Receptor Activator of Nuclear Factor-κB Ligand and Osteoprotegerin: Maintaining the Balance to Prevent Bone Loss

Overview

Journal Clin Interv Aging

Publisher Dove Medical Press

Specialty Geriatrics

Date 2011 Jan 14

PMID 21228900

Citations 88

Authors

Anne-Priscille Trouvin

Vincent Goeb

Affiliations

Soon will be listed here.

Abstract

Bone remodeling requires a precise balance between resorption and formation. It is a complex process that involves numerous factors: hormones, growth factors, vitamins, and cytokines, and notably osteoprotegerin (OPG) and receptor activator for nuclear factor-κB (RANK) ligand. The signaling pathway OPG/RANK/RANKL is key to regulation for maintaining the balance between the activity of osteoblasts and osteoclasts in order to prevent bone loss and ensure a normal bone turnover. In this review, the RANK/RANKL/OPG pathway is described. The multiple interactions of various factors (hormones, cytokines, growth factors, and vitamins) with the OPG/RANK/RANKL pathway are also commented on. Finally, the effects of denosumab, a human monoclonal antibody that binds to RANKL and thereby inhibits the activation of osteoclasts, and of strontium ranelate are also described. Indeed, these two new drugs afford appreciable assistance in daily care practice, helping to prevent bone loss in patients with osteoporosis.

Citing Articles

Sclerostin and OPG/RANK-L system take part in bone remodeling in patients with acromegaly.

Halupczok-Zyla J, Jawiarczyk-Przybylowska A, Bolanowski M Front Endocrinol (Lausanne). 2025; 15:1472680.

PMID: 39741885 PMC: 11685073. DOI: 10.3389/fendo.2024.1472680.

Harnessing curcumin and nanotechnology for enhanced treatment of breast cancer bone metastasis.

Shakori Poshteh S, Alipour S, Varamini P Discov Nano. 2024; 19(1):177.

PMID: 39527354 PMC: 11554965. DOI: 10.1186/s11671-024-04126-1.

Potential Predictive of Thoracic CT Value and Bone Mineral Density T-Value in COPD Complicated with Osteoporosis.

Hu T, Dai S, Yang L, Zhu B Int J Gen Med. 2024; 17:3027-3038.

PMID: 39006914 PMC: 11246664. DOI: 10.2147/IJGM.S466292.

Advantages of Using 3D Spheroid Culture Systems in Toxicological and Pharmacological Assessment for Osteogenesis Research.

Yun C, Kim S, Kim K, Yang M, Byun M, Kim J Int J Mol Sci. 2024; 25(5).

PMID: 38473760 PMC: 10931738. DOI: 10.3390/ijms25052512.

Effects of low-level laser on the expression of interleukin-6, tumor necrosis factor‑α, osteoprotegerin, and receptor activator of nuclear factor-κB ligand in human periodontal ligament cells.

Tang M, Cui Z, Wang Y, Chen Z, Li W, Zhang C Hua Xi Kou Qiang Yi Xue Za Zhi. 2023; 41(5):521-532.

PMID: 37805676 PMC: 10580225. DOI: 10.7518/hxkq.2023.2023133.

References

Eghbali-Fatourechi G, Khosla S, Sanyal A, Boyle W, Lacey D, Riggs B . Role of RANK ligand in mediating increased bone resorption in early postmenopausal women. J Clin Invest. 2003; 111(8):1221-30. PMC: 152939. DOI: 10.1172/JCI17215. View

Indridason O, Franzson L, Sigurdsson G . Serum osteoprotegerin and its relationship with bone mineral density and markers of bone turnover. Osteoporos Int. 2005; 16(4):417-23. DOI: 10.1007/s00198-004-1699-x. View

Rogers A, Saleh G, Hannon R, Greenfield D, Eastell R . Circulating estradiol and osteoprotegerin as determinants of bone turnover and bone density in postmenopausal women. J Clin Endocrinol Metab. 2002; 87(10):4470-5. DOI: 10.1210/jc.2002-020396. View

Lewiecki E, Miller P, McClung M, Cohen S, Bolognese M, Liu Y . Two-year treatment with denosumab (AMG 162) in a randomized phase 2 study of postmenopausal women with low BMD. J Bone Miner Res. 2007; 22(12):1832-41. DOI: 10.1359/jbmr.070809. View

Liu J, Zhao H, Ning G, Zhao Y, Chen Y, Zhang Z . Relationships between the changes of serum levels of OPG and RANKL with age, menopause, bone biochemical markers and bone mineral density in Chinese women aged 20-75. Calcif Tissue Int. 2004; 76(1):1-6. DOI: 10.1007/s00223-004-0007-2. View

Li X, Ominsky M, Stolina M, Warmington K, Geng Z, Niu Q . Increased RANK ligand in bone marrow of orchiectomized rats and prevention of their bone loss by the RANK ligand inhibitor osteoprotegerin. Bone. 2009; 45(4):669-76. DOI: 10.1016/j.bone.2009.06.011. View

Hofbauer L, Hicok K, Chen D, Khosla S . Regulation of osteoprotegerin production by androgens and anti-androgens in human osteoblastic lineage cells. Eur J Endocrinol. 2002; 147(2):269-73. DOI: 10.1530/eje.0.1470269. View

Boyle W, Simonet W, Lacey D . Osteoclast differentiation and activation. Nature. 2003; 423(6937):337-42. DOI: 10.1038/nature01658. View

Bekker P, Holloway D, Rasmussen A, Murphy R, Martin S, Leese P . A single-dose placebo-controlled study of AMG 162, a fully human monoclonal antibody to RANKL, in postmenopausal women. J Bone Miner Res. 2004; 19(7):1059-66. DOI: 10.1359/JBMR.040305. View

10.

Jorgensen H, Kusk P, Madsen B, Fenger M, Lauritzen J . Serum osteoprotegerin (OPG) and the A163G polymorphism in the OPG promoter region are related to peripheral measures of bone mass and fracture odds ratios. J Bone Miner Metab. 2004; 22(2):132-8. DOI: 10.1007/s00774-003-0461-3. View

11.

Lewiecki E . Current and emerging pharmacologic therapies for the management of postmenopausal osteoporosis. J Womens Health (Larchmt). 2009; 18(10):1615-26. DOI: 10.1089/jwh.2008.1086. View

12.

Atkins G, Welldon K, Halbout P, Findlay D . Strontium ranelate treatment of human primary osteoblasts promotes an osteocyte-like phenotype while eliciting an osteoprotegerin response. Osteoporos Int. 2008; 20(4):653-64. DOI: 10.1007/s00198-008-0728-6. View

13.

Kong Y, Yoshida H, Sarosi I, Tan H, Timms E, Capparelli C . OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis. Nature. 1999; 397(6717):315-23. DOI: 10.1038/16852. View

14.

Rogers A, Eastell R . Circulating osteoprotegerin and receptor activator for nuclear factor kappaB ligand: clinical utility in metabolic bone disease assessment. J Clin Endocrinol Metab. 2005; 90(11):6323-31. DOI: 10.1210/jc.2005-0794. View

15.

Nakagawa N, Kinosaki M, Yamaguchi K, Shima N, Yasuda H, Yano K . RANK is the essential signaling receptor for osteoclast differentiation factor in osteoclastogenesis. Biochem Biophys Res Commun. 1999; 253(2):395-400. DOI: 10.1006/bbrc.1998.9788. View

16.

Meunier P, Roux C, Seeman E, Ortolani S, Badurski J, Spector T . The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis. N Engl J Med. 2004; 350(5):459-68. DOI: 10.1056/NEJMoa022436. View

17.

Nakamichi Y, Udagawa N, Kobayashi Y, Nakamura M, Yamamoto Y, Yamashita T . Osteoprotegerin reduces the serum level of receptor activator of NF-kappaB ligand derived from osteoblasts. J Immunol. 2006; 178(1):192-200. DOI: 10.4049/jimmunol.178.1.192. View

18.

Brennan T, Rybchyn M, Green W, Atwa S, Conigrave A, Mason R . Osteoblasts play key roles in the mechanisms of action of strontium ranelate. Br J Pharmacol. 2009; 157(7):1291-300. PMC: 2743848. DOI: 10.1111/j.1476-5381.2009.00305.x. View

19.

Roshandel D, Holliday K, Pye S, Boonen S, Borghs H, Vanderschueren D . Genetic variation in the RANKL/RANK/OPG signaling pathway is associated with bone turnover and bone mineral density in men. J Bone Miner Res. 2010; 25(8):1830-8. DOI: 10.1002/jbmr.78. View

20.

Brown J, Prince R, Deal C, Recker R, Kiel D, de Gregorio L . 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. 2008; 24(1):153-61. DOI: 10.1359/jbmr.0809010. View