The clinical, pathological, and epidemiological relationships between fasting plasma glucose (FPG) concentrations and the sites of lesion in osteoarthritis (OA) were evaluated in 1026 patients. The mean FPG (99 +/- 22.2 mg/dL) was significantly higher in OA (p less than 0.01) than in the normal controls (88 +/- 19.9 mg/dL). In addition, the mean FPG (97.9 +/- 23 mg/dL) was significantly higher in female patients with OA (p less than 0.01) than in an osteoporotic sex-matched control group (92.8 +/- 24.5). FPG concentrations did not vary significantly according to the sites of the OA lesions. Fifty-six (5.5%) OA patients had long-term diabetes mellitus (FPG greater than 140 mg/dl). Few significant differences in the pathological and clinical findings were seen between normoglycemic and hyperglycemic OA patients, only the ESR (p less than 0.01) and pain at rest (p less than 0.02) being higher in the second group. These epidemiological data support the observation that hyperglycemia, which acts on matrix macromolecules, may be related to the development of bone degenerative disease.