This study investigated whether A-79175, an inhibitor of 5-lipoxygenase (5-LO), could stimulate regeneration of bone in a rat model when applied locally at the fracture site.1
A 3-mm unicortical defect was created in the femur of each rat; a polycaprolactone scaffold containing A-79175 was placed within the defect in the right femur while a control scaffold (no drug or drug carrier) was placed in the defect on the left side. Scaffolds containing A-79175 at three different doses were used in different animals and an additional group received a scaffold containing only the drug carrier.
The defects treated with A-79175 at the higher and medium doses (40.4 μg and 6.4 μg drug per implant, respectively) showed significantly higher levels of bone formation after 10 days' healing time compared to control. The high-dose group showed a mean increase in the bone volume to total volume ratio of 28.3 (s.e.m. 8.6; P=0.011), while the medium-dose group had a mean increase of 27.5 (s.e.m. 8.3; P=0.024).
Editor's comment: We all know that cyclooxygenase-1 and -2 (COX-1 and COX-2) inhibition has an inhibitory effect on fracture healing. This group has worked on the opposite pathway, inhibiting 5-LO to increase COX-2. Here they show that a 5-LO inhibitor increases bone formation in a largely dose-dependent manner. While increasing COX-2 systemically may not be prudent, this local effect could be very useful in bone repair.
References
- Cottrell JA, Keshav V, Mitchell A, O'Connor JP. Local inhibition of 5-lipoxygenase enhances bone formation in a rat model. Bone Joint Res 2013; 2:41–50. [DOI] [PMC free article] [PubMed] [Google Scholar]
