Serum FGF-21 levels are associated with worsened radial trabecular bone microarchitecture and decreased radial bone strength in women with anorexia nervosa.

BACKGROUND: Anorexia nervosa (AN) is a psychiatric disorder characterized by self-induced starvation and low body weight. Women with AN have impaired bone formation, low bone mass and an increased risk of fracture. FGF-21 is a hormone secreted by the liver in starvation and FGF-21 transgenic mice have significant bone loss due to an uncoupling of bone resorption and bone formation. We hypothesized that FGF-21 may contribute to the low bone mass state of AN. SUBJECTS AND METHODS: We studied 46 women: 20 with AN (median age [interquartile range]: 27.5 [25, 30.75] years) and 26 normal-weight controls (NWC) of similar age (25 [24, 28.5] years). We investigated associations between serum FGF-21 and 1) aBMD measured by dual energy X-ray absorptiometry, 2) parameters of bone microarchitecture in the distal radius and tibia measured by high-resolution peripheral quantitative CT and 3) bone strength, estimated by microfinite element analysis. RESULTS: FGF-21 levels were similar in AN and NWC (AN: 33.1 [18.1, 117.0] pg/ml vs. NWC: 57.4 [23.8, 107.1] pg/ml; p = 0.54). There was a significant inverse association between log FGF-21 and trabecular number in the radius in both AN (R = -0.57, p \u3c 0.01) and NWC (R=-0.53, p \u3c 0.01) and a significant positive association between log FGF-21 and trabecular separation in the radius in AN (R = 0.50, p \u3c 0.03) and NWC (R = 0.52, p \u3c 0.01). Estimates of radial bone strength were inversely associated with log FGF-21 in AN (R = -0.50, p \u3c 0.03 for both stiffness and failure load). There were no associations between FGF-21 and aBMD, cortical parameters or tibial parameters in the AN or NWC groups. CONCLUSIONS: FGF-21 may be an important determinant of trabecular skeletal homeostasis in AN

The Upregulation of Molecules Related to Tumor Immune Escape in Human Pituitary Adenomas

Human pituitary adenomas are one of the most common intracranial neoplasms. Although most of these tumors are benign and can be treated medically or by transsphenoidal surgery, a subset of these tumors are fast-growing, aggressive, recur, and remain a therapeutic dilemma. Because antibodies against immune checkpoint receptors PD-1 and CLTA-4 are now routinely used for cancer treatment, we quantified the expression of mRNA coding for PD-1, CLTA-4, and their ligands, PD-L1, PD-L2, CD80, and CD86 in human pituitary adenomas and normal pituitary glands, with the ultimate goal of exploiting immune checkpoint therapy in aggressive pituitary adenomas. Aggressive pituitary adenomas demonstrated an increased expression of PD-L2, CD80, and CD86 in compared to that of normal human pituitary glands. Furthermore, aggressive pituitary tumors demonstrated significantly higher levels of CD80 and CD86 compared to non-aggressive tumors. Our results establish a rationale for studying a potential role for immune checkpoint inhibition therapy in the treatment of pituitary adenomas