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Bone & Joint Open
Vol. 5, Issue 8 | Pages 681 - 687
19 Aug 2024
van de Graaf VA Shen TS Wood JA Chen DB MacDessi SJ

Aims

Sagittal plane imbalance (SPI), or asymmetry between extension and flexion gaps, is an important issue in total knee arthroplasty (TKA). The purpose of this study was to compare SPI between kinematic alignment (KA), mechanical alignment (MA), and functional alignment (FA) strategies.

Methods

In 137 robotic-assisted TKAs, extension and flexion stressed gap laxities and bone resections were measured. The primary outcome was the proportion and magnitude of medial and lateral SPI (gap differential > 2.0 mm) for KA, MA, and FA. Secondary outcomes were the proportion of knees with severe (> 4.0 mm) SPI, and resection thicknesses for each technique, with KA as reference.


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_14 | Pages 10 - 10
23 Jul 2024
Al-hasani F Mhadi M
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Meniscal tears commonly co-occur with ACL tears, and many studies address their side, pattern, and distribution. Few studies assess the patient's short-term functional outcome concerning tear radial and circumferential distribution based on the Cooper et al. classification. Meniscal tears require primary adequate treatment to restore knee function. Our hypothesis is to preserve the meniscal rim as much as possible to maintain the load-bearing capacity of the menisci after meniscectomy. The purpose of this study is to document the location and type of meniscal tears that accompany anterior cruciate ligament (ACL) tears and their effect on patient functional outcomes following arthroscopic ACL reconstruction and meniscectomy. This prospective cross-sectional observational study was conducted at AL-BASRA Teaching Hospital in Iraq between July 2018 and January 2020 among patients with combined ipsilateral ACL injury and meniscal tears. A total of 28 active young male patients, aged 18 to 42 years, were included. All patients were subjected to our questionnaire, full history, systemic and regional examination, laboratory investigations, imaging studies, preoperative rehabilitation, and were followed by Lysholm score 6 months postoperatively. All 28 patients were males, with a mean age of 27 ± 0.14 years. The right knee was the most commonly affected in 20/28 patients (71.4%). The medial meniscus was most commonly injured in 11 patients, 7 patients had lateral meniscal tears, and 10 patients had tears in both menisci. The most common tear pattern of the medial meniscus was a bucket handle tear (36.4%), while longitudinal tears were the most frequent in the lateral meniscus (71.4%) (P-value = 0.04). The most common radial tear location was zone E-F (5/28, 17.8%), and the most common circumferential zone affected was the middle and inner third, reported in 50% of tears. Good and excellent outcomes using the Lysholm score after 6 months were obtained in 42.9% and 17.9% of patients, respectively. Better functional scores were associated with lateral meniscal tears, bucket handle tears, tears extending to a more peripheral vascular area, and if no more than one-third of the meniscus was resected (P-value = 0.002). Less favourable outcomes were reported in smokers, posterior horn tears, and when surgery was delayed more than 1 year (P-value = 0.03). We conclude that there is a negative correlation between the amount of meniscus resected and functional outcome. Delayed ACL reconstruction increases the risk of bimeniscal tears. Bucket handle tears are the most common tears, mostly in the medial meniscus, while longitudinal tears are most common in the lateral meniscus. We recommend performing early ACL reconstruction within 12 months to reduce the risk of bimeniscal injuries


The Bone & Joint Journal
Vol. 106-B, Issue 7 | Pages 662 - 668
1 Jul 2024
Ahmed I Metcalfe A

Aims

This study aims to identify the top unanswered research priorities in the field of knee surgery using consensus-based methodology.

Methods

Initial research questions were generated using an online survey sent to all 680 members of the British Association for Surgery of the Knee (BASK). Duplicates were removed and a longlist was generated from this scoping exercise by a panel of 13 experts from across the UK who provided oversight of the process. A modified Delphi process was used to refine the questions and determine a final list. To rank the final list of questions, each question was scored between one (low importance) and ten (high importance) in order to produce the final list.


Bone & Joint Research
Vol. 13, Issue 6 | Pages 279 - 293
7 Jun 2024
Morris JL Letson HL McEwen PC Dobson GP

Aims. Adenosine, lidocaine, and Mg. 2+. (ALM) therapy exerts differential immuno-inflammatory responses in males and females early after anterior cruciate ligament (ACL) reconstruction (ACLR). Our aim was to investigate sex-specific effects of ALM therapy on joint tissue repair and recovery 28 days after surgery. Methods. Male (n = 21) and female (n = 21) adult Sprague-Dawley rats were randomly divided into ALM or Saline control treatment groups. Three days after ACL rupture, animals underwent ACLR. An ALM or saline intravenous infusion was commenced prior to skin incision, and continued for one hour. An intra-articular bolus of ALM or saline was also administered prior to skin closure. Animals were monitored to 28 days, and joint function, pain, inflammatory markers, histopathology, and tissue repair markers were assessed. Results. Despite comparable knee function, ALM-treated males had reduced systemic inflammation, synovial fluid angiogenic and pro-inflammatory mediators, synovitis, and fat pad fibrotic changes, compared to controls. Within the ACL graft, ALM-treated males had increased expression of tissue repair markers, decreased inflammation, increased collagen organization, and improved graft-bone healing. In contrast to males, females had no evidence of persistent systemic inflammation. Compared to controls, ALM-treated females had improved knee extension, gait biomechanics, and elevated synovial macrophage inflammatory protein-1 alpha (MIP-1α). Within the ACL graft, ALM-treated females had decreased inflammation, increased collagen organization, and improved graft-bone healing. In articular cartilage of ALM-treated animals, matrix metalloproteinase (MMP)-13 expression was blunted in males, while in females repair markers were increased. Conclusion. At 28 days, ALM therapy reduces inflammation, augments tissue repair patterns, and improves joint function in a sex-specific manner. The study supports transition to human safety trials. Cite this article: Bone Joint Res 2024;13(6):279–293


The Bone & Joint Journal
Vol. 106-B, Issue 6 | Pages 516 - 521
1 Jun 2024
Al-Hourani K Haddad FS


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_8 | Pages 29 - 29
10 May 2024
Stowers M Rahardja R Nicholson L Svirskis D Hannam J Young S
Full Access

Introduction. Day stay surgery for anterior cruciate ligament (ACL) reconstructions is an increasingly common practice and has driven clinicians to come up with postoperative pain regimes that allow same day mobilisation and a safe and timely discharge. There is a paucity of literature surrounding the use of intraosseous (IO) ropivacaine used as a Bier's block to provide both intraoperative and postoperative analgesia in lower limb surgery. Methods. This patient blinded, pilot study randomised 15 patients undergoing ACL reconstruction to receive either IO ropivacaine 1.5 or 2.0 mg/kg; or 300 mg of ropivacaine as local infiltration (standard of care). Toxic plasma levels of ropivacaine have been defined in the literature and therefore the primary outcome for this study was arterial plasma concentration of ropivacaine as a means to determine its safety profile. Samples were taken via an arterial line at prespecified times after tourniquet deflation. Secondary outcomes that we were interested in included immediate postoperative pain scores using the visual analogue scale (VAS) and perioperative opioid equivalent consumption. Results. Participants had a mean age of 27.8 (SD 9.2) years and 87% (13/15) were male. All patients in the intervention group receiving IO ropivacaine had plasma concentrations well below the threshold for central nervous system (CNS) toxicity (0.60 µg/ml). The highest plasma concentration was achieved in the intervention group receiving 1.5 mg/kg dose of ropivacaine reaching 3.59 mg/ml. This would equate to 0.22 µg/ml of free plasma ropivacaine. There were no differences across the three groups regarding pain scores or perioperative opioid consumption. Conclusions. This study demonstrates that IO administration of 0.2% ropivacaine is both safe and effective in reducing perioperative pain in patients undergoing ACL reconstruction. There may be scope to increase the IO dose further or utilise other analgesics via the IO regional route to improve perioperative pain relief


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_8 | Pages 31 - 31
10 May 2024
Clatworthy M Rahardja R Young S Love H
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Background. Anterior cruciate ligament (ACL) reconstruction with concomitant meniscal injury occurs frequently. Meniscal repair is associated with improved long-term outcomes compared to resection but is also associated with a higher reoperation rate. Knowledge of the risk factors for repair failure may be important in optimizing patient outcomes. Purpose. This study aimed to identify the patient and surgical risk factors for meniscal repair failure, defined as a subsequent meniscectomy, following concurrent primary ACL reconstruction. Methods. Data recorded by the New Zealand ACL Registry and the Accident Compensation Corporation, the New Zealand Government's sole funder of ACL reconstructions and any subsequent surgery, was reviewed. Meniscal repairs performed with concurrent primary ACL reconstruction was included. Root repairs were excluded. Univariate and multivariate survival analysis was performed to identify the patient and surgical risk factors for meniscal repair failure. Results. Between 2014 and 2020, a total of 3,024 meniscal repairs were performed during concurrent primary ACL reconstruction (medial repair = 1,814 and lateral repair = 1,210). The overall failure rate was 6.6% (n = 201) at a mean follow-up of 2.9 years, with a failure occurring in 7.8% of medial meniscal repairs (142 out of 1,814) and 4.9% of lateral meniscal repairs (59 out of 1,210). The risk of medial failure was higher in patients with a hamstring tendon autograft (adjusted HR = 2.20, p = 0.001), patients aged 21–30 years (adjusted HR = 1.60, p = 0.037) and in those with cartilage injury in the medial compartment (adjusted HR = 1.75, p = 0.002). The risk of lateral failure was higher in patients aged ≤ 20 years (adjusted HR = 2.79, p = 0.021) and when the procedure was performed by a surgeon with an annual ACL reconstruction case volume of less than 30 (adjusted HR = 1.84, p = 0.026). Conclusion. When performing meniscal repair during a primary ACL reconstruction, the use of a hamstring tendon autograft, younger age and the presence of concomitant cartilage injury in the medial compartment increases the risk of medial meniscal repair failure, whereas younger age and low surgeon volume increases the risk of lateral meniscal repair failure


Bone & Joint 360
Vol. 13, Issue 2 | Pages 20 - 23
1 Apr 2024

The April 2024 Knee Roundup360 looks at: Challenging the status quo: re-evaluating the impact of obesity on unicompartmental knee arthroplasty outcomes; Timing matters: the link between ACL reconstruction delays and cartilage damage; Custom fit or off the shelf: evaluating patient outcomes in tailored versus standard knee replacements; Revolutionizing knee replacement: a comparative study on robotic-assisted and computer-navigated techniques; Pre-existing knee osteoarthritis and severe joint depression are associated with the need for total knee arthroplasty after tibial plateau fracture in patients aged over 60 years; Modern digital therapies?; A matched study on fracture rates following knee replacement surgeries;


Bone & Joint 360
Vol. 13, Issue 2 | Pages 41 - 44
1 Apr 2024

The April 2024 Children’s orthopaedics Roundup360 looks at: Ultrasonography or radiography for suspected paediatric distal forearm fractures?; Implant density in scoliosis: an important variable?; Gait after paediatric femoral shaft fracture treated with intramedullary nail fixation: a longitudinal prospective study; The opioid dilemma: navigating pain management for children’s bone fractures; 12- to 20-year follow-up of Dega acetabuloplasty in patients with developmental dysplasia of the hip; Physeal fractures of the distal ulna: incidence and risk factors for premature growth arrest; Analysis of growth after transphyseal anterior cruciate ligament reconstruction in children; Management of lateral condyle humeral fracture associated with elbow dislocation in children: a retrospective international multicentre cohort study.


The Bone & Joint Journal
Vol. 106-B, Issue 3 | Pages 249 - 255
1 Mar 2024
Inclan PM Brophy RH Saccone NL Ma Y Pham V Yanik EL

Aims

The purpose of this study is to determine an individual’s age-specific prevalence of total knee arthroplasty (TKA) after cruciate ligament surgery, and to identify clinical and genetic risk factors associated with undergoing TKA.

Methods

This study was a retrospective case-control study using the UK Biobank to identify individuals reporting a history of cruciate ligament surgery. Data from verbal history and procedural codes recorded through the NHS were used to identify instances of TKA. Patient clinical and genetic data were used to identify risk factors for progression from cruciate ligament surgery to TKA. Individuals without a history of cruciate ligament reconstruction were used for comparison.


The Bone & Joint Journal
Vol. 106-B, Issue 3 | Pages 232 - 239
1 Mar 2024
Osmani HT Nicolaou N Anand S Gower J Metcalfe A McDonnell S

Aims

To identify unanswered questions about the prevention, diagnosis, treatment, and rehabilitation and delivery of care of first-time soft-tissue knee injuries (ligament injuries, patella dislocations, meniscal injuries, and articular cartilage) in children (aged 12 years and older) and adults.

Methods

The James Lind Alliance (JLA) methodology for Priority Setting Partnerships was followed. An initial survey invited patients and healthcare professionals from the UK to submit any uncertainties regarding soft-tissue knee injury prevention, diagnosis, treatment, and rehabilitation and delivery of care. Over 1,000 questions were received. From these, 74 questions (identifying common concerns) were formulated and checked against the best available evidence. An interim survey was then conducted and 27 questions were taken forward to the final workshop, held in January 2023, where they were discussed, ranked, and scored in multiple rounds of prioritization. This was conducted by healthcare professionals, patients, and carers.


Bone & Joint Open
Vol. 5, Issue 2 | Pages 94 - 100
5 Feb 2024
Mancino F Kayani B Gabr A Fontalis A Plastow R Haddad FS

Anterior cruciate ligament (ACL) injuries are among the most common and debilitating knee injuries in professional athletes with an incidence in females up to eight-times higher than their male counterparts. ACL injuries can be career-threatening and are associated with increased risk of developing knee osteoarthritis in future life. The increased risk of ACL injury in females has been attributed to various anatomical, developmental, neuromuscular, and hormonal factors. Anatomical and hormonal factors have been identified and investigated as significant contributors including osseous anatomy, ligament laxity, and hamstring muscular recruitment. Postural stability and impact absorption are associated with the stabilizing effort and stress on the ACL during sport activity, increasing the risk of noncontact pivot injury. Female patients have smaller diameter hamstring autografts than males, which may predispose to increased risk of re-rupture following ACL reconstruction and to an increased risk of chondral and meniscal injuries. The addition of an extra-articular tenodesis can reduce the risk of failure; therefore, it should routinely be considered in young elite athletes. Prevention programs target key aspects of training including plyometrics, strengthening, balance, endurance and stability, and neuromuscular training, reducing the risk of ACL injuries in female athletes by up to 90%. Sex disparities in access to training facilities may also play an important role in the risk of ACL injuries between males and females. Similarly, football boots, pitches quality, and football size and weight should be considered and tailored around females’ characteristics. Finally, high levels of personal and sport-related stress have been shown to increase the risk of ACL injury which may be related to alterations in attention and coordination, together with increased muscular tension, and compromise the return to sport after ACL injury. Further investigations are still necessary to better understand and address the risk factors involved in ACL injuries in female athletes. Cite this article: Bone Jt Open 2024;5(2):94–100


The Bone & Joint Journal
Vol. 106-B, Issue 2 | Pages 174 - 181
1 Feb 2024
Mandalia KP Brodeur PG Li LT Ives K Cruz Jr. AI Shah SS

Aims

The aim of this study was to characterize the influence of social deprivation on the rate of complications, readmissions, and revisions following primary total shoulder arthroplasty (TSA), using the Social Deprivation Index (SDI). The SDI is a composite measurement, in percentages, of seven demographic characteristics: living in poverty, with < 12 years of education, single-parent households, living in rented or overcrowded housing, households without a car, and unemployed adults aged < 65 years.

Methods

Patients aged ≥ 40 years, who underwent primary TSA between 2011 and 2017, were identified using International Classification of Diseases (ICD)-9 Clinical Modification and ICD-10 procedure codes for TSA in the New York Statewide Planning and Research Cooperative System database. Readmission, reoperation, and other complications were analyzed using multivariable Cox proportional hazards regression controlling for SDI, age, ethnicity, insurance status, and Charlson Comorbidity Index.


The Bone & Joint Journal
Vol. 106-B, Issue 2 | Pages 195 - 202
1 Feb 2024
Jamshidi K Kargar Shooroki K Ammar W Mirzaei A

Aims

The epiphyseal approach to a chondroblastoma of the intercondylar notch of a child’s distal femur does not provide adequate exposure, thereby necessitating the removal of a substantial amount of unaffected bone to expose the lesion. In this study, we compared the functional outcomes, local recurrence, and surgical complications of treating a chondroblastoma of the distal femoral epiphysis by either an intercondylar or an epiphyseal approach.

Methods

A total of 30 children with a chondroblastoma of the distal femur who had been treated by intraregional curettage and bone grafting were retrospectively reviewed. An intercondylar approach was used in 16 patients (group A) and an epiphyseal approach in 14 (group B). Limb function was assessed using the Musculoskeletal Tumor Society (MSTS) scoring system and Sailhan’s functional criteria.


Bone & Joint 360
Vol. 13, Issue 1 | Pages 16 - 18
1 Feb 2024

The February 2024 Knee Roundup360 looks at: Do patients with hypoallergenic total knee arthroplasty implants for metal allergy do worse? An analysis of healthcare utilizations and patient-reported outcome measures; Defining a successful total knee arthroplasty; Incidence, microbiological studies, and factors associated with periprosthetic joint infection after total knee arthroplasty; A modified Delphi consensus statement on patellar instability; Cause for concern? Significant cement coverage in retrieved metaphyseal cones after revision total knee arthroplasty; Prevalence of post-traumatic osteoarthritis after anterior cruciate ligament injury remains high despite advances in surgical techniques; Cost-effectiveness of arthroscopic partial meniscectomy versus physical therapy for traumatic meniscal tears in patients aged under 45 years.


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_3 | Pages 5 - 5
23 Jan 2024
Awad F Khan F McIntyre J Hathaway L Guro R Kotwal R Chandratreya A
Full Access

Introduction. Anterior cruciate ligament (ACL) injuries represent a significant burden of disease to the orthopaedic surgeon and often necessitate surgical reconstruction in the presence of instability. The hamstring graft has traditionally been used to reconstruct the ACL but the quadriceps tendon (QT) graft has gained popularity due to its relatively low donor site morbidity. Methods. This is a single centre comparative retrospective analysis of prospectively collected data of patients who had an ACL reconstruction (either with single tendon quadrupled hamstring graft or soft tissue quadriceps tendon graft). All surgeries were performed by a single surgeon using the All-inside technique. For this study, there were 20 patients in each group. All patients received the same post-operative rehabilitation protocol and were added to the National Ligament Registry to monitor their patient related outcome scores (PROM). Results. The average age of patients in the QT group was 29 years (16 males, 4 females) and in the hamstring group was 28 years (18 males, 2 females). The most common mechanism of injury in both groups was a contact twisting injury. There were no statistical differences between the two patient groups in regards to PROMS and need for further revision surgery as analysed on the National Ligament Registry. Conclusions. The all soft tissue QT graft seems to be equivocal to quadrupled hamstring graft in terms of patient function and recovery graft characteristics. Further research may be needed to elucidate the long-term results of the all soft tissue QT graft given its recent increase in use


Bone & Joint Open
Vol. 5, Issue 1 | Pages 9 - 19
16 Jan 2024
Dijkstra H van de Kuit A de Groot TM Canta O Groot OQ Oosterhoff JH Doornberg JN

Aims

Machine-learning (ML) prediction models in orthopaedic trauma hold great promise in assisting clinicians in various tasks, such as personalized risk stratification. However, an overview of current applications and critical appraisal to peer-reviewed guidelines is lacking. The objectives of this study are to 1) provide an overview of current ML prediction models in orthopaedic trauma; 2) evaluate the completeness of reporting following the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) statement; and 3) assess the risk of bias following the Prediction model Risk Of Bias Assessment Tool (PROBAST) tool.

Methods

A systematic search screening 3,252 studies identified 45 ML-based prediction models in orthopaedic trauma up to January 2023. The TRIPOD statement assessed transparent reporting and the PROBAST tool the risk of bias.


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_2 | Pages 58 - 58
2 Jan 2024
Camarero-Espinosa S
Full Access

The anterior cruciate ligament (ACL) is the connective tissue located at the end of long bones providing stability to the knee joint. After tear or rupture clinical reconstruction of the tissue remains a challenge due to the particular mechanical properties required for proper functioning of the tissue. The outstanding mechanical properties of the ACL are characterized by a viscoelastic behavior responsible of the dissipation of the loads that are transmitted to the bone. These mechanical properties are the result of a very specialized graded extracellular matrix that transitions smoothly between the heterotypic cells, stiffness and composition of the ACL and the adjacent bone. Thus, mimicking the zonal biochemical composition, cellular phenotype and organization are key to reset the proper functioning of the ACL. We have previously shown how the biochemical composition presented to cells in electrospun scaffolds results in haptokinesis, reverting contact-guidance effects. [1]. Here, we demonstrate that contact guidance can also be disrupted by structural parameters in aligned wavy scaffolds. The presentation of a wavy fiber arrangement affected the cell organization and the deposition of a specific ECM characteristic of fibrocartilage. Cells cultured in wavy scaffolds grew in aggregates, deposited an abundant ECM rich in fibronectin and collagen II, and expressed higher amounts of collagen II, X and tenomodulin as compared to aligned scaffolds. In-vivo implantation in rabbits of triphasic scaffolds accounting for aligned-wavy-aligned zones showed a high cellular infiltration and the formation of an oriented ECM, as compared to traditional aligned scaffolds. [2]


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_2 | Pages 91 - 91
2 Jan 2024
Kamalitdinov T Fujino K Jiang X Madi R Marcelin J Kuntz A Dyment N
Full Access

Despite extensive research aimed at improving surgical outcomes of enthesis injuries, re-tears remain a common problem, as the repairs often lead to fibrovascular scar as opposed to a zonal enthesis. Zonal enthesis formation involves anchoring collagen fibers, synthesizing proteoglycan-rich fibrocartilage, and mineralizing this fibrocartilage [1]. During development, the hedgehog signaling pathway promotes the formation and maturation of fibrocartilage within the zonal tendon-to-bone enthesis [1-4]. However, whether this pathway has a similar role in adult zonal tendon-to-bone repair is not known. Therefore, we developed a murine anterior cruciate ligament (ACL) reconstruction model [5] to better understand the zonal tendon-to-bone repair process and perturb key developmental regulators to determine the extent to which they can promote successful repair in the adult. In doing so, we activated the hedgehog signaling pathway both genetically using transgenic mice and pharmacologically via agonist injections. We demonstrated that both treatments improved the formation of zonal attachments and tunnel integration strength [6]. These improved outcomes were due in part to hedgehog signaling's positive role in proliferation of the bone marrow stromal cell (bMSC) progenitor pool and subsequent fibrocartilage production of bMSC progeny cells that form the attachments. These results suggest that, similar to growth and development, hedgehog signaling promotes the production and maturation of fibrocartilage during tendon-to-bone integration in adults. Lastly, we developed localized drug delivery systems to further improve the treatment of these debilitating injuries in future translational studies. Acknowledgements: This work was supported by NIH R01AR076381, R21AR078429, R00AR067283, F31AR079840, T32AR007132, and P30AR069619, in addition to the McCabe Fund Pilot Award at the University of Pennsylvania


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