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The Bone & Joint Journal
Vol. 106-B, Issue 4 | Pages 387 - 393
1 Apr 2024
Dean BJF Riley N Little C Sheehan W Gidwani S Brewster M Dhiman P Costa ML

Aims. There is a lack of published evidence relating to the rate of nonunion seen in occult scaphoid fractures, diagnosed only after MRI. This study reports the rate of delayed union and nonunion in a cohort of patients with MRI-detected acute scaphoid fractures. Methods. This multicentre cohort study at eight centres in the UK included all patients with an acute scaphoid fracture diagnosed on MRI having presented acutely following wrist trauma with normal radiographs. Data were gathered retrospectively for a minimum of 12 months at each centre. The primary outcome measures were the rate of acute surgery, delayed union, and nonunion. Results. A total of 1,989 patients underwent acute MRI for a suspected scaphoid fracture during the study period, of which 256 patients (12.9%) were diagnosed with a previously occult scaphoid fracture. Of the patients with scaphoid fractures, six underwent early surgical fixation (2.3%) and there was a total of 16 cases of delayed or nonunion (6.3%) in the remaining 250 patients treated with cast immobilization. Of the nine nonunions (3.5%), seven underwent surgery (2.7%), one opted for non-surgical treatment, and one failed to attend follow-up. Of the seven delayed unions (2.7%), one (0.4%) was treated with surgery at two months, one (0.4%) did not attend further follow-up, and the remaining five fractures (1.9%) healed after further cast immobilization. All fractures treated with surgery had united at follow-up. There was one complication of surgery (prominent screw requiring removal). Conclusion. MRI-detected scaphoid fractures are not universally benign, with delayed or nonunion of scaphoid fractures diagnosed only after MRI seen in over 6% despite appropriate initial immobilization, with most of these patients with nonunion requiring surgery to achieve union. This study adds weight to the evidence base supporting the use of early MRI for these patients. Cite this article: Bone Joint J 2024;106-B(4):387–393


Bone & Joint Open
Vol. 4, Issue 8 | Pages 584 - 593
15 Aug 2023
Sainio H Rämö L Reito A Silvasti-Lundell M Lindahl J

Aims. Several previously identified patient-, injury-, and treatment-related factors are associated with the development of nonunion in distal femur fractures. However, the predictive value of these factors is not well defined. We aimed to assess the predictive ability of previously identified risk factors in the development of nonunion leading to secondary surgery in distal femur fractures. Methods. We conducted a retrospective cohort study of adult patients with traumatic distal femur fracture treated with lateral locking plate between 2009 and 2018. The patients who underwent secondary surgery due to fracture healing problem or plate failure were considered having nonunion. Background knowledge of risk factors of distal femur fracture nonunion based on previous literature was used to form an initial set of variables. A logistic regression model was used with previously identified patient- and injury-related variables (age, sex, BMI, diabetes, smoking, periprosthetic fracture, open fracture, trauma energy, fracture zone length, fracture comminution, medial side comminution) in the first analysis and with treatment-related variables (different surgeon-controlled factors, e.g. plate length, screw placement, and proximal fixation) in the second analysis to predict the nonunion leading to secondary surgery in distal femur fractures. Results. We were able to include 299 fractures in 291 patients. Altogether, 31/299 fractures (10%) developed nonunion. In the first analysis, pseudo-R. 2. was 0.27 and area under the receiver operating characteristic curve (AUC) was 0.81. BMI was the most important variable in the prediction. In the second analysis, pseudo-R. 2. was 0.06 and AUC was 0.67. Plate length was the most important variable in the prediction. Conclusion. The model including patient- and injury-related factors had moderate fit and predictive ability in the prediction of distal femur fracture nonunion leading to secondary surgery. BMI was the most important variable in prediction of nonunion. Surgeon-controlled factors had a minor role in prediction of nonunion. Cite this article: Bone Jt Open 2023;4(8):584–593


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_14 | Pages 8 - 8
10 Oct 2023
Leow J Oliver W Bell K Molyneux S Clement N Duckworth A
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To develop a reliable and effective radiological score to assess the healing of isolated ulnar shaft fractures (IUSF), the Radiographic Union Score for Ulna fractures (RUSU). Initially, 20 patients with radiographs six weeks following a non-operatively managed ulnar shaft fracture were selected and scored by three blinded observers. After intraclass correlation (ICC) analysis, a second group of 54 patients with radiographs six weeks after injury (18 who developed a nonunion and 36 who united) were scored by the same observers. In the initial study, interobserver and intraobserver ICC were 0.89 and 0.93, respectively. In the validation study the interobserver ICC was 0.85. The median score for patients who united was significantly higher than those who developed a nonunion (11 vs 7, p<0.001). A ROC curve demonstrated that a RUSU ≤8 had a sensitivity of 88.9% and specificity of 86.1% in identifying patients at risk of nonunion. Patients with a RUSU ≤8 (n = 21) were more likely to develop a nonunion (n = 16/21) than those with a RUSU ≥9 (n = 2/33; OR 49.6, 95% CI 8.6–284.7). Based on a PPV of 76%, if all patients with a RUSU ≤8 underwent fixation at 6-weeks, the number of procedures needed to avoid one nonunion would be 1.3. The RUSU shows good interobserver and intraobserver reliability and is effective in identifying patients at risk of nonunion six weeks after fracture. This tool requires external validation but may enhance the management of patients with isolated ulnar shaft fractures


Bone & Joint Open
Vol. 2, Issue 4 | Pages 227 - 235
1 Apr 2021
Makaram NS Leow JM Clement ND Oliver WM Ng ZH Simpson C Keating JF

Aims. The primary aim of this study was to identify independent predictors associated with nonunion and delayed union of tibial diaphyseal fractures treated with intramedullary nailing. The secondary aim was to assess the Radiological Union Scale for Tibial fractures (RUST) score as an early predictor of tibial fracture nonunion. Methods. A consecutive series of 647 patients who underwent intramedullary nailing for tibial diaphyseal fractures were identified from a trauma database. Demographic data, comorbidities, smoking status, alcohol consumption, use of non-steroidal anti-inflammatory drugs (NSAIDs), and steroid use were documented. Details regarding mechanism of injury, fracture classification, complications, and further surgery were recorded. Nonunion was defined as the requirement for revision surgery to achieve union. Delayed union was defined as a RUST score < 10 at six months postoperatively. Results. There were 41 nonunions (6.3%), of which 13 were infected (31.7%), and 77 delayed unions (11.9%). There were 127 open fractures (19.6%). Adjusting for confounding variables, NSAID use (odds ratio (OR) 3.50; p = 0.042), superficial infection (OR 3.00; p = 0.026), open fractures (OR 5.44; p < 0.001), and high-energy mechanism (OR 2.51; p = 0.040) were independently associated with nonunion. Smoking (OR 1.76; p = 0.034), open fracture (OR 2.82; p = 0.001), and high-energy mechanism (OR 1.81; p = 0.030) were independent predictors associated with delayed union. The RUST score at six-week follow-up was highly predictive of nonunion (sensitivity and specificity of 75%). Conclusion. NSAID use, high-energy mechanisms, open fractures, and superficial infection were independently associated with nonunion in patients with tibial diaphyseal fractures treated with intramedullary nailing. The six-week RUST score may be useful in identifying patients at risk of nonunion. Cite this article: Bone Jt Open 2021;2(4):227–235


The Bone & Joint Journal
Vol. 106-B, Issue 6 | Pages 613 - 622
1 Jun 2024
Shen J Wei Z Wu H Wang X Wang S Wang G Luo F Xie Z

Aims. The aim of the present study was to assess the outcomes of the induced membrane technique (IMT) for the management of infected segmental bone defects, and to analyze predictive factors associated with unfavourable outcomes. Methods. Between May 2012 and December 2020, 203 patients with infected segmental bone defects treated with the IMT were enrolled. The digital medical records of these patients were retrospectively analyzed. Factors associated with unfavourable outcomes were identified through logistic regression analysis. Results. Among the 203 enrolled patients, infection recurred in 27 patients (13.3%) after bone grafting. The union rate was 75.9% (154 patients) after second-stage surgery without additional procedures, and final union was achieved in 173 patients (85.2%) after second-stage surgery with or without additional procedures. The mean healing time was 9.3 months (3 to 37). Multivariate logistic regression analysis of 203 patients showed that the number (≥ two) of debridements (first stage) was an independent risk factor for infection recurrence and nonunion. Larger defect sizes were associated with higher odds of nonunion. After excluding 27 patients with infection recurrence, multivariate analysis of the remaining 176 patients suggested that intramedullary nail plus plate internal fixation, smoking, and an allograft-to-autograft ratio exceeding 1:3 adversely affected healing time. Conclusion. The IMT is an effective method to achieve infection eradication and union in the management of infected segmental bone defects. Our study identified several risk factors associated with unfavourable outcomes. Some of these factors are modifiable, and the risk of adverse outcomes can be reduced by adopting targeted interventions or strategies. Surgeons can fully inform patients with non-modifiable risk factors preoperatively, and may even use other methods for bone defect reconstruction. Cite this article: Bone Joint J 2024;106-B(6):613–622


The Bone & Joint Journal
Vol. 101-B, Issue 10 | Pages 1300 - 1306
1 Oct 2019
Oliver WM Smith TJ Nicholson JA Molyneux SG White TO Clement ND Duckworth AD

Aims. The primary aim of this study was to develop a reliable, effective radiological score to assess the healing of humeral shaft fractures, the Radiographic Union Score for HUmeral fractures (RUSHU). The secondary aim was to assess whether the six-week RUSHU was predictive of nonunion at six months after the injury. Patients and Methods. Initially, 20 patients with radiographs six weeks following a humeral shaft fracture were selected at random from a trauma database and scored by three observers, based on the Radiographic Union Scale for Tibial fractures system. After refinement of the RUSHU criteria, a second group of 60 patients with radiographs six weeks after injury, 40 with fractures that united and 20 with fractures that developed nonunion, were scored by two blinded observers. Results. After refinement, the interobserver intraclass correlation coefficient (ICC) was 0.79 (95% confidence interval (CI) 0.67 to 0.87), indicating substantial agreement. At six weeks after injury, patients whose fractures united had a significantly higher median score than those who developed nonunion (10 vs 7; p < 0.001). A receiver operating characteristic curve determined that a RUSHU cut-off of < 8 was predictive of nonunion (area under the curve = 0.84, 95% CI 0.74 to 0.94). The sensitivity was 75% and specificity 80% with a positive predictive value (PPV) of 65% and a negative predictive value of 86%. Patients with a RUSHU < 8 (n = 23) were more likely to develop nonunion than those with a RUSHU ≥ 8 (n = 37, odds ratio 12.0, 95% CI 3.4 to 42.9). Based on a PPV of 65%, if all patients with a RUSHU < 8 underwent fixation, the number of procedures needed to avoid one nonunion would be 1.5. Conclusion. The RUSHU is reliable and effective in identifying patients at risk of nonunion of a humeral shaft fracture at six weeks after injury. This tool requires external validation but could potentially reduce the morbidity associated with delayed treatment of an established nonunion. Cite this article: Bone Joint J 2019;101-B:1300–1306


The Bone & Joint Journal
Vol. 98-B, Issue 4 | Pages 534 - 541
1 Apr 2016
Tsang STJ Mills LA Frantzias J Baren JP Keating JF Simpson AHRW

Aims. The aim of this study was to identify risk factors for the failure of exchange nailing in nonunion of tibial diaphyseal fractures. . Patients and Methods. A cohort of 102 tibial diaphyseal nonunions in 101 patients with a mean age of 36.9 years (15 to 74) were treated between January 1992 and December 2012 by exchange nailing. Of which 33 (32%) were initially open injuries. The median time from primary fixation to exchange nailing was 6.5 months (interquartile range (IQR) 4.3 to 9.8 months). . The main outcome measures were union, number of secondary fixation procedures required to achieve union and time to union. . Univariate analysis and multiple regression were used to identify risk factors for failure to achieve union. . Results. Multiple causes for the primary nonunion were found for 28 (27%) tibiae, with infection present in 32 (31%). Six patients were lost to follow-up. Further surgical procedures were required in 35 (36%) nonunions. Other fixation modalities were required in five fractures. A single nail exchange procedure achieved union in 60/96 (63%) of all nonunions. Only 11 out of 31 infected nonunions (35.4%) healed after one exchange nail procedure. Up to five repeated exchange nailings, with or without bone grafting, ultimately achieved union in 89 (93%) fractures. The median time to union after exchange nailing was 8.7 months (IQR 5.7 to 14.0 months). Univariate analysis confirmed that an oligotrophic/atrophic pattern of nonunion (p = 0.002), a bone gap of 5 mm or more (p = 0.04) and infection (p < 0.001), were predictive for failure of exchange nailing Multiple regression analysis found that infection was the strongest predictor of failure (p < 0.001). . Conclusion. Exchange nailing is an effective treatment for aseptic tibial diaphyseal nonunion. However, in the presence of severe infection with a highly resistant organism, or extensive sclerosis of the bone, other fixation modalities, such as Ilizarov treatment, should be considered. Take home message: Exchange nailing is an effective treatment for aseptic tibial diaphyseal nonunion. Cite this article: Bone Joint J 2016;98-B:534–41


Bone & Joint Research
Vol. 5, Issue 10 | Pages 512 - 519
1 Oct 2016
Mills L Tsang J Hopper G Keenan G Simpson AHRW

Objectives. A successful outcome following treatment of nonunion requires the correct identification of all of the underlying cause(s) and addressing them appropriately. The aim of this study was to assess the distribution and frequency of causative factors in a consecutive cohort of nonunion patients in order to optimise the management strategy for individual patients presenting with nonunion. Methods. Causes of the nonunion were divided into four categories: mechanical; infection; dead bone with a gap; and host. Prospective and retrospective data of 100 consecutive patients who had undergone surgery for long bone fracture nonunion were analysed. Results. A total of 31% of patients had a single attributable cause, 55% had two causes, 14% had three causes and 1% had all four. Of those (31%) with only a single attributable cause, half were due to a mechanical factor and a quarter had dead bone with a gap. Mechanical causation was found in 59% of all patients, dead bone and a gap was present in 47%, host factors in 43% and infection was a causative factor in 38% of patients. In all, three of 58 patients (5%) thought to be aseptic and two of nine (22%) suspected of possible infection were found to be infected. A total of 100% of previously treated patients no longer considered to have ongoing infection, had multiple positive microbiology results. Conclusion. Two thirds of patients had multiple contributing factors for their nonunion and 5% had entirely unexpected infection. This study highlights the importance of identifying all of the aetiological factors and routinely testing tissue for infection in treating nonunion. It raises key points regarding the inadequacy of a purely radiographic nonunion classification system and the variety of different definitions for atrophic nonunion in the current mainstream classifications used for nonunion. Cite this article: L. Mills, J. Tsang, G. Hopper, G. Keenan, A. H. R. W. Simpson. The multifactorial aetiology of fracture nonunion and the importance of searching for latent infection. Bone Joint Res 2016;5:512–519. DOI: 10.1302/2046-3758.510.BJR-2016-0138


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_4 | Pages 7 - 7
1 Mar 2020
Oliver W Searle H Ng Z Molyneux S White T Clement N Duckworth A
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The primary aim was to identify patient and injury factors independently associated with humeral diaphyseal fracture nonunion after non-operative management. The secondary aim was to determine the effect of management (operative/non-operative) on nonunion. Over a ten-year period, 734 humeral diaphyseal fractures (732 consecutive patients) were retrospectively identified from a trauma database. Follow-up was available for 663 fractures (662 patients; median age 57yrs [16–96], 54% female [n=359/662]) which formed the study cohort. Patient and injury characteristics were recorded. There were 523 patients (79%) managed non-operatively and 139 (21%) managed operatively. Outcome (union/nonunion) was determined from medical records and radiographs. Median follow-up was five months (1.2–74). Nonunion occurred in 22.7% of non-operatively managed injuries (n=119/524). Multivariate analysis demonstrated pre-injury NSAIDs (adjusted OR [AOR] 40.8, 95% CI 2.6–632.3; p=0.008), being underweight (BMI <18.5kg/m2; AOR 7.3, 95% CI 1.3 to 40.2; p=0.022), overweight (BMI 25–29.9kg/m2; AOR 2.5, 95% CI 1.1 to 5.9; p=0.034) and class II obesity (BMI 35–39.9kg/m2; AOR 4.5, 95% CI 1.4 to 15.5; p=0.014) were independently associated with an increased risk of nonunion. Operative fixation was independently associated with a lower risk of nonunion (2.9%, n=4/139) than non-operative management (AOR for non-operative/operative 11.0, 95% CI 2.8 to 43.6; p=0.001). Based upon these results, five patients would need to undergo operative fixation to avoid one nonunion. Pre-injury NSAIDs and BMI were independently associated with nonunion following non-operative management of a humeral diaphyseal fracture. Operative fixation was the independent factor most strongly associated with a lower risk of nonunion


The Bone & Joint Journal
Vol. 103-B, Issue 11 | Pages 1648 - 1655
1 Nov 2021
Jeong S Hwang K Oh C Kim J Sohn OJ Kim JW Cho Y Park KC

Aims. The incidence of atypical femoral fractures (AFFs) continues to increase. However, there are currently few long-term studies on the complications of AFFs and factors affecting them. Therefore, we attempted to investigate the outcomes, complications, and risk factors for complication through mid-term follow-up of more than three years. Methods. From January 2003 to January 2016, 305 patients who underwent surgery for AFFs at six hospitals were enrolled. After exclusion, a total of 147 patients were included with a mean age of 71.6 years (48 to 89) and 146 of whom were female. We retrospectively evaluated medical records, and reviewed radiographs to investigate the fracture site, femur bowing angle, presence of delayed union or nonunion, contralateral AFFs, and peri-implant fracture. A statistical analysis was performed to identify the significance of associated factors. Results. The mean follow-up period was 70.2 months (36 to 191). There were 146 AFFs (99.3%) in female patients and the mean age was 71.6 years (48 to 89). The AFFs were located in the subtrochanter and shaft in 52 cases (35.4%) and 95 (64.6%), respectively. The preoperative mean anterior/lateral femoral bowing angles were 10.5° (SD 5.7°)/6.1° (SD 6.2°). The postoperative mean anterior/lateral bowing values were changed by 8.7° (SD 5.4°)/4.6° (SD 5.9°). Bisphosphonates had been used contemporarily in 115 AFFs (78.2%) for a mean of 52.4 months (1 to 204; SD 45.5) preoperatively. Nailing was performed in 133 AFFs (90.5%), and union was obtained at a mean of 23.6 weeks (7 to 85). Delayed union occurred in 41 (27.9%), and nonunion occurred in 13 (8.8%). Contralateral AFF occurred in 79 patients (53.7%), and the use of a bisphosphonate significantly influenced the occurrence of contralateral AFFs (p = 0.019). Peri-implant fractures occurred in a total of 13 patients (8.8%), and a significant increase was observed in cases with plating (p = 0.021) and high grade of postoperative anterolateral bowing (p = 0.044). Conclusion. The use of a bisphosphonate was found to be a risk factor for contralateral AFF, and high-grade postoperative anterolateral bowing and plate fixation significantly increased the occurrence of peri-implant fractures. Long-term follow-up studies on the bilaterality of AFFs and peri-implant fractures are warranted. Cite this article: Bone Joint J 2021;103-B(11):1648–1655


Bone & Joint Open
Vol. 3, Issue 12 | Pages 953 - 959
23 Dec 2022
Raval P See A Singh HP

Aims. Distal third clavicle (DTC) fractures are increasing in incidence. Due to their instability and nonunion risk, they prove difficult to treat. Several different operative options for DTC fixation are reported but current evidence suggests variability in operative fixation. Given the lack of consensus, our objective was to determine the current epidemiological trends in DTC as well as their management within the UK. Methods. A multicentre retrospective cohort collaborative study was conducted. All patients over the age of 18 with an isolated DTC fracture in 2019 were included. Demographic variables were recorded: age; sex; side of injury; mechanism of injury; modified Neer classification grading; operative technique; fracture union; complications; and subsequent procedures. Baseline characteristics were described for demographic variables. Categorical variables were expressed as frequencies and percentages. Results. A total of 859 patients from 18 different NHS trusts (15 trauma units and three major trauma centres) were included. The mean age was 57 years (18 to 99). Overall, 56% of patients (n = 481) were male. The most common mechanisms of injury were simple fall (57%; n = 487) and high-energy fall (29%; n = 248); 87% (n = 748) were treated conservatively and 54% (n = 463) were Neer type I fractures. Overall, 32% of fractures (n = 275) were type II (22% type IIa (n = 192); 10% type IIb (n = 83)). With regards to operative management, 89% of patients (n = 748) who underwent an operation were under the age of 60. The main fixation methods were: hook plate (n = 47); locking plate (n = 34); tightrope (n = 5); and locking plate and tight rope (n = 7). Conclusion. Our study is the largest epidemiological review of DTC fractures in the UK. It is also the first to review the practice of DTC fixation. Most fractures are being treated nonoperatively. However, younger patients, suffering a higher-energy mechanism of injury, are more likely to undergo surgery. Hook plates are the predominantly used fixation method followed by locking plate. The literature is sparse on the best method of fixation for optimal outcomes for these patients. To answer this, a pragmatic RCT to determine optimal fixation method is required. Cite this article: Bone Jt Open 2022;3(12):953–959


Bone & Joint Research
Vol. 2, Issue 6 | Pages 112 - 115
1 Jun 2013
Ismail HD Phedy P Kholinne E Kusnadi Y Sandhow L Merlina M

Objectives. Nonunion is one of the most troublesome complications to treat in orthopaedics. Former authors believed that atrophic nonunion occurred as a result of lack of mesenchymal stem cells (MSCs). We evaluated the number and viability of MSCs in site of atrophic nonunion compared with those in iliac crest. Methods. We enrolled five patients with neglected atrophic nonunions of long bones confirmed by clinical examinations and plain radiographs into this study. As much as 10 ml bone marrow aspirate was obtained from both the nonunion site and the iliac crest and cultured for three weeks. Cell numbers were counted using a haemocytometer and vitality of the cells was determined by trypan blue staining. The cells were confirmed as MSCs by evaluating their expression marker (CD 105, CD 73, HLA-DR, CD 34, CD 45, CD 14, and CD 19). Cells number and viability were compared between the nonunion and iliac creat sites. Results. After three weeks, numbers of 6.08×10. 6. cells (. sd. 2.07) and 4.98×10. 6. cells (. sd. 1.15) were obtained from the nonunion site and the iliac crest, respectively, with viability of 87.1% (81.7% to 90.8%) and 89.8% (84.7% to 94.5%), respectively. No differences was found between the two sources of MSCs regarding cells number (p = 0.347) and viability (p = 0.175). Conclusions. Our findings showed the existence of MSCs in the site of atrophic nonunion, at a similar number and viability to those isolated from the iliac crest


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 9 | Pages 1218 - 1224
1 Sep 2007
Molloy AP Myerson MS Yoon P

We have treated 14 patients (15 fractures) with nonunion of an intra-articular fracture of the body of the calcaneum. The mean follow-up was six years (2 to 8.5). A total of 14 fractures (93%) had initially been treated operatively with 12 (86%) having non-anatomical reductions. Four feet (27%) had concomitant osteomyelitis. Of the nonunions, 14 (93%) went on to eventual union after an average of two reconstructive procedures. All underwent bone grafting of the nonunion. The eventual outcome was a subtalar arthrodesis in ten (67%) cases, a triple arthrodesis in four (27%) and a nonunion in one (6%). Three patients had a wound dehiscence; all required a local rotation flap. The mean American Orthopaedic Foot and Ankle Society score at latest follow-up was 69, and the mean Visual analogue scale was 3. Of those who were initially employed, 82% (9 of 11) eventually returned to work. We present an algorithm for the treatment of calcaneal nonunion, and conclude that despite a relatively high rate of complication, this complex surgery has a high union rate and a good functional outcome


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_16 | Pages 56 - 56
1 Apr 2013
Dogaki Y Niikura T Lee S Koga T Okumachi E Waki T Kurosaka M
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Introduction. Our previous study using microarray analysis showed that Rad (Ras associated with diabetes) was highly expressed in nonunion. The purpose of this study is to investigate the gene expression and immunolocalization of Rad, and other Ras-related G proteins: Rem1 and Rem2 in fracture/nonunion site using rat experimental models. Hypothesis. We hypothesized that Rad had a significant role in nonunion formation. Materials & Methods. For standard healing model, K-wire was inserted into the femur and a closed fracture was created. Nonunion model was produced by periosteal cauterization at the fracture site. At post-fracture days 3, 7, 10, 14, 21, and 28, RNA was extracted from callus or fibrous tissue for real-time PCR. At day 14, specimens were harvested for immunohistochemistry. Results. Significant difference of Rad gene expression was not observed between standard healing fracture and nonunion at the earlier time points. In contrast, significantly higher expression in nonunion was observed at the later time points. There were no significant differences between standard healing fracture and nonunion in gene expression of Rem1 and Rem2. In immunohistochemical analysis, Rad and Rem1 were detected in the fracture site, and Rem2 was not detected. On the other hand, Rad was only detected in fibrous tissue in nonunion. Discussion & Conclusion. Our results suggest a significant role of Rad in fracture healing and nonunion formation. Rad may become a target agent for treatment of nonunion


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_16 | Pages 28 - 28
1 Apr 2013
Niikura T Lee SY Koga T Dogaki Y Okumachi E Waki T Kurosaka M
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Introduction. Many surgeons assess biological activity of fracture nonunion by the presence or absence of callus using radiograph. However, it is difficult to assess biological activity only by radiographic appearance. Bone scintigraphy reflects blood supply and bone metabolism and is possibly useful to assess biological activity in nonunion cases. Hypothesis. We hypothesized that poor callus visualization did not always mean lack of biological activity. Materials & Methods. Retrospective assessment and comparison of radiographs and Tc-99m bone scintigraphy of 44 patients with uninfected nonunion was done. Results. Uptake was observed at or around the nonunion site in all cases. Three patterns of uptake were noted; Spot type (S): intense uniform uptake, Uneven type (U): uptake with distribution from cold to hot, and Cleft type (C): decreased uptake surrounded by significant uptake on both sides. All 9 cases of hypertrophic nonunion demonstrated the S type. In 21 cases of oligotrophic nonunion, there were 12 S, 5 U and 4 C. In 3 cases of comminuted nonunion, there were 1 U and 2 C. In 5 cases of defect nonunion, there were 1 U and 4 C. In 6 cases of atrophic nonunion, there were 2 U and 4 C. Discussion & Conclusions. Our results suggest that poor callus visualization does not always mean lack of biological activity. The distribution of uptake and the cleft with decreased uptake are helpful findings to assess the necessity of bone graft or other supplementation in nonunion surgery


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_16 | Pages 83 - 83
1 Apr 2013
Sato K Watanabe Y Abe S Harada N Yamanaka K Sakai Y Kaneko T Matsushita T
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Introduction. what size of defect is optimal for creating an atrophic nonunion animal model has not been well defined. Our aim in this study was to establish a clinically relevant model of atrophic nonunion in rat femur by creation of a bone defect to research fracture healing and nonunion. Materials and methods. We used 30 male Fischer 344 rats (aged 10–11 weeks), which were equally divided into six groups. The segmental bone defects to a single femur in each rat were performed by double transverse osteotomy, and different sized defects were created by group for each group (1 mm, 2 mm, 3 mm, 4 mm, 5 mm and 6 mm). The defects were measured and maintained strictly by using an original external fixator. The periosteum for each defect was stripped both proximally and distally. Thereafter, these models were evaluated by radiology and histology. Radiographs were taken at baseline and at intervals of two weeks over a period of 8 weeks. Atrophic nonunion was defined as a lack of continuity and atrophy of both defect ends radiologically and histologically at eight weeks. Results. In the 1 mm defect group, all defects had healed. In the 2 mm group, one-fifth remained atrophic nonunion. In the 3 mm group, three-fifths had atrophic nonunion, and all of the defects of groups of 4 mm and over were atrophic nonunion. Conclusion. This study showed that we were able to predictively produce an atrophic nonunion animal model by creating defects of at least 4 mm in the Fischer 344 rat femur


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 4 | Pages 522 - 529
1 Apr 2009
Ryzewicz M Morgan SJ Linford E Thwing JI de Resende GVP Smith WR

Nonunion of the tibia associated with bone loss, previous infection, obliteration of the intramedullary canal or located in the distal metaphysis poses a challenge to the surgeon and significant morbidity to patients. We retrospectively reviewed the records of 24 patients who were treated by central bone grafting and compared them to those of 20 who were treated with a traditional posterolateral graft. Central bone grafting entails a lateral approach, anterior to the fibula and interosseous membrane which is used to create a central space filled with cancellous iliac crest autograft. Upon consolidation, a tibiofibular synostosis is formed that is strong enough for weight-bearing. This procedure has advantages over other methods of treatment for selected nonunions. Of the 24 patients with central bone grafting, 23 went on to radiographic and clinical union without further intervention. All healed within a mean of 20 weeks (10 to 48). No further bone grafts were required, and few complications were encountered. These results were comparable to those of the 20 patients who underwent posterolateral bone grafting who united at a mean of 31.3 weeks (16 to 60) but one of whom required below-knee amputation for intractable sepsis. Central bone grafting is a safe and effective treatment for difficult nonunions of the tibia


The Bone & Joint Journal
Vol. 98-B, Issue 1 | Pages 125 - 130
1 Jan 2016
Clement ND Goudie EB Brooksbank AJ Chesser TJS Robinson CM

Aims. This study identifies early risk factors for symptomatic nonunion of displaced midshaft fractures of the clavicle that aid identification of an at risk group who may benefit from surgery. . Methods . We performed a retrospective study of 88 patients aged between 16 and 60 years that were managed non-operatively. . Results . The rate of symptomatic nonunion requiring surgery was 14% (n = 13). Smoking (odds ratio (OR) 40.76, 95% confidence intervals (CI) 1.38 to 120.30) and the six week Disabilities of the Arm Shoulder and Hand (DASH) score (OR 1.11, 95% CI 1.01 to 1.22, for each point increase) were independent predictors of nonunion. A six week DASH score of 35 or more was identified as a threshold value to predict nonunion using receiver operating characteristic curve analysis. Smoking and the threshold value in the DASH and were additive risk factors for nonunion, when neither were present the risk of nonunion was 2%, if one or the other were present the nonunion rate was between 17% to 20%, and if both were present the rate increased to 44%. Discussion. Patients with either of these risk factors, which include approximately half of all patients sustaining displaced midshaft fractures of the clavicle, are at an increased risk of developing a symptomatic non-union. Take home message: Smoking and failure of functional return at six weeks are significant predictors of nonunion of the midshaft of the clavicle. Such patients warrant further investigation as to whether they would benefit from early surgical fixation in order to avoid the morbidity of a nonunion. Cite this article: Bone Joint J 2016;98-B:125–30


The Bone & Joint Journal
Vol. 101-B, Issue 11 | Pages 1416 - 1422
1 Nov 2019
Rohilla R Sharma PK Wadhwani J Rohilla S Beniwal R Singh R Devgan A

Aims. In this randomized study, we aimed to compare quality of regenerate in monolateral versus circular frame fixation in 30 patients with infected nonunion of tibia. Patients and Methods. Both groups were comparable in demographic and injury characteristics. A phantom (aluminium step wedge of increasing thickness) was designed to compare the density of regenerate on radiographs. A CT scan was performed at three and six months postoperatively to assess regenerate density. A total of 30 patients (29 male, one female; mean age 32.54 years (18 to 60)) with an infected nonunion of a tibial fracture presenting to our tertiary institute between June 2011 and April 2016 were included in the study. Results. The regenerate mineralization on radiographs was comparable in both groups at two, four, six, and ten months’ follow-up but the rail fixator group had statistically significant higher grades of mineralization when compared with the circular frame group at eight and 12 months’ follow-up. The regenerate mineralization was also higher in the rail fixator group than in the circular frame group on CT at three and six months, although this difference was not statistically significant. Conclusion. Overall, the regenerate mineralization was higher in the monolateral than the circular frame group. A monolateral fixator may be preferred in patients with infected nonunion of the tibia with bone defects up to 7 cm. Cite this article: Bone Joint J 2019;101-B:1416–1422


The Bone & Joint Journal
Vol. 97-B, Issue 8 | Pages 1144 - 1151
1 Aug 2015
Waki T Lee SY Niikura T Iwakura T Dogaki Y Okumachi E Kuroda R Kurosaka M

MicroRNAs (miRNAs ) are small non-coding RNAs that regulate gene expression. We hypothesised that the functions of certain miRNAs and changes to their patterns of expression may be crucial in the pathogenesis of nonunion. Healing fractures and atrophic nonunions produced by periosteal cauterisation were created in the femora of 94 rats, with 1:1 group allocation. At post-fracture days three, seven, ten, 14, 21 and 28, miRNAs were extracted from the newly generated tissue at the fracture site. Microarray and real-time polymerase chain reaction (PCR) analyses of day 14 samples revealed that five miRNAs, miR-31a-3p, miR-31a-5p, miR-146a-5p, miR-146b-5p and miR-223-3p, were highly upregulated in nonunion. Real-time PCR analysis further revealed that, in nonunion, the expression levels of all five of these miRNAs peaked on day 14 and declined thereafter. . Our results suggest that miR-31a-3p, miR-31a-5p, miR-146a-5p, miR-146b-5p and miR-223-3p may play an important role in the development of nonunion. These findings add to the understanding of the molecular mechanism for nonunion formation and may lead to the development of novel therapeutic strategies for its treatment. Cite this article: Bone Joint J 2015; 97-B:1144–51