The role of the serum RANKL/OPG ratio in the healing of intertrochanteric fractures in elderly patients

Wang,Xue-Fei; Zhang,Ya-Kui; Yu,Zhen-Shan; Zhou,Jun-Lin

doi:10.3892/mmr.2013.1335

The role of the serum RANKL/OPG ratio in the healing of intertrochanteric fractures in elderly patients

Authors:
- Xue-Fei Wang
- Ya-Kui Zhang
- Zhen-Shan Yu
- Jun-Lin Zhou
View Affiliations

Affiliations: Department of Orthopedics, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, P.R. China, Department of Orthopedics, The Luhe Teaching Hospital of the Capital Medical University, Beijing 101149, P.R. China
Published online on: February 21, 2013 https://doi.org/10.3892/mmr.2013.1335
Pages: 1169-1172

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Intertrochanteric fractures occur most commonly in elderly patients. Osteoblasts and osteoclasts have been reported to be regulated by the receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG), during bone modeling and remodeling, respectively. Based on these observations, we hypothesized that the serum levels of RANKL, OPG and the RANKL/OPG ratio are important in the healing of intertrochanteric fractures in elderly patients. Enzyme‑linked immunosorbent assays were used to measure the serum concentrations of RANKL and OPG in 36 elderly patients with intertrochanteric fractures and 30 age-matched healthy control subjects, at baseline and 4, 8 and 12 weeks following injury. The RANKL/OPG ratio in the two groups was also evaluated. Similar trends in RANKL and OPG levels were detected during the fracture healing process. The serum levels of RANKL and OPG were higher in the fracture group than in the controls, and were significantly higher at baseline and 4 weeks following injury (P<0.05). Notably, although the RANKL/OPG ratio gradually increased during healing, it was lower in the fracture group than in the control group. The RANKL/OPG ratio was significantly lower immediately after and 4 weeks after injury in the fracture group (P<0.05). Our data suggest a close correlation between higher serum levels of RANKL and OPG and the fracture healing process, indicating that RANKL and OPG are involved in fracture healing. The serum RANKL/OPG ratio also appears to be significant in the healing of intertrochanteric fractures in elderly patients.

View Figures

View References

1	Kesmezacar H, Oğüt T, Bilgili MG, Gökay S and Tenekecioğlu Y: Treatment of intertrochanteric femur fractures in elderly patients: internal fixation or hemiarthroplasty. Acta Orthop Traumatol Turc. 39:287–294. 2005.(In Turkish).
2	Angelini M, McKee MD, Waddell JP, Haidukewych G and Schemitsch EH: Salvage of failed hip fracture fixation. J Orthop Trauma. 23:471–478. 2009. View Article : Google Scholar : PubMed/NCBI
3	Talmo CT and Bono JV: Treatment of intertrochanteric nonunion of the proximal femur using the S-ROM prosthesis. Orthopedics. 31:1252008. View Article : Google Scholar : PubMed/NCBI
4	Dhammi I, Jain A, Singh A, Rehan-Ul-Haq, Mishra P and Jain S: Primary nonunion of intertrochanteric fractures of femur: an analysis of results of valgization and bone grafting. Indian J Orthop. 45:514–519. 2011. View Article : Google Scholar : PubMed/NCBI
5	Looker AC, Bauer DC, Chesnut CH 3rd, Gundberg CM, Hochberg MC, Klee G, Kleerekoper M, Watts NB and Bell NH: Clinical use of biochemical markers of bone remodeling: current status and future directions. Osteoporos Int. 11:467–480. 2000. View Article : Google Scholar : PubMed/NCBI
6	Kurban S and Mehmetoglu I: Osteoprotegerin, RANK and RANK ligand. Turk J Biochem. 34:178–184. 2007.
7	Stejskal D, Bartek J, Pastorková R, Růzicka V, Oral I and Horalík D: Osteoprotegerin, RANK, RANKL. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 145:61–64. 2001. View Article : Google Scholar
8	Khosla S: Minireview: the OPG/RANKL/RANK system. Endocrinology. 142:5050–5055. 2001. View Article : Google Scholar : PubMed/NCBI
9	Kostenuik PJ and Shalhoub V: Osteoprotegerin: a physiological and pharmacological inhibitor of bone resorption. Curr Pharm Des. 7:613–635. 2001. View Article : Google Scholar : PubMed/NCBI
10	Bucay N, Sarosi I, Dunstan CR, Morony S, Tarpley J, Capparelli C, Scully S, Tan HL, Xu W, Lacey DL, Boyle WJ and Simonet WS: Osteoprotegerin-deficient mice develop early onset osteporosis and arterial calcification. Genes Dev. 12:1260–1268. 1998. View Article : Google Scholar : PubMed/NCBI
11	Gravallese EM, Manning C, Tsay A, Naito A, Pan C, Amento E and Goldring SR: Synovial tissue in rheumatoid arthritis is a source of osteoclast differentiation factor. Arthritis Rheum. 43:250–258. 2004.PubMed/NCBI
12	Hafbauer LC and Schoppet M: Clinical implications of the osteoprotegerin/RANKL/RANK system for bone and vascular diseases. JAMA. 292:490–495. 2004. View Article : Google Scholar : PubMed/NCBI
13	Masi L, Simonini G, Giani T, Del Monte F, Giani T, Cimaz R, Vierucci S, Brandi ML and Falcini F: Osteoprotegerin (OPG)/RANKL system in juvenile idiopathic arthitis: is there a potential modulating role for OPG/RANKL in bone injury? J Rheumatol. 31:986–991. 2004.PubMed/NCBI
14	Blaır JM, Zheng Y and Dunstan CR: RANK ligand. Int J Biochem Cell Biol. 39:1077–1081. 2007.
15	Chamoux E, Houde N, L’Eriger K and Roux S: Osteoprotegerin decreases human osteoclast apoptosis by inhibiting the TRAIL pathway. J Cell Physiol. 216:536–542. 2008. View Article : Google Scholar : PubMed/NCBI
16	Boyce BF and Xing L: Function of RANKL/RANK/OPG in bone modeling end remodeling. Arch Biochem Biophys. 473:139–146. 2008. View Article : Google Scholar : PubMed/NCBI
17	Lacey DL, Timms E, Tan HL, et al: Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell. 93:165–176. 1998. View Article : Google Scholar : PubMed/NCBI
18	Simonet WS, Lacey DL, Dunstan CR, et al: Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell. 89:309–319. 1997. View Article : Google Scholar : PubMed/NCBI
19	Son A, Kim MS, Jo H, Byun HM and Shin DM: Effects of inositol 1,4,5-triphosphate on osteoclast differentiation in RANKL-induced osteoclastogenesis. Korean J Physiol Pharmacol. 16:31–36. 2012. View Article : Google Scholar : PubMed/NCBI
20	Schett G, Kiechl S, Redlich K, Oberhollenzer F, Weger S, Egger G, Mayr A, Jocher J, Xu Q, Pietschmann P, Teitelbaum S, Smolen J and Willeit J: Soluble RANKL and risk of non-traumatic fracture. JAMA. 291:1108–1113. 2004. View Article : Google Scholar : PubMed/NCBI
21	Abdallah BM, Stilgren LS, Nissen N, Kassem M, Jørgensen HR and Abrahamsen B: Increased RANKL/OPG mRNA ratio in iliac bone biopsies from women with hip fractures. Calcif Tissue Int. 76:90–97. 2005. View Article : Google Scholar : PubMed/NCBI
22	Yasuda H, Shima N, Nakagawa N, Yamaguchi K, Kinosaki M, Goto M, Mochizuki SI, Tsuda E, Morinaga T, Udagawa N, Takahashi N, Suda T and Higashio K: A novel molecular mechanism modulating osteoclast differentiation and function. Bone. 25:109–113. 1999. View Article : Google Scholar : PubMed/NCBI
23	Wasilewska A, Rybi-Szuminska A and Zoch-Zwierz W: Serum RANKL, osteoprotegerin (OPG), and RANKL/OPG ratio in nephrotic children. Pediatr Nephrol. 25:2067–2075. 2010. View Article : Google Scholar : PubMed/NCBI
24	Hofbauer LC, Khosla S, Dunstan CR, Lacey DL, Boyle WJ and Riggs BL: The roles of osteoprotegerin and osteoprotegerin ligand in the paracrine regulation of bone resorption. J Bone Miner Res. 15:2–12. 2000. View Article : Google Scholar : PubMed/NCBI
25	Coetzee M and Kruger MC: Osteoprotegerin-receptor activator of nuclear factor-kappaB ligand ratio: a new approach to osteoporosis treatment? South Med J. 97:506–511. 2004. View Article : Google Scholar : PubMed/NCBI
26	Tsangari H, Findlay DM, Kuliwaba JS, Atkins GJ and Fazzalari NL: Increased expression of IL-6 and RANK mRNA in human trabecular bone from fragility fracture of the femoral neck. Bone. 35:334–342. 2004. View Article : Google Scholar : PubMed/NCBI