Elevation of Serum Tumor Necrosis Factor α in Patients with Periprosthetic Osteolysis: A Case-Control Study
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.Get Access
Periprosthetic osteolysis is the leading reason for THA revision. The relationship of serum biomarkers with severe radiographic periprosthetic osteolysis has not been defined but may be important to direct future research and clinical therapeutics.
We determined whether there was an association between measurable inflammatory markers (high-sensitivity C-reactive protein [hsCRP]) or inflammatory mediators (tumor necrosis factor α [TNF-α], IL-1β, IL-6, receptor activator of nuclear factor κB ligand [RANKL], and osteoprotegerin [OPG]) and periprosthetic osteolysis.
We identified 15 patients with THAs scheduled for revision surgery because of severe periprosthetic osteolysis. For each study patient, a nonosteolytic, pain-free control patient with THAs was identified and matched for age, sex, time since initial THA, acetabular and femoral component prosthesis material, and prosthesis wear within 1.0 mm/year using a manual wear analysis technique. Overall, the study and control patients had a mean wear rate of 0.25 mm/year since index THA. There were no differences in baseline characteristics between study and control patients in age, sex, BMI, Charlson Comorbidity Index, time since initial THA, UCLA activity score, and acetabular and femoral component type. Serum hsCRP, IL-1β, IL-6, TNF-α, RANKL, and OPG were measured by ELISA in duplicate assays. Differences in values were assessed using the Wilcoxon rank-sum test.
Median TNF-α levels were higher in study patients than in controls (7.1 pg/mL [SD, 11.6 pg/mL] versus 1.5 pg/mL [SD, 1.3 pg/mL]) (p < 0.01). Median IL-6 levels tended to be higher in study patients than in controls (8.9 pg/mL [SD, 13.2 pg/mL] versus 3.5 pg/mL [SD, 0.7 pg/mL]) (p = 0.09). The other serum inflammatory proteins and mediators of bone turnover were not different between groups.
TNF-α is elevated in patients with osteolysis compared to matched controls. The role of TNF-α and its potential as a target of nonsurgical therapy to prevent osteolysis warrant further investigation in larger, prospective studies.
Level of Evidence
Level III, diagnostic study. See Instructions for Authors for a complete description of levels of evidence.
- Bathon JM, Martin RW, Fleischmann RM, Tesser JR, Schiff MH, Keystone EC, Genovese MC, Wasko MC, Moreland LW, Weaver AL, Markenson J, Finck BK. A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis. N Engl J Med. 2000;343:1586–1593. CrossRef
- Blaine TA, Rosier RN, Puzas JE, Looney RJ, Reynolds PR, Reynolds SD, O’Keefe RJ. Increased levels of tumor necrosis factor-alpha and interleukin-6 protein and messenger RNA in human peripheral blood monocytes due to titanium particles. J Bone Joint Surg Am. 1996;78:1181–1192.
- Brännström M, Fridén BE, Jasper M, Norman RJ. Variations in peripheral blood levels of immunoreactive tumor necrosis factor alpha (TNFalpha) throughout the menstrual cycle and secretion of TNFalpha from the human corpus luteum. Eur J Obstet Gynecol Reprod Biol. 1999;83:213–217. CrossRef
- Braun T, Zwerina J. Positive regulators of osteoclastogenesis and bone resorption in rheumatoid arthritis. Arthritis Res Ther. 2011;13:235. CrossRef
- Childs LM, Goater JJ, O’Keefe RJ, Schwarz EM. Effect of anti-tumor necrosis factor-alpha gene therapy on wear debris-induced osteolysis. J Bone Joint Surg Am. 2001;83:1789–1797.
- Claus AM, Engh CA Jr, Sychterz CJ, Xenos JS, Orishimo KF, Engh CA Sr. Radiographic definition of pelvic osteolysis following total hip arthroplasty. J Bone Joint Surg Am. 2003;85:1519–1526.
- Claus AM, Totterman SA, Sychertz CJ, Tamez-Pena JG, Looney RJ, Engh CA. Computed tomography to assess pelvic lysis after hip replacement. Clin Orthop Relat Res. 2004;422:167–174. CrossRef
- Cooper HJ, Ranawat AS, Potter HG, Foo LF, Jawetz ST, Ranawat CS. Magnetic resonance imaging in the diagnosis and management of hip pain after total hip arthroplasty. J Arthroplasty. 2009:24:661–667. CrossRef
- Fiorito S, Magrini L, Goalard C. Pro-inflammatory and anti-inflammatory circulating cytokines and periprosthetic osteolysis. J Bone Joint Surg Br. 2003;85:1202–1206. CrossRef
- Gallo J, Mrazek F, Petrek M. Variation in cytokine genes can contribute to severity of acetabular osteolysis and risk for revision in patients with ABG 1 total hip arthroplasty: a genetic association study. BMC Med Genet. 2009;10:109. CrossRef
- Gilson M, Gossec L, Mariette X, Gherissi D, Guyot MH, Berthelot JM, Wendling D, Michelet C, Dellamonica P, Tubach F, Dougados M, Salmon D. Risk factors for total joint arthroplasty infection in patients receiving tumor necrosis factor alpha-blockers: a case-control study. Arthritis Res Ther. 2010;12:R145. CrossRef
- Harris WH. Wear and periprosthetic osteolysis: the problem. Clin Orthop Relat Res. 2001;393:66–70. CrossRef
- Hernigou P, Intrator L, Bahrami T, Bensussan A, Farcet JP. Interleukin-6 in the blood of patients with total hip arthroplasty without loosening. Clin Orthop Relat Res. 1999;366:147–154. CrossRef
- Kitamura N, Pappedemos PC, Duffy PR 3rd, Stepniewski AS, Hopper RH Jr, Engh CA Jr, Engh CA. The value of anteroposterior pelvic radiographs for evaluating pelvic osteolysis. Clin Orthop Relat Res. 2006;453:239–245. CrossRef
- Maloney WJ, James RE, Smith RL. Human macrophage response to retrieved titanium alloy particles in vitro. Clin Orthop Relat Res. 1996;322:268–278. CrossRef
- Merkel KD, Erdmann JM, McHugh KP, Abu-Amer Y, Ross FP, Teitelbaum SL. Tumor necrosis factor-alpha mediates orthopedic implant osteolysis. Am J Pathol. 1999;154:203–210. CrossRef
- Muc-Wierzgoń M, Baranowski MM, Madej K, Wierzgoń J, Kokot T, Brodziak AJ. Dynamics of diurnal changes in serum concentration of TNF-alpha soluble receptors in gastrointestinal cancer patients. Biol Regul Homeost Agents. 2000;14:204–208.
- Schwarz EM, Campbell D, Totterman S, Boyd A, O’Keefe RJ, Looney RJ. Use of volumetric computerized tomography as a primary outcome measure to evaluate drug efficacy in the prevention of peri-prosthetic osteolysis: a 1-year clinical pilot of etanercept vs. placebo. J Orthop Res. 2003;21:1049–1055. CrossRef
- Shanbhag AS, Hasselman CT, Rubash HE. The John Charnley Award. Inhibition of wear debris mediated osteolysis in a canine total hip arthroplasty model. Clin Orthop Relat Res. 1997;344:33–43. CrossRef
- Walde TA, Weiland DE, Leung SB, Kitamura N, Sychertz CJ, Engh CA Jr, Claus AM, Potter HG, Engh CA Sr. Comparison of CT, MRI, and radiographs in assessing pelvic osteolysis: a cadaveric study. Clin Orthop Relat Res. 2005;437:138–144. CrossRef
- Wan Z, Dorr LD. Natural history of femoral focal osteolysis with proximal ingrowth smooth stem implant. J Arthroplasty. 1996;11:718–725. CrossRef
- Elevation of Serum Tumor Necrosis Factor α in Patients with Periprosthetic Osteolysis: A Case-Control Study
Clinical Orthopaedics and Related Research®
Volume 472, Issue 2 , pp 584-589
- Cover Date
- Print ISSN
- Online ISSN
- Springer US
- Additional Links
- Industry Sectors
- Author Affiliations
- 1. Division of Rheumatology, University of California, San Francisco, 400 Parnassus Avenue, Box 0326, San Francisco, CA, 94143, USA
- 2. Department of Orthopedics, Hospital of Special Surgery, New York, NY, USA
- 3. Division of Rheumatology Hospital for Special Surgery, New York, NY, USA