Relation of <scp>Intra‐Articular</scp> Mineralization to Knee Pain in Knee Osteoarthritis: A Longitudinal Analysis in the <scp>MOST</scp> Study

Liew, Jean W; Jarraya, Mohamed; Guermazi, Ali; Lynch, J.A.; Wang, Na; Rabasa, G.; Jafarzadeh, S. Reza; Nevitt, Michael C.; Torner, James C.; Lewis, Cora E.; Felson, David T.; Neogi, Tuhina

doi:10.1002/art.42649

Cited by 4 publications

References 32 publications

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Intra‐Articular Mineralization on Computerized Tomography of the Knee and Risk of Cartilage Damage: The Multicenter Osteoarthritis Study

Liew,

Jarraya,

Guermazi

et al. 2024

Arthritis & Rheumatology

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OBJECTIVESIntra‐articular (IA) mineralization may contribute to OA structural progression. We studied the association of IA mineralization on knee CT with cartilage damage worsening on knee MRI, with a focus on location‐ and tissue‐specific effects.METHODSParticipants from the Multicenter Osteoarthritis study with knee CTs and MRIs were included. Presence of IA mineralization on CT was defined as a Boston University Calcium Knee Score (BUCKS) >0 anywhere in the knee. Cartilage worsening on MRI was defined as any increase in MRI OA Knee Score (MOAKS) including incident damage. We evaluated the association of whole‐knee, compartment‐specific (i.e., medial or lateral), and subregion‐specific (i.e., location‐matched) IA mineralization at baseline with cartilage worsening at 2‐year follow‐up in the corresponding locations using binomial regression with generalized estimating equations, adjusting for age, sex, and body mass index (BMI).RESULTSWe included 1673 participants (mean age 60 years, 56% female, mean BMI 29 kg/m2). 9.0% had any IA mineralization in the knee and 47.4% had any cartilage worsening on follow‐up. Mineralization of any tissue in the knee, regardless of location, was not associated with MRI cartilage worsening. However, cartilage mineralization was associated with 1.39 (95% CI 1.04, 1.88) times higher risk of cartilage worsening in the same compartment with similar results in subregion‐specific analysis.CONCLUSIONSCT‐detected IA mineralization in the cartilage was associated with higher risk of MRI cartilage worsening in the same compartment and subregion over two years. These findings suggest potential localized, tissue‐specific effects of IA mineralization on cartilage pathology in knee OA.

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Intra‐Articular Mineralization on Computerized Tomography of the Knee and Risk of Cartilage Damage: The Multicenter Osteoarthritis Study

Liew,

Jarraya,

Guermazi

et al. 2024

Arthritis & Rheumatology

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Calcium pyrophosphate deposition disease

Pascart,

Filippou,

Lioté

et al. 2024

The Lancet Rheumatology

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Impact of long-term rapamycin treatment on age-related osteoarthritis in common marmoset

Minton,

Ailiani,

Focht

et al. 2024

Preprint

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Objective: Pharmacologic inhibition of the mechanistic target of rapamycin (mTOR) can attenuate experimental osteoarthritis (OA) in young, male preclinical models. However, the potential of mTOR inhibition as a therapeutic mechanism for OA remains unknown. The goal of this study was to determine if mTOR-inhibition by oral rapamycin can modify OA pathology in the common marmoset, a translational model of age-associated OA. Methods: microCT and histopathologic assessments of the knee were performed on formalin-fixed hindlimbs obtained from common marmosets treated with oral rapamycin (n=24; 1mg/kg/day) or parallel control group (n=41). Rapamycin started at 9.2 ±3.0 years old and lasted until death (2.1±1.5 years). In a subset of marmosets, contralateral hind limbs were collected to determine mTOR signaling in several joint tissues. Results: Rapamycin decreased P-RPS6 Ser235/36 and increased P-Akt2 Ser473 in cartilage, meniscus, and infrapatellar fat pad, suggesting inhibition of mTORC1 but not mTORC2 signaling. Rapamycin-treated marmosets had lower lateral synovium score versus control but there was no difference in the age-related increase in microCT or cartilage OA scores. Subchondral bone thickness and thickness variability were not different with age but were lower in rapamycin-treated geriatric marmosets, which was largely driven by females. Rapamycin also tended to worsen age-related meniscus calcification in female marmosets. Conclusion: Oral rapamycin attenuated mTORC1 signaling and may have caused feedback activation of mTORC2 signaling in joint tissues. Despite modifying site-specific aspects of synovitis, rapamycin did not modify the age-associated increase in OA in geriatric marmosets. Conversely, rapamycin may have had deleterious effects on meniscus calcification and lateral tibia subchondral bone, primarily in geriatric female marmosets.

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Relation of Intra‐Articular Mineralization to Knee Pain in Knee Osteoarthritis: A Longitudinal Analysis in the MOST Study

Cited by 4 publications

References 32 publications

Intra‐Articular Mineralization on Computerized Tomography of the Knee and Risk of Cartilage Damage: The Multicenter Osteoarthritis Study

Intra‐Articular Mineralization on Computerized Tomography of the Knee and Risk of Cartilage Damage: The Multicenter Osteoarthritis Study

Calcium pyrophosphate deposition disease

Impact of long-term rapamycin treatment on age-related osteoarthritis in common marmoset

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