title: Effects of antiresorptive agents on osteomyelitis: novel insights into the pathogenesis of osteonecrosis of the jaw.
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.
authors.affiliation: The Center for Musculoskeletal Research, University of Rochester, Rochester, New York, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.forename: Kirill
authors.initials: K
authors.lastname: Gromov
authors.forename: Steven T
authors.initials: ST
authors.lastname: Proulx
authors.forename: Chao
authors.initials: C
authors.lastname: Xie
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Crane
authors.forename: Kjeld
authors.initials: K
authors.lastname: Søballe
authors.forename: Regis J
authors.initials: RJ
authors.lastname: O'Keefe
authors.forename: Hani A
authors.initials: HA
authors.lastname: Awad
authors.forename: Lianping
authors.initials: L
authors.lastname: Xing
authors.forename: Edward M
authors.initials: EM
authors.lastname: Schwarz
mesh_terms: D000818:Animals; D018441:Biofilms / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D002908:Chronic Disease; D016207:Cytokines / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007109:Immunity / Q000187:drug effects; D015994:Incidence; D007571:Jaw Diseases / Q000139:chemically induced* / Q000453:epidemiology / Q000276:immunology; D051379:Mice; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010010:Osteoclasts / Q000187:drug effects / Q000502:physiology; D010019:Osteomyelitis / Q000139:chemically induced* / Q000150:complications / Q000453:epidemiology / Q000276:immunology; D010020:Osteonecrosis / Q000139:chemically induced* / Q000453:epidemiology / Q000276:immunology; D013203:Staphylococcal Infections / Q000139:chemically induced / Q000150:complications / Q000453:epidemiology
chemical_list: D050071:Bone Density Conservation Agents; D016207:Cytokines; C025940:bone resorption factor
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