The main well recognized action of bisphosphonates (BPs) is their antiresorptive capacity, making them first-line drugs in the treatment of osteoporosis and other metabolic bone diseases. In this review we have compiled other possible actions of BPs, particularly in the areas of immunomodulation, anti-inflammatory capacity and in the prevention of structural joint damage in inflammatory rheumatic diseases. The immunomodulatory capacity of BPs has been focused on the mechanisms involved in the acute-phase response associated with the administration of nitrogen containing BPs (N-BPs), with the stimulus of pro-inflammatory cytokines, through the mevalonate pathway, activation of T-cells and the decrease in the cytotoxic T-lymphocyte antigen-4 (CTLA-4). In relation to their anti-inflammatory capacity, special attention has been given to their effect on preventing structural damage in inflammatory joint diseases and on the differential immune response in bone lesions of the most common and representative inflammatory rheumatic diseases, i.e. rheumatoid arthritis and spondyloarthropathies. The present data indicate that more studies are needed to improve the knowledge on the effect of BPs on inflammatory-mediated diseases and particularly on the prevention and/or treatment of the structural damage in these disorders, since these agents could be a potential useful concomitant therapy.

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