A clinical study on the effects of teriparatide and denosumab on bone metabolism and gut microbiota in osteoporotic fracture patients.

UNLABELLED: This study compared teriparatide and denosumab in patients with osteoporotic fractures. Both treatments improved bone mineral density but showed different patterns of bone metabolism and gut microbiota changes. Variations in gut microbial profiles were associated with bone-related indicators, highlighting a potential link between gut microbiota and treatment-related skeletal responses.

OBJECTIVE

To investigate the effects of teriparatide and denosumab on bone mineral density (BMD), bone turnover markers, and gut microbiota in patients with osteoporotic fractures.

METHODS

This non-randomized, open-label, head-to-head comparative clinical study enrolled patients with osteoporotic fractures who received either subcutaneous teriparatide (20 μg daily) or subcutaneous denosumab (60 mg every six months). All participants received concomitant calcium and vitamin D supplementation. BMD and bone turnover markers were assessed at baseline and after a six-month treatment period. Fecal samples were collected for 16S rDNA sequencing to evaluate alterations in gut microbiota composition.

RESULTS

The study was completed by 108 participants (mean age, 64.8 ± 8.4 years), including 68 in the teriparatide group and 40 in the denosumab group. The statistical analysis revealed significant increases in lumbar spine and hip BMD in the teriparatide and denosumab groups after treatment compared to baseline. OC levels increased significantly more in the teriparatide group than in the denosumab group (P < 0.001), whereas β‑CTX levels decreased more markedly in the denosumab group compared with the teriparatide group (P < 0.001). Both groups showed shifts mainly involving SCFA‑producing gut microbiota. Teriparatide significantly enriched the abundance of Dubosiella and Butyrivibrio, which were positively correlated with L4, hip BMD, and L2 BMD, respectively. In contrast, the denosumab group exhibited an increased abundance of Lacticaseibacillus and a decreased abundance of Holdemanella. Specifically, the abundance of Lacticaseibacillus was negatively correlated with parathyroid hormone (PTH), while the abundance of Holdemanella was positively correlated with osteocalcin (OC), alkaline phosphatase (ALP), and β-CTX and negatively correlated with lumbar spine bone density.

CONCLUSION

Although teriparatide and denosumab increased BMD, they exerted opposite effects on bone turnover. These changes were accompanied by distinct shifts in gut microbiota related to SCFA metabolism, suggesting that the gut-bone axis may be involved in their mechanisms of action.