This basic science tip comes from Fred Nelson, MD, an orthopaedic surgeon in the Department of Orthopedics at Henry Ford Hospital and a clinical associate professor at Wayne State Medical School. Some of Dr. Nelson’s tips go out weekly to more than 3,000 members of the Orthopaedic Research Society (ORS), and all are distributed to more than 30 orthopaedic residency programs. Those not sent to the ORS are periodically reposted in OrthoBuzz with the permission of Dr. Nelson.
One clinical frustration following osteomyelitis debridement is poor bone healing. Impaired bone homeostasis provokes serious variations in bone remodeling that involve multiple inflammatory cytokines.
The chemokines CCL2, CCL3, and CXCL2 are known to be strong chemoattractants for neutrophils during inﬂammatory states, and they play a role during osteoclastogenesis. B cells are also activators of osteoclastognesis and are regulated, in part, by tissue inhibitor of metalloprotease 1 (TIMP-1).
Researchers drilled a 1 mm hole into the proximal tibia of 126 mice. In half of the mice (63), a dose of S. aureus was injected into the canal, while the controls had no bacteria injected. At two weeks, all proximal tibiae were debrided; cultures were taken 3 and 7 days after debridement to assure no residual infection. Cytokine assays and Western blots for CCL2, CCL3, CXCL2, TIMP-1, RANKL, and TNF-α were performed in selected mice in each group. Flow cytometry and histology were also done in selected mice in each group.
In the osteomyelitis group, Western blot analysis identified increased levels of CCL2, CCL3, and CXCL2. Histology revealed increased osteoclastogenesis after osteomyelitis debridement, with calcitonin-receptor and RANKL detection via immunohistochemical and fluorescence staining. There was diminished osteogenesis and proliferation in the osteomyelitis group, but TNF-α expression seemed to have no effect on altered bone regeneration after bone infection. Flow cytometry revealed elevated B cell activity in the osteomyelitis group, with subsequent increased osteoclast activity and accelerated bone resorption.
The researchers propose a RANKL-dependent osteoclastogenesis after debridement for osteomyelitis that is associated with elevated B cells and decreased osteogenesis. These findings could lead to new interventions to improve bone healing during the course of osteomyelitis treatment, particularly following debridement.
Wagner JM, Jaurich H, Wallner C, Abraham S, Becerikli M, Dadras M, Harati K, Duhan V, Khairnar V, Lehnhardt M, Behr B. Diminished bone regeneration after debridement of posttraumatic osteomyelitis is accompanied by altered cytokine levels, elevated B cell activity, and increased osteoclast activity. J Orthop Res. 2017 Mar 6. doi: 10.1002/jor.23555. [Epub ahead of print] PMID: 28263017