Columbia University Vagelos College of Physicians & Surgeons, New York, NY, USA.
Department of Medicine, Columbia University Vagelos College of Physicians & Surgeons, NY, New York, USA.
Osteoporos Int. 2022 Mar;33(3):659-672. doi: 10.1007/s00198-021-06196-8. Epub 2021 Oct 19.
We examined serum IGF-1 in premenopausal IOP, finding relationships that were opposite to those expected: higher IGF-1 was associated with lower bone formation and higher body fat, and lower BMD response to teriparatide. These paradoxical relationships between serum IGF-1, bone, and fat may contribute to the mechanism of idiopathic osteoporosis in premenopausal women.
Premenopausal women with idiopathic osteoporosis (IOP) have marked deficits in bone microarchitecture but variable bone remodeling. We previously reported that those with low tissue-level bone formation rate (BFR) are less responsive to teriparatide and have higher serum IGF-1, a hormone anabolic for osteoblasts and other tissues. The IGF-1 data were unexpected because IGF-1 is low in other forms of low turnover osteoporosis-leading us to hypothesize that IGF-1 relationships are paradoxical in IOP. This study aimed to determine whether IOP women with low BFR have higher IGF-1 and paradoxical IGF-1 relationships in skeletal and non-skeletal tissues, and whether IGF-1 and the related measures predict teriparatide response.
This research is an ancillary study to a 24 month clinical trial of teriparatide for IOP. Baseline assessments were related to trial outcomes: BMD, bone remodeling.
Premenopausal women with IOP(n = 34); bone remodeling status was defined by baseline cancellous BFR/BS on bone biopsy.
Serum IGF-1 parameters, compartmental adiposity (DXA, CT, MRI), serum hormones, and cardiovascular-risk-markers related to fat distribution.
As seen in other populations, lower BFR was associated with higher body fat and poorer teriparatide response. However, in contrast to observations in other populations, low BFR, higher body fat, and poorer teriparatide response were all related to higher IGF-1: IGF-1 Z-score was inversely related to BFR at all bone surfaces (r = - 0.39 to - 0.46; p < 0.05), directly related to central fat (p = 0.05) and leptin (p = 0.03). IGF-1 inversely related to 24 month hip BMD %change (r = - 0.46; p = 0.01).
Paradoxical IGF-1 relationships suggest that abnormal or atypical regulation of bone and fat may contribute to osteoporosis mechanisms in premenopausal IOP.
我们研究了绝经前 IOP 患者的血清 IGF-1，发现了与预期相反的关系：IGF-1 水平较高与较低的骨形成和较高的体脂相关，与特立帕肽的骨密度反应较低相关。这些血清 IGF-1、骨和脂肪之间的矛盾关系可能有助于解释绝经前妇女特发性骨质疏松症的发病机制。
绝经前特发性骨质疏松症（IOP）患者的骨微结构明显不足，但骨重塑情况可变。我们之前报道称，组织水平骨形成率（BFR）较低的患者对特立帕肽的反应较差，且血清 IGF-1 水平较高，IGF-1 是成骨细胞和其他组织的合成代谢激素。IGF-1 数据出乎意料，因为其他低转换骨质疏松症中 IGF-1 水平较低，这使我们假设 IGF-1 关系在 IOP 中是矛盾的。本研究旨在确定 IOP 患者中低 BFR 是否与骨骼和非骨骼组织中更高的 IGF-1 和矛盾的 IGF-1 关系相关，以及 IGF-1 和相关指标是否可预测特立帕肽的反应。
这是一项关于特立帕肽治疗 IOP 的 24 个月临床试验的辅助研究。基线评估与试验结果相关：骨密度、骨重塑。
绝经前特发性骨质疏松症患者（n=34）；骨重塑状态通过骨活检确定的松质骨 BFR/BS 来定义。
血清 IGF-1 相关参数、隔室脂肪（DXA、CT、MRI）、血清激素和与脂肪分布相关的心血管风险标志物。
与其他人群一样，较低的 BFR 与较高的体脂和较差的特立帕肽反应相关。然而，与其他人群的观察结果相反，低 BFR、较高体脂和较差的特立帕肽反应均与较高的 IGF-1 相关：IGF-1 Z 评分与所有骨表面的 BFR 呈负相关（r=-0.39 至-0.46；p<0.05），与中央脂肪（p=0.05）和瘦素（p=0.03）呈正相关。IGF-1 与 24 个月时髋部骨密度百分比变化呈负相关（r=-0.46；p=0.01）。
矛盾的 IGF-1 关系表明，骨和脂肪的异常或非典型调节可能有助于绝经前 IOP 中骨质疏松症的发病机制。
