<p>Study design and analytical framework for disease-first multilayer integration of shared osteoarthritis-osteoporosis pathology.</p>

Bulk cohorts comprised OA synovial and cartilage datasets and OP monocyte, femoral-bone, and osteogenic-stromal-cell datasets; single-cell datasets were used for cellular-context analysis. (B) Disease-first workflow in which OA and OP were analyzed separately before construction of the shared pathological axis and protein-level prioritization; the single-cell layer additionally included external quality-control sensitivity analysis.

(C) Three cumulative evidence layers comprising direction-consistent genes, shared-pathway-supported genes, and genes contained in criteria-positive OA-OP coexpression-module pairs. The three layers contained 9,874, 5,481, and 810 genes, respectively. Pair-specific module correspondence was evaluated using permutation-derived empirical FDR.