The Effects of the AGE Inhibitor Pyridoxamine on Bone in Older Women with Type 2 Diabetes: a Randomized Clinical Trial

• Published in: The journal of clinical endocrinology and metabolism 2024-10
• Main Authors: Brossfield, Aiden V, McMahon, Donald J, Fernando, Jason, Omeragic, Beatriz, Majeed, Rukshana, Agarwal, Sanchita, Sroga, Grazyna E, Wang, Bowen, Vashishth, Deepak, Rubin, Mishaela R
• Format: Article
• Language: English
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/clinem/dgae700

Type 2 diabetes (T2D) patients have reduced bone turnover and increased fractures. Advanced glycation endproducts (AGEs) impair osteoblasts and are implicated in diabetic fractures. Pyridoxamine (PM) is a vitamin B6 metabolite which inhibits formation of AGEs. We hypothesized that PM treatment in older T2D patients, by inhibiting AGEs, would increase bone formation. Double-blind RCT. Academic center. Older T2D women (n=55). Oral PM 200 mg twice daily for one year. The primary outcome was the change in the bone formation marker P1NP. Other outcomes were changes in bone resorption, bone mineral density (BMD), HbA1c and skin autofluorescence (SAF), and in a bone biopsy sub-group, the correlation between bone fluorescent AGEs (fAGEs) and SAF. P1NP increased 23.0% with PM (95% CI: 9, 37; within-group p=0.028) vs. 4.1% with placebo (-9, 17; within-group p=0.576; between-groups p=0.056). BMD increased at the femoral neck (PM: 2.6±5% vs. placebo: -0.9±4%; between-groups p=0.007). Bone resorption markers and SAF did not change. HbA1c decreased (PM: -0.38 ± 0.7% vs. placebo: 0.05 ± 1.7%; between-groups p =0.04). Within the PM group, the HbA1c change correlated inversely with the % P1NP change (r =-0.50, p=0.034). Cortical bone biopsy fAGEs correlated with SAF (r=0.86, p=0.001). Adverse events were similar between groups. PM tended to increase P1NP in older T2D women, as well as increasing bone density and reducing HbA1c. Further studies are needed to investigate the potential of PM as a disease mechanism-directed approach to reduce fractures in T2D.