Principles of Bone Healing

Iain H. Kalfas, MD, FACS Department of Neurosurgery, Section of Spinal Surgery, Cleveland Clinic Foundation, Cleveland, Ohio

Neurosurg Focus. 2001;10(4) 

In This Article

Bone Healing Process

The process of bone graft incorporation in a spinal fusion model is similar to the bone healing process that occurs in fractured long bones.[4] Fracture healing restores the tissue to its original physical and mechanical properties and is influenced by a variety of systemic and local factors. Healing occurs in three distinct but overlapping stages: 1) the early inflammatory stage; 2) the repair stage; and 3) the late remodeling stage.[9,13]

In the inflammatory stage, a hematoma develops within the fracture site during the first few hours and days. Inflammatory cells (macrophages, monocytes, lymphocytes, and polymorphonuclear cells) and fibroblasts infiltrate the bone under prostaglandin mediation. This results in the formation of granulation tissue, ingrowth of vascular tissue, and migration of mesenchymal cells. The primary nutrient and oxygen supply of this early process is provided by the exposed cancellous bone and muscle. The use of antiinflammatory or cytotoxic medication during this 1st week may alter the inflammatory response and inhibit bone healing.

During the repair stage, fibroblasts begin to lay down a stroma that helps support vascular ingrowth. It is during this stage that the presence of nicotine in the system can inhibit this capillary ingrowth.[11,23,24,25] A significantly decreased union rate had been consistently demonstrated in tobacco abusers.[2,3,6]

As vascular ingrowth progresses, a collagen matrix is laid down while osteoid is secreted and subsequently mineralized, which leads to the formation of a soft callus around the repair site. In terms of resistance to movement, this callus is very weak in the first 4 to 6 weeks of the healing process and requires adequate protection in the form of bracing or internal fixation. Eventually, the callus ossifies, forming a bridge of woven bone between the fracture fragments. Alternatively, if proper immobilization is not used, ossification of the callus may not occur, and an unstable fibrous union may develop instead.

Fracture healing is completed during the remodeling stage in which the healing bone is restored to its original shape, structure, and mechanical strength. Remodeling of the bone occurs slowly over months to years and is facilitated by mechanical stress placed on the bone. As the fracture site is exposed to an axial loading force, bone is generally laid down where it is needed and resorbed from where it is not needed. Adequate strength is typically achieved in 3 to 6 months.

Although the physiological stages of bone repair in the spinal fusion model are similar to those that occur in long bone fractures, there are some differences. Unlike long bone fractures, bone grafts are used in spinal fusion procedures. During the spinal fusion healing process, bone grafts are incorporated by an integrated process in which old necrotic bone is slowly resorbed and simultaneously replaced with new viable bone. This incorporation process is termed "creeping substitution."[17,20] Primitive mesenchymal cells differentiate into osteoblasts that deposit osteoid around cores of necrotic bone. This process of bone deposition and remodeling eventually results in the replacement of necrotic bone within the graft.

The most critical period of bone healing is the first 1 to 2 weeks in which inflammation and revascularization occur. The incorporation and remodeling of a bone graft require that mesenchymal cells have vascular access to the graft to differentiate into osteoblasts and osteoclasts. A variety of systemic factors can inhibit bone healing, including cigarette smoking, malnutrition, diabetes, rheumatoid arthritis, and osteoporosis. In particular, during the 1st week of bone healing, steroid medications, cytotoxic agents, and nonsteroidal antiinflammatory medications can have harmful effects. Irradiation of the fusion site within the first 2 to 3 weeks can inhibit cell proliferation and induce an acute vasculitis that significantly compromises bone healing (SE Emery, unpublished data).

Bone grafts are also strongly influenced by local mechanical forces during the remodeling stage. The density, geometry, thickness, and trabecular orientation of bone can change depending on the mechanical demands of the graft. In 1892, Wolff first popularized the concept of structural adaptation of bone, noting that bone placed under compressive or tensile stress is remodeled. Bone is formed where stresses require its presence and resorbed where stresses do not require it.[22,31] This serves to optimize the structural strength of the graft. Conversely, if the graft is significantly shielded from mechanical stresses, as in the case of rigid spinal implants, excessive bone resorption can potentially occur and result in a weakening of the graft. This potential disadvantage of instrumentation needs to be balanced with the beneficial effects that spinal fixation has on the fusion process.


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