2026 ICM on Preclinical Models of Osteoarthritis

International Consensus Meeting on Preclinical Models of Osteoarthritis
Friday, March 27
2:00 to 6:00 PM EST

Results

Following the Spotlight Session on Preclinical Models of Osteoarthritis (OA) at the ORS 2025 Annual Meeting, which focused on several controversial topics in this field, the Journal of Orthopaedic Research (JOR) was approached by several ORS members expressing interest in an International Consensus Meeting (ICM) on five topics within preclinical OA: Aging, Post-Traumatic OA (PTOA), Pain, Obesity, and Microbiome.

These key opinion leaders are managing a year-long Delphi process for the 2026 ICM, which will finish with in-person and virtual voting on ~80 questions at the ORS 2026 Annual Meeting, International Consensus Meeting on Preclinical Models of Osteoarthritis, Friday, March 27 from 2:00 to 6:00 PM EST in Charlotte, NC. Only registered Delegates will be allowed to vote, and the voting results, with interpretations of the greatest research priorities within these topics, will be published in Consensus Articles in JOR.

Below is a schedule of the questions with the Liaison who will make a 2-minute presentation on the Recommendation with Rationale from a systematic review of the literature.

1. Are the mechanisms of aging-associated OA different from those of post-traumatic OA (PTOA)?
2. CANCELLED
3. What other aging-associated musculoskeletal diseases (e.g., osteoporosis, sarcopenia, neurodegenerative, etc.) contribute to age-associated OA in animals?
4. Do all the hallmarks of aging play a role in aging-associated osteoarthritis (OA) development?
5. Does aging change how joint tissues respond to joint injury and thus alter PTOA outcomes?
6. What are the major strain and sex differences in animal models of aging associated OA and how should the field manage these differences?
7. What are the minimum outcome measures required to make conclusions about OA from aging in pre-clinical models (e.g. histology, pain, activity, microbiome, ultrastructure of the joint tissues, subchondral bone changes, et al.).
8. Are Better Animal Models Needed Beyond C57BL/6 Mice to Study Aging-Associated Osteoarthritis?
9. CANCELLED
10. Most studies use null alleles to examine gene function. Should we focus on generating more relevant mouse models that use OA-associated coding or GWAS alleles, which could be generalized and used for drug discovery?
11. Should we recapitulate in our animal models the genetic-epigenetic interactions at play systemically during aging and OA?
12. Does aging alter communication between joint tissues (e.g., cartilage and subchondral bone, fat and cartilage, fat and bone, synovium and cartilage)? Are there interactions that need to be standardized?
13. Given the known natural aging process, should preclinical experiments be designed longitudinally to determine whether a specific order of joint tissues is associated with the onset of pathological changes?
14. Do animal (especially mice) studies of aging-associated OA translate well to human diseases?
15. Most studies use PTOA to test the efficacy of a DMOAD. Should this also be tested in an aging model?
16. What age is an appropriate age to study spontaneous age-related OA in mice?
17.  Is there a need for better standardization in aging-OA animal studies (e.g. age, housing, diet, and water purification technique -> important from a microbiome perspective)?
18. Is there a difference in how pain behavior testing should be conducted in mice with aging-related OA vs other types of OA models?
19. Do the Age-Related Changes in the ECM Promote Chondrocyte Senescence or Does Chondrocyte Senescence Promote Age-Related Changes in the ECM?
20. Are there genetic models of accelerated aging (e.g., Klotho mice) that present with aging-associated osteoarthritis (OA) at a young age?

1. Is there a universal definition of post-traumatic osteoarthritis (PTOA)? Consider both etiology and pathology of the condition.
2. Is there a clear understanding of how current major “PTOA” models induce disease? A) Joint destabilization, B) Mechanical loading, C) Osteochondral fragments
3. Do age and post-injury time-point influence the biological response to joint injury and progression to PTOA?
4. Do sex differences affect response to joint injury?
5. CANCELLED
6. Is there an accepted timeline for the appearance of PTOA that would most clearly relate to the clinical scenario?
7. Are Appropriate Biomarkers Available for Post-Traumatic Osteoarthritis in Animal Models?
8. Do current preclinical models have the appropriate features and outcome measures to appropriately evaluate therapeutic interventions for PTOA?
9. Are there diagnostic or therapeutic interventions that could potentially mitigate or reverse PTOA?

1. Should we define a standard minimum number/list of pain-dependent behavioral outcomes that constitute a robust/complete/reliable pre-clinical study (i.e., that test different pain types/mechanisms? (e.g., von Frey, PAM, weight-bearing, gait analysis, spontaneous behavior etc.)?
2. Can/should we define a minimum set of OA structural measures/outcomes (and their severity) to be used to define OA and thus OA-associated pain for each preclinical model?
3. Can/should we define a minimum time-course over which pain (and associated joint pathology) outcomes should be evaluated, and does this vary with the pre-clinical model?
4. Can/should we define an optimal set of species (rodents vs. large animal models) in which to model, study mechanisms, and test treatment of OA pain?
5. What is the role of studies in veterinary populations with clinical osteoarthritis, such as pet dogs or horses, or equine athletes?
6. How can AI improve the reliability of operant, reflex, or observational nociceptive assays?
7. CANCELLED
8. Can we identify pain mediated by nociceptive mechanisms, neuropathic, and nociplastic mechanisms in experimental models of OA?
9. Should we measure pain vs function vs disability in preclinical OA models – to parallel human “OA illness”?
10. Can/should we include measures on the affective aspects of OA-associated pain e.g. depression, anxiety etc?
11. Which mechanistic endpoints should be incorporated in preclinical experiments to complement painrelated behavior assessment (e.g., should we do electrophysiology, DRG expression/proteomics etc) to define pain phenotypes/endotypes?
12. What are the critical confounders to be considered in preclinical rodent models?
13. Can/should we develop guidelines to standardize the classification of studies testing for prophylactic versus therapeutic treatment effects?
14. Can/should we define a minimum level/size for each pain-dependent behavioral outcome that is relevant/clinically meaningful? This would be both the size of change from baseline to be considered bona fide “OA-pain” and change with any treatment to be considered a meaningful therapeutic effect (similar to clinically meaningful effect size in clinical trials).
15. Can/should we define a standard treatment or set of standard positive control treatments for use across studies to enable standardization and comparison (and arguably sub-typing of pain) e.g. i.a. corticosteroids, gabapentin, anti-NGF?
16. Are there systemic biomarkers of pain that could be used (in parallel with or as surrogates for pain behaviors) in pre-clinical models to define pain phenotypes/chronicity and/or therapeutic subtype?
17. Are there any animal-free in vitro/in silico approaches in development that can replace animal models for studying mechanisms of OA pain?

1. Can the gut microbiome play a role in causing degenerative spine disease in animal models?
2. Can biological manipulation of gut microbiome, such as administration of prebiotics or probiotics have a role in alleviating the pain of osteoarthritis in preclinical models?
3. Do therapeutic modulations of the gut microbiome mitigate osteoarthritis from animal models to clinical efficacy?
4. Can the gut microbiome play a role in causing osteoarthritis that can be studied in animal models?
5. Does the gut microbiome play a role in modulating innate or adaptive immunity of the host that could interact with osteoarthritis?