RANKL inhibition for the management of patients with benign metabolic bone disorders

The receptor activator of NF-kappa B ligand (RANKL) is a member of the TNF receptor superfamily, essential for osteoclastogenesis. It binds to its receptor activator of NF-kappa B on the surface of osteoclast precursors and enhances their differentiation, survival and fusion, while it activates mature osteoclasts and inhibits their apoptosis. The effects of RANKL are counteracted by osteoprotegerin (OPG), a neutralizing decoy receptor. Derangement of the balance in RANKL/OPG action is implicated in the pathophysiology of metabolic bone diseases, including osteoporosis. Current therapies used to prevent or treat metabolic bone diseases are thought to act, at least in part, through modification of the RANKL/OPG dipole. The idea of using a molecule that could specifically bind and neutralize RANKL to decrease bone resorption and subsequent bone loss is appealing. Recombinant OPG was initially tested. Denosumab, a fully human monoclonal antibody against RANKL, is a promising antiresorptive agent under investigation. it rapidly decreases bone turnover markers resulting in a significant increase in bone mineral density and reduction in fracture risk. However, because receptor activator of NF-kappa B activation by RANKL is also essential for T-cell growth and dendritic-cell function, inhibition of its action could simultaneously affect the immune system, leading to susceptibility in infections or malignancies

Thyroid Autoimmunity in the Context of Type 2 Diabetes Mellitus: Implications for Vitamin D

Vitamin D deficiency has been associated with both type 2 diabetes mellitus (T2DM) and autoimmune disorders. The association of vitamin D with T2DM and thyroid autoimmunity (TAI) has not been investigated. Thus, we aimed to explore the putative association between T2DM and thyroid autoimmunity (TAI) focusing on the role of 25-hydroxy-vitamin D (25(OH)D). Study population included 264 T2DM patients and 234 controls. To explore the potential association between 25(OH)D and thyroid autoimmunity while controlling for potential confounders-namely, age, gender, body mass index, and presence of T2DM-multivariate logistic regression analyses were undertaken. Patients with T2DM were younger ( < 0.001) and had significantly lower 25(OH)D levels ( < 0.001) and higher anti-TPO titers ( = 0.005). Multivariable logistic regression analyses suggested that T2DM and 25(OH)D levels were significantly associated with the presence of thyroid autoimmunity. In an elderly population of diabetic patients and controls with a high prevalence of vitamin D deficiency/insufficiency, a patient with T2DM was found to be 2.5 times more likely to have thyroid autoimmunity compared to a nondiabetic individual and the higher the serum 25(OH)D levels were, the higher this chance was

Thyroid Autoimmunity in the Context of Type 2 Diabetes Mellitus: Implications for Vitamin D

Vitamin D deficiency has been associated with both type 2 diabetes mellitus (T2DM) and autoimmune disorders. The association of vitamin D with T2DM and thyroid autoimmunity (TAI) has not been investigated. Thus, we aimed to explore the putative association between T2DM and thyroid autoimmunity (TAI) focusing on the role of 25-hydroxy-vitamin D (25(OH)D). Study population included 264 T2DM patients and 234 controls. To explore the potential association between 25(OH)D and thyroid autoimmunity while controlling for potential confounders—namely, age, gender, body mass index, and presence of T2DM—multivariate logistic regression analyses were undertaken. Patients with T2DM were younger (P<0.001) and had significantly lower 25(OH)D levels (P<0.001) and higher anti-TPO titers (P=0.005). Multivariable logistic regression analyses suggested that T2DM and 25(OH)D levels were significantly associated with the presence of thyroid autoimmunity. In an elderly population of diabetic patients and controls with a high prevalence of vitamin D deficiency/insufficiency, a patient with T2DM was found to be 2.5 times more likely to have thyroid autoimmunity compared to a nondiabetic individual and the higher the serum 25(OH)D levels were, the higher this chance was