Disuse osteoporosis of the greater tuberosity is a consequence of rotator cuff tear. This is a significant problem as the tendon is implanted into a trough within the greater tuberosity during repair. Failure of the repair is a common complication (up to 50%). We hypothesized that failure in re-implantation is due to deficient bone cell response to mechanical stimulation in the tuberosity. In order to establish whether these cells are capable of responding appropriately to mechanical stimuli, the response of bone cells derived from the tuberosity was compared with that of cells derived from the acromion. This was measured in terms of strain related increases in alkaline phosphatase (ALP) activity, nitric oxide (NO) and prostaglandin (PG) production (which are recognised markers of osteoblast differentiation and their response to mechanical strain). Primary osteoblasts were cultured from samples of acromion and greater tuberosity taken during routine rotator cuff repair (n=5 pairs). The derived cells were placed under cyclic strain at a physiological magnitude for 10 min at 1Hz using well established controls. Samples of media were analysed for changes in NO and PG production and the cells were reacted for ALP. Cells were stimulated with dexamethasone, ascorbic acid and beta-glycerophosphate (established mediators of osteoblast differentiation) then reacted for ALP. Preliminary results suggest that cells derived from the acromion exhibit significant increases in cellular NO release and in ALP activity, whereas cells derived from the humeral greater tuberosity fail to exhibit any such increases. In marked contrast cells derived from both sites exhibit increases in ALP activity in response to dexamethasone, ascorbic acid and beta-glycerophosphate treatment. The results suggest that whilst cells derived from the tuberosity after rotator cuff tear respond appropriately to chemical and hormonal stimuli, they are compromised in their ability to respond to mechanical stimulation. It is tempting to speculate that such relationships are also evident in vivo and that they underpin reimplantation failures.