Bone homeostasis is maintained by a balance between bone resorption by osteoclasts and bone formation by osteoblasts. Osteoclast maturation requires stimulation by RANKL on osteoblasts and various stimuli. Pro-inflammatory cytokines such as IL-1 and TNF-alpha cause an imbalance in bone metabolism by favouring bone resorption via the induction of RANKL on osteoblasts and induction of osteoclast maturation. These inflammatory signals originate from the immune system, the largest source of cell-derived regulatory signals and such immunological signals to the bone induce osteoclast maturation, resulting in secondary osteoporosis. Actually, such phenomena mainly occur at the interface between proliferating synovium and bone tissue in rheumatoid arthritis (RA). Thus, therapeutic strategies for these conditions, an anti-TNF-alpha antibody, effective for treating RA disease activity, also reduce secondary osteoporosis and joint destruction.