Aims. A number of anti-retroviral therapies (ART) have been implicated in potentially contributing to HIV-associated bone disease. The aim of this study was to evaluate the effect of combination ART on the fracture healing process. Methods. A total of 16 adult male Wistar rats were randomly divided into two groups (n = eight each): Group 1 was given a combination of Tenfovir 30 mg, Lamivudine 30 mg, and Efavirenz 60 mg per day orally, whereas Group 2 was used as a control. After one week of medication preload, all rats underwent a standardized surgical procedure of mid-shaft tibial osteotomy fixed by intramedullary nail with no gap at the fracture site. Progress in fracture healing was monitored regularly for eight weeks. Further evaluations were carried out after euthanasia by micro-CT, mechanically and histologically. Two blinded orthopaedic surgeons used the Radiological Union Scoring system for the Tibia (RUST) to determine fracture healing. Results. The fracture healing process was different between the two groups at week 4 after surgery; only two out of eight rats showed full healing in Group 1 (ART-treated), while seven out of eight rats had bone union in Group 2 (control) (p = 0.040). However, at week eight postoperatively, there was no statistical difference in bone healing; seven out of eight progressed to full union in both groups. Conclusion. This study demonstrated that combination ART resulted in delayed fracture healing at week 4 after surgery in rats, but did not result in the development of nonunion. Cite this article: Bone Joint Res 2022;11(8):585–593

In this retrospective study we evaluated the method of acute shortening and distraction osteogenesis for the treatment of tibial nonunion with bone loss in 17 patients with a mean age of 36 years (10 to 58). The mean bone loss was 5.6 cm (3 to 10). In infected cases, we performed the treatment in two stages. The mean follow-up time was 43.5 months (24 to 96). The mean time in external fixation was 8.0 months (4 to 13) and the mean external fixator index was 1.4 months/cm (1.1 to 1.8). There was no recurrence of infection. The bone evaluation results were excellent in 16 patients and good in one, while functional results were excellent in 15 and good in two. The complication rate was 1.2 per patient. We conclude that acute shortening and distraction osteogenesis is a safe, reliable and successful method for the treatment of tibial nonunion with bone loss, with a shorter period of treatment and lower rate of complication

Aims. This study aimed to investigate the role of quantitative histological analysis in the diagnosis of fracture-related infection (FRI). Patients and Methods. The clinical features, microbiology culture results, and histological analysis in 156 surgically treated nonunions were used to stratify the likelihood of associated infection. There were 64 confirmed infected nonunions (one or more confirmatory criteria: pus, sinus, and bacterial growth in two or more samples), 66 aseptic nonunions (no confirmatory criteria), and 26 possibly infected nonunions (pathogen identified from a single specimen and no confirmatory criteria). The histological inflammatory response was assessed by average neutrophil polymorph (NPs) counts per high-power field (HPF) and compared with the established diagnosis. Results. Assuming a cut-off of over five neutrophils per high-power field to diagnose septic nonunion, there was 80% sensitivity and 100% specificity (accuracy 90%). Using a cut-off of no neutrophils seen in any high-power field to diagnose aseptic nonunion, there was a sensitivity of 85% and a specificity of 98% (accuracy 92%). Conclusion. Histology can be used in a bimodal fashion as a diagnostic test for FRI. The presence of more than five NPs/HPF had a positive predictive value for infected nonunion of 100%, while the complete absence of any NPs is almost always indicative of an aseptic nonunion (positive predictive value of 98%). Cite this article: Bone Joint J 2018;100-B:966–72

Successful healing of a nine-year tibial nonunion resistant to six previous surgical procedures was achieved by tissue engineering. We used autologous bone marrow stromal cells (BMSCs) expanded to 5 × 10. 6. cells after three weeks’ tissue culture. Calcium sulphate (CaSO. 4. ) in pellet form was combined with these cells at operation. The nonunion was clinically and radiologically healed two months after implantation. This is the description of on healing of a long-standing tibial nonunion by tissue engineering. The successful combination of BMSCs and CaSO. 4. has not to our knowledge been reported in a clinical setting

We describe the use of a vascularised periosteal patch onlay graft based on the 1,2 intercompartmental supraretinacular artery in the management of 11 patients (ten men, one woman) with chronic nonunion involving the proximal third of the scaphoid. The mean age of the patients was 31 years (21 to 45) with the dominant hand affected in eight. Six of the patients were smokers and three had undergone previous surgery to the scaphoid. All of the proximal fragments were avascular. The presence of union was assessed using longitudinal axis CT. Only three patients progressed to union of the scaphoid and four required a salvage operation for a symptomatic nonunion. The remaining four patients with a persistent nonunion are asymptomatic with low pain scores, good grip strength and a functional range of wrist movement. Although this technique has potential technical advantages over vascularised pedicled bone grafting, the rate of union has been disappointing and we do not recommend it as a method of treatment

We used the Ilizarov circular external fixator to treat 16 patients with persistent nonunion of the diaphysis of the humerus despite surgical treatment. All patients had pain and severe functional impairment of the affected arm. In ten, nonunion followed intramedullary nailing. We successfully treated these by a closed technique. The nail was left in place and the fracture compressed over it. The fractures of the other six patients had previously been fixed by various methods. We explored these nonunions, removed the fixation devices and excised fibrous tissue and dead bone before stabilising with the Ilizarov fixator. In five patients union was achieved. Bone grafting was not required. In the single patient in whom treatment failed, there had been a severely comminuted open fracture. All except one patient had reduction of pain, and all reported an improvement in function

We describe a new surgical treatment of atrophic nonunion of the clavicle. The nonunion is excised by cuts at 45° to the long axis and repair uses 3.5 mm pelvic reconstruction or dynamic compression plates, with a lag screw to provide interfragmentary compression. The site is grafted with cancellous bone. We have been successful in all seven patients, with early return to normal function. The consequent narrowing of the shoulder girdle is fully acceptable for appearance and function

Aims. Biofilm formation is one of the primary reasons for the difficulty in treating implant-related infections (IRIs). Focused high-energy extracorporeal shockwave therapy (fhESWT), which is a treatment modality for fracture nonunions, has been shown to have a direct antibacterial effect on planktonic bacteria. The goal of the present study was to investigate the effect of fhESWT on Staphylococcus aureus biofilms in vitro in the presence and absence of antibiotic agents. Methods. S. aureus biofilms were grown on titanium discs (13 mm × 4 mm) in a bioreactor for 48 hours. Shockwaves were applied with either 250, 500, or 1,000 impulses onto the discs surrounded by either phosphate-buffered saline or antibiotic (rifampin alone or in combination with nafcillin). The number of viable bacteria was determined by quantitative culture after sonication. Representative samples were taken for scanning electron microscopy. Results. The application of fhESWT led to a ten-fold reduction in bacterial counts on the metal discs for all impulse numbers compared to the control (p < 0.001). Increasing the number of impulses did not further reduce bacterial counts in the absence of antibiotics (all p > 0.289). Antibiotics alone reduced the number of bacteria on the discs; however, the combined application of the fhESWT and antibiotic administration further reduced the bacterial count compared to the antibiotic treatment only (p = 0.032). Conclusion. The use of fhESWT significantly reduced the colony-forming unit (CFU) count of a S. aureus biofilm in our model independently, and in combination with antibiotics. Therefore, the supplementary application of fhESWT could be a helpful tool in the treatment of IFIs in certain cases, including infected nonunions. Cite this article: Bone Joint Res 2021;10(1):77–84

Aims. The primary aim of this study was to establish the cost-effectiveness of the early fixation of displaced midshaft clavicle fractures. Patients and Methods. A cost analysis was conducted within a randomized controlled trial comparing conservative management (n = 92) versus early plate fixation (n = 86) of displaced midshaft clavicular fractures. The incremental cost-effectiveness ratio (ICER) was used to express the cost per quality-adjusted life-year (QALY). The Six-Dimension Short-Form Health Survey (SF-6D) score was used as the preference-based health index to calculate the cost per QALY at 12 months after the injury. Results. The mean 12-month SF-6D was 0.9522 (95% confidence interval (CI) 0.9355 to 0.9689) following conservative management and 0.9607 (95% CI 0.9447 to 0.9767) following fixation, giving an advantage for fixation of 0.0085, which was not statistically significant (p = 0.46). The mean cost per patient was £1322.69 for conservative management and £5405.32 for early fixation. This gave an ICER of £480 309.41 per QALY. For a threshold of £20 000 per QALY, the benefit of fixation would need to be present for 24 years to be cost-effective compared with conservative treatment. Linear regression analysis identified nonunion as the only factor to adversely influence the SF-6D at 12 months (p < 0.001). Conclusion. Routine plate fixation of displaced midshaft clavicular fractures is not cost-effective. Nonunion following conservative management has an increased morbidity with comparable expense to early fixation. This may suggest that a targeted approach of fixation in patients who are at higher risk of nonunion would be more cost-effective than the routine fixation of all displaced fractures. Cite this article: Bone Joint J 2019;101-B:995–1001

We have reviewed a series of 56 consecutive patients treated by the Ilizarov circular fixator for various combinations of nonunion, malunion and infection of fractures. We used segmental excision, distraction osteogenesis and gradual correction of the deformity as appropriate. Treatment was effective in eliminating 40 out of 46 nonunions and all 22 infections. There were two cases of refracture some months after removal of the frame, both of which healed securely in a second frame. Correction of malunion was good in the coronal plane but there was a tendency to anterior angulation, often occurring in the regenerate bone rather than at the original fracture site, after removal of the frame. This was associated with very slow maturation of regenerate bone in some patients, occurring largely, but not exclusively, in those who smoked heavily. Patients expressed high levels of satisfaction with the outcome, despite relatively modest improvements in pain and function, presumably because their longstanding and intractable nonunion had been treated. None the less, the degree of satisfaction correlated strongly with the degree of improvement in pain and function. We emphasise the importance of a multidisciplinary team in the assessment and support of patients undergoing long and demanding treatment. The Ilizarov method is valuable, but research is needed to overcome the problems of delayed maturation of the regenerate and slow or insecure healing of the docking site

The management of nonunion following high tibial osteotomy by total knee replacement (TKR) has been reported previously. We have extended the treatment to embrace cases with an infected high tibial osteotomy by performing an initial debridement with a period of antibiotic treatment followed by TKR. We have reviewed the results of seven knees in six patients with a mean follow-up of 40.5 months (20 to 57) after the staged TKR. At the latest follow-up, all the pseudarthroses had healed and there had been no recurrence of infection. The mean Hospital for Special Surgery knee score improved from 51.2 (35 to 73) to a mean of 91.7 (84 to 98) at final review. Management of nonunion following high tibial osteotomy with a TKR can be extended to infected cases when treated in two stages with a debridement and antibiotic therapy prior to TKR

Indomethacin is commonly administered for the prophylaxis of heterotopic ossification (HO) after the surgical treatment of acetabular fractures. Non-steroidal anti-inflammatory drugs such as indomethacin, have been associated with delayed healing of fractures and mechanically weaker callus. Our aim was to determine if patients with an acetabular fracture, who received indomethacin for prophylaxis against HO, were at risk of delayed healing or nonunion of any associated fractures of long bones. We reviewed 282 patients who had had open reduction and internal fixation of an acetabular fracture. Patients at risk of HO were randomised to receive either radiation therapy (XRT) or indomethacin. Of these patients, 112 had sustained at least one concomitant fracture of a long bone; 36 needed no prophylaxis, 38 received focal radiation and 38 received indomethacin. Fifteen patients developed 16 nonunions. When comparing patients who received indomethacin with those who did not, a significant difference was noted in the rate of nonunion (26% v 7%; p = 0.004). Patients with concurrent fractures of the acetabulum and long bones who receive indomethacin have a significantly greater risk of nonunion of the fractures of the long bones when compared with those who receive XRT or no prophylaxis

We report the results in 24 consecutive patients treated from 1976 to 1991 for nonunion of olecranon fractures. Their mean age was 42 years, and the mean interval from fracture to treatment for nonunion was 19 months. Management was by rehabilitation and activity as tolerated for three, continued immobilisation for one, and operative treatment for 20. Operations included excision of the olecranon fragment (1), osteosynthesis (16), and joint replacement (3). Four patients also had distraction arthroplasty. At a mean follow-up of 18 months no patient had severe residual elbow pain but three had moderate and six had mild symptoms. The mean arc of motion was 98 degrees representing an average improvement of 11 degrees. Twelve patients had an excellent result, four good, six fair, and two a poor result. Union had been achieved in 15 of the 16 patients treated by osteosynthesis

We undertook a retrospective study of 50 consecutive patients (41 male, 9 female) with an infected nonunion and bone defect of the femoral shaft who had been treated by radical debridement and distraction osteogenesis. Their mean age was 29.9 years (9 to 58) and they had a mean of 3.8 (2 to 19) previous operations. They were followed for a mean of 5.9 years (2.0 to 19.0). The mean duration of the distraction osteogenesis was 24.5 months (2 to 39). Pin-track infection was observed in all patients. The range of knee movement was reduced and there was a mean residual leg-length discrepancy of 1.9 cm (0 to 8) after treatment. One patient required hip disarticulation to manage intractable sepsis. In all, 13 patients had persistant pain. Bony union was achieved in 49 patients at a mean of 20.7 months (12 to 35). Although distraction osteogenesis is commonly used for the treatment of infected femoral nonunion with bone defects, it is associated with a high rate of complications

Aims. The aim of this study was to establish a reliable method for producing 3D reconstruction of sonographic callus. Methods. A cohort of ten closed tibial shaft fractures managed with intramedullary nailing underwent ultrasound scanning at two, six, and 12 weeks post-surgery. Ultrasound capture was performed using infrared tracking technology to map each image to a 3D lattice. Using echo intensity, semi-automated mapping was performed to produce an anatomical 3D representation of the fracture site. Two reviewers independently performed 3D reconstructions and kappa coefficient was used to determine agreement. A further validation study was undertaken with ten reviewers to estimate the clinical application of this imaging technique using the intraclass correlation coefficient (ICC). Results. Nine of the ten patients achieved union at six months. At six weeks, seven patients had bridging callus of ≥ one cortex on the 3D reconstruction and when present all achieved union. Compared to six-week radiographs, no bridging callus was present in any patient. Of the three patients lacking sonographic bridging callus, one went onto a nonunion (77.8% sensitive and 100% specific to predict union). At 12 weeks, nine patients had bridging callus at ≥ one cortex on 3D reconstruction (100%-sensitive and 100%-specific to predict union). Presence of sonographic bridging callus on 3D reconstruction demonstrated excellent reviewer agreement on ICC at 0.87 (95% confidence interval 0.74 to 0.96). Conclusion. 3D fracture reconstruction can be created using multiple ultrasound images in order to evaluate the presence of bridging callus. This imaging modality has the potential to enhance the usability and accuracy of identification of early fracture healing. Cite this article: Bone Joint Res 2021;10(12):759–766

The re-establishment of vascularity is an early event in fracture healing; upregulation of angiogenesis may therefore promote the formation of bone. We have investigated the capacity of vascular endothelial growth factor (VEGF) to stimulate the formation of bone in an experimental atrophic nonunion model. Three groups of eight rabbits underwent a standard nonunion operation. This was followed by interfragmentary deposition of 100 μg VEGF, carrier alone or autograft. After seven weeks, torsional failure tests and callus size confirmed that VEGF-treated osteotomies had united whereas the carrier-treated osteotomies failed to unite. The biomechanical properties of the groups treated with VEGF and autograft were identical. There was no difference in bone blood flow. We considered that VEGF stimulated the formation of competent bone in an environment deprived of its normal vascularisation and osteoprogenitor cell supply. It could be used to enhance the healing of fractures predisposed to nonunion

This study identified variables which influence the outcome of surgical management on 126 ununited scaphoid fractures managed by internal fixation and non-vascular bone grafting. The site of fracture was defined by a new method: the ratio of the length of the proximal fragment to the sum of the lengths of both fragments, calculated using specific views in the plain radiographs. Bone healing occurred in 71% (89) of cases. Only the site of nonunion (p = 1 × 10. −6. ) and the delay to surgery (p = 0.001) remained significant on multivariate analysis. The effect of surgical delay on the probability of union increased as the fracture site moved proximally. A prediction model was produced by stepwise logistic regression analysis, enabling the surgeon to predict the success of surgery where the site of the nonunion and delay to surgery is known

Nonunion of the humerus with bone loss and shortening due to osteomyelitis is rare but difficult to treat. We describe our experience with a callus distraction technique using a monolateral external fixator for the treatment of this condition. Between October 1994 and January 2004, 11 patients were treated. There were seven males and four females, with a mean age of 14 years (10 to 17). The mean bone loss was 1.9 cm (1 to 2.7) and the mean length discrepancy in the upper limb was 5.6 cm (3.5 to 8.0). The mean follow-up was for 106 months (54 to 166). The mean external fixation index was 34.8 days/cm (29.8 to 40.5). The mean lengthening was 9.5 cm (5.5 to 13.4). There were seven excellent results, three good and one poor. There were nine excellent functional results and two good. The treatment of humeral nonunion with bone loss and shortening due to osteomyelitis by callus distraction is a safe and effective means of improving function and cosmesis

We have retrospectively reviewed the clinical and radiological results in 204 consecutive adult patients who had surgical correction of 70 late post-traumatic pelvic nonunions and 134 malalignments. The deformed pelvises were subdivided into united (true), unstable, ununited, and partially stable malalignments with heterotopic bone. The principal complaints were of pain, pelvic instability, sitting imbalance, and apparent limb-length discrepancy. After surgery, 195 patients (96%) achieved a primary union and 144 (71%) had slight, intermittent or no pelvic pain, while pelvic instability was entirely eliminated. Overall, 131 patients (64.2%) were extremely satisfied, 58 (28.4%) were satisfied and 15 (7.4%) were unsatisfied. After reconstruction of the malaligned pelvises, 67 results (50%) were anatomical, 47 (35%) were satisfactory and 20 (15%) were unsatisfactory. For a pelvic nonunion with local osteopenia and malalignment, stabilisation of all three pelvic columns is recommended. True pelvic (united) malunions were the most satisfactorily realigned and had the fewest complications. Ununited and unstable malalignments, especially those with heterotopic bone, had the poorest corrections and the most neurological complications. A therapeutic alternative, by the local resection of a symptomatic bony prominence, and fixation in situ of a posterior pelvic nonunion, gives highly effective symptomatic relief with fewer complications. Despite this, many patients had persistent low back pain

Aims. Arthrodesis is rarely used as a salvage procedure for patients with a chronically infected total knee arthroplasty (TKA), and little information is available about the outcome. The aim of this study was to assess the reliability, durability, and safety of this procedure as the definitive treatment for complex, chronically infected TKA, in a current series of patients. Methods. We retrospectively identified 41 patients (41 TKAs) with a complex infected TKA, who were treated between 2002 and 2016 using a deliberate, two-stage knee arthrodesis. Their mean age was 64 years (34 to 88) and their mean body mass index (BMI) was 39 kg/m. 2. (25 to 79). The mean follow-up was four years (2 to 9). The extensor mechanism (EM) was deficient in 27 patients (66%) and flap cover was required in 14 (34%). Most patients were host grade B (56%) or C (29%), and limb grade 3 (71%), according to the classification of McPherson et al. A total of 12 patients (29%) had polymicrobial infections and 20 (49%) had multi-drug resistant organisms; fixation involved an intramedullary nail in 25 (61%), an external fixator in ten (24%), and dual plates in six (15%). Results. Survivorship free from amputation, persistent infection, and reoperation, other than removal of an external fixator, at five years was 95% (95% confidence interval (CI) 89% to 100%), 85% (95% CI 75% to 95%), and 64% (95% CI 46% to 82%), respectively. Reoperation, other than removal of an external fixator, occurred in 13 patients (32%). After the initial treatment, radiological nonunion developed in ten knees (24%). Nonunion was significantly correlated with persistent infection (p = 0.006) and external fixation (p = 0.005). Of those patients who achieved limb salvage, 34 (87%) remained mobile and 31 (79%) had ‘absent’ or ‘minimal’ pain ratings. Conclusion. Knee arthrodesis using a two-stage protocol achieved a survivorship free from amputation for persistent infection of 95% at five years with 87% of patients were mobile at final follow-up. However, early reoperation was common (32%). This is not surprising as this series included worst-case infected TKAs in which two-thirds of the patients had a disrupted EM, one-third required flap cover, and most had polymicrobial or multi-drug resistant organisms. Cite this article: Bone Joint J 2020;102-B(6 Supple A):170–175