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The Bone & Joint Journal
Vol. 105-B, Issue 7 | Pages 808 - 814
1 Jul 2023
Gundavda MK Lazarides AL Burke ZDC Focaccia M Griffin AM Tsoi KM Ferguson PC Wunder JS

Aims

The preoperative grading of chondrosarcomas of bone that accurately predicts surgical management is difficult for surgeons, radiologists, and pathologists. There are often discrepancies in grade between the initial biopsy and the final histology. Recent advances in the use of imaging methods have shown promise in the ability to predict the final grade. The most important clinical distinction is between grade 1 chondrosarcomas, which are amenable to curettage, and resection-grade chondrosarcomas (grade 2 and 3) which require en bloc resection. The aim of this study was to evaluate the use of a Radiological Aggressiveness Score (RAS) to predict the grade of primary chondrosarcomas in long bones and thus to guide management.

Methods

A total of 113 patients with a primary chondrosarcoma of a long bone presenting between January 2001 and December 2021 were identified on retrospective review of a single oncology centre’s prospectively collected database. The nine-parameter RAS included variables from radiographs and MRI scans. The best cut-off of parameters to predict the final grade of chondrosarcoma after resection was determined using a receiver operating characteristic curve (ROC), and this was correlated with the biopsy grade.


Bone & Joint Open
Vol. 5, Issue 11 | Pages 962 - 970
4 Nov 2024
Suter C Mattila H Ibounig T Sumrein BO Launonen A Järvinen TLN Lähdeoja T Rämö L

Aims. Though most humeral shaft fractures heal nonoperatively, up to one-third may lead to nonunion with inferior outcomes. The Radiographic Union Score for HUmeral Fractures (RUSHU) was created to identify high-risk patients for nonunion. Our study evaluated the RUSHU’s prognostic performance at six and 12 weeks in discriminating nonunion within a significantly larger cohort than before. Methods. Our study included 226 nonoperatively treated humeral shaft fractures. We evaluated the interobserver reliability and intraobserver reproducibility of RUSHU scoring using intraclass correlation coefficients (ICCs). Additionally, we determined the optimal cut-off thresholds for predicting nonunion using the receiver operating characteristic (ROC) method. Results. The RUSHU demonstrated good interobserver reliability with an ICC of 0.78 (95% CI 0.72 to 0.83) at six weeks and 0.77 (95% CI 0.71 to 0.82) at 12 weeks. Intraobserver reproducibility was good or excellent for all analyses. Area under the curve in the ROC analysis was 0.83 (95% CI 0.77 to 0.88) at six weeks and 0.89 (95% CI 0.84 to 0.93) at 12 weeks, indicating excellent discrimination. The optimal cut-off values for predicting nonunion were ≤ eight points at six weeks and ≤ nine points at 12 weeks, providing the best specificity-sensitivity trade-off. Conclusion. The RUSHU proves to be a reliable and reproducible radiological scoring system that aids in identifying patients at risk of nonunion at both six and 12 weeks post-injury during non-surgical treatment of humeral shaft fractures. The statistically optimal cut-off values for predicting nonunion are ≤ eight at six weeks and ≤ nine points at 12 weeks post-injury


Bone & Joint 360
Vol. 12, Issue 6 | Pages 39 - 42
1 Dec 2023

The December 2023 Oncology Roundup. 360. looks at: A single osteotomy technique for frozen autograft; Complications, function, and survival of tumour-devitalized autografts used in patients with limb-sparing surgery; Is liquid nitrogen recycled bone and vascular fibula the biological reconstruction of choice?; Solitary pulmonary metastases at first recurrence of osteosarcoma; Is a radiological score able to predict resection-grade chondrosarcoma in primary intraosseous lesions of the long bones?; Open versus core needle biopsy in lower-limb sarcoma – current practice patterns and patient outcomes; Natural history of intraosseous low-grade chondroid lesions of the proximal humerus; Local treatment modalities and event-free survival in patients with localized Ewing’s sarcoma; Awaiting biopsy results in solitary pathological proximal femoral fractures


Bone & Joint Research
Vol. 10, Issue 10 | Pages 659 - 667
1 Oct 2021
Osagie-Clouard L Meeson R Sanghani-Kerai A Bostrom M Briggs T Blunn G

Aims. A growing number of fractures progress to delayed or nonunion, causing significant morbidity and socioeconomic impact. Localized delivery of stem cells and subcutaneous parathyroid hormone (PTH) has been shown individually to accelerate bony regeneration. This study aimed to combine the therapies with the aim of upregulating fracture healing. Methods. A 1.5 mm femoral osteotomy (delayed union model) was created in 48 female juvenile Wistar rats, aged six to nine months, and stabilized using an external fixator. At day 0, animals were treated with intrafracture injections of 1 × 10. 6. cells/kg bone marrow mesenchymal stem cells (MSCs) suspended in fibrin, daily subcutaneous injections of high (100 μg/kg) or low (25 μg/kg) dose PTH 1-34, or a combination of PTH and MSCs. A group with an empty gap served as a control. Five weeks post-surgery, the femur was excised for radiological, histomorphometric, micro-CT, and mechanical analysis. Results. Combination therapy treatment led to increased callus formation compared to controls. In the high-dose combination group there was significantly greater mineralized tissue volume and trabecular parameters compared to controls (p = 0.039). This translated to significantly improved stiffness (and ultimate load to failure (p = 0.049). The high-dose combination therapy group had the most significant improvement in mean modified Radiographic Union Score for Tibia fractures (RUST) compared to controls (13.8 (SD 1.3) vs 5.8 (SD 0.5)). All groups demonstrated significant increases in the radiological scores – RUST and Allen score – histologically compared to controls. Conclusion. We demonstrate the beneficial effect of localized MSC injections on fracture healing combined with low- or high-dose teriparatide, with efficacy dependent on PTH dose. Cite this article: Bone Joint Res 2021;10(10):659–667


Bone & Joint Open
Vol. 1, Issue 12 | Pages 720 - 730
1 Dec 2020
Galloway AM van-Hille T Perry DC Holton C Mason L Richards S Siddle HJ Comer C

Aims. Perthes’ disease is a condition leading to necrosis of the femoral head. It is most common in children aged four to nine years, affecting around one per 1,200 children in the UK. Management typically includes non-surgical treatment options, such as physiotherapy with/without surgical intervention. However, there is significant variation in care with no consensus on the most effective treatment option. Methods. This systematic review aims to evaluate the effectiveness of non-surgical interventions for the treatment of Perthes’ disease. Comparative studies (experimental or observational) of any non-surgical intervention compared directly with any alternative intervention (surgical, non-surgical or no intervention) were identified from: Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), EMcare, Allied and Complementary Medicine Database (AMED), and the Physiotherapy Evidence Database (PEDro). Data were extracted on interventions compared and methodological quality. For post-intervention primary outcome of radiological scores (Stulberg and/or Mose), event rates for poor scores were calculated with significance values. Secondary outcomes included functional measures, such as range of movement, and patient-reported outcomes such as health-related quality of life. Results. In all, 15 studies (1,745 participants) were eligible for inclusion: eight prospective cohort studies, seven retrospective cohort studies, and no randomized controlled trials were identified. Non-surgical interventions largely focused on orthotic management (14/15 studies) and physical interventions such as muscle strengthening or stretching (5/15 studies). Most studies were of high/unknown risk of bias, and the range of patient outcomes was very limited, as was reporting of treatment protocols. Similar proportions of children achieving poor radiological outcomes were found for orthotic management and physical interventions, such as physiotherapy or weightbearing alteration, compared with surgical interventions or no intervention. Conclusion. Evidence from non-randomized studies found no robust evidence regarding the most effective non-surgical interventions for the treatment of children with Perthes’ disease. Future research, employing randomized trial designs, and reporting a wider range of patient outcomes is urgently needed to inform clinical practice. Cite this article: Bone Jt Open 2020;1-12:720–730


Bone & Joint 360
Vol. 12, Issue 5 | Pages 39 - 42
1 Oct 2023

The October 2023 Oncology Roundup360 looks at: Are pathological fractures in patients with osteosarcoma associated with worse survival outcomes?; Spotting the difference: how secondary osteosarcoma manifests in retinoblastoma survivors versus conventional cases; Accuracy of MRI scans in predicting intra-articular joint involvement in high-grade sarcomas around the knee; Endoprosthetic reconstruction for lower extremity soft-tissue sarcomas with bone involvement; Local relapse of soft-tissue sarcoma of the extremities or trunk wall operated on with wide margins without radiation therapy; 3D-printed, custom-made prostheses in patients who had resection of tumours of the hand and foot; Long-term follow-up for low-grade chondrosarcoma; Evaluation of local recurrence and diagnostic discordance in chondrosarcoma patients undergoing preoperative biopsy; Radiological scoring and resection grade for intraosseous chondrosarcoma.


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


Bone & Joint Open
Vol. 5, Issue 2 | Pages 147 - 153
19 Feb 2024
Hazra S Saha N Mallick SK Saraf A Kumar S Ghosh S Chandra M

Aims

Posterior column plating through the single anterior approach reduces the morbidity in acetabular fractures that require stabilization of both the columns. The aim of this study is to assess the effectiveness of posterior column plating through the anterior intrapelvic approach (AIP) in the management of acetabular fractures.

Methods

We retrospectively reviewed the data from R G Kar Medical College, Kolkata, India, from June 2018 to April 2023. Overall, there were 34 acetabulum fractures involving both columns managed by medial buttress plating of posterior column. The posterior column of the acetabular fracture was fixed through the AIP approach with buttress plate on medial surface of posterior column. Mean follow-up was 25 months (13 to 58). Accuracy of reduction and effectiveness of this technique were measured by assessing the Merle d’Aubigné score and Matta’s radiological grading at one year and at latest follow-up.


Aims. To compare time dependent functional improvement for patients with medial, respectively lateral knee osteoarthritis (OA) after treatment with opening wedge osteotomy relieving the pressure on the osteoarthritic part of the knee. Methods. In all, 49 patients (52 knees) with a mean age of 47 years (31 to 64) underwent high tibial osteotomies (HTO), and 24 patients with a mean age of 48 years (31 to 62) low femoral osteotomies (LFO) with opening wedge technique due to medial, respectively lateral knee OA with malalignment. All osteotomies were stabilized with a Puddu plate and bone grafting performed in the same time period (2000 to 2008). The patients were evaluated by the Knee Injury and Osteoarthritis Outcome Score (KOOS) pre-operatively and at six months, and at one, two, five, and ten years postoperatively. The knee OA was graded according to the Ahlbäck and Kellgren-Lawrence radiological scoring systems. Results. The mean angular corrections were 8.0° (4° to 12°) for the HTO and 9.6° (4° to 20°) for the LFO. Both the pre-operative KOOS and the osteoarthritic gradings were similar for the two patient groups. The five subscores of KOOS increased significantly during the postoperative period (p < 0.001 to 0.029) levelling out after one year in both groups. The KOOS subscore symptoms was significantly higher for patients with HTO than those with LFO at all follow-up times, for sport and recreation in the period one to five years, and for pain and quality of life at two to five years (p < 0.001 to 0.009). Eight HTOs (15%) and five LFOs (21%) were converted to total knee arthroplasty after mean 6.7 years (2.0 to 9.8) and 5.4 years (4.0 to 8.0) respectively. The ten-year osteotomy survival rates were 88% for the HTO and 79% for the LFO (p = 0.745). Conclusion. Patients with unicompartmental knee OA improved after a corrective opening wedge osteotomy, but four of the five subscores of KOOS were significantly higher for those with medial than those with lateral OA in most of the ten-year follow-up period. Cite this article: Bone Joint Open 2020;1-7:346–354


The Bone & Joint Journal
Vol. 105-B, Issue 4 | Pages 449 - 454
15 Mar 2023
Zhang C Wang C Duan N Zhou D Ma T

Aims

The aim of this study was to assess the safety and clinical outcome of patients with a femoral shaft fracture and a previous complex post-traumatic femoral malunion who were treated with a clamshell osteotomy and fixation with an intramedullary nail (IMN).

Methods

The study involved a retrospective analysis of 23 patients. All had a previous, operatively managed, femoral shaft fracture with malunion due to hardware failure. They were treated with a clamshell osteotomy between May 2015 and March 2020. The mean age was 42.6 years (26 to 62) and 15 (65.2%) were male. The mean follow-up was 2.3 years (1 to 5). Details from their medical records were analyzed. Clinical outcomes were assessed using the quality of correction of the deformity, functional recovery, the healing time of the fracture, and complications.


The Bone & Joint Journal
Vol. 106-B, Issue 5 | Pages 468 - 474
1 May 2024
d'Amato M Flevas DA Salari P Bornes TD Brenneis M Boettner F Sculco PK Baldini A

Aims

Obtaining solid implant fixation is crucial in revision total knee arthroplasty (rTKA) to avoid aseptic loosening, a major reason for re-revision. This study aims to validate a novel grading system that quantifies implant fixation across three anatomical zones (epiphysis, metaphysis, diaphysis).

Methods

Based on pre-, intra-, and postoperative assessments, the novel grading system allocates a quantitative score (0, 0.5, or 1 point) for the quality of fixation achieved in each anatomical zone. The criteria used by the algorithm to assign the score include the bone quality, the size of the bone defect, and the type of fixation used. A consecutive cohort of 245 patients undergoing rTKA from 2012 to 2018 were evaluated using the current novel scoring system and followed prospectively. In addition, 100 first-time revision cases were assessed radiologically from the original cohort and graded by three observers to evaluate the intra- and inter-rater reliability of the novel radiological grading system.


Bone & Joint Research
Vol. 13, Issue 3 | Pages 127 - 135
22 Mar 2024
Puetzler J Vallejo Diaz A Gosheger G Schulze M Arens D Zeiter S Siverino C Richards RG Moriarty TF

Aims

Fracture-related infection (FRI) is commonly classified based on the time of onset of symptoms. Early infections (< two weeks) are treated with debridement, antibiotics, and implant retention (DAIR). For late infections (> ten weeks), guidelines recommend implant removal due to tolerant biofilms. For delayed infections (two to ten weeks), recommendations are unclear. In this study we compared infection clearance and bone healing in early and delayed FRI treated with DAIR in a rabbit model.

Methods

Staphylococcus aureus was inoculated into a humeral osteotomy in 17 rabbits after plate osteosynthesis. Infection developed for one week (early group, n = 6) or four weeks (delayed group, n = 6) before DAIR (systemic antibiotics: two weeks, nafcillin + rifampin; four weeks, levofloxacin + rifampin). A control group (n = 5) received revision surgery after four weeks without antibiotics. Bacteriology of humerus, soft-tissue, and implants was performed seven weeks after revision surgery. Bone healing was assessed using a modified radiological union scale in tibial fractures (mRUST).


Bone & Joint Research
Vol. 13, Issue 10 | Pages 546 - 558
4 Oct 2024
Li Y Wuermanbieke S Wang F Mu W Ji B Guo X Zou C Chen Y Zhang X Cao L

Aims

The optimum type of antibiotics and their administration route for treating Gram-negative (GN) periprosthetic joint infection (PJI) remain controversial. This study aimed to determine the GN bacterial species and antibacterial resistance rates related to clinical GN-PJI, and to determine the efficacy and safety of intra-articular (IA) antibiotic injection after one-stage revision in a GN pathogen-induced PJI rat model of total knee arthroplasty.

Methods

A total of 36 consecutive PJI patients who had been infected with GN bacteria between February 2015 and December 2021 were retrospectively recruited in order to analyze the GN bacterial species involvement and antibacterial resistance rates. Antibiotic susceptibility assays of the GN bacterial species were performed to screen for the most sensitive antibiotic, which was then used to treat the most common GN pathogen-induced PJI rat model. The rats were randomized either to a PJI control group or to three meropenem groups (intraperitoneal (IP), IA, and IP + IA groups). After two weeks of treatment, infection control level, the side effects, and the volume of antibiotic use were evaluated.


Bone & Joint Open
Vol. 5, Issue 4 | Pages 277 - 285
8 Apr 2024
Khetan V Baxter I Hampton M Spencer A Anderson A

Aims

The mean age of patients undergoing total knee arthroplasty (TKA) has reduced with time. Younger patients have increased expectations following TKA. Aseptic loosening of the tibial component is the most common cause of failure of TKA in the UK. Interest in cementless TKA has re-emerged due to its encouraging results in the younger patient population. We review a large series of tantalum trabecular metal cementless implants in patients who are at the highest risk of revision surgery.

Methods

A total of 454 consecutive patients who underwent cementless TKA between August 2004 and December 2021 were reviewed. The mean follow-up was ten years. Plain radiographs were analyzed for radiolucent lines. Patients who underwent revision TKA were recorded, and the cause for revision was determined. Data from the National Joint Registry for England, Wales, Northern Island, the Isle of Man and the States of Guernsey (NJR) were compared with our series.


Bone & Joint Open
Vol. 4, Issue 3 | Pages 146 - 157
7 Mar 2023
Camilleri-Brennan J James S McDaid C Adamson J Jones K O'Carroll G Akhter Z Eltayeb M Sharma H

Aims

Chronic osteomyelitis (COM) of the lower limb in adults can be surgically managed by either limb reconstruction or amputation. This scoping review aims to map the outcomes used in studies surgically managing COM in order to aid future development of a core outcome set.

Methods

A total of 11 databases were searched. A subset of studies published between 1 October 2020 and 1 January 2011 from a larger review mapping research on limb reconstruction and limb amputation for the management of lower limb COM were eligible. All outcomes were extracted and recorded verbatim. Outcomes were grouped and categorized as per the revised Williamson and Clarke taxonomy.


Bone & Joint 360
Vol. 11, Issue 5 | Pages 20 - 23
1 Oct 2022


Bone & Joint Open
Vol. 3, Issue 7 | Pages 566 - 572
18 Jul 2022
Oliver WM Molyneux SG White TO Clement ND Duckworth AD

Aims

The primary aim was to estimate the cost-effectiveness of routine operative fixation for all patients with humeral shaft fractures. The secondary aim was to estimate the health economic implications of using a Radiographic Union Score for HUmeral fractures (RUSHU) of < 8 to facilitate selective fixation for patients at risk of nonunion.

Methods

From 2008 to 2017, 215 patients (mean age 57 yrs (17 to 18), 61% female (n = 130/215)) with a nonoperatively managed humeral diaphyseal fracture were retrospectively identified. Union was achieved in 77% (n = 165/215) after initial nonoperative management, with 23% (n = 50/215) uniting after surgery for nonunion. The EuroQol five-dimension three-level health index (EQ-5D-3L) was obtained via postal survey. Multiple regression was used to determine the independent influence of patient, injury, and management factors upon the EQ-5D-3L. An incremental cost-effectiveness ratio (ICER) of < £20,000 per quality-adjusted life-year (QALY) gained was considered cost-effective.


The Journal of Bone & Joint Surgery British Volume
Vol. 85-B, Issue 7 | Pages 994 - 998
1 Sep 2003
Fuchs S Sandmann C Skwara A Chylarecki C

Tibiotalar fusion is considered to be the standard treatment for end-stage post-traumatic arthritis of the ankle. We report a retrospective, objective long-term study of the quality of life of 17 patients with 18 arthrodeses of the ankle, over a period of more than 20 years. We looked particularly for correlation between clinical and radiological signs of osteoarthritis in adjoining joints. At serial physical examinations, clinical grades were awarded according to the Olerud Molander Ankle (OMA) score. Any degree of degenerative change in the adjoining joints was recorded on standing radiographs. Patients filled out a SF-36 Health Survey form. Subjectively, 50% of patients were not handicapped in the performance of daily activities and 44% were in the same job as at the time of injury. At follow-up the mean OMA score was 59.4 points, the visual analogue scale was 1.99 and the radiological score was 2.7. The SF-36 for physical function, emotional disturbance and bodily pain revealed significant deficits. There was a significant correlation between the OMA and the radiological score (p = 0.05), and between the clinical and the SF-36 score (p = 0.01), but no significant correlation between the radiological score and the SF-36 score. Arthrodesis of the ankle leads to deficits in the functional outcome, to limitations in the activities of daily living and to radiological changes in the adjoining joints. The clinical outcome score correlates closely with the SF-36 score


The Bone & Joint Journal
Vol. 95-B, Issue 12 | Pages 1610 - 1616
1 Dec 2013
Epinette J Asencio G Essig J Llagonne B Nourissat C

We report a multicentre prospective consecutive study assessing the long-term outcome of the proximally hydroxyapatite (HA)-coated ABG II monobloc femoral component in a series of 1148 hips in 1053 patients with a mean age at surgery of 64.77 years (22 to 80) at a mean follow-up of 10.84 years (10 to 15.25). At latest follow-up, the mean total Harris hip score was 94.7 points (. sd. ; 6.87; 49 to 100), and the mean Merle d’Aubigné–Postel score was 17.6 points (. sd. 1.12; 7 to 18). The mean total Engh radiological score score was 21.54 (. sd. 5.77; 3.5 to 27), with 95.81% of ‘confirmed ingrowth’, according to Engh’s classification. With aseptic loosening or pain as endpoints, three AGB II stems (0.26%) failed, giving a 99.7% survival rate (. se. 0.002; 95% confidence interval (CI) 0.994 to 1) at 14 years’ follow-up. The survival of patients ≤ 50 years of age (99.0% (. se. 0.011; 95% CI 0.969 to 1)) did not differ significantly from those of patients aged > 50 years (99.8% (. se. 0.002; 95% CI 0.994 to 1)). This study confirmed the excellent long-term results currently achieved with the ABG II proximally HA-coated monobloc stem. Cite this article: Bone Joint J 2013;95-B:1610–16


Bone & Joint Open
Vol. 2, Issue 10 | Pages 796 - 805
1 Oct 2021
Plumarom Y Wilkinson BG Willey MC An Q Marsh L Karam MD

Aims

The modified Radiological Union Scale for Tibia (mRUST) fractures score was developed in order to assess progress to union and define a numerical assessment of fracture healing of metadiaphyseal fractures. This score has been shown to be valuable in predicting radiological union; however, there is no information on the sensitivity, specificity, and accuracy of this index for various cut-off scores. The aim of this study is to evaluate sensitivity, specificity, accuracy, and cut-off points of the mRUST score for the diagnosis of metadiaphyseal fractures healing.

Methods

A cohort of 146 distal femur fractures were retrospectively identified at our institution. After excluding AO/OTA type B fractures, nonunions, follow-up less than 12 weeks, and patients aged less than 16 years, 104 sets of radiographs were included for analysis. Anteroposterior and lateral femur radiographs at six weeks, 12 weeks, 24 weeks, and final follow-up were separately scored by three surgeons using the mRUST score. The sensitivity and specificity of mean mRUST score were calculated using clinical and further radiological findings as a gold standard for ultimate fracture healing. A receiver operating characteristic curve was also performed to determine the cut-off points at each time point.