Brossfield Aiden V, McMahon Donald J, Fernando Jason, Omeragic Beatriz, Majeed Rukshana, Agarwal Sanchita, Sroga Grazyna E, Wang Bowen, Vashishth Deepak, Rubin Mishaela R
Metabolic Bone Disease Unit, Vagelos College of Physicians & Surgeons, Columbia University Irving Medical Center, New York, NY 10032, USA.
Department of Biomedical Engineering, Shirley Ann Jackson, PhD Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA.
J Clin Endocrinol Metab. 2025 Mar 17;110(4):961-972. doi: 10.1210/clinem/dgae700.
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.
We hypothesized that PM treatment in older patients with T2D, by inhibiting AGEs, would increase bone formation.
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.
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.
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.
2型糖尿病（T2D）患者的骨转换降低且骨折风险增加。晚期糖基化终末产物（AGEs）会损害成骨细胞，并与糖尿病性骨折有关。吡哆胺（PM）是一种维生素B6代谢产物，可抑制AGEs的形成。
我们假设，在老年T2D患者中，PM通过抑制AGEs，会增加骨形成。
这是一项在学术中心进行的双盲随机对照试验。纳入老年T2D女性患者（n = 55）。给予口服PM 200mg，每日两次，持续1年。主要结局是骨形成标志物I型前胶原氨基端前肽（P1NP）的变化。其他结局包括骨吸收、骨密度（BMD）、糖化血红蛋白（HbA1c）和皮肤自发荧光（SAF）的变化，以及在骨活检亚组中，骨荧光AGEs（fAGEs）与SAF之间的相关性。
与安慰剂组相比，PM组的P1NP增加了23.0%（95%CI 9，37；组内P = 0.028），而安慰剂组增加了4.1%（-9，17；组内P = 0.576；组间P = 0.056）。股骨颈骨密度增加（PM组为2.6±5%，安慰剂组为-0.9±4%；组间P = 0.007）。骨吸收标志物和SAF没有变化。HbA1c降低（PM组为-0.38±0.7%，安慰剂组为0.05±1.7%；组间P = 0.04）。在PM组中，HbA1c的变化与P1NP变化百分比呈负相关（r = -0.50，P = 0.034）。皮质骨活检fAGEs与SAF相关（r = 0.86，P = 0.001）。两组间不良事件相似。
PM倾向于增加老年T2D女性患者的P1NP，同时增加骨密度并降低HbA1c。需要进一步研究以探讨PM作为一种针对疾病机制的方法来降低T2D患者骨折风险的潜力。
