Department of Obstetrics & Gynecology and Division of Gynecological Oncology, University Hospitals Leuven, Katholieke Universiteit Leuven, Herestraat 49, 3000 Leuven, Belgium.
Steroids. 2011 Jul;76(8):781-5. doi: 10.1016/j.steroids.2011.02.034. Epub 2011 Mar 4.
The third generation aromatase inhibitors (AIs) have become an established component of postmenopausal estrogen receptor positive breast cancer therapy. Unfortunately, up to half of AI-users experience the AI-induced musculoskeletal syndrome (AIMSS) (arthralgia, carpal tunnel syndrome, start pains, stiffness, etc.), which can severely impact quality of life and treatment compliance. We have previously demonstrated that loss of hand grip strength is part of AIMSS and involves tenosynovial changes and fluid retention in joints.
Our presentation during this AI-symposium focuses on available literature regarding AIMSS with new data from a prospective study generating a hypothesis for its pathogenesis. Profound estrogen deprivation as a consequence of AI-use is thought to be the underlying reason but the exact pathway remains unknown. A potential hypothesis is that the growth hormone/insulin like growth factor-I (GH/IGF-I) pathway may be involved. This possibility is based on the non-linear association between body mass index (BMI) and loss of hand grip strength that we observed. It appears that in lean and overweight women, hand grip strength decreases most following intake of an AI. This observation suggests an underlying biological process which probably evolves through the GH/IGF-I pathway, controlled by sex steroids.
Estrogen deprivation leads to incapacitating AIMSS and hampers treatment compliance. In our search for the missing link between 'lowering postmenopausal estrogens' and 'arthralgia' we here report on AI-induced changes in grip strength by BMI which we believe are hypothesis generating for an effect of AIs on the GH/IGF-I axis. This needs to be explored prospectively.
第三代芳香酶抑制剂（AIs）已成为绝经后雌激素受体阳性乳腺癌治疗的标准组成部分。不幸的是，多达一半的 AI 使用者会出现 AI 诱导的肌肉骨骼综合征（AIMSS）（关节痛、腕管综合征、起始痛、僵硬等），这会严重影响生活质量和治疗依从性。我们之前已经证明，手部握力丧失是 AIMSS 的一部分，涉及到滑液囊和关节液的变化。
在本次 AI 研讨会上，我们将重点介绍有关 AIMSS 的现有文献，并结合一项前瞻性研究的新数据提出其发病机制的假说。AI 使用导致的雌激素严重缺乏被认为是其潜在原因，但确切的途径尚不清楚。一种潜在的假说认为，生长激素/胰岛素样生长因子-I（GH/IGF-I）途径可能与之相关。这一可能性基于我们观察到的身体质量指数（BMI）与手部握力丧失之间的非线性关联。似乎在瘦人和超重女性中，在 AI 摄入后，手部握力下降最为明显。这一观察表明存在一种潜在的生物学过程，可能通过 GH/IGF-I 途径，受性激素控制。
雌激素缺乏导致致残性 AIMSS，并阻碍治疗依从性。在我们寻找“降低绝经后雌激素”和“关节痛”之间缺失的联系的过程中，我们报告了 AI 对 BMI 引起的握力变化的影响，我们认为这为 AI 对 GH/IGF-I 轴的影响提供了假说生成的依据。这需要前瞻性地探索。
