Bone Healing Gone Wrong: Pathological Fracture Healing and Non-Unions—Overview of Basic and Clinical Aspects and Systematic Review of Risk Factors

Abstract

Bone healing is a multifarious process involving mesenchymal stem cells, osteoprogenitor cells, macrophages, osteoblasts and -clasts, and chondrocytes to restore the osseous tissue. Particularly in long bones including the tibia, clavicle, humerus and femur, this process fails in 2–10% of all fractures, with devastating effects for the patient and the healthcare system. Underlying reasons for this failure are manifold, from lack of biomechanical stability to impaired biological host conditions and wound-immanent intricacies. In this review, we describe the cellular components involved in impaired bone healing and how they interfere with the delicately orchestrated processes of bone repair and formation. We subsequently outline and weigh the risk factors for the development of non-unions that have been established in the literature. Therapeutic prospects are illustrated and put into clinical perspective, before the applicability of biomarkers is finally discussed.

Cigarette smoke and nicotine effect on human mesenchymal stromal cell wound healing and osteogenic differentiation capacity

“…Smoking is one of the main risk factors for impaired bone healing 23 , but the exact cellular mechanism is not fully known. In this study, we specifically addressed the role of mesenchymal stem cells in vitro, while bone healing at the cellular level in vivo is a complex and lengthy process involving the influx of inflammatory cells in the acute phase, followed by the activation of mesenchymal cells, as reviewed by Marsell and Einhorn 11 , which serve as the effector cells in connective tissue regeneration and healing.…”

Metabolic regulation by biomaterials in osteoblast

“…These factors are critical for creating an ideal scaffold ( Bian et al, 2013 ). The EO pathway is responsible for the majority of bone growth, as it triggers undifferentiated stem cells to differentiate into functional osteocytes through external factors like a mineralized platform, akin to the IMO pathway ( Saul et al, 2023 ). Researchers are interested in stimulating EO for bone regeneration.…”

Modeling the Osteogenic Potential of Decellularized Human Bone Particles by Tuning their Size Distribution Through a Sonic Microfragmentation Approach

“…In considering trauma‐induced fractures, it is estimated that up to 10% of all fractures fail to heal within 6 months, a condition known as non‐union, causing severe secondary functional deficits in patients. [ 7 ]…”

“…In considering trauma-induced fractures, it is estimated that up to 10% of all fractures fail to heal within 6 months, a condition known as non-union, causing severe secondary functional deficits in patients. [7] To support bone regeneration, a large number of procedures and bone substitutes were investigated over the years. [8] Nevertheless, autograft transplantation remains the golden standard since it supports osteoinduction, osteoconduction, and osteogenesis.…”