ABSTRACT Osteoarthritis (OA) is a highly heterogeneous disease, with aging as its strongest risk factor. However, much of the preclinical OA research disproportionately relies on post‐traumatic OA (PTOA) models in young animals. To address this gap, the Aging Section of the 2026 International Consensus Meeting (ICM) on Preclinical Models of OA convened experts and used the Delphi method to provide consensus guidance on studying age‐associated OA. Eighteen questions concerning pain, biomechanics, genetics, metabolism, sex/hormonal differences and translational modeling were evaluated and voted upon at the 2026 Orthopedic Research Society (ORS) annual meeting. The consensus concluded that although age‐associated OA and post‐traumatic OA (PTOA) share pathological features, they are characterized by distinct mechanistic profiles, particularly in their inflammatory responses, mitochondrial dysfunction, and tissue‐remodeling processes. Furthermore, delegates concluded that age‐associated OA is a manifestation of broader aging biology, influenced by the hallmarks of aging, systemic physiology and interacting joint tissues. When evaluating these complex interactions, the available data demonstrate that no single ideal animal model exists. Instead, researchers must utilize a fit‐for‐purpose model ecosystem that explicitly accounts for sex, endocrine aging, and genetic background. The consensus also recommends employing multimodal outcome measures spanning structural, behavioral, and molecular domains rather than relying solely on structural pathology. Ultimately, age‐associated models should serve as a complementary framework to PTOA models. Integrating this specific biological context is essential to improve translational relevance and identify biologically relevant mechanism‐based interventions for the aging patient populations most affected by the disorder.
ABSTRACT Volar lunate facet (VLF) fractures are prone to loss of reduction after volar plating. We used finite element analysis (FEA) and cadaveric testing to identify failure mechanisms and determine how screw configuration alters load transfer. A CT‐derived radius model with a 10 × 15 × 5‐mm VLF fragment was fixed with a 4‐hole hook plate using locking and nonlocking (NL) screws. A 500‐N radiolunate compressive load was applied, and von Mises stresses were quantified. Sensitivity analyses varied loading, bone density, fracture characteristics, and implant material. Ten distal radii underwent cyclic loading followed by load‐to‐failure testing; failure modes and locations were compared with FEA hotspots. FEA identified two stress concentrations: the distal plate contour/screw‐hole region and the ulnar hook insertion into the VLF fragment. In the baseline 1[NL]&3[NL] construct, peak construct and radius stresses were 697.2 and 154.6 MPa. The 1[NL]&2[NL] configuration produced the lowest stresses (54.5 and 27.3 MPa), whereas locking hole 3 reduced construct stress to 587.2 MPa. Cadaver failure load was 1239.2 ± 438.5 N (range: 630.0–1990.1 N); failures were loss of reduction/fracture dislocation (4/10) or plate failure (6/10), with failure locations corresponding to FEA hotspots. Off‐axis loading, reduced bone density, and fracture‐line translation increased construct stress and altered hotspot location. FEA‐predicted hook–fragment stress corresponded to loss of reduction, whereas distal plate stress corresponded to plate failure. Among modeled configurations, 1[NL]&2[NL] minimized construct and radius stress, although unbalanced cadaveric groups preclude claims of clinical superiority. These findings support fragment capture while minimizing distal plate stress.
The initial fixation of the acetabular cup is crucial for outcomes in total hip arthroplasty (THA); however, stability is evaluated subjectively. We developed a Laser Resonance Frequency Analysis (Laser-RFA) system using low-output laser-induced vibration to objectively assess fixation. This study demonstrates the relationship between fixation strength and vibrational characteristics and evaluates surgeons' tactile assessment. In laboratory experiments, acetabular cups were press-fit into polyurethane simulated bone and stimulated with frequency-swept laser irradiation (preliminary laboratory experiment: 1500-4500 Hz; modified-condition: 2250-2750 Hz). Peak frequencies measured by the Laser Doppler vibrometer were correlated with fixation strength. In the clinical study, peak frequencies from microphone-recorded vibrations were compared between cases with and without screw fixation based on intraoperative tactile assessment. In a supplemental experiment, surgeons were divided into skilled and non-skilled groups. Participants implanted an acetabular cup into simulated bone, and tactile fixation strength was quantified. Periodic waveforms were identified in the preliminary experiment, and six peaks (Waves A-F) were defined in the modified-condition laboratory experiment. Waves A and B showed negative correlations with fixation strength, whereas Waves C-F showed positive correlations. Clinically, peak frequencies were lower in cases requiring screw fixation than in those not requiring screw fixation (approximately 2900 vs. 3050 Hz; p < 0.003). The supplemental experiment showed significant differences in fixation strength across all tactile assessment levels in the skilled group, whereas no significant differences were observed in the non-skilled group. These findings indicate Laser-RFA objectively assesses acetabular cup fixation and reflects the tactile assessment of experienced surgeons.
Horses serve as a translational model for human osteoarthritis (OA) due to their comparable joint size, cartilage thickness, and incidence of naturally occurring disease. Overexpression of microRNA-181a-5p has been implicated in cartilage degradation in OA, and its inhibition using locked nucleic acid antisense oligonucleotides (LNA-miR-181a-5p ASOs) represents a potential therapeutic strategy. This study evaluated the safety of intraarticular (IA) LNA-miR-181a-5p ASO injection in clinically normal horse fetlock joints. Twelve horses were randomized to receive two IA injections, 28 days apart, of either low-dose [2000 & micro;g (n = 6)] or high-dose [4000 & micro;g (n = 6)] LNA-miR-181a-5p ASO. Over 56 days, variables assessed included physical examinations, joint assessments (effusion, circumference, temperature), lameness scores, and biofluid analyses. Physical and lameness evaluation variables remained similar to baseline and did not differ by dose (p > 0.05). Joint effusion was mildly increased in high-dose joints at Day 3 post-injection (p < 0.05), while circumference, temperature, and hematologic and biochemical variables remained similar to baseline, and did not differ by dose (p > 0.05). A transient, dose-independent increase (p < 0.05) in nucleated cell count at day 3 following each injection was observed, consistent with post-arthrocentesis inflammation. Synovial fluid IL-1 beta and PGE(2) concentrations did not differ across doses and timepoints (p > 0.05). Although TNF-alpha concentrations were greater in the high-dose group (p < 0.05), values were variable across horses, even prior to treatment. Overall, IA LNA-miR-181a-5p ASO was well tolerated in clinically normal horse fetlocks, with only transient inflammatory changes, supporting its evaluation as a potential OA therapy.
The F-actin cytoskeleton regulates chondrocyte morphology, cell-matrix interactions, and phenotype. Abnormal chondrocyte properties observed in non-degenerate human cartilage suggest early phenotypic de-differentiation that may contribute to weakening of the extracellular matrix. This study investigated the relationships between in situ chondrocyte volume, clustering, morphology, and F-actin organization, and examined whether the formation of cytoplasmic processes was an active cellular event. Fresh ex vivo human femoral head cartilage explants from 22 patients were graded individually as non-degenerate (G0) or mildly degenerate (G1). Explants were labeled with Cell Tracker and phalloidin to visualize chondrocytes and F-actin, respectively, and imaged using confocal laser scanning microscopy. G1 explants were additionally exposed to hypo-osmotic pressure (170 mOsm, 10 min) to assess changes to the morphology of the cytoplasmic processes. Large chondrocytes with spheroidal morphology demonstrated increased F-actin levels and redistribution in both G0 and G1 cartilage (p < 0.05). Clustered chondrocytes exhibited significantly increased F-actin content and altered distribution with degeneration (p <= 0.0004). Chondrocytes possessing cytoplasmic processes exhibited marked focal F-actin accumulation within the extensions (p < 0.0001). In G0 cartilage, F-actin localized predominantly at the base of processes, whereas in G1 cartilage, it extended throughout both the base and body of the process. Hypo-osmotic challenge significantly increased chondrocyte volume and process width (p < 0.01; p < 0.0001), but not process length, despite clear swelling of the cell body. These findings demonstrated that active cytoskeletal F-actin remodeling may accompany early chondrocyte morphological changes associated with human cartilage degeneration, as occurs in osteoarthritis.
