Prevention of glucocorticoid-induced impairment of bone metabolism-a randomized, placebo-controlled, single centre proof-of-concept clinical trial.

Abstract

Oral glucocorticoid (GC) therapy rapidly and deleteriously affects bone metabolism and blood glucose regulation. The gut microbiota regulates bone metabolism and a prior study found that Limosilactobacillus reuteri ATCC PTA6475 (L. reuteri) reduced bone loss over 12 mo in older women. Mice treated either with broad-spectrum antibiotics or with L. reuteri did not experience GC-induced trabecular bone loss. This proof-of-concept, randomized, double-blind, placebo-controlled trial aimed to investigate if daily supplementation with L. reuteri, compared with placebo, could mitigate or prevent the negative effects of oral GC on bone turnover and blood glucose regulation in healthy young adults. Twenty-one men and 29 women, aged 18-45, were randomized to either placebo or L. reuteri (1 × 10¹⁰ CFU/d) treatment for 2 wk, followed by open-label oral prednisolone 25 mg daily for 7 d. Primary outcomes were changes in blood bone status indices (osteocalcin, C-terminal telopeptide cross-links of collagen type-I (CTX), and type-I procollagen intact N-terminal propeptide [PINP]) from baseline to 7 d after starting oral GC. Secondary endpoints included changes in blood glucose levels using continuous glucose monitoring during the same period (ClinicalTrials.gov NCT04767711). Blood samples were collected from participants in the morning after overnight fasting. Forty-six participants completed the 30-d study. The L. reuteri and placebo groups were well balanced in terms of baseline characteristics (age, BMI, sex, dietary intake, and physical activity). No significant differences were found between L. reuteri vs placebo for percent changes in CTX (-0.3 [95%CI -19.2-18.7], p = .98) or PINP (4.2 [-6.3-14.8], p = .43), or in osteocalcin levels (14.2 [-7.8-36.3], p = .21), although the group-to-group difference in osteocalcin was larger. There was no effect of treatment on mean blood glucose (-0.1 [-0.3-0.1] mmol/L, p = .28). In conclusion, we failed to detect a significant effect of L. reuteri supplementation on GC-related adverse effects on bone status indices in this proof-of-concept RCT. Larger studies are needed to identify any potential smaller effects.