The Orienting Study

Calcium pyrophosphate crystal deposition (CPPD) will be assessed using the OMERACT Ultrasound Scoring System for CPPD at patient level and at joint level. Each anatomical site will be graded on a semi-quantitative scale from 0 to 3. According to the clinical scenario and the clinician decision, patients will undergo an US examination of the affected joints. Case by case the following joints will be evaluated: shoulder, elbow, wrist, hand, hip, knee, ankle, Achilles tendon, foot. The total score will be calculated as the sum of scores across all evaluated sites and normalized by the number of sites assessed per patient. The measure will be assessed longitudinally to evaluate changes in crystal deposition over time.

Assessment of the extent of monosodium urate (MSU) crystal deposition Calcium pyrophosphate crystal deposition (CPPD) will be assessed using the OMERACT Ultrasound Scoring System for Gout Lesions (double contour sign, tophi, aggregates). Each lesion will be graded on a semi-quantitative scale from 0 to 3. A total score will be calculated by summing scores across all evaluated joints. According to the clinical scenario and the clinician decision, patients will undergo an US examination of the affected joints. Case by case the following joints will be evaluated: shoulder, elbow, wrist, hand, hip, knee, ankle, Achilles tendon, foot. The total score will be calculated as the sum of scores across all evaluated sites and normalized by the number of sites assessed per patient. The measure will be assessed longitudinally to evaluate changes in crystal deposition over time.

Bone erosions will be assessed using the OMERACT Ultrasound Scoring System for Bone Erosions. Each site will be graded from 0 to 3 and summed across all evaluated joints to obtain a total erosion score. The measure will be assessed longitudinally to evaluate changes over time.

Osteophytes will be assessed using the OMERACT Ultrasound Scoring System for Osteophytes. Each site will be graded from 0 to 3 and summed across all evaluated joints to obtain a total osteophyte score. The measure will be assessed longitudinally to evaluate changes over time.

Change From Baseline in Erythrocyte Sedimentation Rate (ESR mm/h) between patients with CPPD and gout and disease-controls with OA

Change From Baseline in C-Reactive Protein (CRP mg/L) between CPPD and Gout patients and controls with OA

Synovitis will be evaluated thanks to Global OMERACT-EULAR Synovitis Score (GLOESS). Ultrasound evaluation will be performed on clinically relevant joints and anatomical structures as determined by the treating physician.

Tenosynovitis will be assessed using the OMERACT ultrasound scoring system on a semi-quantitative scale. Ultrasound evaluation will be performed on clinically relevant joints and anatomical structures as determined by the treating physician.

Joint effusion will be assessed using ultrasound on a semi-quantitative scale from 0 to 3. The joints to be evaluated will be selected according to the clinician's judgement

The number of tender joints will be assessed using the 68-joint count method.

The number of swollen joints will be assessed using the 66-joint count method.

Disease activity will be assessed by the physician using a visual analog scale (0-100)

Scale (0-100)

Scale (0-100)

Scale (0-100)

Score (0-3) for every item of the questionnaire, then the sum is calculated

Cardiovascular risk will be estimated using SCORE2 and SCORE2-OP algorithms, depending on patient's age. Both scores express a percentage (%) of the 10-year risk.

Occurrence of cardiovascular events recorded during follow-up (Number of events / % of patients)

Phenotypes of calcium pyrophosphate deposition (CPPD) disease and gout will be classified according to established classification criteria (ACR/EULAR recommendations and G-CAN consensus respectively).

Serum soluble urokinase plasminogen activator receptor (suPAR) levels will be measured using an ELISA-based assay on blood and/or synovial fluid, whenever the patients undergo arthrocentesis for other reasons

Measurment of intima-media thickness (CMIT) at ultrasound of carothid arteries performed as part of routine care will be collected to assess increased atherosclerotic risk. The European Society of Cardiology (ESC) often highlights CMIT> 0.9 as a critical threshold to determine an increased risk

On radiographs and CT, osteoarthritis severity will be evaluated based on osteophytes, joint space narrowing, and subchondral bone changes, using a semi-quantitative grading scale (e.g., Kellgren-Lawrence grade 0-4 for radiographs). On MRI, joint damage will be assessed including cartilage integrity and other structural abnormalities using appropriate semi-quantitative scoring systems (WORMS, MOAKS)

Biological samples (bone, cartilage, synovial membrane, ligaments/tendons, synovial fluid) collected during clinically indicated arthroplasty procedures will be analyzed using histology, immunohistochemistry, and Raman spectroscopy to assess tissue morphology, inflammatory features, and crystal deposition.

The presence of coronary stenosis at Coronary Computed Tomography Angiography (CCTA) will be recorded. An obstructive stenosis occupies more than 50% of the lumen.

Bone mineral density (BMD) will be measured using dual-energy X-ray absorptiometry at the lumbar spine and proximal femur. Results will be expressed in g/cm², T-scores, and Z-scores. Bone status will be classified as normal, osteopenia, or osteoporosis according to World Health Organization criteria.

CPP and MSU crystal deposition in articular or periarticular structures at other imaging modalities (X-rays, CT scans, MRI) will be qualitatively assessed and documented as presence/absence.