Fracture risks and their mechanisms in atopic dermatitis, focusing on receptor activator of nuclear factor kappa-B ligand.

ABSTRACT

Recent multiple studies have shown that the long-term consequences of atopic dermatitis (AD) include an increased risk of osteoporosis and fracture, especially an increase in hip, pelvic, spinal and wrist fractures. AD is very common worldwide, and some kinds of fractures, such as hip fractures, are associated with increased mortality, which has a substantial socioeconomic impact; however, the precise mechanisms for this remain unclear. Receptor activator of nuclear factor kappa-Β (RANK) ligand (RANKL) and osteoprotegerin (OPG) are members of the tumour necrosis factor ligand and receptor family, members of which also are known as bone biomarkers. Alterations in the RANKL/RANK/OPG system and the balance among these factors (represented by the RANKL/OPG ratio) are central to the pathogenesis of bone loss from osteoporosis, and it is postulated that there is a potential association between the serum levels of RANKL and OPG, and bone density or fracture. Recently, our research group demonstrated that the serum RANKL/OPG ratio positively correlated with AD severity and suggests fracture risk in older women with AD. This review summarizes and discusses the risk and mechanisms of osteoporotic fracture in AD. RANKL may be involved in the pathogenesis of AD, regarding not only bone abnormality but also inflammation. Although further investigation will be needed to verify the hypotheses, recent findings may provide new insights into the pathogenesis of AD and therapeutic targets.