OBJECTIVE: This study explored whether osteoblast metabolism in trabecular bone of failed total hip replacement (fTHR) in primary osteoarthritis (OA) plays a role in differential failure. METHODS: Osteoblast cell cultures were prepared from metaphyseal trabecular bone of normal individuals, OA patients, OA patients with fTHR with massive cavitary osteolysis (fTHR-O) and without massive cavitary osteolysis (fTHR-NO). Osteoblasts were characterized by measuring osteocalcin, cellular alkaline phosphatase (ALP), and urokinase plasminogen activator (uPA) activity. The cellular metabolic activity was also evaluated by measuring the production of interleukin (IL)-1beta, IL-6, and prostaglandin E2 (PGE2). RESULTS: ALP activity was increased in osteoblasts from patients with OA and fTHR-O compared to normal controls and fTHR-NO. Osteocalcin release was increased only in fTHR-O compared to all other groups. uPA activity was highest in the subgroup of "high metabolic OA" and in fTHR-O, while it was lowest in the subgroup of "low metabolic OA" and in fTHR-NO. IL-6 and PGE2 production was higher in the high metabolic OA and fTHR-O compared to fTHR-NO and low metabolic OA patients. CONCLUSION: Osteoblasts from fTHR-O and a subgroup of OA patients present similarly increased osteoblast markers compared to normal subjects, the low metabolic OA subgroup, and fTHR-NO. This information suggests the differential role of osteoblasts in osteolysis pathophysiology in primary THR surgery. The pertinence of the differential high and low metabolic activities of osteoblasts to the pathophysiology of OA remains to be fully established.