Hypertrophic Callus Research Articles

Spontaneous healing of a 14 cm diaphyseal cortical defect of the tibia

Post–traumatic bone defects present a difficult treatment problem for the orthopaedic trauma surgeon but modern techniques have made segmental reconstruction feasible. Experiences with the Ilizarov technique [1] and bone segment transport over unreamed intramedullary nails [2,3] have produced good results in the management of large diaphyseal cortical defects. Alternative treatment options include massive autologous bone grafting, free vascularised fibula transfer as well as tibiofibular synostosis [4–6]. Spontaneous healing of bone defects and hypertrophic callus formation have been described when associated with head injury [7] as well as in children [8] but in the literature we did not find any case similar to the here presented.

Platelet-derived growth factor-alpha receptor expression supports the growth of conventional chondrosarcoma and is associated with adverse outcome.

Bone cells are important targets of platelet-derived growth factors (PDGFs) because they stimulate proliferation of osteoblasts and chondrocytes. In this study we wanted to determine the expression of PDGF-AA and PDGF-alpha receptor in conventional chondrosarcomas and to compare the results with those obtained from benign enchondromas and non-neoplastic cartilage tissue. Sixty-seven chondrosarcomas, 20 enchondromas, and 5 specimens of healthy cartilage as well as 7 specimens of hypertrophic callus cartilage were immunohistochemically analyzed for the expression of PDGF-AA and PDGF-alpha receptor, respectively. Additionally, the proliferation activity was examined with the MIB-1 antibody. Clinical follow-up data were available from 53 patients. A significant overexpression of receptor and factor was found in chondrosarcomas as compared with enchondromas (PDGF-AA p = 0.013, PDGF-alpha receptor p <0.001). MIB-1 values were significantly higher in chondrosarcomas (p <0.001). In healthy joint cartilage no staining was detectable, whereas reactive cartilage of callus formation showed high expression levels. PDGF-alpha receptor expression was significantly higher in grade 3 chondrosarcomas compared with grade 2 (p = 0.022) and grade 1 tumors (p = 0.002). Survival analysis documented a significantly shorter overall survival for patients with high PDGF-alpha receptor expression (p = 0.0172, log-rank test). Because PDGF-alpha receptor expression positively correlates with the aggressiveness of chondrosarcoma, it may be considered as a possible target for novel therapeutic strategies.

Behaviour of an artery enclosed within a normal or hypertrophic callus of a long-bone fracture

The behaviour of the brachial artery enclosed in a hypertrophic or a normal callus was investigated in experimentally produced fractures of the humerus in 22 dogs. The brachial artery was displaced in a bony groove created at the fractured ends of the bone. The fracture was immobilized with a metal plate and four screws. The progress of the callus formation was studied and the patency of the artery was evaluated. In 15 out of the 22 animals a medium-sized or hypertrophic callus had developed that engulfed the brachial artery without obstructing its lumen and blood flow. In five dogs the fracture site was infected and the resultant osteomyelitis obstructed the artery. In the remaining two dogs the arterial lumen was extremely narrowed, due to breaking of the plate and formation of pseudarthrosis in one and injury of the artery in the other. Unless complicated by infection resulting in vascular occlusion, callus at the fracture site may engulf an artery without interference in its patency and blood flow. The possible involvement of a functioning artery within a callus or a mass of heterotopic ossification (myositis ossificans) should be kept in mind during surgical treatment of old fractures, hypertrophic callus with pseudarthrosis or extensive heterotopic ossification.

Effects of macrophage activation on bone healing

In this study the effect of macrophage activation on bone healing was investigated in rats. In three groups of rats, an osteotomy of the femoral bone was performed and then nailed. Macrophages were activated by semisoluble aminated glucan. In one group of animals this was applied locally, in another group it was applied systemically (intraperitoneally), and the third group served as control. Eight rats in each group were killed after 4, 8, and 12 weeks, and the mechanical characteristics of the healing osteotomies were evaluated. We found that local activation of macrophages induced an immature hypertrophic callus with reduced biomechanical characteristics, as evaluated by bending moment, rigidity, and energy absorption. There were no significant differences between the rats subjected to systemic macrophage activation and the control rats. We conclude that local macrophage activation during the initial phase of bone repair impairs healing.

Extremity fractures in the patient with a traumatic brain injury.

Extremity fractures are common in patients with traumatic brain injuries (TBIs). These injuries are often inadequately treated and occasionally are completely missed due to the unique problems inherent to the TBI patient. However, appropriate evaluation of the TBI patient allows prompt diagnosis and optimal treatment of extremity fractures. The increased survival rate of these patients has resulted in a greater emphasis on minimizing dysfunction and disability, especially that due to concomitant orthopaedic trauma. Advances in anesthestic technique permit earlier operative fixation of extremity fractures. Most injuries, particularly those in the lower extremity, require operative stabilization to allow early mobilization and rehabilitation. Upper extremity fractures are often associated with peripheral nerve injuries. Heterotopic ossification is common, especially about the elbow and hip. Contrary to prevalent belief, fracture healing is not necessarily accelerated in the TBI patient; hypertrophic callus, myositis ossificans, and heterotopic ossification occur frequently and are often misperceived as accelerated healing.

Post-traumatic hormonal disturbances: prolactin as a link between head injury and enhanced osteogenesis.

Traumatic brain injury (TBI) combined with fractures of long bones or large joints is often associated with enhanced osteogenesis (early fracture healing accompanied by hypertrophic callus formation and/or heterotopic ossifications). Humoral factors that cause enhanced osteogenesis in patients with TBI are not yet identified. The aim of this study was to reveal if post-traumatic change(s) of hormone levels in patients with TBI and bone fractures could be associated with the phenomenon of enhanced osteogenesis. The blood values of adrenocorticotropic hormone (ACTH), cortisol, growth hormone (GH), parathyroid hormone (PTH) and prolactin (PRL) were studied weekly over a period of three months after injury in patients with bone fractures only, those with TBI only or combined bone fractures and TBI (patients exerting enhanced osteogenesis). Stress-hormones, ACTH and cortisol, or the hormones related to the bone growth (GH and PTH) did not show any particular post-traumatic changes in the blood of patients with combined injury that could be associated with the enhanced osteogenesis. On the other hand, patients with combined bone fractures and TBI accompanied by enhanced osteogenesis had significantly elevated PRL levels in blood during the 5th week of the post-traumatic period. Thus, the maximal PRL values were measured at the time when in this group of patients fractures were in consolidation and hypertrophic callus or heterotopic ossifications were developing (as verified by x-ray imaging). Hence, PRL does not only influence physiology of the bone metabolism but also seems to be one of the humoral factors involved in the phenomenon of enhanced osteogenesis in patients with TBI.

INJURY TO THE BRACHIAL PLEXUS BY A FRAGMENT OF BONE AFTER FRACTURE OF THE CLAVICLE

Clavicular fractures are occasionally responsible for lesions of the brachial plexus. The symptoms are usually delayed and due to compression by hypertrophic callus, nonunion or a subclavian pseudoaneurysm. We describe a patient in whom a displaced bone fragment was pressing on the retroclavicular part of the brachial plexus, leading to early symptoms of a lesion of the posterior cord. Internal fixation of the clavicle and external neurolysis of the brachial plexus gave an almost full recovery.

Post-traumatic dynamic change of carboxyterminal propeptide of type I procollagen, alkaline phosphatase and its isoenzymes as predictors for enhanced osteogenesis in patients with severe head injury.

Patients suffering from severe head injury and fractures of long bones or large joints often show enhanced osteogenesis, with hypertrophic callus formation and/or heterotopic ossifications. The advantage of this phenomenon is early consolidation of the fractures. An extreme disadvantage is extensive periarticular calcification, resulting in complete ankylosis of the affected joint. In spite of numerous efforts aimed at clarifying the way in which severe head injury can influence osteogenesis at a distant site, this phenomenon is still not understood. The process, once started, seems irreversible, but if diagnosed in time, could be prevented with non-steroid anti-inflammatory drugs that inhibit development of heterotopic ossifications. The major prerequisite for testing this possibility is to define parameters of an early diagnosis of enhanced osteogenesis. Thus, the aim of this study was to test whether serum values of some parameters related to bone regeneration could allow an early prediction of enhanced ossification following bone fracture in patients with severe head injury. Samples of sera were obtained from three groups of injured patients: fractures of long bones or large joints only (n = 6), severe head injury only (n = 8), severe head injury and fractures of long bones and large joints (n = 7) and from a group of apparently healthy volunteers (n = 10). The values for alkaline phosphatase (ALP), the bone isoenzyme, and the carboxy terminal propeptide of type I procollagen (PICP) were significantly higher (5-20 times as high) in patients with severe head injury and bone or joint fractures than in any other group. Significantly increased concentrations of PICP were already found in the 1st week after injury, and those of ALP and of the bone isoenzyme increased during the 2nd week after injury. Results show that these parameters are helpful for an early diagnosis of enhanced osteogenesis and heterotopic ossifications in patients with severe head injury and bone fractures. Further studies are necessary to verify these findings, while analysis of reasons for the specific patterns of dynamic change of these parameters could lead to better understanding of the mechanisms underlying the uncontrolled bone formation.

Basic fibroblast growth factor (BFGF) immunoreactivity as a possible link between head injury and impaired bone fracture healing

Healing of fractures of long bones or large joints is often accelerated in patients with severe traumatic brain injury (TBI). However, in these patients an early fracture healing is accompanied by hypertrophic callus formation or heterotopic ossifications which might even result in an ankylosis of the affected joints. It seems that enhanced osteogenesis in patients suffering from TBI could be caused by some humoral factors, since the sera of these patients strongly promote the growth of osteoblast cells in vitro. However, humoral growth promoting factors which could perhaps induce enhanced osteogenesis are not yet identified. Hence, the aim of this study was to analyse if basic fibroblast growth factor (bFGF) could be related to the phenomenon of enhanced osteogenesis, since bFGF stimulates the growth of osteoblasts in vitro and could be found both in the brain and the bone tissue. For that purpose the values of bFGF immunoreactivity were determined in the sera of patients with TBI and bone fractures ( n = 8) as well as in the sera of patients with either TBI alone ( n = 10) or bone fractures alone ( n = 7), during a period of three months after injury. Quantification of the bFGF immunoreactivity was done using the ELISA based on monoclonal antibodies raised against the recombinant human bFGF. The bFGF immune-reactivity values obtained were also compared with the values determined in the sera of normal, healthy persons ( n = 9). In the group of patients with bone fractures alone only a transient increase of bFGF immunoreactivity (threefold above the normal values) was observed in the second week after injury. A similar increase of the values of bFGF immunoreactivity was also determined in the sera of patients with TBI only, but it lasted longer (from the 1st until the 7th to 8th week after injury). In the case of patients with TBI and bone fractures a specific pattern of post-traumatic dynamic change of the values of serum bFGF immunoreactivity was observed. Namely, the increase of bFGF immunoreactivity (up to seven-fold above the normal values) was determined even during the first week after injury. Afterwards, periods of high values of bFGF immunoreactivity observed during the 2nd, 4th and the 7–10th weeks after injury were interrupted by sudden decreases even to the normal values (during the 3rd and the 5–6th week after injury). Thus, post-traumatic increase of the serum bFGF immunoreactivity was induced both by bone fractures and TBI, while the unusual pattern of its changes could be related to the phenomenon of enhanced osteogenesis in the patients with brain injury.

A method for operative stabilization of multiple rib fractures in patients with flail chest

A treatment protocol for patients with flail chest was designed by the authors in 1983. It utilizes internal fixation of multiple segmentally fractured ribs for patients who, despite epidural analgesia, have continued compromised cough or gas exchange due to poor chest wall mechanics or require a thoracotomy for repair of lung parenchyma, bronchial injury, or control of bleeding. Most commonly, the procedure is accomplished through an extensile incision, which facilitates mobilization of the scapula and is a mid-flail segment thoracotomy. The fractured ribs are stabilized in a specific sequence utilizing template-based, molded reconstruction plates 2.7 mm in thickness. We have found that stabilization of the segmentally fractured ribs with this method confers good overall stability to the flail segment. By encouraging healing “per primum,” the method avoids cross-healing between ribs due to hypertrophic callus and thereby avoids the stiff chest wall segments, restricted chest wall motion, and chest wall pain that are common late sequelae of this injury when traditionally managed. The authors recommend that concomitant ipsilateral fractures of the clavicle be managed by open reduction and internal fixation so as to set the mobilized scapula anatomically on the chest wall.

Late lesions of the brachial plexus after fracture of the clavicle

Fractures of the clavicle, particularly those which are markedly displaced, may, in rare instances cause injury to the subclavian vessels and the brachial plexus which manifest progressively days or weeks after the initial trauma. More often than not, however, a costo-clavicular compression syndrome appears months or years after the clavicular fracture as a result of constriction by scar which invests the neuro-vascular bundle, by a secondary aneurysm or by hypertrophic callus. The authors report 16 such cases, one of which was treated conservatively, thirteen treated by surgical intervention while two cases are awaiting operation. These patients represent just over 1% of brachial plexus lesions seen over a period of twenty years in two surgical centres. Operative treatment consists of reduction of the clavicular deformity, possibly first rib resection, liberation of the plexus and correction of a vascular lesion as required. The outcome is usually good.

Clinical and radiological features of osteogenesis imperfecta type IVA.

This paper reports a survey of 78 patients with osteogenesis imperfecta (OI) type IVA, the variant that causes the greatest difficulties in differential diagnosis. A subgroup of children aged between five and eleven were compared with a control group from local schools. Among the OI children there were, apart from the high number of fractures, also significantly increased incidences of bruising, nosebleeds, excessive sweating and hypermobility of joints. Although none of the children with OI type IV had the dark blue or grey sclerae of the type I disease, an appreciable number had pale blue sclerae in early childhood. Radiologically normal bone texture was seen at the time of the first fracture in 10 out of 17 patients. Hypertrophic callus was seen in five patients and metaphyseal fractures in four. We hope that the information on this large group of patients will assist in the prevention of diagnostic difficulties.

Effect of instability of experimental fracture healing.

Bilateral tibial osteotomy with fracturing of the fibula was performed on ten Wistar rats weighing 300--350 g. Intramedullary nailing was performed with 1.4 mm nails after reaming. On the left side solid stainless rods were used, while on the right side the nails had a middle part made of titanium-nickel wire covered with polyvinylchloride (PVC), giving the nail a high degree of flexibility. After 8 weeks, nine of the ten flexible nails showed fracture of the central wire. The continuity was, however, maintained by the PVC tube. The bones with flexible nailing always showed hypertrophic callus while there was only scanty callus on the side with rigid nailing. Strength, deformation at fracture and stiffness were measured in a three-point bending test after removal of the solid nails and the fibulae. The strength of the tibiae was greatest on the side with flexible nailing, as was the deformation at fracture. The mean stiffness was higher in the bones with rigid nails, but the difference here was not statistically discernible.