Secondary healing occurs in fractures treated with stress sharing devices such as casts, Kirschner wires (K wires), intramedullary

rods, and external fixation devices. These devices align the bone fragments but do not compress the fracture gap, therefore allowing for some degree of motion. Secondary healing is te most common type of bone healing. Secondary healing involves not only the response of the bone itself but also of the periosteum and the soft tissue around the fracture site. The response from the periosteum is thought to be critical to callus formation and is enhanced by slight motion and inhibited by rigid fixation. Secondary healing is rapid and can bridge a gap as large as half of the diameter of the fractured bone. Fractures are considered clinically healed when the bone is stable and pain free. Roentgenographic/radiological healing has occurred when trabecular or cortical bone crosses the fracture site as evidenced by x-ray. Panjabi et al found by comparing radiographic evaluation of fracture healing to failure strength of healing osteotomies that the best radiological indicator of clinical healing was cortical continuity and the poorest indicator was the callus area. In general, radiographic information alone is not sufficient to accurately assess the biomechanical strength of a healing fracture. Stages of fracture healing.. fracture healing generally occurs in three stages. Inflammatory, repair and remodeling, although some authors break these into six stages. These stages may overlap and events that begin in one stage may continue into the following stage. The length of each stage varies with the location and severity of the fracture and associated injuries and other local and systemic factors. The inflammatory stage of fracture healing typically lasts 1-2 weeks. When a bone is injured, both the bone and its blood supply are disrupted. Disruption of the blood vessels in and around the bone leads to formation of a hematoma at the injury site. The organization of this hematoma is the first step of fracture repair. The hematoma causes various molecules and cells to initiate the healing process. Such molecules, including cytokines, interleukins and various growth factors, regulate the early stages of healing, including proliferation and differentiation. Open fractures, or those treated surgically may not have hematoma at the fracture site and may therefore heal more slowly. Soon after the hematoma forms, inflammatory cells, including neutrophils, acrophages, and phagocytes, invade the area. Along with osteoclasts, these cells remove the damaged and necrotic tissue near the distal adges of the fractures and lay the groundwork for the repair stage to begin. Radiographically, the fracture line becomes more visible as the necrotic material is removed, which is why some hairline fractures are not evident on x-ray until days after the initial injury. The repair stage usually begins within 2 weeks of the fracture and lasts several months. It is characterized by the differentiation of mesenchymal stem cells into cell types necessary for tissue restoration, including osteoblasts, osteoclasts, chondroblasts, fibroblasts and angioblasts. The fracture site is invaded by chondrocytes and fibroblasts, which lay down a matrix for the callus composed of collagen, glycosaminoglycan (GAG), and proteoglycans. Initially, soft callus composed mainly of fibrous tissue and cartilage with small amount of bone is formed. Osteoblasts then mineralize this soft callus, converting it to a hard callus and increasing the stability of the fracture. However, this immature bone is still weaker than normal bone, particularly in response to torque, and therefore must be protected.

Delayed union or nonunion, as described later in this chapter, generally result from errors in this phase of healing. This repair stage ends when the fracture is clinically stable. Radiographically, the fracture line begins to disappear during this stage. During the remodeling stage, which can take months or years to complete, osteoblasts and osteoclasts replace the immature, poorly organized bone with mature, organized laminar bone, making the fracture site more stable. The ultimate goal of this stage is to restore the bone to its original strength and structure, giving it the ability to withstand the usual stresses placed on it. During this stage, areas of bone that sustain little stress are reabsorbed by osteoclasts, while more bone is laid down by osteoblasts in areas with high stress. Mechanical loading of the fracture site is needed to facilitate strong callus formation, fracture alignment and ultimately lamellar remodeling. Over time, the medullary canal inside the bone reforms and angular, although not rotational, deformities may correct. By the end of remodeling, the fracture line is no longer visible radiographically and the bone at the fracture site should have the same stiffness as normal bone. Because a fully healedfracture is often stronger than the surrounding bone, subsequent application of an excessive load to the whole bone generally does not cause a fracture at the original fracture site but rather above or below the fracture site. Addititonally despite successful fracture healing, the overall density of the bones in the involved limb may be decreased for years. Prognosis for fracture healing. Although the length of time for fracture healing varies, there is a typical rate at which fractures heal and some predictable variability based on the location and nature of the fracture and the type of fixation. For example, a distal radial fracture is expected to heal within 6-8 weeks, whereas a midshaft femur fracture may require 6 months. The location and stability of the fracture can also affect how much callus forms. For example, metaphyseal fractures tend to heal with little callus formation because there is little surrounding periosteum and because the interdigitation and impaction of the fracture keeps the site stable and limits the fracture gap. In contrast, disaphyseal fractures tend to form a large callus because they are not impacted and have a larger fracture gap and more periosteum. Fractures caused by high speed or high force impacts often heal slowly because there is more soft tissue and vascular damage in the area of the fracture and more fracture comminution. Open fractures also tend to heal more slowly than closed fractures because of the amount of soft tissue damage and bone loss, as well as fractures displacement and increased infection risk. Infection around a fracture not only compromises healing but may also lead to chronic infection of the bone known as osteomyelitis. Intraarticular fractures may also heal slowly because they can require surgical intervention to assure good joint alignment. Some fractures heal more slowly than expected or fail to heal at all. Slow healing is known as delayed union and failure to heal is known as nonunion. Nonunion is generally defined as failing to heal after 6-8 months. When a fracture fails to heal, cartilage or fibrocartilage forms over the fracture surfaces and the cavity between the fracture surfaces fills with fluid that resembles normal joint or bursal fluid. The false joint or pseudoarthrosis may or may not be painful but will always be unstable. A fibrous union formed

by dense cartilage or fibrocartilage band may also be an end result and although it will stabilize the fracture site and may be painless, this union does not restore normal strength. Common risk factors for delayed fracture healing include diabetes mellitus, smoking, long term steroid use, nonsteroidal anti-inflammatory drugs (NSAIDs) and other medications, and poor nutrition. Diabetes is thought to impair fracture healing by causing a defect in collagen or collagen cross linking. Cigarette smoking interferes with osteoblasts activity. Nicotine can also impair healing by causing vasoconstriction and inhibiting angiogenesis, both of which can reduce blood flow to the fracture site. Human who smoke have been found to have more complication with fracture healing, including infections, amputations and nonunions or malunions, and slower healing rates than their nonsmoking counterparts. In animal studies, those exposed to nicotine also healed more slowly and had a higher percentage of nonunions.nicotine has also been shown to inhibit vascularization of bone grafts in rabbits although the exact mechanism remains unclear. Castillo and colleagues evaluated healing in patients with traumatic unilateral open tibial fractures and found that current and previous smoker were 37% and 32%, respectively, less likely than nonsmokers to achieve union. Current smoker were twice as likely to develop osteomyelitis but were at no greater for developing other types of infection. Clinical observation parallel these studies. With over 50 million smokers in the United States, it is important that the clinician and the patient take into consideration that smoking may delay fracture healing and increase the risk of complications and thus contribute to a poorer functional outcome. Corticosteroids can delay fracture healing and increase the risk for fractures. Delayed healing is thought to be due to decreased synthesis of organic bone matrix components and slowed differentiation of osteoblasts from mesenchymal cells. NSAIDs are also thought to slow fracture healing. The evidence for this is from a variety of animal studies and one retrospective series using high doses of intramuscular ketorolac after spinal fusion in human subjects. A doses dependent relationship was found between that particular NSAID and nonunion rates. Certain antibiotics, specifically fluoroquinolones such as ciprofloxacin and levofloxacin, have also been shown to delay fracture healing, especially early in the course of fracture repair. Randomized controlled trials (RCTs) have shown that animals given these drugs after a fracture have fractures with less mature callus formation and decreased torsional strength and stiffness, suggesting that administration of fluoroquinolones during the early stages of fracture repair may also compromise fracture healing in humans. Nutrition also influences fracture repair as the energy required for the body to heal a fracture is substantial. To synthesize large volumes of collagen, proteoglycans and other matrix constituents, cells need a steady supply of the components of these molecules specifically proteins and carbohydrates. Fractures that would heal rapidly in wellnourished patients may fail to heal in patients with severe malnutrition. Jensen et al found a 42% incidence of clinical or subclinical malnutrition in patients undergoing orthopedic procedures. It has been reported that a single long bone fracture can temporarily increase metabolic requirements by 20% to 25% and that multiple injuries or infections can increase this requirements by as much as 50%. Specifically, it has been shown that fracture callus strength is reduced in patients with protein deficiencies. Therefore it is important that patients eat balanced diet to optimize their healing potential.

A patient s age can also influence the rate of fracture healing. Infants have the most rapid rate of fracture healing and the rate of fracture healing declines with age. Fracture healing in adults and the elderly follows the same sequence but in the elderly it is often slower and less effective. For some fractures, age related changes and significant enough to alter the treatment patterns. For example, a non displaced closed femoral fracture in a 3 year old child may be effectively managed with a cast with restoration of tissue structure and function in 6 weeks, whereas a 70 year old patient may require surgery and may take up to 6 months for an outcome that is much less predictable. The amount of soft tissue damage also affects the rate of fracture healing. The time for a bone to heal is greatly prolonged in fractures that have more soft tissue stripping or damage. Studies have shown that muscle damage slow bone healing. If the fracture site loses its intrinsic vascularity as result of periosteal stripping from surgery or injury, comminution, or a large initial displacement, the extrinsic blood supply becomes imperative for fracture healing. The extrinsic blood supply of bone comes mainly from the muscles, as well as the soft tissues, that surround it. Experimentally, ischemic bone will not revascularization until the surrounding soft tissue envelope does so. Therefore if the soft tissue envelope is damaged, bone healing will be delayed. Most studies show that the incidence nonunion is higher with open fractures than with close fractures. Godina also found that delayed closure time increased total healing time. The average healing time 6 months for primary closure and 12.8 months for delayed closure. The presence of infection can also slow or prevent fracture healing. Infection may cause necrosis of normal tissue, as well as edema and thrombosis of blood vessels.