Osteoporosis in rheumatoid arthritis: role of the vitamin D/parathyroid hormone system

Abstract

RBRE-172; No. of Pages 8 r e v b r a s r e u m a t o l . 2 0 1 4;x x x(x x):xxx-xxx REVISTA BRASILEIRA DE REUMATOLOGIA w w w . r e u m a t o l o g i a . c o m . b r Available online xxx Keywords: Cholecalciferol PTH Osteoporosis Rheumatoid arthritis a b s t r a c t Osteoporosis is a well-established extra-articular feature of rheumatoid arthritis (RA). Systemic inflammation seems to play a crucial role in causing an alteration of multiple homeostatic systems implied in bone health, such as the RANK/RANKL/Osteoprotegerin and Wnt/␤ catenin pathways; several other causal factors have been called into question, including the chronic use of corticosteroids. Since vitamin D exerts important immune-regulatory roles, it has been claimed that derangement of the vitamin D/parathyroid hormone (PTH)system, a well-known determinant of bone health, may play a pathogenic role in autoimmunity; animal models and clinical data support this hypothesis. Furthermore, RA patients seem to be relatively refractory to vitamin D-induced PTH suppression. Therefore, the link between RA and osteoporosis might in part be due to alterations in the vitamin D/PTH system. A better understanding of the pathophysiology of this system may be crucial to prevent and cure osteoporosis in patients with inflammatory/autoimmune diseases. A major clinical correlate of the strict cooperation and interdependence between vitamin D and PTH is that correction of the vitamin D deficiency, at least in autoimmune diseases, should be targeted to PTH suppression. Osteoporose na artrite reumatoide: papel do sistema vitamina D/HPTPalavras chave: Colecalciferol HPT Osteoporose Artrite reumatoide r e s u m o A osteoporose é uma característica extra-articular bem estabelecida da artrite reumatoide (AR). A inflamação sistêmica parece ser essencial para causar uma alteração em múltiplos sistemas homeostáticos implicados na saúde óssea, como as vias RANK/RANKL/osteoprotegerina e Wnt/␤ catenina; vários outros fatores causais têm sido implicados, como o uso crônico de corticosteroides. Como a vitamina D exerce funç ões RBRE-172; No. of Pages 8 2 r e v b r a s r e u m a t o l . 2 0 1 4;x x x(x x):xxx-xxx imunorreguladoras importantes, tem-se afirmado que o desarranjo do sistema vitamina D/hormônio paratireóideo (HPT), um determinante bem conhecido da saúde óssea, pode desempenhar um papel patogênico na autoimunidade; estudos com animais e dados clíni-cos apoiam essa hipótese. Além disso, os pacientes com AR parecem ser relativamente refratários à supressão de HPT induzida pela vitamina D. Portanto, a ligação entre a AR e a osteoporose pode ser em parte causada por alteraç ões no sistema vitamina D/HPT. Uma melhor compreensão da fisiopatologia desse sistema pode ser crucial para prevenir e curar a osteoporose em pacientes com doenças inflamatórias/autoimunes. A maior evidência da correlação clínica de cooperação e interdependência entre a vitamina D e o HPT é que a correção da deficiência de vitamina D, pelo menos nas doenças autoimunes, deve ser orientada para a supressão do H...

Hormonal and Genetic Role Affecting the Bone Resorption in Patients with Osteoporosis

“…In addition to age and menopause factors, risk factors that also affect bone mass and density include early bone density (which is brought at birth) and the availability of calcium. Another factor that plays a role in bone remodeling regulation is vitamin D, where vitamin D supplementation is proven to increase bone density, and often occurs in menopausal women [9]. Other regulators are parathyroid hormones and various cytokines and enzymes that act as both regulators and koreseptor in differentiation as well Activity of bone cells.…”

“…The second receptor PTH2 (hPTH2-R) does not bind to PTHrP, present in the brain, placenta, and pancreas. PTH works directly on the bone, improves bone resorption and mobilizes calcium [9,11]. With the exception of increasing plasma calcium, PTH also increases the excretion of phosphate in the urinary tract so as to decrease plasma phosphate levels.…”

“…Calcitriol is synthesized in the liver and kidneys with vitamin D ingredients, from food and vitamin D3 from skin synthesis due to sun exposure. It has a VDR (Vitamin D Receptor) gene receptor which is a pathogenesis of osteoporosis, osteoarthritis, diabetes mellitus, breast and prostate cancer, and physiology in weight reduction [9]. Parathyroid hormone is needed to convert calsifediol to calsitriol because this hormone is the main stimulator of the activity of 1-α hydroxylase in the kidneys.…”

“…Conversely this tropical hormone secretion is also controlled in part by TRH (Thyrotropin releasing hormone) secreted by the hypothalamus. Some are also controlled by negative feedback mechanisms by the circulating free thyroxin hormone in the blood that inhibits the work of the anterior pituitary and hypothalamus [9,13]. Through this path, changes in the inner and external environment of the body will cause an adjustment to the secretion of thyroxine hormones in the form of T4 (tetraiodotironin) and T3 (triiodotironin).…”

“…Women lose 1-5% bone mass during the first year at the beginning of menopause, then bone mass disappears slowly. The condition of osteoporosis and bone loss in the oral cavity is an asymptomatic symptom, usually only known after the onset of bone fractures and tooth mobillity [8,9]. Physiologically, the risk of missing teeth becomes higher with advancing age, increasing the need for dental prostheses.…”