CHARGE is an acronym referring to the features of this rare syndromic condition: (C) coloboma of the iris or retina; (H) heart defects or cardiac malformations; (A) atresia/stenosis of the the elbow has great potential for fracture healing but is very sensitive to prolonged immobilization which can easily lead to intraarticular adherences and stiffness.
In addition, when both radius and ulna are fractured, the interosseus membrane facilitates communication between the regenerative environments. Such extensive injuries around the proximal forearm can lead to heterotopic ossifications and synostosis which decreases sagittal range of motion through impingement and even block the rotational movement through bone bridges.
The inflammatory phase is one of the initiating factors for bone healing. The exact role of the various cytokines involved in bone healing on osteoblast biology is not entirely clarified1. The understanding of the molecular and cellular mechanism of fracture healing can facilitate the fracture management and the treatment of impaired bone healing2. System wide inflammatory conditions also modulate the primary processes of fracture management which could explain the shock induction in polytraumatic patients, as well as increased ossifications associated with head injuries. We aimed to review and describe this intricate process of bone metabolism, with particular focus on abnormal function and exemplifying it with a series of clinical cases that will justify their practical importance.
Scope of the present review is to analyze all the recent literature focused on the immunopathological pathways around the elbow joint in order to identify relevant topics which could be useful to improve clinical practice. In addition, we searched on the electronic database of our clinic, over a period of 5 years, in order to obtain a broad view of the surgically treated elbow fractures/dislocations. At the end we refined the results in order to discard multiple or inappropriate coding. Virtually, all simple radial head fractures and elbow dislocations were treated as outpatients and, thus, not included in our results. We then pursued to identify the surgical treatment for any complication of the elbow joint regardless its etiology and providing evidence for relevant cases.
Three directions of clinically relevant immunepathological researches were identified: ?fracture healing and nonunion?, ?induced membranes technique? and ?heterotopic ossifications?. Out of 106 admissions for traumatic injuries about the elbow, the majority were olecranon fractures, followed by fractures of the distal humerus.Virtually all osteosynthesis for the olecranon were performed using K wires and figure eight cerclage, with a trend towards bicortical fixation.
This construct was also the most frequent to require removal and had favorable outcomes. The distal humerus fractures, on the other hand, often led to ROM limitations and ossifications which persisted even after implant removal. A total of 14 cases were surgically treated for important residual functional limitations: 6 distal humerus fractures, 4 unstable dislocations (terrible triad), one distal humerus non union, one radioulnar proximal synostosis, one bad connected proximal ulna fracture and one extended tumoral resection of the proximal ulna.
Fracture Healing and Lack of Union Whenever a fracture occurs, bone and surrounding soft tissues are ruptured. The immediate consequence is the release of inflammatory mediators and the formation of an hematoma. This is deemed the acute inflammatory phase; it peaks within 24 hours and develops under hypoxic conditions. The tumor necrosis factorα (TNFα) and interleukins 1 and 6 (IL1, IL6) are the major regulators3.
Then, the callus fills with cartilage formed from specialized mature mesenchymal stem cells recruited by stromal cellderived factor1 and Gproteincoupled receptor CXCR44. Vascular endothelial growth factor (VEGF)dependent pathway is the responsible for revascularization and neoangiogenesis at the fracture site. The cartilage then calcifies and is replaced with woven bone which confers rigidity3. In an animal model, a study by Toben et al5 compared the healing process of a fracture be tween normal and imunodeficient hosts.
Recombination of activated gene 1 deprived (RAG1/) organisms showed more bone and less cartilage with an accelerated endochondral ossification. In addition, they had less lymphocytes and reduced expression of inflammatory cytokines apart from IL10. Nam et al6 performed a similar research using immunodeficient (recombination activating gene 2) mice as a model of impaired injury re pair.
IL17F was determined to be an important contributor for the cellular response in osteogen esis and supposed to be produced by Th17 subset of Tlymphocytes. General administration of prostaglandin (Pg) E receptor 4 ligands, such as prostaglandin E2, appears to support fracture healing. In a study by Tanaka et al7, the total vol ume of cortical bone, as well as the mineral con tent, increased proportionally with the Pg dose by accelerating the local turnover.A skeletogenesis regulator, the betacatenin pathway, activates T cell factor dependent transcription and posi tively regulates osteoblasts. Chen et al8 demon strated that, in early stages of fracture repair, betacatenin differentiates pluripotent mesenchymal cells to either osteoblasts or chondrocytes. After wards, betacatenin continues to exert a positive regulation on osteoblasts.
Sclerostin is a glycoprotein secreted by osteocytes which inhibits os teoblastogenesis via Wnt signaling. Furthermore, sclerostin neutralizes antibodies leading to in creased bone mineralization in animal models of osteoporosis. Systemic administration of SclAb III also results in an increased mineral density and histological bone deposition in a noncritical size defect as early as the first week. These find ings might provide its potential use in complicat ed fractures and nonunions9,10.
Osteoclasts cross presents antigens to induce transcription factor Scurfin (also known as forkhead box P3 and en coded by Foxp3) in CD8+ Tcell. In an animal model for hormonal osteoporosis, this process was showed to limite bone loss while to increase bone density11 (Figure 1).