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Differential effects of biologic versus bisphosphonate inhibition of wear debris‐induced osteolysis assessed by longitudinal micro‐CT
Author(s) -
Tsutsumi Ryosuke,
Hock Colleen,
Bechtold C. Dustin,
Proulx Steven T.,
Bukata Susan V.,
Ito Hiromu,
A. Awad Hani,
Nakamura Takashi,
O'Keefe Regis J.,
Schwarz Edward M.
Publication year - 2008
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.20620
Subject(s) - calvaria , osteolysis , bone resorption , osteoprotegerin , bisphosphonate , in vivo , medicine , osteoclast , resorption , endocrinology , urology , chemistry , in vitro , dentistry , osteoporosis , receptor , biology , biochemistry , microbiology and biotechnology , activator (genetics)
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 ± 0.23mm 3 versus 0.15 ± 0.067mm 3 ; 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, 2008