Osteoclastogenesis and osteoclast activation in dialysis-related amyloid osteopathy

Dialysis-related amyloid osteopathy (DRAO) is characterized by local osteoarticular lytic lesions, which sometimes cause a pathological fracture and reduce the quality of life in affected patients. In DRAO, active osteoclastic bone resorption is found at the bone surface facing the invaded synovial tissue and/or intervertebral disc, whereas reactive bone formation is absent. The eroded bone surface is covered with osteoclasts, suggesting the local promotion of osteoclastogenesis and osteoclast activation around DRAO. Inflammatory cells infiltrating the synovial tissue are likely to promote inflammatory osteolysis. Three possible pathways can be considered for the osteoclastogenesis and/or osteoclast activation in inflammatory osteolysis in DRAO: (1) indirect action of the inflammatory cytokines through the receptor activator of nuclear factor-kappaB ligand/osteoprotegerin ligand (RANKL/OPGL) expression in osteoblasts, (2) direct action of inflammatory cytokines, and (3) RANKL/OPGL expression in inflammatory cells. To apply antiosteoclastic agents as another therapy for DRAO, we have to clarify the roles of those pathways in local osteoclastogenesis and/or osteoclast activation.