Abstract
Summary
The negative impact of NSAIDs on fracture healing appears not to pertain to fractures in cancellous bone. Possibly this is because of a higher prevalence of MSCs in cancellous bone, making recruitment of distant cells via inflammatory signals less important.
Introduction
It is well established that cox inhibitors (NSAIDs) impair fracture healing, also in humans. However, as they provide good pain relief it is unclear when to avoid these drugs. The healing process in cortical and cancellous fractures differs regarding progenitor cell sources, and inflammation might be involved in the recruitment of cells from distant sources. We therefore hypothesised that fractures in cancellous bone are less sensitive to reduced inflammation due to cox inhibitors.
Methods
Indomethacin was used to study the role of an NSAID on shaft and metaphyseal fracture healing. 40 male 10 week old C57/bl6 mice were used, 20 of which received a stabilised mid-shaft femur fracture, whilst the other 20 received a screw inserted into the cancellous bone of the proximal tibia on one side, and a drill hole in the same area on the contralateral side. Half of the mice received injections of 1 mg/kg bodyweight of Indomethacin, twice daily for 14 days. The other half received saline. The effect of the treatment on the fracture healing was evaluated with mechanical testing, µCT, and histology.
Results
Biomechanical testing (pull-out force for the screws) could detect no significant effect of indomethacin on the cancellous fracture healing. A reduction in force by more than 21 % could be excluded with 95 % confidence. The drill holes contained new bone, but µCT of this bone showed no effect of treatment on BMD, BV/TV, trabecular thickness, or trabecular number. Analysis of shaft healing is not yet completed. µCT of the first 12 femurs is available. A difference between the groups was obvious on visual inspection: Blind sorting, based on amount of callus, could identify all 6 indomethacin treated femurs and none of the controls as having an inferior callus response. More data will follow.
Discussion/Conclusion
NSAIDs had no visible effect on metaphyseal healing, but a dramatic effect on the shaft fractures. Possibly, prostaglandin signaling is important for recruitment of progenitor cells to the shaft callus, whereas such cells are already present within the metaphyseal marrow.
