Endocrine Abstracts

Background: Glucocorticoids are crucial for treating various medical conditions due to their beneficial immunosuppressive effects. However, glucocorticoids also carry a high risk for osteoporosis. Notably, within just a few months of glucocorticoid therapy, bone density can be significantly reduced, and up to 5% of patients undergoing such treatment may experience fractures. There is promising evidence from preclinical studies and observations in patients with type 2 diabetes that metformin may prevent glucocorticoid-induced osteoporosis. We aim to investigate whether metformin prevents glucocorticoid-induced osteoporosis as assessed by biochemical markers of bone turnover in healthy subjects.

Methods: In a randomized, placebo-controlled, cross-over trial, we compared metformin to placebo during high-dose glucocorticoid treatment in 18 lean, healthy males. All participants received prednisone 30 mg/d for two 7-day periods separated by a 28-day washout period. During one period, participants additionally had metformin; during the other, they received a placebo. In an exploratory analysis, we assessed changes in bone turnover markers before and after glucocorticoid treatment in both study phases.

Results: 18 male subjects (mean age 27, standard deviation [SD] ±5.2 years, BMI 22.9±1.8 kg/m²) were enrolled in the study. During glucocorticoid treatment, serum C-terminal telopeptide (CTX) increased with placebo but remained stable with metformin (placebo: 0.2±0.2 ng/ml; metformin 0.06±0.2 ng/ml, P=0.03). Serum procollagen I Intact N-terminal (PINP) decreased with both treatments (placebo: -20.6±11.8 ng/ml; metformin -22.3±16.7 ng/ml, P=0.7). Serum osteocalcin decreased with both treatments (placebo -10.8±6.9 mg/l; metformin -12.1±9.4 mg/l, P=0.3).

Conclusion: Our study demonstrated that metformin has a protective effect during GC-therapy with diminished bone resorption, while no effect on bone formation can be observed. These findings indicate that metformin may have a promising role in mitigating some of the detrimental effects of glucocorticoids on bone health.