A variety of biological, mechanical, and physical therapeutic modalities of varying complexity, efficacy, cost, and safety profile have been developed to enhance bone healing. There have been sporadic reports of spontaneous bone formation after repeated cold exposure. In this study we report for the first time, the anabolic effect of cold exposure on bone healing in vivo resulting in a doubling of bone volume. Although the precise mechanism is not fully understood, cold is well known to stimulate osteoclastogenesis and modulate inflammation. The impact of this finding is considerable for tissue regeneration because cold application is noninvasive, safe, and easily implemented.
Keywords: angiogenesis; bone regeneration; cold; hypoxia; mouse model; osteoclasts.