IVDD is the main cause of low back pain in the elderly. Although IVDD is related to many factors, such as inflammation, trauma, hormones, genetics and other factors, the specific mechanism of IVDD is still unclear [1–4]. Studies have shown that oxidative stress and inflammation may play a key role in the process of IVDD. In recent years, various antioxidant and anti-inflammatory molecules or drugs have become research hotspots in the field of IVDD [3–4, 13]. Previous studies demonstrated the expression of ER in human IVD tissue and found that estrogen can enhance the antioxidant and anti-inflammatory capacity of NPCs, reduce apoptosis of NPCs, and promote the expression of ECM, such as aggrecan and type II collagen. Further studies have shown that estrogen can delay IVDD by activating NF-κB and PI3K-Akt signaling pathways [4, 6–7]. Clinical studies have found that the degree of IVDD in postmenopausal women is higher than that in premenopausal women . And OVX results in a significant decrease in estrogen levels in women and promotes IVDD in a long period of time . Therefore, estrogen may be one of the effective drugs to delay IVDD.
Aromatase is a cytochrome P450 enzyme encoded by the CYP19A1 gene that converts androgens into estrogens. Aromatase promotes estrogen production mainly in the ovaries of premenopausal women. In postmenopausal women, it occurs mainly in peripheral tissues. Aromatase has been found to be expressed in many tissues, including placenta, central nervous system, bone, muscle, etc. AI is currently mainly applied in endocrine therapy for postmenopausal breast cancer patients, which can effectively reduce tumor recurrence and metastasis and improve the survival of patients [8–9]. AI can also cause side effects, such as AI associated musculoskeletal syndrome (AIMSS), whose main symptoms include aralgia, myalgia, joint stiffness, and tendinopathy. AIMSS has been proposed to be associated with estrogen deficiency in the musculoskeletal and nervous system [10–12]. Our previous high-throughput sequencing results proved the expression of aromatase in NPCs , but there is no relevant study on the effect of AI on IVDs. In this study, we analyzed the clinical data of postmenopausal breast cancer patients to evaluate whether application of AI could affect the process of IVDD.
We divided breast cancer patients into the AI group and the non-AI group, based on whether they received AI as endocrine therapy after surgery. No significant difference was present in basic clinical information (age, BMI, postoperative history) and basic diseases (hypertension, diabetes, coronary heart disease) between the two groups.
The physiological curvature of lumbar spine is mainly represented by LL. Previous studies on LL have found that the occurrence of low back pain is related to the reduction of LL.The reduction of LL results in changes in the biomechanical structure of the lumbar spine and exacerbates IVDD . This study showed that although the comparison was not statistically significant in LL between the two groups, the LL of both groups was lower than that of normal adults in previous studies, which may be related to age increase, weight and other factors .
Osteoporosis is a common systemic disease in the elderly, especially in postmenopausal women, often resulting in vertebral compression fractures . Bone mineral density (BMD) is an important indicator to evaluate the degree of osteoporosis, but the relationship between BMD and IVDD is not very clear so far, and most studies support the negative correlation between BMD and IVDD [11, 16]. Through autopsy, Wang et al. found that under the influence of removal of peripheral osteophytes and calcification of cartilage endplate, increased vertebral BMD would lead to more severe IVDD . Kaiser et al. used quantitative computed tomography (QCT) to detect regional BMD of L3 vertebral body and evaluate the health status of adjacent L2/3 and L3/4 IVDs, and found that BMD of male and female gradually decreases with age. However, after the exclusion of age, increased BMD was found to be associated with decreased disc height . AI further reduce estrogen levels in tissues by inhibiting aromatase in peripheral tissues, resulting in further bone loss . We measured CT densities of 5 vertebral bodies, and the average vertebral CT density were used to evaluate vertebral BMD. We found that the average vertebral CT density in the AI group was lower than that in the non-AI group, but the comparison was not statistically significant, which may be due to the fact that anti-osteoporosis therapy (calcium and vitamin D agents) in postmenopausal women with breast cancer has somewhat slowed down the bone loss.
Intervertebral height is a parameter that reflects the height of the disc, which decreases when the disc degenerates or herniates. Previous studies have shown that the DHI of patients with lumbar disc herniation (LDH) is lower than that of patients without LDH, which may be caused by the thinning of endplate thickness and the increase of anterior and posterior extension caused by IVDD . Akeda K et al. found that DHI of the elderly was significantly lower within 10 years, accompanied by an increase in Pfirrmann grading . This study showed that L1/2, L2/3 and L3/4 DHI in the AI group were significantly lower than those in the non-AI group, but No significant differences were present in L4/5 and L5/S1 DHI and average DHI. The reason may be that the lower lumbar spine (L4/5, L5/S1) is a common site of lumbar degenerative diseases such as LDH, which is affected by a variety of factors, such as trauma and strain, and hormone level may not be the dominant factor.
We can compare between the nucleus pulposus and annulus fibrosus signal change through MRI, and use the modified Pfirrmann grading system to evaluate degree of IVDD [4–5, 21]. Previous studies have proved that estrogen level is an important factor affecting IVDD. Wang et al. found that the signal in the T2 weighted imaging of MRI in postmenopausal women was significantly lower than that in premenopausal women (higher modified Pfirrmann grading), indicating more severe disc degeneration . Zhao et al. compared lumbar MRI data of patients undergoing ovariectomy and normal patients, and found that ovariectomy resulted in decreased estrogen level and further accelerated IVDD, manifested by a higher modified Pfirrmann grading . We found that the modified Pfirrmann grading was significantly higher in the AI group, except for L5/S1. This result is similar to that of lumbar DHI, suggesting that long-term AI promote IVDD, which is more remarkable in the upper lumbar spine.
This study also has some limitations. This study is a retrospective cross-sectional study with a small sample size and many interfering factors, which may affect the evaluation of AI for IVDD. Prospective studies with a larger sample size is needed to assess the effect of AI on IVDD with long-term follow-up.