Hormone therapy-induced joint pain
Analysis and Management Strategies for Joint Pain in Hong Kong Breast Cancer Patients with Aromatase Inhibitors (AIs)
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For postmenopausal women with hormone receptor–positive breast cancer, aromatase inhibitors (AIs) are an essential therapy to extend survival and reduce recurrence risk. They are usually prescribed for at least five years. However, the most common side effect—arthralgia—should not be underestimated, as it can severely affect treatment adherence. Discontinuation rates are reported to be as high as 13–22%. Without proper understanding and management, patients may miss the full therapeutic benefit.
Introduction
Clinical Characteristics and Epidemiology
Aromatase inhibitor–induced arthralgia (AIA) most often affects the wrists, fingers, and knees. It usually presents as symmetrical joint pain and may be accompanied by carpal tunnel syndrome, trigger finger, morning stiffness, myalgia, and reduced grip strength. Symptoms typically emerge within several weeks to months of starting therapy, peaking around six months. Approximately 20–50% of patients experience AIA, with around 20% discontinuing therapy due to pain (Annals of Oncology).
Pathophysiology
There is currently no standardized diagnostic criterion for AIA, and the underlying mechanisms remain unclear. Proposed mechanisms include:
- Rapid estrogen depletion: Estrogen plays a protective role in pain modulation and joint health. Its loss may disrupt cartilage and synovial fluid balance (Biology Insights, MDPI).
- Immune and inflammatory activation: Elevated levels of IL-1, IL-6, and TNF-α may influence the RANK signaling pathway, worsening joint inflammation (Frontiers, MDPI).
Impact and Risk Factors
AIA significantly reduces quality of life and may lead up to 20% of patients to discontinue therapy (ATAC trial, Cancer Network, Annals of Oncology). Risk factors include:
- High body mass index (BMI > 30)
- Prior taxane-based chemotherapy
- Pre-existing rheumatologic or degenerative joint disease (NDNR)
治療與管理策略（多維整合）
| Non-Pharmacological Interventions |
● Acupuncture: Clinical studies indicate that acupuncture can effectively alleviate pain. Approximately 58% of patients receiving true acupuncture reported ≥50% pain improvement, compared with 33% in the sham acupuncture group and 31% in the control group. ● Aerobic and Resistance Exercise / Rehabilitation: Systematic reviews support regular physical activity as one of the most effective strategies. A biopsychosocial multidimensional approach is recommended. |
| Nutritional Support |
● High-dose Vitamin D₃: Studies show that many patients have suboptimal Vitamin D₃ levels, and supplementation has been associated with clinical pain reduction (approximately 23%). ● Curcumin and Fish Oil: Both possess anti-inflammatory potential. Some osteoarthritis studies support their efficacy, though large-scale RCTs specifically for AIA remain limited. |
| Pharmacological Strategy Adjustments |
● Switching to Tamoxifen or other AIs (e.g., Exemestane): Changing medication may improve symptoms. Some cases show that patients intolerant to Anastrozole can switch to Letrozole and maintain use for at least 6 months. ● Analgesics and Antidepressants: For patients with significant pain, NSAIDs or prescribed pain relievers and antidepressants may be added, under physician guidance and monitoring. |
Practical Guidelines for Hong Kong Patients
- Pre-treatment education: Patients should be informed about the possibility of AIA and management strategies before initiating therapy to strengthen preparedness and coping.
- Early intervention: Even mild symptoms warrant prompt integrative management (e.g., acupuncture, exercise, rehabilitation).
- Nutritional and lifestyle support: Vitamin D₃ levels should be monitored and supplemented as needed. Patients should be encouraged to exercise regularly and maintain a healthy weight.
- Tailored pharmacological adjustments: Therapy modification should be individualized, balancing efficacy and safety.
- Multidisciplinary collaboration: Close coordination between oncology, rehabilitation, and pain management specialists ensures adherence and treatment continuity.
Conclusion
Although aromatase inhibitor–induced arthralgia is a common and challenging side effect, it is not insurmountable. With a comprehensive, multi-dimensional, and ecosystem-based management approach, symptoms can be alleviated, quality of life improved, and adherence strengthened—ensuring patients receive the full benefit of therapy without compromising outcomes.
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References
- Annals of Oncology. (2019). Aromatase inhibitor‑induced arthralgia: a review. Annals of Oncology.MDPI+15Annals of Oncology+15ScienceDirect+15
- Biology Insights. (2025, ~2 weeks ago). Why Do Aromatase Inhibitors Cause Joint Pain?. Biology Insights.Biology Insights+1
- Frontiers in Endocrinology. (2021). Aromatase Inhibitor‑Associated Musculoskeletal Syndrome. Frontiers in Endocrinology. Frontiers+2SpringerLink+2
- Current Physical Medicine and Rehabilitation Reports. (2021). Aromatase Inhibitor‑induced Musculoskeletal Syndrome: a Review of Rehabilitation Interventions. SpringerLink
- Presant, C. A., Bosserman, L., Young, T., et al. (2010). Naturopathic Management of Arthralgias Associated with Aromatase Inhibitor Therapy. Naturopathic Pain Medicine. NDNR+2ASCOPubs+2
- Verywell Health. (2016). Managing Bone Pain While Taking Hormone Therapy. Verywell Health. Verywell Health
- (2017). Here’s a Promising Way to Treat Pain in Breast Cancer Treatment. Time.MDPI+15TIME+15JBUON+15
- (n.d.). Current management of aromatase inhibitor‑induced arthralgia. JBUON.MDPI+15JBUON+15ScienceDirect+15
- Curr Oncol. (2010). Management of Aromatase Inhibitor–Induced Arthralgia. Current Oncology. MDPI+1