Effects of antiresorptive agents on osteomyelitis

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.

[1]  E. Schwarz,et al.  VEGF-C, a Lymphatic Growth Factor, Is a RANKL Target Gene in Osteoclasts That Enhances Osteoclastic Bone Resorption through an Autocrine Mechanism* , 2008, Journal of Biological Chemistry.

[2]  E. Schwarz,et al.  Quantitative mouse model of implant‐associated osteomyelitis and the kinetics of microbial growth, osteolysis, and humoral immunity , 2008, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[3]  A. Allegra,et al.  Patients with bisphosphonates‐associated osteonecrosis of the jaw have reduced circulating endothelial cells , 2007, Hematological oncology.

[4]  M. O. Papuga,et al.  Longitudinal assessment of synovial, lymph node, and bone volumes in inflammatory arthritis in mice by in vivo magnetic resonance imaging and microfocal computed tomography. , 2007, Arthritis and rheumatism.

[5]  C. Beck,et al.  MRI and Quantification of Draining Lymph Node Function in Inflammatory Arthritis , 2007, Annals of the New York Academy of Sciences.

[6]  Roberta B Carey,et al.  Invasive methicillin-resistant Staphylococcus aureus infections in the United States. , 2007, JAMA.

[7]  S. Silverman,et al.  Bisphosphonate‐Associated Osteonecrosis of the Jaw: Report of a Task Force of the American Society for Bone and Mineral Research , 2007, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[8]  N. Bishop,et al.  Osteoclast-poor human osteopetrosis due to mutations in the gene encoding RANKL , 2007, Nature Genetics.

[9]  P. Louis,et al.  Bisphosphonates and osteonecrosis of the jaws: science and rationale. , 2007, Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics.

[10]  J. Vermorken,et al.  Osteonecrosis of the jaw related to the use of bisphosphonates , 2007, Current opinion in oncology.

[11]  C. Farah,et al.  Bisphosphonate-related osteonecrosis of the jaws: a comprehensive review. , 2007, Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology.

[12]  E. Schwarz,et al.  Clinical development of anti-RANKL therapy , 2007, Arthritis research & therapy.

[13]  M. Fleming,et al.  Lymphedema Therapy Reduces the Volume of Edema and Pain in Patients with Breast Cancer , 2007, Annals of Surgical Oncology.

[14]  S. Teitelbaum Osteoclasts: what do they do and how do they do it? , 2007, The American journal of pathology.

[15]  M. Drezner,et al.  Osteonecrosis of the Jaw: More Research Needed , 2006, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[16]  T. Hansen,et al.  Osteonecrosis of the jaws in patients treated with bisphosphonates - histomorphologic analysis in comparison with infected osteoradionecrosis. , 2006, Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology.

[17]  B. Masri,et al.  The management of peri-prosthetic infection in total joint arthroplasty. , 2006, The Journal of bone and joint surgery. British volume.

[18]  R. Guldberg,et al.  Periosteal Progenitor Cell Fate in Segmental Cortical Bone Graft Transplantations: Implications for Functional Tissue Engineering , 2005, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[19]  R. Marx,et al.  Bisphosphonate-induced exposed bone (osteonecrosis/osteopetrosis) of the jaws: risk factors, recognition, prevention, and treatment. , 2005, Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons.

[20]  S. Wright,et al.  Chronic diffuse sclerosing osteomyelitis treated with risedronate. , 2005, The Journal of rheumatology.

[21]  C. Marek,et al.  Bisphosphonate osteochemonecrosis (bis-phossy jaw): is this phossy jaw of the 21st century? , 2005, Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons.

[22]  Hiromu Ito,et al.  Remodeling of cortical bone allografts mediated by adherent rAAV-RANKL and VEGF gene therapy , 2005, Nature Medicine.

[23]  C. Scully,et al.  Avascular jaw osteonecrosis in association with cancer chemotherapy: series of 10 cases. , 2005, Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology.

[24]  R. Darouiche Treatment of infections associated with surgical implants. , 2004, The New England journal of medicine.

[25]  R. Faggioni,et al.  Regulatory effects of osteoprotegerin on cellular and humoral immune responses. , 2003, Clinical immunology.

[26]  R. Marx Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. , 2003, Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons.

[27]  T. J. Rosenberg,et al.  Osteonecrosis of the jaws associated with the use of bisphosphonates: a review of 63 cases. , 2004, Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons.

[28]  J. Dubost,et al.  Pamidronate in the treatment of diffuse sclerosing osteomyelitis of the mandible. , 2001, Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics.

[29]  E M Schwarz,et al.  Quantitative small‐animal surrogate to evaluate drug efficacy in preventing wear debris‐induced osteolysis , 2000, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[30]  T. Martin,et al.  Therapeutic approaches to bone diseases. , 2000, Science.

[31]  Kevin P. Francis,et al.  Monitoring Bioluminescent Staphylococcus aureusInfections in Living Mice Using a Novel luxABCDEConstruct , 2000, Infection and Immunity.

[32]  W. Dougall,et al.  RANK is essential for osteoclast and lymph node development. , 1999, Genes & development.

[33]  P. Rüegsegger,et al.  Direct Three‐Dimensional Morphometric Analysis of Human Cancellous Bone: Microstructural Data from Spine, Femur, Iliac Crest, and Calcaneus , 1999, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[34]  R. Steinman,et al.  TRANCE, a Tumor Necrosis Factor Family Member Critical for CD40 Ligand–independent T Helper Cell Activation , 1999, The Journal of experimental medicine.

[35]  S. Morony,et al.  OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis , 1999, Nature.

[36]  R. Dubose,et al.  A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function , 1997, Nature.

[37]  C. Lowenstein,et al.  Tumor necrosis factor-alpha is required in the protective immune response against Mycobacterium tuberculosis in mice. , 1995, Immunity.

[38]  E. Schwarz,et al.  Systemic tumor necrosis factor α mediates an increase in peripheral CD11bhigh osteoclast precursors in tumor necrosis factor α–transgenic mice , 2004 .

[39]  E. Schwarz,et al.  Systemic tumor necrosis factor alpha mediates an increase in peripheral CD11bhigh osteoclast precursors in tumor necrosis factor alpha-transgenic mice. , 2004, Arthritis and rheumatism.

[40]  J. Smolen,et al.  Arthritis Induces Lymphocytic Bone Marrow Inflammation and Endosteal Bone Formation , 2004 .