Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand.
Auckland District Health Board, Auckland, New Zealand.
Calcif Tissue Int. 2020 Apr;106(4):386-391. doi: 10.1007/s00223-019-00653-7. Epub 2020 Jan 2.
Studies in mice have suggested that osteocalcin plays an important role in glucose and fat metabolism. Since anti-resorptive drugs reduce circulating levels of osteocalcin they might be associated with increased fat mass and an increased risk of diabetes. Positive changes in body weight have been found in trials of alendronate and denosumab, but no significant effect in a previous trial of zoledronate. Whether those weight differences were in fat or lean mass is unknown. There were no effects of anti-resorptive treatments on fasting glucose concentrations or incidence of diabetes in those three studies. We have used our recent trial comparing zoledronate and placebo over 6 years in 2000 older osteopenic women to re-examine these questions. Both treatment groups lost body weight during the study (placebo 1.65 kg, zoledronate 1.05 kg), and this was significantly greater in the placebo group (P = 0.01). Both groups lost lean mass, and this loss was marginally (0.17 kg) but significantly (P = 0.02) greater in those receiving zoledronate. The placebo group had a mean loss of fat mass of 0.63 kg but there was no change in fat mass in the zoledronate group (between-groups comparison, P = 0.007). In the placebo group, there were 20 new diagnoses of diabetes, and in the zoledronate group, 19 (P = 0.87). Zoledronate prevented age-related loss of fat mass in these late postmenopausal women. The present study is the first to document a significant effect of zoledronate treatment on body weight, confirming results previously found with alendronate and denosumab. It also demonstrates that this is principally an effect to maintain fat mass rather than influencing lean mass, raising an important physiological question as to how anti-resorptive drugs have this effect on intermediary metabolism. It is possible that this anti-catabolic action contributes to the beneficial effects of anti-resorptive drugs on bone and longevity.
研究表明，骨钙素在葡萄糖和脂肪代谢中发挥重要作用。由于抗吸收药物会降低循环中的骨钙素水平，它们可能与脂肪量增加和糖尿病风险增加有关。阿伦膦酸盐和地舒单抗的试验中发现体重有积极变化，但唑来膦酸盐的先前试验中没有显著影响。这些体重差异是脂肪还是瘦肉量尚不清楚。在这三项研究中，抗吸收治疗对空腹血糖浓度或糖尿病的发生率均无影响。我们利用最近一项比较唑来膦酸盐和安慰剂治疗 2000 名骨质疏松妇女 6 年的试验来重新研究这些问题。两组在研究期间体重均减轻（安慰剂组 1.65 公斤，唑来膦酸盐组 1.05 公斤），且安慰剂组的体重减轻更为显著（P=0.01）。两组均损失瘦体重，且唑来膦酸盐组的损失略高（0.17 公斤），但有统计学意义（P=0.02）。安慰剂组的平均脂肪量减少 0.63 公斤，但唑来膦酸盐组的脂肪量没有变化（组间比较，P=0.007）。安慰剂组有 20 例新诊断为糖尿病，唑来膦酸盐组有 19 例（P=0.87）。唑来膦酸盐可防止这些绝经后期妇女的年龄相关性脂肪量丢失。本研究首次证明唑来膦酸盐治疗对体重有显著影响，证实了先前在阿伦膦酸盐和地舒单抗研究中发现的结果。它还表明，这主要是维持脂肪量的效果，而不是影响瘦体重，这就提出了一个重要的生理问题，即抗吸收药物如何对中间代谢产生这种影响。抗分解代谢作用可能有助于抗吸收药物对骨骼和长寿的有益作用。
