Bench-to-bedside strategies for osteoporotic fracture: From osteoimmunology to mechanosensation

Abstract

Osteoporosis is characterized by a decrease in bone mass and strength, rendering people prone to osteoporotic fractures caused by low-energy forces. The primary treatment strategy for osteoporotic fractures is surgery; however, the compromised and comminuted bones in osteoporotic fracture sites are not conducive to optimum reduction and rigid fixation. In addition, these patients always exhibit accompanying aging-related disorders, including high inflammatory status, decreased mechanical loading and abnormal skeletal metabolism, which are disadvantages for fracture healing around sites that have undergone orthopedic procedures. Since the incidence of osteoporosis is expected to increase worldwide, orthopedic surgeons should pay more attention to comprehensive strategies for improving the poor prognosis of osteoporotic fractures. Herein, we highlight the molecular basis of osteoimmunology and bone mechanosensation in different healing phases of elderly osteoporotic fractures, guiding perioperative management to alleviate the unfavorable effects of insufficient mechanical loading, high inflammatory levels and pathogen infection. The well-informed pharmacologic and surgical intervention, including treatment with anti-inflammatory drugs and sufficient application of antibiotics, as well as bench-to-bedside strategies for bone augmentation and hardware selection, should be made according to a comprehensive understanding of bone biomechanical properties in addition to the remodeling status of osteoporotic bones, which is necessary for creating proper biological and mechanical environments for bone union and remodeling. Multidisciplinary collaboration will facilitate the improvement of overall osteoporotic care and reduction of secondary fracture incidence.

Osteoimmunology: The Regulatory Roles of T Lymphocytes in Osteoporosis

“…T cell therapy may be a potentially therapeutic approach to osteoporosis. For example, anti-inflammatory therapies have shown good potential in an animal model, although they have not been widely used clinically to treat osteoporosis ( 101 ). Immune modulation therapy such as probiotics was considered as a novel strategy for bone loss ( 102 – 104 ).…”

IL-33/IL-31 Axis in Osteoporosis

“…Matrix resorption is therefore controlled by cells embedded within the matrix itself [21,22]. Each cytokine of the complex network of regulatory factors involved in bone remodeling has pleiotropic functions and exerts different effects depending on the target cells and the influence of other cytokines in the specific microenvironment [23,24]. Osteoclastogenic cytokines, such as interleukin (IL)-6, IL-17, interferon (IFN)-γ and tumor necrosis factor (TNF)-α, the macrophage-colony stimulating factor (M-CSF) and monocyte chemoattractant protein-1 (MCP-1), promote bone resorption and inhibit osteoblasts, whereas other cytokines, such as IL-4, IL-10, transforming growth factor (TGF)-β, and IL-12, suppress osteoclasts and promote osteogenesis.…”

Hydroxyapatite based biocomposite scaffold: A highly biocompatible material for bone regeneration

“…Skeletal disorders and trauma have become a global, functional problem and a clinical challenge for bones and fractures ( Lems and Raterman, 2017 , Xie et al, 2019 ). A bone graft autologously is known as the good scaffolds for fixing bone defects and fractures, which has an exceptional bone fusion therapeutic effect ( Nandi et al, 2010 ).…”