Osteoporosis and inflammation / Osteoporose e inflamação

Several inflammatory diseases such as rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, celiac disease, cystic fibrosis and chronic obstructive pulmonary disease have been associated to bone resorption. The link between osteoclast, macrophage colony stimulating factor and pro-inflammatory cytokines, especially tumor necrosis factor-α and interleukin-1 explain the association between inflammation and osteoporosis. These diseases are related to osteoporosis and high fracture risk independent of other risk factors common to inflammatory diseases such as reduced physical activity, poor nutritional status, hypovitaminosis D, decrease in calcium intake and glucocorticoid treatment. Erythrocyte sedimentation rate and C-reactive protein should always be performed, but the indication about when to perform the densitometry test should be analyzed for each disease. Bisphosphonates are nowadays the best choice of therapy but new medications such as denosumab, IL-1 receptor antagonist, and TNF-α antibody have risen as new potential treatments for osteoporosis secondary to inflammation.

Diversas doenças inflamatórias têm sido associadas à reabsorção óssea, como a artrite reumatoide, o lúpus eritematoso sistêmico, a doença inflamatória intestinal, a doença celíaca, a fibrose cística e a doença pulmonar obstrutiva crônica. A ligação entre osteoclastos, fator estimulador de colônia de macrófagos e citocinas pró-inflamatórias, principalmente o fator de necrose tumoral-α e interleucina-1, explica a associação entre a inflamação e a osteoporose. Essas doenças estão relacionadas com osteoporose e aumento do risco de fratura, independentemente de outros fatores de risco comuns às doenças inflamatórias, tais como redução da atividade física, estado nutricional, hipovitaminose D, diminuição da ingestão de cálcio e uso de glicocorticoides. A velocidade de hemossedimentação e proteína C-reativa devem ser sempre realizadas, mas a indicação do exame de densitometria óssea deve ser analisada em cada doença. Os bisfosfonatos são atualmente a melhor opção de terapia, mas novos medicamentos, tais como denosumabe, antagonista do receptor de IL-1 e anticorpos anti-TNF-α, surgem como novos potenciais tratamentos para a osteoporose secundária à inflamação.

RANK, RANKL and osteoprotegerin in arthritic bone loss

Rheumatoid arthritis is characterized by the presence of inflammatory synovitis and destruction of joint cartilage and bone. Tissue proteinases released by synovia, chondrocytes and pannus can cause cartilage destruction and cytokine-activated osteoclasts have been implicated in bone erosions. Rheumatoid arthritis synovial tissues produce a variety of cytokines and growth factors that induce monocyte differentiation to osteoclasts and their proliferation, activation and longer survival in tissues. More recently, a major role in bone erosion has been attributed to the receptor activator of nuclear factor kappa B ligand (RANKL) released by activated lymphocytes and osteoblasts. In fact, osteoclasts are markedly activated after RANKL binding to the cognate RANK expressed on the surface of these cells. RANKL expression can be upregulated by bone-resorbing factors such as glucocorticoids, vitamin D3, interleukin 1 (IL-1), IL-6, IL-11, IL-17, tumor necrosis factor-alpha, prostaglandin E subscrito 2, or parathyroid hormone-related peptide. Supporting this idea, inhibition of RANKL by osteoprotegerin, a natural soluble RANKL receptor, prevents bone loss in experimental models. Tumor growth factor-ß released from bone during active bone resorption has been suggested as one feedback mechanism for upregulating osteoprotegerin and estrogen can increase its production on osteoblasts. Modulation of these systems provides the opportunity to inhibit bone loss and deformity in chronic arthritis.