Fracture-related infection in osteoporotic bone causes more severe infection and further delays healing

Jie Li; Ronald Man Yeung Wong; Yik Lok Chung; Sharon Shui Yee Leung; Simon Kwoon-Ho Chow; Margaret Ip; Wing-Hoi Cheung

doi:10.1302/2046-3758.112.BJR-2021-0299.R1

Fracture-related infection in osteoporotic bone causes more severe infection and further delays healing

Bone Joint Res. 2022 Feb;11(2):49-60. doi: 10.1302/2046-3758.112.BJR-2021-0299.R1.

Authors

Jie Li¹, Ronald Man Yeung Wong¹, Yik Lok Chung¹, Sharon Shui Yee Leung², Simon Kwoon-Ho Chow¹, Margaret Ip³, Wing-Hoi Cheung¹

Affiliations

¹ Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Hong Kong, China.
² School of Pharmacy, The Chinese University of Hong Kong, Hong Kong, China.
³ Department of Microbiology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.

PMID: 35100815
PMCID: PMC8882324
DOI: 10.1302/2046-3758.112.BJR-2021-0299.R1

Abstract

Aims: With the ageing population, fragility fractures have become one of the most common conditions. The objective of this study was to investigate whether microbiological outcomes and fracture-healing in osteoporotic bone is worse than normal bone with fracture-related infection (FRI).

Methods: A total of 120 six-month-old Sprague-Dawley (SD) rats were randomized to six groups: Sham, sham + infection (Sham-Inf), sham with infection + antibiotics (Sham-Inf-A), ovariectomized (OVX), OVX + infection (OVX-Inf), and OVX + infection + antibiotics (OVX-Inf-A). Open femoral diaphysis fractures with Kirschner wire fixation were performed. Staphylococcus aureus at 4 × 10⁴ colony-forming units (CFU)/ml was inoculated. Rats were euthanized at four and eight weeks post-surgery. Radiography, micro-CT, haematoxylin-eosin, mechanical testing, immunohistochemistry (IHC), gram staining, agar plating, crystal violet staining, and scanning electron microscopy were performed.

Results: Agar plating analysis revealed a higher bacterial load in bone (p = 0.002), and gram staining showed higher cortical bone colonization (p = 0.039) in OVX-Inf compared to Sham-Inf. OVX-Inf showed significantly increased callus area (p = 0.013), but decreased high-density bone volume (p = 0.023) compared to Sham-Inf. IHC staining showed a significantly increased expression of TNF-α in OVX-Inf compared to OVX (p = 0.049). Significantly reduced bacterial load on bone (p = 0.001), enhanced ultimate load (p = 0.001), and energy to failure were observed in Sham-Inf-A compared to Sham-Inf (p = 0.028), but not in OVX-Inf-A compared to OVX-Inf.

Conclusion: In osteoporotic bone with FRI, infection was more severe with more bone lysis and higher bacterial load, and fracture-healing was further delayed. Systemic antibiotics significantly reduced bacterial load and enhanced callus quality and strength in normal bone with FRI, but not in osteoporotic bone. Cite this article: Bone Joint Res 2022;11(2):49-60.

Keywords: Cortical bone; Fracture healing; Fracture related infection; Fracture-related infection (FRI); Osteoporosis; antibiotics; bone lysis; infection; osteoporotic bone; rat model; staining; systemic antibiotics.