Impact of low bone mass and antiresorptive therapy on antibiotic efficacy in a rat model of orthopedic device-related infection

J Orthop Res. 2021 Feb;39(2):415-425. doi: 10.1002/jor.24951. Epub 2020 Dec 23.


A significant proportion of orthopedic devices are implanted in osteoporotic patients, but it is currently unclear how estrogen deficiency and/or exposure to antiresorptive bisphosphonates (BPs) influence orthopedic device-related infection (ODRI), or response to therapy. The aim of this study is to characterize the bone changes resulting from Staphylococcus epidermidis infection in a rodent ODRI model and to determine if ovariectomy (OVX) or BP treatment influences the infection or the success of antibiotic therapy. A sterile or S. epidermidis-contaminated screw was implanted into the proximal tibia of skeletally mature female Wistar rats (n = 6-9 per group). Bone changes were monitored over 28 days using in vivo micro-computed tomography scanning. OVX was performed 12 weeks before screw implantation. The BP zoledronic acid (ZOL) was administered 4 days before screw insertion. A combination antibiotic regimen (rifampin plus cefazolin) was administered from Days 7-21. In skeletally healthy animals, S. epidermidis induced marked changes in bone, with peak osteolysis occurring at Day 9 and woven bone deposition and periosteal mineralization from Day 14 onwards. Antibiotic therapy cleared the infection in the majority of animals (2/9 infected) but did not affect bone responses. OVX did not affect the pattern of infection-induced changes in bone, nor bacterial load, but reduced antibiotic efficacy (5/9 infected). ZOL treatment did not protect from osteolysis in OVX animals, or further affect antibiotic efficacy (5/9 infected) but did significantly increase the bacterial load. This study suggests that both BPs and OVX can influence host responses to bone infections involving S. epidermidis.

Keywords: Staphylococcus epidermidis; antibiotics; bisphosphonate; in vivo micro-CT; osteomyelitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / therapeutic use*
  • Bone Density Conservation Agents / adverse effects*
  • Bone and Bones / diagnostic imaging
  • Bone and Bones / drug effects*
  • Disease Models, Animal
  • Estrogens / deficiency
  • Female
  • Prosthesis-Related Infections / complications
  • Prosthesis-Related Infections / diagnostic imaging
  • Prosthesis-Related Infections / drug therapy*
  • Rats
  • Rats, Wistar
  • Staphylococcal Infections / complications
  • Staphylococcal Infections / diagnostic imaging
  • Staphylococcal Infections / drug therapy*
  • Staphylococcus epidermidis
  • X-Ray Microtomography


  • Anti-Bacterial Agents
  • Bone Density Conservation Agents
  • Estrogens