Improving Bone Formation in Osteoporosis Through In Vitro Mechanical Stimulation Compared to Biochemical Stimuli

Study Design: Laboratory investigation. Objectives: To determine and compare the ability of cellular mechanical stimulation to enhance the production of osteogenic precursor cells (OPCs) from osteoporotic bone relative to stimulation with chemical factors. Summary of Background Data: Abnormalities in the number and function of bone-forming osteoblasts play a central role in the pathophysiological processes leading to osteoporosis. Normal osteoblast production and function are regulated by chemical growth factors and mechanical signals. Nevertheless, the responses of OPCs from osteoporotic bone to mechanical signals remain poorly understood. Methods: Transpedicular aspiration of 5 cc of vertebral body bone marrow was performed in osteoporotic patients undergoing instrumented spinal fusion. Mesenchymal stem cells (MSCs) were isolated and subjected to either mechanical stimulation (4000 με elongation) or biochemical stimulation with BMP-2or PDGF at three different concentrations (0.0001, 1, and 100 ng/mL). MSC proliferation was assessed using the alamarBlue assay and the quantity of OPCs was estimated by measuring alkaline phosphatase (AP) activity and normalized to DNA content. Results: A total of 4 osteoporotic patients (3F:1M, average DXA=-2.9) were enrolled. Although there was a trend toward improved osteoporotic MSC proliferation after biochemical stimulation in a dose-dependent manner compared to mechanical stimulation, this only reached statistical significance for PDGF at its highest concentration (p<0.05). With regard to the quantity of OPCs within this cell population, mechanical stimulation on average resulted in an approximately 50% improvement in normalized AP activity compared to MSCs stimulated with BMP-2 (p<0.05) and 130% compared to PDGF (p<0.0005) at the highest concentrations. Conclusion: PDGF-mediated pathways involved in the proliferation of osteoporotic MSCs may remain relatively intact compared to those involving BMP-2 or mechanical forces. However, mechanical signals may be more effective than biochemical ones in promoting osteoporotic MSCs to differentiate along an osteoprogenitor lineage. Level of Evidence: Basic Science. Journal of Nature and Science, 1(4):e63, 2015