Osteoporosis – a complication that needs to be better managed in breast cancer patients treated with AIs Aromatase inhibitors (AIs) have been widely used as an important drug in the endocrine treatment of postmenopausal women with breast cancer, and the prevention and treatment of their possible side effects are receiving increasing attention. The prevention and treatment of bone loss due to AIs is one of the issues that require attention. Menopause is one of the risk factors for osteoporosis in women, and osteoporosis leads to decreased bone strength and increased risk of fracture. Postmenopausal women with breast cancer are at an even higher risk for osteoporosis because many treatments for breast cancer increase the risk of osteoporosis, such as chemotherapy, ovarian removal and the use of AIs. The mechanism of bone loss due to AIs The mechanism of bone loss due to AIs is mainly related to the decrease of estrogen level in the body. Estrogen can increase the sensitivity of thyroid C cells to calcium, promote the secretion of calcitonin, inhibit osteoclast activity, inhibit the bone resorption effect of parathyroid hormone, and also increase the calcium uptake by the small intestine. The loss of estrogen secretion from the ovaries in postmenopausal women, however, leaves only low levels of estrogen levels through the conversion of androgen precursors secreted by the adrenal glands via aromatase, so that postmenopausal women taking aromatase inhibitors (AIs) can further reduce circulating levels of estrogen, leading to accelerated bone loss and increased fracture risk. This increased risk of osteoporosis and fracture due to AIs is known as aromatase inhibitor therapy-related bone loss (AIBL). There are currently three generations of AIs, with most of the currently used ones being the third generation, which include the nonsteroidal anastrozole (anastrozole) and letrozole (letrozole) and the steroidal exemestane (exemestane). In pilot studies such as ATAC, ARNO/ABCSG-8, BIG 1-98, and MA-17, it was observed that treatment with nonsteroidal AIs (anastrozole or letrozole) resulted in lower bone mineral density (BMD), a significant increase or trend toward an increase in fracture incidence, and more newly diagnosed osteoporosis in subjects compared to controls. The results of the IES study with steroidal AIs (exemestane) showed that fractures were more frequent in the exemestane follow-up group, although there was no statistical difference compared to the tamoxifen continuous treatment group (3,1% vs. 2,3%, P>0,05), and there were also more newly diagnosed osteoporosis in the exemestane follow-up group than in the tamoxifen continuous treatment group. This means that both steroidal and nonsteroidal AIs lead to increased bone loss and higher fracture risk in postmenopausal women. Prevention and treatment of bone loss associated with aromatase inhibitor therapy (AIBL) The American society of clinical oncology (ASCO) has published guidelines for monitoring and treating bone loss in women with breast cancer, which mention that breast cancer patients at high risk for osteoporosis need regular bone mineral density ( BMD) screening. Dual-energy x-ray absorptiometry (DXA) is currently the primary method of BMD measurement. BMD measurement targets: According to the bone health guidelines published by the American Society of Clinical Oncology (ASCO) in 2003, it is stated that the high-risk factors for osteoporosis in breast cancer patients are: 1. age >65 years; 2. age between 60-64 years with family history of osteoporosis, weight <70 kg, previous non-traumatic fractures, lack of exercise lifestyle, smoking and other risk factors; 3. AIs at any postmenopausal age; 4. Premenopausal treatment related to premature menopause. The guidelines recommend that patients with appeal risk factors should have a BMD test at the beginning of AI treatment and be reviewed annually thereafter. Diagnostic criteria for BMD: The World Health Organization (WHO) has established the following criteria for bone mass measurement at the spine, hip, or wrist in menopausal women: (1) normal: T value ≥ -1,0; (2) low bone mass (reduced bone mass): -1,0 > T value > -2,5; (3) osteoporosis: T value ≤ -2,5. Recommendations for prevention and treatment of bone loss associated with aromatase inhibitor therapy (AIBL): For patients with long-term use of For patients with bone loss due to long-term use of AIs, the following measures can be taken for prevention and treatment: 1. Establish a good lifestyle such as regular exercise, increase outdoor activities, prevent falls, encourage smoking cessation and limit alcohol consumption, etc. 2. 2. Adequate daily supplementation of elemental calcium and vitamin D ASCO guidelines recommend adequate amounts of calcium (1200mg/day) and vitamin D (400-600mg/day) for women with breast cancer regardless of whether they have a high or low risk of osteoporosis. The results of the VITAL study, a phase III randomized, placebo-controlled, double-blind trial that included 147 women with breast cancer, were presented at the 2012 ASCO Annual Meeting and found that the addition of vitamin D3 (30,000 IU/week) to letrozole treatment reduced skeletal muscle pain (about 50% of breast cancer patients taking AI reported musculoskeletal pain or symptom (about 50% of breast cancer patients taking AI reported increased musculoskeletal pain or symptoms and 18%-30% reported fatigue, which are important reasons for women to improve termination of treatment), and the ability of physicians to reduce pain, fatigue, and other problems associated with treatment has an important impact on improving patient compliance. 3. Use of bisphosphonates Bisphosphonates are drugs that inhibit bone resorption, inhibit osteoclast activity, and reduce bone loss. It is an efficacious drug for postmenopausal women with osteoporosis. For osteoporosis due to cancer treatment, there are many studies showing its effectiveness in maintaining bone mass and preventing osteoporosis. And for those with rapid bone loss due to oncology treatment, intravenous bisphosphonates are better tolerated and adhered to than oral ones, such as zoledronic acid (zoledronic). The results of established studies have shown that intravenous zoledronic acid prevents bone loss due to AIs and leads to increased BMD in the spine and total hip. Recommendations for the use of zoledronic acid: start bisphosphonates in patients with a BMD score (T-Score) below -2,5, consider bisphosphonates in patients with a BMD score (T-Score) between -2,5 and -1,0, and do not recommend bisphosphonates in patients with a BMD score (T-Score) above -1,0. The use of bisphosphonates for osteoporosis is not the same as for bone metastases, but can be used every 3-6 months and the dosing should be adjusted according to the change in BMD score after treatment.