Summary: A secreted member of the TNF receptor superfamily that negatively regulates osteoclastogenesis. It is a soluble decoy receptor of RANK LIGAND that inhibits both CELL DIFFERENTIATION and function of OSTEOCLASTS by inhibiting the interaction between RANK LIGAND and RECEPTOR ACTIVATOR OF NUCLEAR FACTOR-KAPPA B.

Top Publications

  1. Hofbauer L, Heufelder A. Clinical review 114: hot topic. The role of receptor activator of nuclear factor-kappaB ligand and osteoprotegerin in the pathogenesis and treatment of metabolic bone diseases. J Clin Endocrinol Metab. 2000;85:2355-63 pubmed
  2. Yu Z, Sanders A, Owen S, Cheng S, Yang X, Jiang W. Expression of Osteoprotegrin Is Enhanced in Lung Cancer Tissues and Promotes Aggressive Cellular Traits in H3122 Lung Cancer Cells. Anticancer Res. 2017;37:4277-4283 pubmed
    ..OPG may be a potential driver of lung cancer cells and therefore might have potential in therapy and diagnostics. ..
  3. Vezzani G, Quartesan S, Cancellara P, Camporesi E, Mangar D, Bernasek T, et al. Hyperbaric oxygen therapy modulates serum OPG/RANKL in femoral head necrosis patients. J Enzyme Inhib Med Chem. 2017;32:707-711 pubmed publisher
    ..We investigated if HBOT upregulates serum osteoprotegerin (OPG) and/or inhibits osteoclast activation...
  4. Ozaki Y, Koide M, Furuya Y, Ninomiya T, Yasuda H, Nakamura M, et al. Treatment of OPG-deficient mice with WP9QY, a RANKL-binding peptide, recovers alveolar bone loss by suppressing osteoclastogenesis and enhancing osteoblastogenesis. PLoS ONE. 2017;12:e0184904 pubmed publisher
    ..express two key molecules for osteoclast differentiation, receptor activator of NF-?B ligand (RANKL) and osteoprotegerin (OPG), a soluble decoy receptor for RANKL...
  5. Tschiderer L, Willeit J, Schett G, Kiechl S, Willeit P. Osteoprotegerin concentration and risk of cardiovascular outcomes in nine general population studies: Literature-based meta-analysis involving 26,442 participants. PLoS ONE. 2017;12:e0183910 pubmed publisher
    Recent experimental and epidemiological studies have suggested that osteoprotegerin, a key regulator in bone metabolism, may be involved in vascular calcification and atherosclerosis...
  6. Irtiuga O, Zhiduleva E, Dubrovskaia O, Moiseeva O. [Concentration of osteoprotegerin and RANKL in blood serum of patients with aortic stenosis]. Kardiologiia. 2014;54:44-8 pubmed
    to compare blood serum levels of osteoprotegerin (OPG) and soluble receptor activator of nuclear factor B ligand (sRANKL) in patients with different morphological variants of stenosis...
  7. El Khassawna T, Merboth F, Malhan D, Bocker W, Daghma D, Stoetzel S, et al. Osteocyte Regulation of Receptor Activator of NF-?B Ligand/Osteoprotegerin in a Sheep Model of Osteoporosis. Am J Pathol. 2017;187:1686-1699 pubmed publisher
    ..However, the quantification of receptor activator of NF-?B ligand (RANKL) and osteoprotegerin (OPG) signaling in osteocytes was not studied in sheep...
  8. Bergdolt S, Kovtun A, Hägele Y, Liedert A, Schinke T, Amling M, et al. Osteoblast-specific overexpression of complement receptor C5aR1 impairs fracture healing. PLoS ONE. 2017;12:e0179512 pubmed publisher
    ..Additional trauma significantly impaired fracture healing, particularly in Col1a1-C5aR1 mice. In conclusion, the data indicate that C5aR1 signaling in osteoblasts plays a detrimental role in bone regeneration after fracture. ..
  9. Kruzliak P, Berezin A, Kremzer A, Samura T, Benacka R, Mozos I, et al. Global Longitudinal Strain and Strain Rate in Type Two Diabetes Patients with Chronic Heart Failure: Relevance to Osteoprotegerin. Folia Med (Plovdiv). 2016;58:164-173 pubmed publisher
    ..Serum adiponectin, NT-pro brain natriuretic peptide (BNP), osteoprotegerin, and hs- C-reactive protein (CRP) were determined at baseline by ELISA...

More Information


  1. Maria S, Swanson M, Enderby L, D Amico F, Enderby B, Samsonraj R, et al. Melatonin-micronutrients Osteopenia Treatment Study (MOTS): a translational study assessing melatonin, strontium (citrate), vitamin D3 and vitamin K2 (MK7) on bone density, bone marker turnover and health related quality of life in postmenopausal ost. Aging (Albany NY). 2017;9:256-285 pubmed publisher
    ..In adipose-derived human MSCs, MSDK induced osteoblastogenesis. These findings provide both clinical and mechanistic support for the use of MSDK for the prevention or treatment of osteopenia, osteoporosis or other bone-related diseases...
  2. Atkins G, Haynes D, Graves S, Evdokiou A, Hay S, Bouralexis S, et al. Expression of osteoclast differentiation signals by stromal elements of giant cell tumors. J Bone Miner Res. 2000;15:640-9 pubmed
    ..we investigated expression of the ODF receptor on osteoclast precursors, RANK, as well as the ODF inhibitor osteoprotegerin (OPG), and another TNF-ligand superfamily member, TRAIL, previously shown to abrogate the inhibitory effects ..
  3. Apolikhin O, Sivkov A, Konstantinova O, Slominskii P, Tupitsyna T, Kalinichenko D. [Early diagnosis of risk for developing calcium oxalate urolithiasis]. Urologiia. 2017;:5-8 pubmed
  4. Okamoto K, Nakashima T, Shinohara M, Negishi Koga T, Komatsu N, Terashima A, et al. Osteoimmunology: The Conceptual Framework Unifying the Immune and Skeletal Systems. Physiol Rev. 2017;97:1295-1349 pubmed publisher
    ..The concept of a unified osteoimmune system will be absolutely indispensable for basic and translational approaches to diseases related to bone and/or the immune system. ..
  5. Krajewska Włodarczyk M, Stompor T. [Osteoporosis and vascular calcification in rheumatoid arthritis - the role of osteoprotegerin and sclerostin]. Pol Merkur Lekarski. 2017;43:41-47 pubmed
    ..intensification of vascular calcification seem to be associated with the increase of plasma concentration of osteoprotegerin (OPG) and sclerostin - the regulatory proteins of the RANKL/RANK/OPG system and the Wnt/?-catenin pathway...
  6. Trawitzki B, Lilge L, de Figueiredo F, Macedo A, Issa J. Low-intensity laser therapy efficacy evaluation in mice subjected to acute arthritis condition. J Photochem Photobiol B. 2017;174:126-132 pubmed publisher
    ..05). LILT showed signs of an anti-inflammatory effect when applied once, but promoted increased resorptive area when used for two sessions, indicating the importance of a controlled LILT protocol to reach therapeutic effects. ..
  7. Thomas R, Guise T, Yin J, Elliott J, Horwood N, Martin T, et al. Breast cancer cells interact with osteoblasts to support osteoclast formation. Endocrinology. 1999;140:4451-8 pubmed
    ..well as its cognate signaling receptor, receptor activator of NFkappaB (RANK), and a secreted decoy receptor osteoprotegerin (OPG) that limits RANKL's biological action...
  8. Brabnikova Maresova K, Jarosova K, Pavelka K, Stepan J. Serum sclerostin in high-activity adult patients with juvenile idiopathic arthritis. Arthritis Res Ther. 2014;16:460 pubmed publisher
    ..bone turnover markers and serum concentrations of soluble receptor activator of nuclear factor κB ligand, osteoprotegerin, dickkopf Wnt signalling pathway inhibitor 1 (Dkk1) and sclerostin were evaluated...
  9. Wei C, You F, Mei L, Jian S, Qiang C. Total glucosides of paeony prevents juxta-articular bone loss in experimental arthritis. BMC Complement Altern Med. 2013;13:186 pubmed publisher
    ..Histological analysis and mRNA expression of receptor activator of nuclear factor-B ligand (RANKL) and osteoprotegerin (OPG) were evaluated in joint tissues...
  10. Park B, Song H, Kwon J, Cho S, Jang S, Kim M, et al. Effects of Salvia miltiorrhiza extract with supplemental liquefied calcium on osteoporosis in calcium-deficient ovariectomized mice. BMC Complement Altern Med. 2017;17:545 pubmed publisher
    ..This result implies the possibility of a pharmacological intervention specifically directed toward a disease such as osteoporosis where decreased bone strength increases the risk of a broken bone . ..
  11. Fortner R, Sarink D, Schock H, Johnson T, Tjønneland A, Olsen A, et al. Osteoprotegerin and breast cancer risk by hormone receptor subtype: a nested case-control study in the EPIC cohort. BMC Med. 2017;15:26 pubmed publisher
    Circulating osteoprotegerin (OPG), a member of the receptor activator of nuclear factor kappa-B (RANK) axis, may influence breast cancer risk via its role as the decoy receptor for both the RANK ligand (RANKL) and tumor necrosis factor-..
  12. de Oliveira L, de Araújo A, de Araújo Júnior R, Barboza C, Borges B, da Silva J. Low-level laser therapy (780 nm) combined with collagen sponge scaffold promotes repair of rat cranial critical-size defects and increases TGF-?, FGF-2, OPG/RANK and osteocalcin expression. Int J Exp Pathol. 2017;98:75-85 pubmed publisher
    ..evaluation of transforming growth factor-beta (TGF-?), fibroblast growth factor-2 (FGF-2), osteoprotegerin (OPG) and receptor activator of nuclear factor ? (RANK)...
  13. Hauser B, Riches P, Gilchrist T, Visconti M, Wilson J, Ralston S. Autoantibodies to osteoprotegerin are associated with increased bone resorption in rheumatoid arthritis. Ann Rheum Dis. 2015;74:1631-2 pubmed publisher
  14. Elmusrati A, Pilborough A, Khurram S, Lambert D. Cancer-associated fibroblasts promote bone invasion in oral squamous cell carcinoma. Br J Cancer. 2017;117:867-875 pubmed publisher
    ..This study is the first to describe a functional role for CAFs in bone invasion and turnover, identifying a novel potential therapeutic target and diagnostic indicator in this difficult to treat bone invasive malignancy. ..
  15. Knevel R, de Rooy D, Saxne T, Lindqvist E, Leijsma M, Daha N, et al. A genetic variant in osteoprotegerin is associated with progression of joint destruction in rheumatoid arthritis. Arthritis Res Ther. 2014;16:R108 pubmed publisher
    ..This bone resorption is inhibited by osteoprotegerin (OPG) which prevents RANKL-RANK interactions...
  16. Tao Y, Wang Z, Wang L, Shi J, Guo X, Zhou W, et al. Downregulation of miR-106b attenuates inflammatory responses and joint damage in collagen-induced arthritis. Rheumatology (Oxford). 2017;56:1804-1813 pubmed publisher
    ..Moreover, miR-106b inhibitor treatment suppressed RANK ligand (RANKL) expression, increased osteoprotegerin (OPG) expression and reduced the RANKL:OPG ratio in CIA mice...
  17. Xi L, Cao H, Chen Y. OPG/RANK/RANKL axis in atrial fibrillation. Cardiology. 2013;125:174-5 pubmed publisher
  18. Sliwicka E, Cisoń T, Kasprzak Z, Nowak A, Pilaczyńska Szcześniak Ł. Serum irisin and myostatin levels after 2 weeks of high-altitude climbing. PLoS ONE. 2017;12:e0181259 pubmed publisher
    ..concentrations of irisin, myostatin, 25(OH)D, interleukin-6, myoglobin, high-sensitivity C-reactive protein, osteoprotegerin, and high-sensitivity soluble receptor activator of NF-?B ligand (sRANKL) were performed before and after ..
  19. Abu El Asrar A, Struyf S, Mohammad G, Gouwy M, Rytinx P, Siddiquei M, et al. Osteoprotegerin Is a New Regulator of Inflammation and Angiogenesis in Proliferative Diabetic Retinopathy. Invest Ophthalmol Vis Sci. 2017;58:3189-3201 pubmed publisher
    b>Osteoprotegerin (OPG) is a novel regulator of endothelial cell function, angiogenesis, and vasculogenesis...
  20. Raimondo A, Lembo S, Di Caprio R, Donnarumma G, Monfrecola G, Balato N, et al. Psoriatic cutaneous inflammation promotes human monocyte differentiation into active osteoclasts, facilitating bone damage. Eur J Immunol. 2017;47:1062-1074 pubmed publisher
    ..The addition of osteoprotegerin, a RANKL inhibitor, to monocyte cultures treated with supernatant from stimulated skin did not completely ..
  21. Park O, Kim J, Yang J, Yun C, Han S. Muramyl Dipeptide, a Shared Structural Motif of Peptidoglycans, Is a Novel Inducer of Bone Formation through Induction of Runx2. J Bone Miner Res. 2017;32:1455-1468 pubmed publisher
    ..no direct effect, MDP indirectly attenuated osteoclast differentiation through downregulation of the RANKL/osteoprotegerin (OPG) ratio...
  22. Dolci G, Portela L, Onofre de Souza D, Medeiros Fossati A. Atorvastatin-induced osteoclast inhibition reduces orthodontic relapse. Am J Orthod Dentofacial Orthop. 2017;151:528-538 pubmed publisher
    ..ATV) might affect orthodontic relapse and osteoclastogenesis by modulating expression of RANKL and osteoprotegerin (OPG), crucial molecules involved in bone turnover...
  23. Irtyuga O, Malashicheva A, Zhiduleva E, Freylikhman O, Rotar O, Bäck M, et al. NOTCH1 Mutations in Aortic Stenosis: Association with Osteoprotegerin/RANK/RANKL. Biomed Res Int. 2017;2017:6917907 pubmed publisher
    ..is known to be important in the pathogenesis of calcific aortic valve disease, possibly through regulators of osteoprotegerin (OPG), receptor activator of nuclear factor ?B (RANK), and its ligand (RANKL) system...
  24. Cao F, Liu X, Cao X, Wang S, Fu K, Zhao Y, et al. Fibroblast growth factor 21 plays an inhibitory role in vascular calcification in vitro through OPG/RANKL system. Biochem Biophys Res Commun. 2017;491:578-586 pubmed publisher
    ..factor(RUNX)-2 and nuclear factor-kappa B ligand (RANKL) were down-regulated, whereas the expression of osteoprotegerin (OPG) increased...
  25. Spirlandeli A, Dick de Paula I, Zamarioli A, Jorgetti V, Ramalho L, Nogueira Barbosa M, et al. Hepatic Osteodystrophy: The Mechanism of Bone Loss in Hepatocellular Disease and the Effects of Pamidronate Treatment. Clinics (Sao Paulo). 2017;72:231-237 pubmed publisher
    ..Taken together, these results suggest that bone resorption is the main mechanism of bone loss in chronic hepatocellular disease in mice. ..
  26. Rimondi E, di Iasio M, Gonelli A, Celeghini C, Secchiero P, Zauli G. Hydrogen sulfide down-regulates the expression and release of osteoprotegerin (OPG) by vascular endothelial cells. Invest New Drugs. 2012;30:1731-5 pubmed publisher
  27. Bartold P, Cantley M, Haynes D. Mechanisms and control of pathologic bone loss in periodontitis. Periodontol 2000. 2010;53:55-69 pubmed publisher
  28. Madarász E, Tamás G, Tabak A, Speer G, Lakatos P, Kerenyi Z. Osteoprotegerin levels in women with prior gestational diabetes mellitus. Diabetes Care. 2009;32:e5 pubmed publisher