Osteoporosis in Skin Diseases

Abstract

Osteoporosis (OP) is defined as a generalized skeletal disease characterized by low bone mass and an alteration of the microarchitecture that lead to an increase in bone fragility and, therefore, an increased risk of fractures. It must be considered today as a true public health problem and the most widespread metabolic bone disease that affects more than 200 million people worldwide. Under physiological conditions, there is a balance between bone formation and bone resorption necessary for skeletal homeostasis. In pathological situations, this balance is altered in favor of osteoclast (OC)-mediated bone resorption. During chronic inflammation, the balance between bone formation and bone resorption may be considerably affected, contributing to a net prevalence of osteoclastogenesis. Skin diseases are the fourth cause of human disease in the world, affecting approximately one third of the world's population with a prevalence in elderly men. Inflammation and the various associated cytokine patterns are the basis of both osteoporosis and most skin pathologies. Moreover, dermatological patients also undergo local or systemic treatments with glucocorticoids and immunosuppressants that could increase the risk of osteoporosis. Therefore, particular attention should be paid to bone health in these patients. The purpose of the present review is to take stock of the knowledge in this still quite unexplored field, despite the frequency of such conditions in clinical practice.

Keywords: atopic dermatitis; bone; dermatology; eczema; osteoporosis; pemphigus; psoriasis; skeletal health; skin; skin diseases; urticaria; vitiligo.

Figure 1

The nuclear factor-κB receptor activator (NF-κB) RANK/RANKL/OPG pathway. The production of nuclear factor-κB receptor activator (NF-κB) ligand (RANKL) leads to a greater differentiation of macrophages into osteoclasts. Bone resorption is stimulated by active osteoclasts, RANKL, and parathyroid hormone (PTH), while it is inhibited by osteoprotegerin (OPG).

Figure 2

Physiological effects of vitamin D (VD) on the skin. Modulation of keratinocyte production, prevention or promotion of apoptosis (dose dependent), and promotion of the production of structural proteins of the stratum corneum by increasing the skin barrier.

Figure 3

Role of inflammatory cytokines involved in psoriasis on bone remodeling. The increase in interleukin (IL)-6, IL-17, IL-33, interferon-gamma (INF-γ), tumor necrosis factor (TNF)-α, and osteopontin (OPN) increases the secretion of RANKL, which promotes the differentiation of macrophages in pre-fusion osteoclasts, then in multinucleated osteoclasts, and finally in activated osteoclasts, increasing bone resorption.

Figure 4

Mechanisms underlying bone resorption in patients with chronic urticaria (CU). Increased cytokines (TNF-α, IL-1β, IL-6, C-reactive protein (CRP), leptin, adiponectin) in metabolic syndrome and mediators produced by mast cells (IL-6, PCR, D-dimer, fibrin, degranulation products) lead to the activation of RANKL, which promotes the differentiation of macrophages in pre-fusion osteoclasts, then in multinucleated osteoclasts, and finally in activated osteoclasts, increasing bone resorption.

Figure 5

Predisposing and protective factors of bone remodeling in atopic dermatitis (AD). Predisposing factors: malnutrition (low calcium diet, vitamin D, poor physical activity), smoking, topical steroids, oral steroids, alcohol, obesity, IL-17; protective factors: TH2 response with OCP inhibition and increased production of IL-4, IL-5, IL-10, IL-13.

Figure 6

Cytokine interaction between osteoporosis, vitiligo, melanoma, and pemphigus. The action of cytokines produced during vitiligo (IL-6, IL-12, IL-17), melanoma (IL-6, IL-1 beta, FokI F, Siglec-15), and pemphigus (IL-6, IL-17, IL-1, TNF) are involved in the process of bone resorption.