IBMS BoneKEy | Perspective

Effects of RANKL inhibition on inflammation and immunity

Sylvie Ferrari-Lacraz
Serge Ferrari

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DOI:10.1138/20090369

Abstract

Receptor activator of nuclear factor-κB ligand, RANKL, is a member of the TNF superfamily and its actions are not limited to bone, but also affect markedly the maturation and activation of the immune system (). Consequently, the development of denosumab – a fully human monoclonal antibody to RANKL – for use as a novel therapeutic agent in osteoporosis, rheumatoid arthritis (RA) and cancer, may give rise to some questions as to its immunological safety. However, recent reports claim that contrary to anti-TNFs, the bone- and cartilage-sparing effects of denosumab in patients with RA are not coupled with any apparent amelioration on the clinical score of joint inflammation (). Admittedly, this observation suggests that RANKL is not a major pro-inflammatory cytokine in this setting, and the lack of effect of RANKL inhibition on the immune system is at times taken as a point in fact, but is this the right conclusion?

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