Little is known regarding the association between ultrasonographic (US) findings and biomarkers of bone and cartilage in individuals with knee osteoarthritis (OA). We investigated (1) US findings in early-stage knee OA and (2) the association between US findings and bone/cartilage biomarkers. A population cohort aged 35-55 years (n = 106) with early-stage knee OA was investigated. US examination was performed according to European League against Rheumatism (EULAR) guidelines using a 7.5-MHz probe. Biomarkers of bone resorption (CTx-I) and formation (PINP), cartilage resorption (U-CTx-II) and synthesis (S-PIIANP), and general bone and cartilage biomarkers (OC, COMP) were assessed. The most prevalent US findings were tendon calcification, synovial thickening, and suprapatellar effusion. In women, the presence of tendon calcification and Baker's cysts could predict 36% of the variability in U-CTx-II levels. The presence of osteophytes and tendon calcification predicted up to 38% of the variability of PIIANP concentration. Defects in subchondral bone, meniscal changes, and effusion predicted up to 29% of the variability in COMP levels. Tendon calcification was related to cartilage synthesis (based on PIIANP levels) in men and to cartilage degradation (based on U-CTx-II concentrations) in women. US signs of synovitis were reflected metabolically by markers of joint tissue metabolism. Tendon calcification, synovial thickening, and effusion were common US findings in early-stage knee OA. US-detectable findings were substantially responsible for the variability in bone and cartilage biomarkers, associations reflective of the active metabolism of soft tissues in early-stage OA.