Pyridoxamine Promising in Enhancing Bone Health and Reducing HbA1c in Older Women with Type 2 Diabetes: Study
USA: A recent study has found that in older postmenopausal women with type 2 diabetes (T2D), pyridoxamine treatment may help prevent fractures and protect bone tissue by targeting advanced glycation end products, while also reducing levels of A1c, an early glycation product. The findings were published online in The Journal of Clinical Endocrinology & Metabolism on October 8, 2024.
Patients with type 2 diabetes experience reduced bone turnover and an increased risk of fractures. Advanced glycation end products (AGEs) impair osteoblast function and are linked to diabetic fractures. Pyridoxamine (PM), a metabolite of vitamin B6, inhibits AGE formation. Given this, Mishaela R Rubin, Metabolic Bone Disease Unit, Vagelos College of Physicians & Surgeons, Columbia University Irving Medical Center, New York, NY, USA, and colleagues hypothesized that PM treatment in older patients with T2D could enhance bone formation by inhibiting AGEs.
For this purpose, the researchers conducted a double-blind randomized controlled trial at an academic center, involving 55 older women with type 2 diabetes. Participants received 200 mg of oral pyridoxamine twice daily for one year.
The primary outcome was the change in the bone formation marker P1NP. Secondary outcomes included changes in bone resorption, bone mineral density (BMD), HbA1c, and skin autofluorescence (SAF). In a subgroup undergoing bone biopsy, the researchers also examined the correlation between bone fluorescent AGEs (fAGEs) and SAF. The safety of pyridoxamine was assessed by monitoring neurologic symptoms and adverse events, as high doses of the parent vitamin B6 have been associated with neurotoxicity.
Key Findings:
- P1NP increased by 23.0% with PM compared to 4.1% with placebo.
- Bone mineral density increased at the femoral neck (PM 2.6 ± 5% versus placebo −0.9 ± 4%; between groups).
- Bone resorption markers and skin autofluorescence did not show significant changes.
- HbA1c decreased with PM (−0.38 ± 0.7% versus placebo 0.05 ± 1.7%; between groups).
- Within the PM group, the change in HbA1c correlated inversely with the % change in P1NP (r = −0.50).
- In the cortical bone biopsy subgroup, fluorescent AGEs correlated with SAF (r = 0.86).
- Adverse events were similar between the PM and placebo groups.
Pyridoxamine showed a trend toward increasing P1NP, improving bone density, and reducing HbA1c in older women with T2D. More research is needed to explore its potential as a treatment to reduce fractures in T2D by targeting the disease's underlying mechanisms.
Reference:
Brossfield, A. V., McMahon, D. J., Fernando, J., Omeragic, B., Majeed, R., Agarwal, S., Sroga, G. E., Wang, B., Vashishth, D., & Rubin, M. R. The Effects of the AGE Inhibitor Pyridoxamine on Bone in Older Women With Type 2 Diabetes: A Randomized Clinical Trial. The Journal of Clinical Endocrinology & Metabolism. https://doi.org/10.1210/clinem/dgae700
