Enhancement of osteoporotic fracture healing by vibration treatment: The role of osteocytes.

The prevalence of osteoporotic fracture is high due to global aging problem. Delayed and impaired healing in osteoporotic fractures increase the socioeconomic burden significantly. Through intensive animal and clinical research in recent years, the pathogenesis of osteoporotic fracture healing is unveiled, including decreased inflammatory response, reduced mesenchymal stem cells and deteriorated angiogenesis, etc. The enhancement of osteoporotic fracture healing is important in shortening hospitalization, thus reducing related complications. Mechanical stimulation is currently the most well-accepted approach for rehabilitation of osteoporotic fracture patients. Some new interventions providing mechanical signals were explored extensively in recent years, including vibration treatment, and osteoporotic fracture healing was found to respond very well to these signals. Vibration treatment could accelerate osteoporotic fracture healing with improved callus formation, mineralization and remodeling. However, the mechanism of how osteoporotic fracture bones sense mechanical signals and relay to bone formation remains unanswered. Osteocytes are the most abundant cells in bone tissues. Cumulative evidence confirm that osteocyte is a type of mechanosensory cell and shows altered morphology and reduced cell density during aging. Meanwhile, osteocytes serve as endocrine cells to regulate bone and mineral homeostasis. However, the contribution of osteocytes in osteoporotic fracture healing is largely unknown. A recent in vivo study was conducted to examine the morphological and functional changes of osteocytes after vibration treatment in an osteoporotic metaphyseal fracture rat model. The findings demonstrated that vibration treatment induced significant outgrowth of canaliculi and altered expression of various proteins (E11, DMP1, FGF23 and sclerostin), particularly osteocyte-specific dentin matrix protein 1 (DMP1) which was greatly increased. DMP1 may play a major role in relaying mechanical signals to bone formation, which may require further experiments to consolidate. Most importantly, vibration treatment significantly increased the mineralization and accelerated the osteoporotic fracture healing in metaphyseal fracture model. In summary, osteocyte is the major cell type to sense mechanical signals and facilitate downstream healing in osteoporotic fracture bone. Vibration treatment has good potential to be translated for clinical application to benefit osteoporotic fracture patients, while randomized controlled trials are required to validate its efficacy.