone Miner Res. 2010;25:1886–94.
  10. Kostenuik PJ, et al. J Bone Miner Res. 2009;24:182–95.
  11. Tsourdi E, et al. Bone. 2017;105:11–7.
  12. Pazianas M, et al. Bonekey Rep. 2014;3:529.
  13. Augat P, et al. Age Ageing. 2006;35(Suppl 2):ii27–31.

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