Noggin levels in nonalcoholic fatty liver disease: the effect of vitamin E treatment

Aim: The evaluation of (a) noggin levels in patients with simple steatosis (SS) vs. nonalcoholic steatohepatitis (NASH) vs. controls, and (b) the effect of combined spironolactone plus vitamin E vs. vitamin E monotherapy on noggin levels in biopsy-proven patients with nonalcoholic fatty liver disease (NAFLD). Methods: In the case-control study, 15 patients with SS, 16 with NASH, and 24 controls were included. In the randomized controlled trial, NAFLD patients were assigned to vitamin E (400 IU/d) or spironolactone (25 mg/d) plus vitamin E for 52 weeks. Results: Noggin levels were lower in SS (5.8 ± 1.5 pmol/l) and NASH (8.7 ± 2.4 pmol/l) patients than in controls (13.7 ± 2.7 pmol/l; p for trend = 0.040), but were similar in SS and NASH patients. After adjustment for potential cofounders, log(noggin) remained different between groups. Log(noggin) levels similarly increased post-treatment in both groups: log(noggin) was not different between groups (p = 0.20), but increased within groups over time (p < 0.001), without a significant group × time interaction (p = 0.62). Log(noggin) significantly increased at month 2 post-treatment (p = 0.008 vs. baseline) and remained stable thereafter. Conclusions: Lower noggin levels were observed in NAFLD patients than in controls. Noggin levels increased similarly by either combined low-dose spironolactone plus vitamin E or vitamin E monotherapy. Trial registration: NCT01147523. © 2018, Hellenic Endocrine Society

Noggin levels in nonalcoholic fatty liver disease: the effect of vitamin E treatment.

AIM The evaluation of (a) noggin levels in patients with simple steatosis (SS) vs. nonalcoholic steatohepatitis (NASH) vs. controls, and (b) the effect of combined spironolactone plus vitamin E vs. vitamin E monotherapy on noggin levels in biopsy-proven patients with nonalcoholic fatty liver disease (NAFLD). METHODS In the case-control study, 15 patients with SS, 16 with NASH, and 24 controls were included. In the randomized controlled trial, NAFLD patients were assigned to vitamin E (400 IU/d) or spironolactone (25 mg/d) plus vitamin E for 52 weeks. RESULTS Noggin levels were lower in SS (5.8 ± 1.5 pmol/l) and NASH (8.7 ± 2.4 pmol/l) patients than in controls (13.7 ± 2.7 pmol/l; p for trend = 0.040), but were similar in SS and NASH patients. After adjustment for potential cofounders, log(noggin) remained different between groups. Log(noggin) levels similarly increased post-treatment in both groups: log(noggin) was not different between groups (p = 0.20), but increased within groups over time (p < 0.001), without a significant group × time interaction (p = 0.62). Log(noggin) significantly increased at month 2 post-treatment (p = 0.008 vs. baseline) and remained stable thereafter. CONCLUSIONS Lower noggin levels were observed in NAFLD patients than in controls. Noggin levels increased similarly by either combined low-dose spironolactone plus vitamin E or vitamin E monotherapy. TRIAL REGISTRATION NCT01147523

Denosumab effects on serum levels of the bone morphogenetic proteins antagonist noggin in patients with transfusion-dependent thalassemia and osteoporosis

Introduction: Noggin is an antagonist of bone morphogenetic proteins (BMPs) and has a strong effect on osteogenesis. Osteoporosis is a common complication of transfusion dependent beta-thalassemia (TDT) and denosumab has been recently emerged as a promising therapeutic option. This was a post hoc investigation of serum noggin levels among TDT patients with osteoporosis who participated in a randomized, placebo-control, phase 2b study. Methods: Patients received either 60 mg denosumab (n = 32) or placebo (n = 31) every 6 months for 12 months. Noggin was measured, for the first time in thalassemia patients, at baseline and at 12 months, using a recently developed high sensitivity fluorescent immunoassay. Results: Both groups showed a significant increase in noggin serum levels (denosumab p &lt; 0.001; placebo p &lt; 0.0001). Interestingly, the increase was higher in the placebo group. Furthermore, we observed a strong correlation between noggin and wrist bone mineral density (r = −0.641, p = 0.002) only in the denosumab group. Conclusion: In conclusion, higher noggin levels reflected more BMP inhibition, since our assay detects free bioactive noggin, which in turn impaired bone formation in placebo group. Therefore, denosumab possibly regulates noggin and favours bone turnover in TDT patients with osteoporosis through a novel mechanism of action. © 2019, © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor &amp; Francis Group