Aromatase Inhibitors—Induced Musculoskeletal Disorders: Current Knowledge on Clinical and Molecular Aspects

Tenti, Sara; Correale, Pierpaolo; Cheleschi, Sara; Fioravanti, Antonella; Pirtoli, Luigi

doi:10.3390/ijms21165625

Cited by 64 publications

(57 citation statements)

References 184 publications

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“…Previous research has reported that sustained mechanical load could activate Wnt/β-catenin signaling in the development of osteoarthritis 58 . And activation of Wnt/β-catenin signaling led to apoptosis of IVD cells and increase of ECM degradation enzymes, thereby accelerating matrix degradation and promoting IVDD progression 52 , 59 .…”

Section: Discussionmentioning

confidence: 99%

Aberrant spinal mechanical loading stress triggers intervertebral disc degeneration by inducing pyroptosis and nerve ingrowth

Bao²,

Yao

et al. 2021

Sci Rep

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Aberrant mechanical factor is one of the etiologies of the intervertebral disc (IVD) degeneration (IVDD). However, the exact molecular mechanism of spinal mechanical loading stress-induced IVDD has yet to be elucidated due to a lack of an ideal and stable IVDD animal model. The present study aimed to establish a stable IVDD mouse model and evaluated the effect of aberrant spinal mechanical loading on the pathogenesis of IVDD. Eight-week-old male mice were treated with lumbar spine instability (LSI) surgery to induce IVDD. The progression of IVDD was evaluated by μCT and Safranin O/Fast green staining analysis. The metabolism of extracellular matrix, ingrowth of sensory nerves, pyroptosis in IVDs tissues were determined by immunohistological or real-time PCR analysis. The apoptosis of IVD cells was tested by TUNEL assay. IVDD modeling was successfully produced by LSI surgery, with substantial reductions in IVD height, BS/TV, Tb.N. and lower IVD score. LSI administration led to the histologic change of disc degeneration, disruption of the matrix metabolism, promotion of apoptosis of IVD cells and invasion of sensory nerves into annulus fibrosus, as well as induction of pyroptosis. Moreover, LSI surgery activated Wnt signaling in IVD tissues. Mechanical instability caused by LSI surgery accelerates the disc matrix degradation, nerve invasion, pyroptosis, and eventually lead to IVDD, which provided an alternative mouse IVDD model.

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Section: Discussionmentioning

confidence: 99%

Aberrant spinal mechanical loading stress triggers intervertebral disc degeneration by inducing pyroptosis and nerve ingrowth

Bao²,

Yao

et al. 2021

Sci Rep

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“…However, they are not free of adverse effects ( 43 ). AI-associated arthralgia (AIA) is characterized by symmetrical joint pain, mostly affecting hands, wrists, and knees, which might have significant impact on patients’ QOL and compliance of treatment ( 44 ). On the individual level, breast cancer could induce anxiety and depression, as patients cannot help but worry about their future.…”

Section: Discussionmentioning

confidence: 99%

Physical Therapies for Psychosomatic Symptoms and Quality of Life Induced by Aromatase Inhibitors in Breast Cancer Patients: A Systematic Review and Meta-Analysis

Zhu

Chen

et al. 2021

Front. Oncol.

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ObjectiveTo evaluate the effects of Physical Therapies (PTs) on improvement in psychosomatic symptoms and quality of life (QOL) in breast cancer patients.Data SourcesSeven databases (MEDLINE, EMBASE, Cochrane CENTRAL, China National Knowledge Infrastructure, Wangfang, VIP, and China Biology Medicine disc databases) were systematically searched from the database inception through May 18, 2021.Study SelectionRandomized controlled trials (RCTs) which compared acupuncture or exercise with a sham control or usual care for the treatment of aromatase inhibitors (AIs)-related psychosomatic symptoms and QOL.Data Extraction and SynthesisData were screened and extracted independently using predesigned forms. The quality of RCTs was assessed with the Cochrane Handbook for Systematic Reviews of Interventions. The effect size was calculated via random-effects modeling. The quality of evidence was evaluated with the Grading of Recommendations Assessment, Development and Evaluation approach.Main Outcomes and MeasuresThe score of pain was measured with BPI scale and Western Ontario and the McMaster Universities Index (WOMAC) scale. Emotional state was measured with Pittsburgh Sleep Quality Index (PSQI), Hospital Anxiety and Depression Scale (HADS-A), and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue). The QOL score was measured by self-reported measurements, including the Functional Assessment of Cancer Therapy-General (FACT-G) scale and 36-Item Short Form Survey (SF-36) scale.ResultsEleven RCTs (with 830 patients) were included in the systematic review, and data from 10 RCTs (with 798 patients) were used in the meta-analysis. Results showed acupuncture significantly reduced worst pain scores (P < 0.00001, I2 = 83.5%) [SMD = −0.81, 95% CI (−1.51, −0.11)], but the effect of exercise therapies was not significant in overall change in worst pain scores (P =0.006, I2 = 72.3%) [SMD = −0.30, 95% CI (−0.76, 0.16)]. Both acupuncture and exercise resulted in little to no difference in overall change in HADS-A subscale (P = 0.026<0.05, I2 = 79.8%) [WMD = −0.21, 95% CI (−3.44, 3.03)], PSQI subscale (P = 0.488, I2 = 0%) [WMD = 0.98, 95% CI (−0.57, 2.53)], and FACIT-Fatigue subscale (P = 0.022<0.05, I2 = 81.0%) [WMD = 1.6, 95% CI (−5.75, 8.94)]. Exercise (compared with usual care) was associated with improving overall change in health-related QOL (subscales of SF-36 tool) (P = 0, I2 = 72.1%) [WMD = 7.97, 95% CI (5.68, 10.25)] and cancer-specific QOL (subscales of FACT-G tool) (P = 0.304, I2 = 16%) [WMD = 1.16, 95% CI (0.34, 1.97)].Conclusions and RelevanceThis systematic review and meta-analysis suggested that based on moderate-level evidence, acupuncture was associated with significant reductions in pain intensity, and exercise might improve QOL in breast cancer patients treated with AIs. However, in psychosomatic symptoms such as anxiety, sleep disturbance, and fatigue, acupuncture and exercise training did not result in significant improvements.

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“…It is utilized at a daily dose of 2.5–7.5 mg for five days, from the third day of the menstrual cycle [ 104 ]. Proponents believe that aromatase inhibitors are superior to CC, easy to use, and safe, but clinical consequences show a risk of osteoporosis, as well as adverse effects on the cardiovascular system and lipid levels [ 105 , 106 ]. Although some aromatase inhibitors may replace CC as first-line drug therapies, CC is still considered the drug of first choice for women with PCOS.…”

Section: Selective Estrogen Receptor Modulatorsmentioning

confidence: 99%

Estrogen Receptors in Polycystic Ovary Syndrome

Deng

Lian

et al. 2021

Cells

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Female infertility is mainly caused by ovulation disorders, which affect female reproduction and pregnancy worldwide, with polycystic ovary syndrome (PCOS) being the most prevalent of these. PCOS is a frequent endocrine disease that is associated with abnormal function of the female sex hormone estrogen and estrogen receptors (ERs). Estrogens mediate genomic effects through ERα and ERβ in target tissues. The G-protein-coupled estrogen receptor (GPER) has recently been described as mediating the non-genomic signaling of estrogen. Changes in estrogen receptor signaling pathways affect cellular activities, such as ovulation; cell cycle phase; and cell proliferation, migration, and invasion. Over the years, some selective estrogen receptor modulators (SERMs) have made substantial strides in clinical applications for subfertility with PCOS, such as tamoxifen and clomiphene, however the role of ER in PCOS still needs to be understood. This article focuses on the recent progress in PCOS caused by the abnormal expression of estrogen and ERs in the ovaries and uterus, and the clinical application of related targeted small-molecule drugs.

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Aromatase Inhibitors—Induced Musculoskeletal Disorders: Current Knowledge on Clinical and Molecular Aspects

Cited by 64 publications

References 184 publications

Aberrant spinal mechanical loading stress triggers intervertebral disc degeneration by inducing pyroptosis and nerve ingrowth

Aberrant spinal mechanical loading stress triggers intervertebral disc degeneration by inducing pyroptosis and nerve ingrowth

Physical Therapies for Psychosomatic Symptoms and Quality of Life Induced by Aromatase Inhibitors in Breast Cancer Patients: A Systematic Review and Meta-Analysis

Estrogen Receptors in Polycystic Ovary Syndrome

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