The process of fracture healing requires a precise balance of biology and stabilization during the healing process. There are four pillars for adequate bone healing: mechanics, osteogenic cells, scaffolds, and growth factors. In some circumstances, this process does not go as expected, and healing does not occur without additional intervention. Definitions vary among different studies, but overall, a diagnosis can be made when there is no evidence of progression of the healing process for 3 months or no healing after 9 months of the injury. This condition will not only have a detrimental effect on the patient’s quality of life, comparable to advanced hip arthrosis and worse than congestive heart failure; but it also has a high impact on the total care costs, double the cost of fractures that heal adequately. Despite the different options available, the treatment of tibial nonunions still is challenging for the surgeon.,,,
The "diamond concept” was introduced by Giannoudis et al., aiming to describe what is needed to achieve adequate fracture healing. This concept highlights the importance of three biological factors: osteogenic cells, osteoconductive scaffolds, and growth factors, and a fourth factor known as mechanical stabilization. If one or more of these factors are altered, adequate fracture healing will be threatened.
Approximately 6 million fractures are reported per year in the United States. Of these, between 1.9% to 15% result in nonunion. This rate will vary depending on the fractured bone and the characteristics of the fracture (i.e., open vs. closed). In tibial fractures, the rate of non-union is close to 1.1% if treated nonoperatively and nearly 5% if treated operatively. The likelihood of nonunion drastically increases in cases of open fractures.
As mentioned, an adequate interplay between host biology, reduction technique, and surgical stabilization is the key to achieve fracture healing. The development of a nonunion is multifactorial. Factors that contribute to the development of a nonunion include the following, listed here with known risk factors:
Fracture and Injury-Related Factors
Biology and Patient-Related Factors (Local and Systemic)
Biological factors are dependent on the patient host and surgical technique.
Host factors that can affect the biology at the fracture site include the presence of underlying comorbidities (e.g. diabetes), medication (e.g. steroids, non-steroidal anti-inflammatory drugs).
Nonunions can also be caused by local infection.
The evaluation of patients with a suspected or established nonunion should begin with a thorough review of the medical history so risk factors can be identified. Collect information about the type of fracture, fixation method, and previous treatments. When interviewing patients, they might manifest the persistence of pain at the fracture site and/or functional limitations. One indication that a nonunion is not present is the patient will not have pain with ambulation or when using the extremity. The physical exam should be done in a standard fashion, with an evaluation of the neurovascular status and range of motion. Special attention should be drawn to any signs of infection (skin or soft tissue changes) and mobility at the fracture site, which might indicate the absence of adequate callus formation.
It is challenging to clinically diagnose septic versus aseptic nonunion . As the management varies significantly based on the presence or absence of sepsis, so ruling it out is of prime concern whilst evaluating a case of non-union. In general, patients with a suspected nonunion should be initially evaluated as per the following:
Imaging: plain radiographs, including AP, lateral, oblique, and weight-bearing films. It is important to look for signs (e.g., gaps or callus formation) or absence of healing, bone quality, signs of infection, associated deformities or length discrepancies, as well as the characteristics of the two fragments (i.e., contact, stability, and bone loss). Once this has been done, the nonunion can be adequately categorized as atrophic, hypertrophic, or oligotrophic. If possible, a comparison with original and postoperative follow-up films should be done to create a timeline and a better understanding of the nonunion process . In cases where the fracture site cannot be adequately visualized as a consequence of the hardware or the bone quality, a CT scan is advised. This study will allow better identification of the fracture site and assessment of any rotational deformity. Finally, bone scans can be used to assess bone metabolism. Radiologic studies should be complemented with
Depending on its cause, nonunion classifications are as follows:
Treatment of nonunions should aim to achieve healing of the fracture while preserving functionality. The following are available options for the treatment of non-unions:
Conservative treatment/weight-bearing: In some circumstances and special patient characteristics (e.g., elderly patients not eligible for operative treatments), nonunions can be treated with weight-bearing and watchful waiting. Weight-bearing can be coupled with operative methods such as dynamization or bone excision.
Ultrasound (low-intensity pulsed ultrasound [LIPUS]): Low sine waves will promote bone healing by increasing the osteoblastic response .
Injection of bone marrow aspirate percutaneously 
Extracorporeal shock wave therapy: This was reported to be as equally effective as an operative intervention for cases of stable hypertrophic nonunion .
Septic versus aseptic non-union is the key variable when planning a surgical strategy to manage a case of tibial non-union, hence intraoperative culture should always be performed to diagnose a subclinical infection. Other variables to consider for management are patient's characteristics, the site of non-union, radiologic findings, presence, or absence of angular or rotational deformities . A staged approach is a gold standard when managing septic tibial nonunions . Whilst a single procedure can suffice in managing aseptic tibial non-union .
Single-stage approach: This involves surgical debridement of all non-viable tissues and bone ends, multiple cultures to be taken from the nonunion site or canal reaming followed by revision open reduction and internal fixation or exchange nailing. Antibiotic administration is tailored to culture results and sensitivities . When open treatment is essential, autologous bone grafting has been recommended as an adjunct .
Staged approach: usually indicated for septic tibial nonunion. This involves steps to control infection followed by definitive surgery.
The following are details of operative treatment options and adjuncts reported in the literature:
Nail dynamization and nail exchange: Nail Dynamization and exchange have two similar indications; comminuted fractures and absence of cortical contact after IM Nail .
Fibular Osteotomy (Partial fibulectomy): This procedure can be done on its own or most commonly combined with other procedures. This is mainly indicated where the tibial non-union is causing significant malalignment . Two important requisites have to be fulfilled, a stable nonunion and the fibulectomy has to be done in another site different .
Open Reduction and Internal Fixation with plate and screws: This is an effective procedure in managing non-union especially when intramedullary nailing is contraindicated or not technically possible. Outcomes are equivalent to other methods in terms of successful healing and incidence of complications .
Locking compression plates: It is indicated for managing nonunion of the metaphyseal diaphyseal junction fractures, where the outcomes of exchange nailing would be doubtful. The procedure is performed along with bone grafting and without the removal of the underlying nail by gaining unicortical purchase fixation with locking head screws. It has been shown to have predictable good results .
Bone grafting: Traditionally, iliac crest bone graft has been used when poor vascular supply is present. This treatment option aims to provide an adequate environment for bone formation (biological factors of the diamond concept).
Amputation: Considered when adequate functional outcomes cannot be achieved.
Delayed unions are fractures with a slow progression to healing and require some type of intervention.
Prognosis of tibial fractures can be evaluated using the RUST (Radiographic Union Score for Tibial fractures) score, in which all the bone cortices are evaluated, looking for the presence/absence of fracture line and bone callus. The Nonunion Risk Determination (NURD) score considered are the RUST scores, open/closed fracture, compartment syndrome, fracture classification (IIIB tibia), concomitant chronic disease, smoking status, infection, female sex, and American Society of Anesthesiologists (ASA) score. This model allows the clinician to identify those patients at risk of nonunion within 3 months of injury .
The reported average healing time for cases of aseptic tibial nonunion treated with reaming and exchange nailing was from 5 to 9 months  and the union rates reported to be between 72% and 100% .
This condition has myriad presentations, and each patient and their expectations are different, so the surgeon must act accordingly. Consult plastic surgery in those cases in which the soft tissue is compromised or a flap is expected and infectious diseases in cases of an infected nonunion. Consult with physical and occupational therapy should be considered, aiming to achieve independence and early range of motion.
Keep in mind the "diamond concept." Minimizing the risk of nonunion is based on patient factors and surgeon-related factors (mechanical). The following can help a practitioner avoid additional risk factors to the patient:
Non-union of the tibia may occur for many reasons. Thus, these patients are best managed by an interprofessional team that includes an orthopedic surgeon, physical therapist, infectious disease expert, vascular surgeon, plastic surgeon and wound care nurses. [Level V]
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