4.7 Article

The impact of osteoporosis and diabetes on fracture healing under different loading conditions

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ELSEVIER IRELAND LTD
DOI: 10.1016/j.cmpb.2023.107952

Keywords

Bone fracture healing; Osteoporosis; Diabetes; Mechanical instability; Macrophages; Mesenchymal stem cells

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This study investigates the combined effects of osteoporosis and diabetes on fracture healing process by developing numerical models. The results show that osteoporotic fractures have higher instability and disruption in mesenchymal stem cells' proliferation and differentiation compared to non-osteoporotic fractures. Moreover, when osteoporosis coexists with diabetes, the healing process of fractures can be severely impaired.
Background: Osteoporosis and diabetes are two prevalent conditions among the elderly population. Each of these conditions can profoundly influence the fracture healing process by disturbing the associated inflammatory process. However, the combined effects of osteoporosis and diabetes on fracture healing remain unclear. Therefore, the purpose of the present study is to investigate the role of osteoporosis and diabetes in fracture healing and the underlying mechanisms by developing numerical models. Method: This study introduces a numerical model that consists of a three-dimensional model of a tibia fracture stabilized by a Locking Compression Plate (LCP), coupled with a two-dimensional axisymmetric model which illustrates the transport and reactions of cells and cytokines throughout the inflammatory phase in early fracture healing. First, the model parameters were calibrated using available experimental data. The model was then implemented to predict the healing outcomes of fractures under five varied conditions, consisting of both osteoporotic and non-osteoporotic bones, each subjected to different physiological loads. Results: The instability of the fracture callus can significantly escalate in osteoporotic fractures (e.g., when a 150 N physiological load is applied, the unstable region of the osteoporotic fracture callus can reach 26 %, in contrast to 12 % in non-osteoporotic fractures). Additionally, the mesenchymal stem cells (MSCs) proliferation and differentiation can be disrupted in osteoporotic fracture compared to non-osteoporotic fractures (e.g., on the 10th day post-fracture, the decrease in the concentration of MSCs, osteoblasts, and chondrocytes in osteoporotic fractures is nearly double that in non-osteoporotic fractures under a 150 N). Finally, the healing process of fractures can suffer significant impairment when osteoporosis coexists with diabetes (e.g., the concentration of MSCs can be drastically reduced by nearly 37 % in osteoporotic fractures under diabetic conditions when subjected to a load of 200 N) Conclusions: Fracture calluses destabilized by osteoporosis can negatively affect the fracture healing process by disrupting the proliferation and differentiation of mesenchymal stem cells (MSCs). Moreover, when osteoporosis coexists with diabetes, the fracture healing process can severely impair the fracture healing outcomes.

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