Possible association of psoriasis and reduced bone mineral density due to increased TNF-alpha and IL-6 concentrations

Abstract

Psoriasis is a chronic erythematosquamous disease affecting about 2-3% of the population. It is generally considered to be a T cell-mediated disorder. Psoriasis is characterized by Th1-type cytokine pattern with the predominant secretion of IL-2, IL-6, IFN-gamma and TNF-alpha. Such cytokine pattern is sufficient in inducing keratinocyte hyperproliferation, a hallmark of psoriasis. It seems that development of psoriatic lesions is mediated by TNF-alpha and proliferation of local T cells is dependent on local TNF-alpha production. IL-6 enhances activation, proliferation and chemotaxis of T cells into psoriatic lesions. It is also a direct keratinocyte mitogen that could directly stimulate keratinocyte proliferation. Data of possible association between psoriasis and reduced bone mineral density (BMD) are limited and therefore, not fully conclusive. The major limitation of two studies reported so far was small sample size. Based on increased concentrations of TNF-alpha and IL-6 in psoriasis we hypothesized that these patients are more prone to osteoporosis than healthy subjects. TNF-alpha enhances bone resorption via stimulating osteoclast development and activity as well as bone formation. On the other hand, IL-6 is also a potent stimulator of bone resorption. Moreover, increased production of TNF-alpha and IL-6 has been found in postmenopausal women with osteoporosis. Several lines of evidence support our hypothesis; higher value of IL-6 was recorded in children with idiopathic osteoporosis than in healthy controls; TNF-alpha knock-out mice do not lose bone after ovariectomy; polymorphism of TNFRSF1B gene which encodes 75 Kd TNF receptor is associated with BMD; treatment with anti-TNF-alpha antibody exert beneficial effect on bone metabolism in patients with rheumatoid arthritis and finally, raloxifene inhibit osteoclast activity by reducing TNF-alpha and IL-6 synthesis. However, our hypothesis raised number of questions. Are increased serum concentrations of TNF-alpha and IL-6 mirrored by increased concentrations of these cytokines on the local level? Furthermore, could other cytokines relevant in the pathogenesis of the psoriasis, first of all IFN-gamma, modulate the risk of osteoporosis? Thus, a large prospective, case-control study with the data on BMD, biochemical parameters of bone turnover and fractures have to be done to test our hypothesis.