Authors: Li, Dan; Gromov, Kirill; Proulx, Steven T.¹; Xie, Chao¹; Li, Jie¹; Crane, Daniel P.¹; Søballe, Kjeld²; O'Keefe, Regis J.¹; Awad, Hani A.; Xing, Lianping¹; Schwarz, Edward M.¹

Source: Annals of the New York Academy of Sciences, Volume 1192, Number 1, March 2010 , pp. 84-94(11)

Publisher: Wiley-Blackwell

Abstract:

The effects of antiresorptive agents (e.g., alendronate [Aln], osteoprotegerin [OPG]) on bone infection are unknown. Thus, their effects on implant-associated osteomyelitis (OM) were investigated in mice using PBS (placebo), gentamycin, and etanercept (TNFR:Fc) controls. None of the drugs affected humoral immunity, angiogenesis, or chronic infection. However, the significant (P < 0.05 vs. PBS) inhibition of cortical osteolysis and decreased draining lymph node size in Aln- and OPG-treated mice was associated with a significant (P < 0.05) increase in the incidence of high-grade infections during the establishment of OM. In contrast, the high-grade infections in TNFR:Fc-treated mice were associated with immunosuppression, as evidenced by the absence of granulomas and presence of Gram⁺ biofilm in the bone marrow. Collectively, these findings indicate that although antiresorptive agents do not exacerbate chronic OM, they can increase the bacterial load during early infection by decreasing lymphatic drainage and preventing the removal of necrotic bone that harbors the bacteria.

Keywords: osteomyelitis; antiresorptive therapy; TNFR:Fc

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1749-6632.2009.05210.x

Affiliations: 1: The Center for Musculoskeletal Research, University of Rochester, Rochester, New York, USA 2: Department of Orthopedics, Aarhus University Hospital, Aarhus, Denmark

Publication date: 2010-03-01

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• In this Subject: Biology ,  Organic Chemistry ,  Physics (General)
• By this author: Li, Dan ;  Gromov, Kirill ;  Proulx, Steven T. ;  Xie, Chao ;  Li, Jie ;  Crane, Daniel P. ;  Søballe, Kjeld ;  O'Keefe, Regis J. ;  Awad, Hani A. ;  Xing, Lianping ;  Schwarz, Edward M.

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