Journal Article

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

Agarwal, Sanchita, Majeed, Rukshana, Rubin, Mishaela R, Brossfield, Aiden V, Omeragic, Beatriz, Vashishth, Deepak, Sroga, Grazyna E, Fernando, Jason, Wang, Bowen, McMahon, Donald J

2025

Overview

Abstract Context Patients with type 2 diabetes (T2D) have reduced bone turnover and increased fractures. Advanced glycation end products (AGEs) impair osteoblasts and are implicated in diabetic fractures. Pyridoxamine (PM) is a vitamin B6 metabolite that inhibits formation of AGEs. Objective We hypothesized that PM treatment in older patients with T2D, by inhibiting AGEs, would increase bone formation. Methods This was a double-blind randomized controlled trial at an academic center. Older women with T2D were included (n = 55). Oral PM 200 mg twice daily for 1 year was given. 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 subgroup, the correlation between bone fluorescent AGEs (fAGEs) and SAF. Results P1NP increased 23.0% with PM (95% CI 9, 37; within group P = .028) vs 4.1% with placebo (−9, 17; within group P = .576; between groups P = .056). BMD increased at the femoral neck (PM 2.6 ± 5% vs placebo −0.9 ± 4%; between groups P = .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 = .04). Within the PM group, the HbA1c change correlated inversely with the % P1NP change (r = −0.50, P = .034). Cortical bone biopsy fAGEs correlated with SAF (r = 0.86, P = .001). Adverse events were similar between groups. Conclusion PM tended to increase P1NP in older women with T2D, 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.

• Publisher: Oxford University Press
• Subject: Advanced glycosylation end products / Aged / Biomarkers / Biopsy / Bone and Bones - drug effects / Bone and Bones - metabolism / Bone density / Bone Density - drug effects / Bone growth / Bone mineral density / Bone Remodeling - drug effects / Bone resorption / Bone turnover / Bones / Clinical trials / Cortical bone / Denosumab / Density / Diabetes / Diabetes mellitus (non-insulin dependent) / Diabetes Mellitus, Type 2 - complications / Diabetes Mellitus, Type 2 - drug therapy / Diabetes Mellitus, Type 2 - metabolism / Double-Blind Method / Female / Fractures / Glycated Hemoglobin - analysis / Glycation End Products, Advanced - antagonists & inhibitors / Glycation End Products, Advanced - metabolism / Glycosylated hemoglobin / Humans / Metabolites / Middle Aged / Middle aged women / Osteogenesis / Osteogenesis - drug effects / Patients / Peptide Fragments / Placebos / Procollagen - blood / Pyridoxamine - administration & dosage / Pyridoxamine - pharmacology / Pyridoxamine - therapeutic use / Skin / Type 2 diabetes / Vitamin B6