Biological effects of bisphosphonates in patients with rheumatoid arthritis

Loss of bone mineral density(BMD) has frequently been observed in patients with rheumatoid arthritis (RA) and main causes of osteoporosis were reported to be steroid osteoporosis, postmenoposal osteoporosis, and disuse bone atrophy associated with polyarticular impairment. It is becoming clear that the increase in bone resorption such as these osteoporosis and RA is underling the molecular mechanism; the facilitation of osteoclast differentiation and activation by the inflammatory cytokines TNFalpha and IL-1. Bisphosphonates, which are taken up by osteoclasts and macrophages to inhibit the activity of these cytokines, are expected to function as an inhibitor of inflammation induced by these cells. Bisphosphonates reduce also osteoclast numbers and activity by induction of osteoclast apoptosis, and could be a therapeutic goal for new anti-osteoclast drugs. As for the periarticular osteoporosis, bisphosphonate has also anti inflammatory effects and inhibition of bone destruction in RA.