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The Bone & Joint Journal
Vol. 104-B, Issue 8 | Pages 963 - 971
1 Aug 2022
Sun Z Liu W Liu H Li J Hu Y Tu B Wang W Fan C

Aims

Heterotopic ossification (HO) is a common complication after elbow trauma and can cause severe upper limb disability. Although multiple prognostic factors have been reported to be associated with the development of post-traumatic HO, no model has yet been able to combine these predictors more succinctly to convey prognostic information and medical measures to patients. Therefore, this study aimed to identify prognostic factors leading to the formation of HO after surgery for elbow trauma, and to establish and validate a nomogram to predict the probability of HO formation in such particular injuries.

Methods

This multicentre case-control study comprised 200 patients with post-traumatic elbow HO and 229 patients who had elbow trauma but without HO formation between July 2019 and December 2020. Features possibly associated with HO formation were obtained. The least absolute shrinkage and selection operator regression model was used to optimize feature selection. Multivariable logistic regression analysis was applied to build the new nomogram: the Shanghai post-Traumatic Elbow Heterotopic Ossification Prediction model (STEHOP). STEHOP was validated by concordance index (C-index) and calibration plot. Internal validation was conducted using bootstrapping validation.


The Bone & Joint Journal
Vol. 104-B, Issue 7 | Pages 781 - 785
1 Jul 2022
Ferraro SL Williams DN Millis MB

Aims

The aim of this study was to understand the experience of mature patients who undergo a periacetabular osteotomy (PAO), a major hip-preserving surgical procedure that treats symptomatic hip dysplasia by realigning the acetabulum. Our aim was to improve our understanding of how the operation affected the lives of patients and their families, with a long-term goal of improving their experience.

Methods

We used a phenomenological approach with in-depth, semi-structured interviews to investigate the experience of seven female patients, aged between 25 and 40 years, who underwent a PAO. A modified homogeneity sampling approach coupled with criterion sampling was used. Inclusion criteria involved having at least one child at home and being in a committed relationship with a spouse or partner.


The Bone & Joint Journal
Vol. 104-B, Issue 9 | Pages 1095 - 1100
1 Sep 2022
McNally MA Ferguson JY Scarborough M Ramsden A Stubbs DA Atkins BL

Aims

Excision of chronic osteomyelitic bone creates a dead space which must be managed to avoid early recurrence of infection. Systemic antibiotics cannot penetrate this space in high concentrations, so local treatment has become an attractive adjunct to surgery. The aim of this study was to present the mid- to long-term results of local treatment with gentamicin in a bioabsorbable ceramic carrier.

Methods

A prospective series of 100 patients with Cierny-Mader Types III and IV chronic ostemyelitis, affecting 105 bones, were treated with a single-stage procedure including debridement, deep tissue sampling, local and systemic antibiotics, stabilization, and immediate skin closure. Chronic osteomyelitis was confirmed using strict diagnostic criteria. The mean follow-up was 6.05 years (4.2 to 8.4).


The Bone & Joint Journal
Vol. 104-B, Issue 9 | Pages 1081 - 1088
1 Sep 2022
Behman AL Bradley CS Maddock CL Sharma S Kelley SP

Aims

There is no consensus regarding optimum timing and frequency of ultrasound (US) for monitoring response to Pavlik harness (PH) treatment in developmental dysplasia of the hip (DDH). The purpose of our study was to determine if a limited-frequency hip US assessment had an adverse effect on treatment outcomes compared to traditional comprehensive US monitoring.

Methods

This study was a single-centre noninferiority randomized controlled trial. Infants aged under six months whose hips were reduced and centred in the harness at initiation of treatment (stable dysplastic or subluxable), or initially decentred (subluxated or dislocated) but reduced and centred within four weeks of PH treatment, were randomized to our current standard US monitoring protocol (every clinic visit) or to a limited-frequency US protocol (US only at end of treatment). Groups were compared based on α angle and femoral head coverage at the end of PH treatment, acetabular indices, and International Hip Dysplasia Institute (IHDI) grade on one-year follow-up radiographs.


The Bone & Joint Journal
Vol. 104-B, Issue 9 | Pages 1025 - 1031
1 Sep 2022
Thummala AR Xi Y Middleton E Kohli A Chhabra A Wells J

Aims

Pelvic tilt is believed to affect the symptomology of osteoarthritis (OA) of the hip by alterations in joint movement, dysplasia of the hip by modification of acetabular cover, and femoroacetabular impingement by influencing the impingement-free range of motion. While the apparent role of pelvic tilt in hip pathology has been reported, the exact effects of many forms of treatment on pelvic tilt are unknown. The primary aim of this study was to investigate the effects of surgery on pelvic tilt in these three groups of patients.

Methods

The demographic, radiological, and outcome data for all patients operated on by the senior author between October 2016 and January 2020 were identified from a prospective registry, and all those who underwent surgery with a primary diagnosis of OA, dysplasia, or femoroacetabular impingement were considered for inclusion. Pelvic tilt was assessed on anteroposterior (AP) standing radiographs using the pre- and postoperative pubic symphysis to sacroiliac joint (PS-SI) distance, and the outcomes were assessed with the Hip Outcome Score (HOS), International Hip Outcome Tool (iHOT-12), and Harris Hip Score (HHS).


The Bone & Joint Journal
Vol. 101-B, Issue 9 | Pages 1168 - 1176
1 Sep 2019
Calder PR McKay JE Timms AJ Roskrow T Fugazzotto S Edel P Goodier WD

Aims. The Precice intramedullary limb-lengthening system has demonstrated significant benefits over external fixation lengthening methods, leading to a paradigm shift in limb lengthening. This study compares outcomes following antegrade and retrograde femoral lengthening in both adolescent and adult patients. Patients and Methods. A retrospective review of prospectively collected data was undertaken of a consecutive series of 107 femoral lengthening operations in 92 patients. In total, 73 antegrade nails and 34 retrograde nails were inserted. Outcome was assessed by the regenerate healing index (HI), hip and knee range of movement (ROM), and the presence of any complications. Results. The mean lengthening was 4.65 cm (1.5 to 8) in the antegrade group and 4.64 cm (1.6 to 8) in the retrograde group. Of the 107 lengthenings, 100 had sufficient datapoints to calculate the mean HI. This was 31.6 days/cm (15 to 108). There was a trend toward a lower (better) HI with an antegrade nail and better outcomes in adolescent patients, but these were not statistically significant. Hip and knee ROM was maintained and/or improved following commencement of femoral lengthening in 44 patients (60%) of antegrade nails and 13 patients (38%) of retrograde nails. In female patients, loss of movement occurred both earlier and following less total length achieved. Minor implant complications included locking bolt migration and in one patient deformity of the nail, but no implant failed to lengthen and there were no deep infections. Three patients had delayed union, five patients required surgical intervention for joint contracture. Conclusion. This study confirms excellent results in femoral lengthening with antegrade and retrograde Precice nails. There is a trend for better healing and less restriction in hip and knee movement following antegrade nails. There are clinical scenarios, that mandate the use of a retrograde nail. However, when these are not present, we recommend the use of antegrade nailing. Cite this article: Bone Joint J 2019;101-B:1168–1176


The Bone & Joint Journal
Vol. 97-B, Issue 3 | Pages 383 - 390
1 Mar 2015
Mariconda M Costa GG Cerbasi S Recano P Aitanti E Gambacorta M Misasi M

Several studies have reported the rate of post-operative mortality after the surgical treatment of a fracture of the hip, but few data are available regarding the delayed morbidity. In this prospective study, we identified 568 patients who underwent surgery for a fracture of the hip and who were followed for one year. Multivariate analysis was carried out to identify possible predictors of mortality and morbidity. The 30-day, four-month and one-year rates of mortality were 4.3%, 11.4%, and 18.8%, respectively. General complications and pre-operative comorbidities represented the basic predictors of mortality at any time interval (p < 0.01). In-hospital, four-month and one-year general complications occurred in 29.4%, 18.6% and 6.7% of patients, respectively. After adjusting for confounding variables, comorbidities and poor cognitive status determined the likelihood of early and delayed general complications, respectively (p < 0.001). Operative delay was the main predictor of the length of hospital stay (p < 0.001) and was directly related to in-hospital (p = 0.017) and four-month complications (p = 0.008). Cite this article: Bone Joint J 2015;97-B:383–90


The Bone & Joint Journal
Vol. 104-B, Issue 6 | Pages 680 - 686
1 Jun 2022
Robinson JR Bruce D Davies H Porteous AJ Murray JRD Howells NR

Aims

The best surgical strategy for the management of displaced bucket-handle (BH) meniscal tears in an anterior cruciate ligament (ACL)-deficient knee is unclear. Combining meniscal repair with ACL reconstruction (ACLR) is thought to improve meniscal healing rates; however, patients with displaced BH meniscal tears may lack extension. This leads some to advocate staged surgery to avoid postoperative stiffness and loss of range of motion (ROM) following ACLR.

Methods

We reviewed the data for a consecutive series of 88 patients (mean age 27.1 years (15 to 49); 65 male (74%) and 23 female (26%)) who underwent single-stage repair of a displaced BH meniscal tear (67 medial (76%) and 21 lateral (24%)) with concomitant hamstring autograft ACLR. The patient-reported outcome measures (PROMs) EuroQol visual analogue scale (EQ-VAS), EuroQol five-dimension health questionnaire (EQ-5D), Knee injury and Osteoarthritis Outcome Score (KOOS), International Knee Documentation Committee score (IKDC), and Tegner score were recorded at final follow-up. A Kaplan-Meier survival analysis was performed to estimate meniscal repair survivorship. Analyses were performed with different cut-offs for meniscal and ACL injury-to-surgery time (within three weeks, three to ten weeks, and more than ten weeks).


Bone & Joint Research
Vol. 11, Issue 9 | Pages 669 - 678
1 Sep 2022
Clement RGE Hall AC Wong SJ Howie SEM Simpson AHRW

Aims

Staphylococcus aureus is a major cause of septic arthritis, and in vitro studies suggest α haemolysin (Hla) is responsible for chondrocyte death. We used an in vivo murine joint model to compare inoculation with wild type S. aureus 8325-4 with a Hla-deficient strain DU1090 on chondrocyte viability, tissue histology, and joint biomechanics. The aim was to compare the actions of S. aureus Hla alone with those of the animal’s immune response to infection.

Methods

Adult male C57Bl/6 mice (n = 75) were randomized into three groups to receive 1.0 to 1.4 × 107 colony-forming units (CFUs)/ml of 8325-4, DU1090, or saline into the right stifle joint. Chondrocyte death was assessed by confocal microscopy. Histological changes to inoculated joints were graded for inflammatory responses along with gait, weight changes, and limb swelling.


The Bone & Joint Journal
Vol. 97-B, Issue 1 | Pages 104 - 108
1 Jan 2015
Bretherton CP Parker MJ

There has been extensive discussion about the effect of delay to surgery on mortality in patients sustaining a fracture of the hip. Despite the low level of evidence provided by many studies, a consensus has been accepted that delay of > 48 hours is detrimental to survival. The aim of this prospective observational study was to determine if early surgery confers a survival benefit at 30 days. Between 1989 and 2013, data were prospectively collected on patients sustaining a fracture of the hip at Peterborough City Hospital. They were divided into groups according to the time interval between admission and surgery. These thresholds ranged from <  6 hours to between 49 and 72 hours. The outcome which was assessed was the 30-day mortality. Adjustment for confounders was performed using multivariate binary logistic regression analysis. In all, 6638 patients aged > 60 years were included. . Worsening American Society of Anaesthesiologists grade (p < 0.001), increased age (p <  0.001) and extracapsular fracture (p < 0.019) increased the risk of 30-day mortality. . Increasing mobility score (p = 0.014), mini mental test score (p < 0.001) and female gender (p = 0.014) improved survival. After adjusting for these confounders, surgery before 12 hours improved survival compared with surgery after 12 hours (p = 0.013). Beyond this the increasing delay to surgery did not significantly affect the 30-day mortality. Cite this article: Bone Joint J 2015;97-B:104–8


The Bone & Joint Journal
Vol. 101-B, Issue 7_Supple_C | Pages 17 - 21
1 Jul 2019
Schroer WC LeMarr AR Mills K Childress AL Morton DJ Reedy ME

Aims. To date, no study has demonstrated an improvement in postoperative outcomes following elective joint arthroplasty with a focus on nutritional intervention for patients with preoperative hypoalbuminaemia. In this prospective study, we evaluated differences in the hospital length of stay (LOS), rate of re-admission, and total patient charges for a malnourished patient study population who received a specific nutrition protocol before surgery. Patients and Methods. An analytical report was extracted from the electronic medical record (EMR; Epic, Verona, Wisconsin) of a five-hospital network joint arthroplasty patient data set between 2014 and 2017. A total of 4733 patients underwent joint arthroplasty and had preoperative measurement of albumin levels: 2220 at four hospitals and 2513 at the study hospital. Albumin ≤ 3.4 g/l, designated as malnutrition, was found in 543 patients (11.5%). A nutritional intervention programme focusing on a high-protein, anti-inflammatory diet was initiated in January 2017 at one study hospital. Hospital LOS, re-admission rate, and 90-day charges were compared for differential change between patients in study and control hospitals for all elective hip and knee arthroplasty patients, and for malnourished patients over time as the nutrition intervention was implemented. Results. Malnourished patients with nutritional intervention at the study hospital had shorter hospital LOS beginning in 2017 than malnourished patients at control hospitals during the same period (p = 0.04). Similarly, this cohort had significantly lower primary hospitalization charges, charges associated with hospital re-admissions, and 90-day total charges (p < 0.001). Inclusion of covariant potential confounders (age, anaemia, diabetes, and obesity) did not alter the conclusions of the primary statistical analysis. Conclusion. Joint arthroplasty outcomes were positively affected in study patients with low albumin when a high-protein, anti-inflammatory diet was encouraged. Elective surgery was neither cancelled nor delayed with a malnutrition designation. While the entire network population experienced improved postoperative outcomes, malnourished control patients did not experience this improvement. This study demonstrated that education on malnutrition can benefit patients. Cite this article: Bone Joint J 2019;101-B(7 Supple C):17–21


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. 104-B, Issue 6 | Pages 721 - 728
1 Jun 2022
Johansen A Ojeda-Thies C Poacher AT Hall AJ Brent L Ahern EC Costa ML

Aims

The aim of this study was to explore current use of the Global Fragility Fracture Network (FFN) Minimum Common Dataset (MCD) within established national hip fracture registries, and to propose a revised MCD to enable international benchmarking for hip fracture care.

Methods

We compared all ten established national hip fracture registries: England, Wales, and Northern Ireland; Scotland; Australia and New Zealand; Republic of Ireland; Germany; the Netherlands; Sweden; Norway; Denmark; and Spain. We tabulated all questions included in each registry, and cross-referenced them against the 32 questions of the MCD dataset. Having identified those questions consistently used in the majority of national audits, and which additional fields were used less commonly, we then used consensus methods to establish a revised MCD.


Bone & Joint Research
Vol. 8, Issue 7 | Pages 313 - 322
1 Jul 2019
Hanberg P Lund A Søballe K Bue M

Objectives. Meropenem may be an important drug in the treatment of open tibial fractures and chronic osteomyelitis. Therefore, the objective of this study was to describe meropenem pharmacokinetics in plasma, subcutaneous adipose tissue (SCT), and cancellous bone using microdialysis in a porcine model. Methods. Six female pigs were assigned to receive 1000 mg of meropenem intravenously over five minutes. Measurements of meropenem were obtained from plasma, SCT, and cancellous bone for eight hours thereafter. Microdialysis was applied for sampling in solid tissues. The meropenem concentrations were determined using ultra-high-performance liquid chromatography. Results. The penetration of meropenem into cancellous bone, expressed as the ratio of plasma to cancellous bone area under the concentration-curve from zero to the last measured value, was incomplete and delayed. The time with concentration above the minimal inhibitory concentration (T. >MIC. ), for an MIC of 0.5 μg/ml, was shorter for cancellous bone in comparison with both plasma and SCT. For MICs above 0.5 μg/ml, T. >MIC. in cancellous bone was only shorter than SCT. Considering an MIC of 4 μg/ml, no animals achieved the target of 40% T. >MIC. in plasma and cancellous bone, while less than 20% achieved it in SCT. Conclusion. The main finding of this study was short T. >MIC. in cancellous bone after intravenous administration of 1000 mg meropenem. Consequently, in order to achieve sufficient tissue concentration in the cases of open tibial fractures and chronic osteomyelitis, supplemental application of meropenem may be necessary. Cite this article: P. Hanberg, A. Lund, K. Søballe, M. Bue. Single-dose pharmacokinetics of meropenem in porcine cancellous bone determined by microdialysis: An animal study. Bone Joint Res 2019;8:342–348. DOI: 10.1302/2046-3758.87.BJR-2018-0308.R1


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.


Bone & Joint 360
Vol. 11, Issue 3 | Pages 43 - 45
1 Jun 2022


The Bone & Joint Journal
Vol. 104-B, Issue 7 | Pages 894 - 901
1 Jul 2022
Aebischer AS Hau R de Steiger RN Holder C Wall CJ

Aims

The aim of this study was to investigate the rate of revision for distal femoral arthroplasty (DFA) performed as a primary procedure for native knee fractures using data from the Australian Orthopaedic Association National Joint Arthroplasty Registry (AOANJRR).

Methods

Data from the AOANJRR were obtained for DFA performed as primary procedures for native knee fractures from 1 September 1999 to 31 December 2020. Pathological fractures and revision for failed internal fixation were excluded. The five prostheses identified were the Global Modular Arthroplasty System, the Modular Arthroplasty System, the Modular Universal Tumour And Revision System, the Orthopaedic Salvage System, and the Segmental System. Patient demographic data (age, sex, and American Society of Anesthesiologists grade) were obtained, where available. Kaplan-Meier estimates of survival were used to determine the rate of revision, and the reasons for revision and mortality data were examined.


The Bone & Joint Journal
Vol. 104-B, Issue 7 | Pages 792 - 800
1 Jul 2022
Gustafsson K Kvist J Zhou C Eriksson M Rolfson O

Aims

The aim of this study was to estimate time to arthroplasty among patients with hip and knee osteoarthritis (OA), and to identify factors at enrolment to first-line intervention that are prognostic for progression to surgery.

Methods

In this longitudinal register-based observational study, we identified 72,069 patients with hip and knee OA in the Better Management of Patients with Osteoarthritis Register (BOA), who were referred for first-line OA intervention, between May 2008 and December 2016. Patients were followed until the first primary arthroplasty surgery before 31 December 2016, stratified into a hip and a knee OA cohort. Data were analyzed with Kaplan-Meier and multivariable-adjusted Cox regression.


The Bone & Joint Journal
Vol. 101-B, Issue 6 | Pages 682 - 690
1 Jun 2019
Scheidegger P Horn Lang T Schweizer C Zwicky L Hintermann B

Aims. There is little information about how to manage patients with a recurvatum deformity of the distal tibia and osteoarthritis (OA) of the ankle. The aim of this study was to evaluate the functional and radiological outcome of addressing this deformity using a flexion osteotomy and to assess the progression of OA after this procedure. Patients and Methods. A total of 39 patients (12 women, 27 men; mean age 47 years (28 to 72)) with a distal tibial recurvatum deformity were treated with a flexion osteotomy, between 2010 and 2015. Nine patients (23%) subsequently required conversion to either a total ankle arthroplasty (seven) or an arthrodesis (two) after a mean of 21 months (9 to 36). A total of 30 patients (77%), with a mean follow-up of 30 months (24 to 76), remained for further evaluation. Functional outcome, sagittal ankle joint OA using a modified Kellgren and Lawrence Score, tibial lateral surface (TLS) angle, and talar offset ratio (TOR) were evaluated on pre- and postoperative weight-bearing radiographs. Results. Postoperatively, the mean score for pain, using a visual analogue scale, decreased significantly from 4.3 to 2.5 points and the mean American Orthopaedic Foot & Ankle Society (AOFAS) hindfoot score improved significantly from 59 to 75 points (both p < 0.001). The mean TLS angle increased significantly by 6.6°; the mean TOR decreased significantly by 0.24 (p < 0.001). Radiological evaluation showed an improvement or no progression of sagittal ankle joint OA in 32 ankles (82%), while seven ankles (18%) showed further progression. Conclusion. A flexion osteotomy effectively improved the congruency of the ankle joint. In 30 patients (77%), the joint could be saved, whereas in nine patients (23%), the treatment delayed a joint-sacrificing procedure. Cite this article: Bone Joint J 2019;101-B:682–690


Bone & Joint Research
Vol. 11, Issue 8 | Pages 594 - 607
17 Aug 2022
Zhou Y Li J Xu F Ji E Wang C Pan Z

Aims

Osteoarthritis (OA) is a common degenerative joint disease characterized by chronic inflammatory articular cartilage degradation. Long noncoding RNAs (lncRNAs) have been previously indicated to play an important role in inflammation-related diseases. Herein, the current study set out to explore the involvement of lncRNA H19 in OA.

Methods

Firstly, OA mouse models and interleukin (IL)-1β-induced mouse chondrocytes were established. Expression patterns of IL-38 were determined in the synovial fluid and cartilage tissues from OA patients. Furthermore, the targeting relationship between lncRNA H19, tumour protein p53 (TP53), and IL-38 was determined by means of dual-luciferase reporter gene, chromatin immunoprecipitation, and RNA immunoprecipitation assays. Subsequent to gain- and loss-of-function assays, the levels of cartilage damage and proinflammatory factors were further detected using safranin O-fast green staining and enzyme-linked immunosorbent assay (ELISA) in vivo, respectively, while chondrocyte apoptosis was measured using Terminal deoxynucleotidyl transferase dUTP Nick-End Labeling (TUNEL) in vitro.