Differential effects of biologic versus bisphosphonate inhibition of wear debris‐induced osteolysis assessed by longitudinal micro‐CT
Open Access
- 10 April 2008
- journal article
- research article
- Published by Wiley in Journal of Orthopaedic Research
- Vol. 26 (10), 1340-1346
- https://doi.org/10.1002/jor.20620
Abstract
Aseptic loosening of total joint replacements is caused by wear debris‐induced osteoclastic bone resorption, for which bisphosphonates (BPs) and RANK antagonists have been developed. Although BPs are effective in preventing metabolic bone loss, they are less effective for inflammatory bone loss. Because this difference has been attributed to the antiapoptotic inflammatory signals that protect osteoclasts from BP‐induced apoptosis, but not RANK antagonists, we tested the hypothesis that osteoprotegerin (OPG) is more effective in preventing wear debris‐induced osteolysis than zoledronic acid (ZA) or alendronate (Aln) in the murine calvaria model using in vivo micro‐CT and traditional histology. Although micro‐CT proved to be incompatible with titanium (Ti) particles, we were able to demonstrate a 3.2‐fold increase in osteolytic volume over 10 days induced by polyethylene (PE) particles versus sham controls (0.49 ± 0.23mm3 versus 0.15 ± 0.067mm3; p < 0.01). Although OPG and high‐dose ZA completely inhibited this PE‐induced osteolysis (p < 0.001), pharmacological doses of ZA and Aln were less effective but still reached statistical significance (p < 0.05). Traditional histomorphometry of the sagital suture area of calvaria from both Ti and PE‐treated mice confirmed the remarkable suppression of resorption by OPG (p < 0.001) versus the lack of effect by physiological BPs. The differences in drug effects on osteolysis were largely explained by the significant difference in osteoclast numbers observed between OPG versus BPs in both Ti‐ and PE‐treated calvaria; and linear regression analyses that demonstrated a highly significant correlation between osteolysis volume and sagittal suture area versus osteoclast numbers (p < 0.001). © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:1340–1346, 2008Keywords
This publication has 38 references indexed in Scilit:
- Clinical development of anti-RANKL therapyArthritis Research & Therapy, 2007
- Aseptic loosening of total joint replacements: mechanisms underlying osteolysis and potential therapiesArthritis Research & Therapy, 2007
- Efficacy and Safety of Zoledronic Acid in Patients with Breast Cancer Metastatic to Bone: A Multicenter Clinical TrialThe Oncologist, 2006
- Tumor necrosis factor prevents alendronate‐induced osteoclast apoptosis in vivo by stimulating Bcl‐xL expression through Ets‐2Arthritis & Rheumatism, 2005
- Polyethylene and titanium particles induce osteolysis by similar, lymphocyte‐independent, mechanismsJournal of Orthopaedic Research, 2005
- Ten Years' Experience with Alendronate for Osteoporosis in Postmenopausal WomenNew England Journal of Medicine, 2004
- Variation in the TNF Gene Promoter and Risk of Osteolysis After Total Hip ArthroplastyJournal of Bone and Mineral Research, 2003
- Osteoclast differentiation and activationNature, 2003
- In Vivo RANK Signaling Blockade Using the Receptor Activator of NF-κB:Fc Effectively Prevents and Ameliorates Wear Debris-Induced Osteolysis via Osteoclast Depletion Without Inhibiting OsteogenesisJournal of Bone and Mineral Research, 2002
- Inhibition of Wear Debris Mediated Osteolysis in a Canine Total Hip Arthroplasty ModelPublished by Ovid Technologies (Wolters Kluwer Health) ,1997