Grey Andrew, Bolland Mark, Gamble Greg, Wattie Diana, Horne Anne, Davidson James, Reid Ian R
Department of Medicine, University of Auckland, and LabPlus, Auckland City Hospital, New Zealand.
J Clin Endocrinol Metab. 2007 Apr;92(4):1305-10. doi: 10.1210/jc.2006-2646. Epub 2007 Jan 30.
Thiazolidinediones, which are peroxisome proliferator-activated receptor-gamma agonists, are widely prescribed to patients with disorders characterized by insulin resistance. Preclinical studies suggest that peroxisome proliferator-activated receptor-gamma signaling negatively regulates bone formation and bone density. Human data on the skeletal effects of thiazolidinediones are currently available only from observational studies.
The objective of the study was to determine whether rosiglitazone, a thiazolidinedione, inhibits bone formation.
The study was a 14-wk randomized, double-blind, placebo-controlled trial.
The study was conducted in the general community.
Fifty healthy, postmenopausal women participated in the study.
Intervention was rosiglitazone 8 mg/d.
The primary end point was biochemical markers of bone formation, and secondary end points were a bone resorption marker and bone mineral density.
The osteoblast markers procollagen type I N-terminal propeptide and osteocalcin declined by 13% (P<0.005 vs. placebo) and 10% (P=0.04 vs. placebo), respectively, in the rosiglitazone group. These changes were evident by 4 wk and persisted for the duration of the study. There was no change in the serum beta-C-terminal telopeptide of type I collagen, a marker of bone resorption (P=0.9 vs. placebo). Total hip bone density fell in the rosiglitazone group (mean change from baseline rosiglitazone -1.9%, placebo -0.2%; between-group difference 1.7%, 95% confidence interval 0.6-2.7, P<0.01); lumbar spine bone density fell significantly from baseline values in the rosiglitazone group (P=0.02 vs. baseline) but was not significantly different between groups (mean change from baseline rosiglitazone -1.2%, placebo -0.2%; between-group difference 1.0%, 95% confidence interval -0.2-2.3, P=0.13).
Short-term therapy with rosiglitazone exerts detrimental skeletal effects by inhibiting bone formation. Skeletal end points should be included in future long-term studies of thiazolidinedione use.
噻唑烷二酮类药物是过氧化物酶体增殖物激活受体γ激动剂，被广泛用于治疗以胰岛素抵抗为特征的疾病患者。临床前研究表明，过氧化物酶体增殖物激活受体γ信号通路对骨形成和骨密度起负调节作用。目前关于噻唑烷二酮类药物骨骼效应的人体数据仅来自观察性研究。
本研究旨在确定噻唑烷二酮类药物罗格列酮是否会抑制骨形成。
本研究为一项为期14周的随机、双盲、安慰剂对照试验。
研究在普通社区进行。
50名健康的绝经后女性参与了本研究。
干预药物为罗格列酮，剂量为8毫克/天。
主要终点是骨形成的生化标志物，次要终点是骨吸收标志物和骨密度。
罗格列酮组中，成骨细胞标志物I型前胶原N端前肽和骨钙素分别下降了13%（与安慰剂相比，P<0.005）和10%（与安慰剂相比，P=0.04）。这些变化在4周时就很明显，并在研究期间持续存在。骨吸收标志物I型胶原血清β- C末端肽没有变化（与安慰剂相比，P=0.9）。罗格列酮组全髋骨密度下降（罗格列酮组相对于基线的平均变化为-1.9%，安慰剂组为-0.2%；组间差异为1.7%，95%置信区间为0.6 - 2.7，P<0.01）；罗格列酮组腰椎骨密度相对于基线值显著下降（与基线相比，P=0.02），但组间差异不显著（罗格列酮组相对于基线的平均变化为-1.2%，安慰剂组为-0.2%；组间差异为1.0%，95%置信区间为-0.2 - 2.3，P=0.13）。
罗格列酮短期治疗通过抑制骨形成对骨骼产生有害影响。噻唑烷二酮类药物使用的未来长期研究应纳入骨骼终点指标。
