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The Bone & Joint Journal
Vol. 106-B, Issue 2 | Pages 158 - 165
1 Feb 2024
Nasser AAHH Sidhu M Prakash R Mahmood A

Aims. Periprosthetic fractures (PPFs) around the knee are challenging injuries. This study aims to describe the characteristics of knee PPFs and the impact of patient demographics, fracture types, and management modalities on in-hospital mortality. Methods. Using a multicentre study design, independent of registry data, we included adult patients sustaining a PPF around a knee arthroplasty between 1 January 2010 and 31 December 2019. Univariate, then multivariable, logistic regression analyses were performed to study the impact of patient, fracture, and treatment on mortality. Results. Out of a total of 1,667 patients in the PPF study database, 420 patients were included. The in-hospital mortality rate was 6.4%. Multivariable analyses suggested that American Society of Anesthesiologists (ASA) grade, history of peripheral vascular disease (PVD), history of rheumatic disease, fracture around a loose implant, and cerebrovascular accident (CVA) during hospital stay were each independently associated with mortality. Each point increase in ASA grade independently correlated with a four-fold greater mortality risk (odds ratio (OR) 4.1 (95% confidence interval (CI) 1.19 to 14.06); p = 0.026). Patients with PVD have a nine-fold increase in mortality risk (OR 9.1 (95% CI 1.25 to 66.47); p = 0.030) and patients with rheumatic disease have a 6.8-fold increase in mortality risk (OR 6.8 (95% CI 1.32 to 34.68); p = 0.022). Patients with a fracture around a loose implant (Unified Classification System (UCS) B2) have a 20-fold increase in mortality, compared to UCS A1 (OR 20.9 (95% CI 1.61 to 271.38); p = 0.020). Mode of management was not a significant predictor of mortality. Patients managed with revision arthroplasty had a significantly longer length of stay (median 16 days; p = 0.029) and higher rates of return to theatre, compared to patients treated nonoperatively or with fixation. Conclusion. The mortality rate in PPFs around the knee is similar to that for native distal femur and neck of femur fragility fractures. Patients with certain modifiable risk factors should be optimized. A national PPF database and standardized management guidelines are currently required to understand these complex injuries and to improve patient outcomes. Cite this article: Bone Joint J 2024;106-B(2):158–165


Bone & Joint Open
Vol. 5, Issue 3 | Pages 236 - 242
22 Mar 2024
Guryel E McEwan J Qureshi AA Robertson A Ahluwalia R

Aims. Ankle fractures are common injuries and the third most common fragility fracture. In all, 40% of ankle fractures in the frail are open and represent a complex clinical scenario, with morbidity and mortality rates similar to hip fracture patients. They have a higher risk of complications, such as wound infections, malunion, hospital-acquired infections, pressure sores, veno-thromboembolic events, and significant sarcopaenia from prolonged bed rest. Methods. A modified Delphi method was used and a group of experts with a vested interest in best practice were invited from the British Foot and Ankle Society (BOFAS), British Orthopaedic Association (BOA), Orthopaedic Trauma Society (OTS), British Association of Plastic & Reconstructive Surgeons (BAPRAS), British Geriatric Society (BGS), and the British Limb Reconstruction Society (BLRS). Results. In the first stage, there were 36 respondents to the survey, with over 70% stating their unit treats more than 20 such cases per year. There was a 50:50 split regarding if the timing of surgery should be within 36 hours, as per the hip fracture guidelines, or 72 hours, as per the open fracture guidelines. Overall, 75% would attempt primary wound closure and 25% would utilize a local flap. There was no orthopaedic agreement on fixation, and 75% would permit weightbearing immediately. In the second stage, performed at the BLRS meeting, experts discussed the survey results and agreed upon a consensus for the management of open elderly ankle fractures. Conclusion. A mutually agreed consensus from the expert panel was reached to enable the best practice for the management of patients with frailty with an open ankle fracture: 1) all units managing lower limb fragility fractures should do so through a cohorted multidisciplinary pathway. This pathway should follow the standards laid down in the "care of the older or frail orthopaedic trauma patient" British Orthopaedic Association Standards for Trauma and Orthopaedics (BOAST) guideline. These patients have low bone density, and we should recommend full falls and bone health assessment; 2) all open lower limb fragility fractures should be treated in a single stage within 24 hours of injury if possible; 3) all patients with fragility fractures of the lower limb should be considered for mobilisation on the day following surgery; 4) all patients with lower limb open fragility fractures should be considered for tissue sparing, with judicious debridement as a default; 5) all patients with open lower limb fragility fractures should be managed by a consultant plastic surgeon with primary closure wherever possible; and 6) the method of fixation must allow for immediate unrestricted weightbearing. Cite this article: Bone Jt Open 2024;5(3):236–242


Bone & Joint Open
Vol. 3, Issue 7 | Pages 529 - 535
1 Jul 2022
Wormald JCR Rodrigues JN Cook JA Prieto-Alhambra D Costa ML

Aims. Hand trauma accounts for one in five of emergency department attendances, with a UK incidence of over five million injuries/year and 250,000 operations/year. Surgical site infection (SSI) in hand trauma surgery leads to further interventions, poor outcomes, and prolonged recovery, but has been poorly researched. Antimicrobial sutures have been recognized by both the World Health Organization and the National Institute for Clinical Excellence as potentially effective for reducing SSI. They have never been studied in hand trauma surgery: a completely different patient group and clinical pathway to previous randomized clinical trials (RCTs) of these sutures. Antimicrobial sutures are expensive, and further research in hand trauma is warranted before they become standard of care. The aim of this protocol is to conduct a feasibility study of antimicrobial sutures in patients undergoing hand trauma surgery to establish acceptability, compliance, and retention for a definitive trial. Methods. A two-arm, multicentre feasibility RCT of 116 adult participants with hand and wrist injuries, randomized to either antimicrobial sutures or standard sutures. Study participants and outcome assessors will be blinded to treatment allocation. Outcome measures will be recorded at baseline (preoperatively), 30 days, 90 days, and six months, and will include SSI, patient-reported outcome measures, and return to work. Conclusion. This will inform a definitive trial of antimicrobial sutures in the hand and wrist, and will help to inform future upper limb trauma trials. The results of this research will be shared with the medical community through high impact publication and presentation. Cite this article: Bone Jt Open 2022;3(7):529–535


Bone & Joint 360
Vol. 12, Issue 3 | Pages 30 - 32
1 Jun 2023

The June 2023 Spine Roundup. 360. looks at: Characteristics and comparative study of thoracolumbar spine injury and dislocation fracture due to tertiary trauma; Sublingual sufentanil for postoperative pain management after lumbar spinal fusion surgery; Minimally invasive bipolar technique for adult neuromuscular scoliosis; Predictive factors for degenerative lumbar spinal stenosis; Lumbosacral transitional vertebrae and lumbar fusion surgery at level L4/5; Does recall of preoperative scores contaminate trial outcomes? A randomized controlled trial; Vancomycin in fibrin glue for prevention of SSI; Perioperative nutritional supplementation decreases wound healing complications following elective lumbar spine surgery: a randomized controlled trial


The Bone & Joint Journal
Vol. 103-B, Issue 7 | Pages 1284 - 1291
1 Jul 2021
Carter TH Karunaratne BJ Oliver WM Murray IR White TO Reid JT Duckworth AD

Aims. Acute distal biceps tendon repair reduces fatigue-related pain and minimizes loss of supination of the forearm and strength of flexion of the elbow. We report the short- and long-term outcome following repair using fixation with a cortical button techqniue. Methods. Between October 2010 and July 2018, 102 patients with a mean age of 43 years (19 to 67), including 101 males, underwent distal biceps tendon repair less than six weeks after the injury, using cortical button fixation. The primary short-term outcome measure was the rate of complications. The primary long-term outcome measure was the abbreviated Disabilities of the Arm, Shoulder and Hand (QuickDASH) score. Secondary outcomes included the Oxford Elbow Score (OES), EuroQol five-dimension three-level score (EQ-5D-3L), satisfaction, and return to function. Results. Eight patients (7.8%) had a major complication and 34 (33.3%) had a minor complication. Major complications included re-rupture (n = 3; 2.9%), unrecovered nerve injury (n = 4; 3.9%), and surgery for heterotopic ossification (n = 1; 1.0%). Three patients (2.9%) overall required further surgery for a complication. Minor complications included neurapraxia (n = 27; 26.5%) and superficial infection (n = 7; 6.9%). A total of 33 nerve injuries occurred in 31 patients (30.4%). At a mean follow-up of five years (1 to 9.8) outcomes were available for 86 patients (84.3%). The median QuickDASH, OES, EQ-5D-3L, and satisfaction scores were 1.2 (IQR 0 to 5.1), 48 (IQR 46 to 48), 0.80 (IQR 0.72 to 1.0), and 100/100 (IQR 90 to 100), respectively. Most patients were able to return to work (81/83, 97.6%) and sport (51/62,82.3%). Unrecovered nerve injury was associated with an inferior outcome according to the QuickDASH (p = 0.005), OES (p = 0.004), EQ-5D-3L (p = 0.010), and satisfaction (p = 0.024). Multiple linear regression analysis identified an unrecovered nerve injury to be strongly associated with an inferior outcome according to the QuickDASH score (p < 0.001), along with infection (p < 0.001), although re-rupture (p = 0.440) and further surgery (p = 0.652) were not. Conclusion. Acute distal biceps tendon repair using cortical button fixation was found to result in excellent patient-reported outcomes and health-related quality of life. Although rare, unrecovered nerve injury adversely affects outcome. Cite this article: Bone Joint J 2021;103-B(7):1284–1291


Bone & Joint 360
Vol. 12, Issue 4 | Pages 26 - 29
1 Aug 2023

The August 2023 Shoulder & Elbow Roundup360 looks at: Motor control or strengthening exercises for rotator cuff-related shoulder pain? A multi-arm randomized controlled trial; Does the choice of antibiotic prophylaxis influence reoperation rate in primary shoulder arthroplasty?; Common shoulder injuries in sport: grading the evidence; The use of medial support screw was associated with axillary nerve injury after plate fixation of proximal humeral fracture using a minimally invasive deltoid-splitting approach; MRI predicts outcomes of conservative treatment in patients with lateral epicondylitis; Association between surgeon volume and patient outcomes after elective shoulder arthroplasty; Arthroscopic decompression of calcific tendinitis without cuff repair; Functional outcome after nonoperative management of minimally displaced greater tuberosity fractures and predictors of poorer patient experience


Bone & Joint 360
Vol. 13, Issue 2 | Pages 30 - 33
1 Apr 2024

The April 2024 Shoulder & Elbow Roundup. 360. looks at: Acute rehabilitation following traumatic anterior shoulder dislocation (ARTISAN): pragmatic, multicentre, randomized controlled trial; Prevalence and predisposing factors of neuropathic pain in patients with rotator cuff tears; Are two plates better than one? The clavicle fracture reimagined; A single cell atlas of frozen shoulder capsule identifies features associated with inflammatory fibrosis resolution; Complication rates and deprivation go hand in hand with total shoulder arthroplasty; Longitudinal instability injuries of the forearm; A better than “best-fit circle” method for glenoid bone loss assessment; 3D supraspinatus muscle volume and intramuscular fatty infiltration after arthroscopic rotator cuff repair


Bone & Joint 360
Vol. 12, Issue 5 | Pages 27 - 30
1 Oct 2023

The October 2023 Wrist & Hand Roundup. 360. looks at: Distal radius fracture management: surgeon factors markedly influence decision-making; Fracture-dislocation of the radiocarpal joint: bony and capsuloligamentar management, outcomes, and long-term complications; Exploring the role of artificial intelligence chatbot in the management of scaphoid fractures; Role of ultrasonography for evaluation of nerve recovery in repaired median nerve lacerations; Four weeks versus six weeks of immobilization in a cast following closed reduction for displaced distal radial fractures in adult patients: a multicentre randomized controlled trial; Rehabilitation following flexor tendon injury in Zone 2: a randomized controlled study; On the road again: return to driving following minor hand surgery; Open versus single- or dual-portal endoscopic carpal tunnel release: a meta-analysis of randomized controlled trials


Bone & Joint 360
Vol. 12, Issue 2 | Pages 19 - 24
1 Apr 2023

The April 2023 Foot & Ankle Roundup. 360. looks at: Outcomes following a two-stage revision total ankle arthroplasty for periprosthetic joint infection; Temporary bridge plate fixation and joint motion after an unstable Lisfranc injury; Outcomes of fusion in type II os naviculare; Total ankle arthroplasty versus arthrodesis for end-stage ankle osteoarthritis; Normal saline for plantar fasciitis: placebo or therapeutic?; Distraction arthroplasty for ankle osteoarthritis: does it work?; Let there be movement: ankle arthroplasty after previous fusion; Morbidity and mortality after diabetic Charcot foot arthropathy



Bone & Joint 360
Vol. 12, Issue 1 | Pages 42 - 45
1 Feb 2023

The February 2023 Children’s orthopaedics Roundup. 360. looks at: Trends in management of paediatric distal radius buckle fractures; Pelvic osteotomy in patients with previous sacral-alar-iliac fixation; Sacral-alar-iliac fixation in patients with previous pelvic osteotomy; Idiopathic toe walking: an update on natural history, diagnosis, and treatment; A prediction model for treatment decisions in distal radial physeal injuries: a multicentre retrospective study; Angular deformities after percutaneous epiphysiodesis for leg length discrepancy; MRI assessment of anterior coverage is predictive of future radiological coverage; Predictive scoring for recurrent patellar instability after a first-time patellar dislocation


The Bone & Joint Journal
Vol. 103-B, Issue 6 | Pages 1047 - 1054
1 Jun 2021
Keene DJ Knight R Bruce J Dutton SJ Tutton E Achten J Costa ML

Aims. To identify the prevalence of neuropathic pain after lower limb fracture surgery, assess associations with pain severity, quality of life and disability, and determine baseline predictors of chronic neuropathic pain at three and at six months post-injury. Methods. Secondary analysis of a UK multicentre randomized controlled trial (Wound Healing in Surgery for Trauma; WHiST) dataset including adults aged 16 years or over following surgery for lower limb major trauma. The trial recruited 1,547 participants from 24 trauma centres. Neuropathic pain was measured at three and six months using the Doleur Neuropathique Questionnaire (DN4); 701 participants provided a DN4 score at three months and 781 at six months. Overall, 933 participants provided DN4 for at least one time point. Physical disability (Disability Rating Index (DRI) 0 to 100) and health-related quality-of-life (EuroQol five-dimension five-level; EQ-5D-5L) were measured. Candidate predictors of neuropathic pain included sex, age, BMI, injury mechanism, concurrent injury, diabetes, smoking, alcohol, analgaesia use pre-injury, index surgery location, fixation type, Injury Severity Score, open injury, and wound care. Results. The median age of the participants was 51 years (interquartile range 35 to 64). At three and six months post-injury respectively, 32% (222/702) and 30% (234/787) had neuropathic pain, 56% (396/702) and 53% (413/787) had chronic pain without neuropathic characteristics, and the remainder were pain-free. Pain severity was higher among those with neuropathic pain. Linear regression analyses found that those with neuropathic pain at six months post-injury had more physical disability (DRI adjusted mean difference 11.49 (95% confidence interval (CI) 7.84 to 15.14; p < 0.001) and poorer quality of life (EQ-5D utility -0.15 (95% CI -0.19 to -0.11); p < 0.001) compared to those without neuropathic characteristics. Logistic regression identified that prognostic factors of younger age, current smoker, below knee fracture, concurrent injuries, and regular analgaesia pre-injury were associated with higher odds of post-injury neuropathic pain. Conclusion. Pain with neuropathic characteristics is common after lower limb fracture surgery and persists to six months post-injury. Persistent neuropathic pain is associated with substantially poorer recovery. Further attention to identify neuropathic pain post-lower limb injury, predicting patients at risk, and targeting interventions, is indicated. Cite this article: Bone Joint J 2021;103-B(6):1047–1054


Bone & Joint Open
Vol. 2, Issue 6 | Pages 414 - 421
1 Jun 2021
Kim SK Nguyen C Avins AL Abrams GD

Aims. The aim of this study was to screen the entire genome for genetic markers associated with risk for anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) injury. Methods. Genome-wide association (GWA) analyses were performed using data from the Kaiser Permanente Research Board (KPRB) and the UK Biobank. ACL and PCL injury cases were identified based on electronic health records from KPRB and the UK Biobank. GWA analyses from both cohorts were tested for ACL and PCL injury using a logistic regression model adjusting for sex, height, weight, age at enrolment, and race/ethnicity using allele counts for single nucleotide polymorphisms (SNPs). The data from the two GWA studies were combined in a meta-analysis. Candidate genes previously reported to show an association with ACL injury in athletes were also tested for association from the meta-analysis data from the KPRB and the UK Biobank GWA studies. Results. There was a total of 2,214 cases of ACL and PCL injury and 519,869 controls within the two cohorts, with three loci demonstrating a genome-wide significant association in the meta-analysis: INHBA, AEBP2, and LOC101927869. Of the eight candidate genes previously studied in the literature, six were present in the current dataset, and only COL3A1 (rs1800255) showed a significant association (p = 0.006). Conclusion. Genetic markers in three novel loci in this study and one previously-studied candidate gene were identified as potential risk factors for ACL and PCL injury and deserve further validation and investigation of molecular mechanisms. Cite this article: Bone Jt Open 2021;2(6):414–421


Bone & Joint 360
Vol. 13, Issue 4 | Pages 29 - 31
2 Aug 2024

The August 2024 Spine Roundup. 360. looks at: Laminectomy adjacent to instrumented fusion increases adjacent segment disease; Influence of the timing of surgery for cervical spinal cord injury without bone injury in the elderly: a retrospective multicentre study; Lumbar vertebral body tethering: single-centre outcomes and reoperations in a consecutive series of 106 patients; Machine-learning algorithms for predicting Cobb angle beyond 25° in female adolescent idiopathic scoliosis patients; Pain in adolescent idiopathic scoliosis; Teriparatide prevents surgery for osteoporotic vertebral compression fracture


Bone & Joint Open
Vol. 3, Issue 3 | Pages 189 - 195
4 Mar 2022
Atwan Y Sprague S Slobogean GP Bzovsky S Jeray KJ Petrisor B Bhandari M Schemitsch E

Aims. To evaluate the impact of negative pressure wound therapy (NPWT) on the odds of having deep infections and health-related quality of life (HRQoL) following open fractures. Methods. Patients from the Fluid Lavage in Open Fracture Wounds (FLOW) trial with Gustilo-Anderson grade II or III open fractures within the lower limb were included in this secondary analysis. Using mixed effects logistic regression, we assessed the impact of NPWT on deep wound infection requiring surgical intervention within 12 months post-injury. Using multilevel model analyses, we evaluated the impact of NPWT on the Physical Component Summary (PCS) of the 12-Item Short-Form Health Survey (SF-12) at 12 months post-injury. Results. After applying inverse probability treatment weighting to adjust for the influence of injury characteristics on type of dressing used, 1,322 participants were assessed. The odds of developing a deep infection requiring operative management within 12 months of initial surgery was 4.52-times higher in patients who received NPWT compared to those who received a standard wound dressing (95% confidence interval (CI) 1.84 to 11.12; p = 0.001). Overall, 1,040 participants were included in our HRQoL analysis, and those treated with NPWT had statistically significantly lower mean SF-12 PCS post-fracture (p < 0.001). These differences did not reach the minimally important difference for the SF-12 PCS. Conclusion. Our analysis found that patients treated with NPWT had higher odds of developing a deep infection requiring operative management within 12 months post-fracture. Due to possible residual confounding with the worst cases being treated with NPWT, we are unable to determine if NPWT has a negative effect or is simply a marker of worse injuries or poor access to early soft-tissue coverage. Regardless, our results suggest that the use of this treatment requires further evaluation. Cite this article: Bone Jt Open 2022;3(3):189–195


Bone & Joint Open
Vol. 5, Issue 8 | Pages 652 - 661
8 Aug 2024
Taha R Davis T Montgomery A Karantana A

Aims. The aims of this study were to describe the epidemiology of metacarpal shaft fractures (MSFs), assess variation in treatment and complications following standard care, document hospital resource use, and explore factors associated with treatment modality. Methods. A multicentre, cross-sectional retrospective study of MSFs at six centres in the UK. We collected and analyzed healthcare records, operative notes, and radiographs of adults presenting within ten days of a MSF affecting the second to fifth metacarpal between 1 August 2016 and 31 July 2017. Total emergency department (ED) attendances were used to estimate prevalence. Results. A total of 793 patients (75% male, 25% female) with 897 MSFs were included, comprising 0.1% of 837,212 ED attendances. The annual incidence of MSF was 40 per 100,000. The median age was 27 years (IQR 21 to 41); the highest incidence was in men aged 16 to 24 years. Transverse fractures were the most common. Over 80% of all fractures were treated non-surgically, with variation across centres. Overall, 12 types of non-surgical and six types of surgical treatment were used. Fracture pattern, complexity, displacement, and age determined choice of treatment. Patients who were treated surgically required more radiographs and longer radiological and outpatient follow-up, and were more likely to be referred for therapy. Complications occurred in 5% of patients (39/793). Most patients attended planned follow-up, with 20% (160/783) failing to attend at least one or more clinic appointments. Conclusion. MSFs are common hand injuries among young, working (economically active) men, but there is considerable heterogeneity in treatment, rehabilitation, and resource use. They are a burden on healthcare resources and society, thus further research is needed to optimize treatment. Cite this article: Bone Jt Open 2024;5(8):652–661


The Bone & Joint Journal
Vol. 105-B, Issue 7 | Pages 795 - 800
1 Jul 2023
Parsons N Achten J Costa ML

Aims. To report the outcomes of patients with a fracture of the distal tibia who were treated with intramedullary nail versus locking plate in the five years after participating in the Fixation of Distal Tibia fracture (FixDT) trial. Methods. The FixDT trial reported the results for 321 patients randomized to nail or locking plate fixation in the first 12 months after their injury. In this follow-up study, we report the results of 170 of the original participants who agreed to be followed up until five years. Participants reported their Disability Rating Index (DRI) and health-related quality of life (EuroQol five-dimension three-level questionnaire) annually by self-reported questionnaire. Further surgical interventions related to the fracture were also recorded. Results. There was no evidence of a difference in patient-reported disability, health-related quality of life, or the need for further surgery between participants treated with either type of fixation at five years. Considering the combined results for all participants, there was no significant change in DRI scores after the first 12 months of follow-up (difference between 12 and 24 months, 3.3 (95% confidence interval -1.8 to 8.5); p = 0.203), with patients reporting around 20% disability at five years. Conclusion. This study shows that the moderate levels of disability and reduced quality of life reported by participants 12 months after a fracture of the distal tibia persist in the medium term, with little evidence of improvement after the first year. Cite this article: Bone Joint J 2023;105-B(7):795–800


Bone & Joint Research
Vol. 11, Issue 11 | Pages 814 - 825
14 Nov 2022
Ponkilainen V Kuitunen I Liukkonen R Vaajala M Reito A Uimonen M

Aims. The aim of this systematic review and meta-analysis was to gather epidemiological information on selected musculoskeletal injuries and to provide pooled injury-specific incidence rates. Methods. PubMed (National Library of Medicine) and Scopus (Elsevier) databases were searched. Articles were eligible for inclusion if they reported incidence rate (or count with population at risk), contained data on adult population, and were written in English language. The number of cases and population at risk were collected, and the pooled incidence rates (per 100,000 person-years) with 95% confidence intervals (CIs) were calculated by using either a fixed or random effects model. Results. The screening of titles yielded 206 articles eligible for inclusion in the study. Of these, 173 (84%) articles provided sufficient information to be included in the pooled incidence rates. Incidences of fractures were investigated in 154 studies, and the most common fractures in the whole adult population based on the pooled incidence rates were distal radius fractures (212.0, 95% CI 178.1 to 252.4 per 100,000 person-years), finger fractures (117.1, 95% CI 105.3 to 130.2 per 100,000 person-years), and hip fractures (112.9, 95% CI 82.2 to 154.9 per 100,000 person-years). The most common sprains and dislocations were ankle sprains (429.4, 95% CI 243.0 to 759.0 per 100,000 person-years) and first-time patellar dislocations (32.8, 95% CI 21.6 to 49.7 per 100,000 person-years). The most common injuries were anterior cruciate ligament (17.5, 95% CI 6.0 to 50.2 per 100,000 person-years) and Achilles (13.7, 95% CI 9.6 to 19.5 per 100,000 person-years) ruptures. Conclusion. The presented pooled incidence estimates serve as important references in assessing the global economic and social burden of musculoskeletal injuries. Cite this article: Bone Joint Res 2022;11(11):814–825


Bone & Joint Research
Vol. 13, Issue 1 | Pages 4 - 18
2 Jan 2024
Wang Y Wu Z Yan G Li S Zhang Y Li G Wu C

Aims. cAMP response element binding protein (CREB1) is involved in the progression of osteoarthritis (OA). However, available findings about the role of CREB1 in OA are inconsistent. 666-15 is a potent and selective CREB1 inhibitor, but its role in OA is unclear. This study aimed to investigate the precise role of CREB1 in OA, and whether 666-15 exerts an anti-OA effect. Methods. CREB1 activity and expression of a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS4) in cells and tissues were measured by immunoblotting and immunohistochemical (IHC) staining. The effect of 666-15 on chondrocyte viability and apoptosis was examined by cell counting kit-8 (CCK-8) assay, JC-10, and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) staining. The effect of 666-15 on the microstructure of subchondral bone, and the synthesis and catabolism of cartilage, in anterior cruciate ligament transection mice were detected by micro-CT, safranin O and fast green (S/F), immunohistochemical staining, and enzyme-linked immunosorbent assay (ELISA). Results. CREB1 was hyperactive in osteoarthritic articular cartilage, interleukin (IL)-1β-treated cartilage explants, and IL-1β- or carbonyl cyanide 3-chlorophenylhydrazone (CCCP)-treated chondrocytes. 666-15 enhanced cell viability of OA-like chondrocytes and alleviated IL-1β- or CCCP-induced chondrocyte injury through inhibition of mitochondrial dysfunction-associated apoptosis. Moreover, inhibition of CREB1 by 666-15 suppressed expression of ADAMTS4. Additionally, 666-15 alleviated joint degeneration in an ACLT mouse model. Conclusion. Hyperactive CREB1 played a critical role in OA development, and 666-15 exerted anti-IL-1β or anti-CCCP effects in vitro as well as joint-protective effects in vivo. 666-15 may therefore be used as a promising anti-OA drug. Cite this article: Bone Joint Res 2024;13(1):4–18


Bone & Joint Open
Vol. 3, Issue 11 | Pages 850 - 858
2 Nov 2022
Khoriati A Fozo ZA Al-Hilfi L Tennent D

Aims. The management of mid-shaft clavicle fractures (MSCFs) has evolved over the last three decades. Controversy exists over which specific fracture patterns to treat and when. This review aims to synthesize the literature in order to formulate an appropriate management algorithm for these injuries in both adolescents and adults. Methods. This is a systematic review of clinical studies comparing the outcomes of operative and nonoperative treatments for MSCFs in the past 15 years. The literature was searched using, PubMed, Google scholar, OVID Medline, and Embase. All databases were searched with identical search terms: mid-shaft clavicle fractures (± fixation) (± nonoperative). Results. Using the search criteria identified, 247 studies were deemed eligible. Following initial screening, 220 studies were excluded on the basis that they were duplicates and/or irrelevant to the research question being posed. A total of 27 full-text articles remained and were included in the final review. The majority of the meta-analyses draw the same conclusions, which are that operatively treated fractures have lower nonunion and malunion rates but that, in those fractures which unite (either operative or nonoperative), the functional outcomes are the same at six months. Conclusion. With regard to the adolescent population, the existing body of evidence is insufficient to support the use of routine operative management. Regarding adult fractures, the key to identifying patients who benefit from operative management lies in the identification of risk factors for nonunion. We present an algorithm that can be used to guide both the patient and the surgeon in a joint decision-making process, in order to optimize patient satisfaction and outcomes. Cite this article: Bone Jt Open 2022;3(11):850–858