Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA.
Department of Statistics and The Biostatistics Center, George Washington University, Washington, D.C., USA.
Osteoporos Int. 2021 Nov;32(11):2279-2287. doi: 10.1007/s00198-021-05989-1. Epub 2021 Jun 4.
In the Diabetes Prevention Program Outcome Study (DPPOS), a cohort at high risk of diabetes, randomization to intensive lifestyle intervention or metformin, both associated with weight loss, did not have long-term negative effects on BMD compared with the placebo group. Potential positive effects of metformin on bone warrant further investigation.
Randomization to lifestyle intervention (ILS) or metformin in the Diabetes Prevention Program (DPP) resulted in weight loss and reduced progression to diabetes. Weight loss is associated with reduced bone mineral density (BMD), but the long-term effects of these interventions on BMD are unknown. In the DPP Outcome Study (DPPOS), we determined if randomization to ILS or metformin, compared with placebo, was associated with differences in BMD approximately 16 years later.
Of 3234 DPP participants, 2779 continued in DPPOS and were offered ILS in group format. Those randomized to metformin were offered unmasked metformin. At DPPOS year 12, 1367 participants had dual-energy X-ray absorptiometry scans. BMD in metformin and ILS groups was compared to placebo using sex-specific linear regression models, adjusted for age, race/ethnicity, and weight and weight-bearing activity at DPP baseline.
At DPPOS year 12, mean age was 66.5 (±9.5) years. Femoral neck BMD was similar in the ILS and placebo groups in men (difference = -0.021 g/cm, 95%CI (-0.063, 0.021)) and in women (+0.014 g/cm, 95%CI (-0.014, 0.042)). Femoral neck BMD was higher in the metformin compared to placebo group although not statistically different in men (+0.017 g/cm, 95% CI (-0.023, 0.058)) and in women (+0.019 g/cm, 95% CI (-0.009, 0.047)). Prevalence of osteoporosis was low and similar across treatment groups in men (0.9%; p=0.745) and women (2.4%; p=0.466).
In a cohort at high risk of diabetes, lifestyle intervention or metformin did not appear to have long-term negative effects on BMD. Potential positive effects of metformin on bone warrant further research.
在糖尿病预防计划（DPP）的一项高糖尿病风险队列中，与安慰剂组相比，随机分配到强化生活方式干预或二甲双胍组（均与体重减轻相关），并未对 BMD 产生长期负面影响。二甲双胍对骨骼的潜在积极影响需要进一步研究。
DPP 中的生活方式干预（ILS）或二甲双胍随机分组导致体重减轻，并减少了糖尿病的进展。体重减轻与骨密度（BMD）降低有关，但这些干预措施对 BMD 的长期影响尚不清楚。在 DPP 结果研究（DPPOS）中，我们确定与安慰剂相比，ILS 或二甲双胍的随机分组是否与大约 16 年后的 BMD 差异有关。
在 3234 名 DPP 参与者中，2779 名继续参加 DPPOS，并以小组形式提供 ILS。随机分配到二甲双胍的参与者提供了未掩蔽的二甲双胍。在 DPPOS 第 12 年，有 1367 名参与者进行了双能 X 线吸收法扫描。使用性别特异性线性回归模型比较了二甲双胍和 ILS 组与安慰剂组的 BMD，模型调整了 DPP 基线时的年龄、种族/民族以及体重和体重承受活动。
在 DPPOS 第 12 年，平均年龄为 66.5（±9.5）岁。男性中，ILS 组和安慰剂组的股骨颈 BMD 相似（差异=-0.021 g/cm，95%CI（-0.063，0.021）），女性中差异为+0.014 g/cm（95%CI（-0.014，0.042））。与安慰剂组相比，尽管在男性中差异无统计学意义（+0.017 g/cm，95%CI（-0.023，0.058））和女性中差异无统计学意义（+0.019 g/cm，95%CI（-0.009，0.047）），但接受二甲双胍治疗的患者股骨颈 BMD 更高。男性（0.9%；p=0.745）和女性（2.4%；p=0.466）的骨质疏松症患病率较低，且在各治疗组中相似。
在高糖尿病风险队列中，生活方式干预或二甲双胍似乎对 BMD 没有长期负面影响。二甲双胍对骨骼的潜在积极影响需要进一步研究。
