Pain definition: “An unpleasant sensory and emotional experience associated with actual or potential tissue injury or described in terms of such damage.”
(International Association for the Study of Pain
 
Figure 1. Pain and the quality of life (Qol)
Figure 1. Pain and the quality of life (Qol)
Definitions(6): 
AI Arthralgia (AIA) = joints pain/stiffness NOT caused by arthritis
AI-induced musculoskeletal syndrome (AIMSS) = arthralgia or joint pain + musculoskeletal pain + carpal tunnel syndrome + joint stiffness + paresthesia

Aromatase Inhibitors Arthralgia (AIA)(1,2,5)
Major criteria:
  • Currently taking aromatase inhibitors (AI) 
  • Joint pain which has developed or worsened since starting AI 
  • Joint pain improves or resolves within 2 weeks of stopping AI
  • Joint pain returns upon resuming AI.
Minor criteria:
  • Symmetrical joint pains
  • Pain in hands and/or wrists
  • Carpal tunnel syndrome
  • Decreased grip strength
  • Morning stiffness
  • Improvement in joint discomfort with use or exercise
Diagnosis: all of the following major criteria, and at least three minor criteria
  • 44-47% women - joint pain and stiffness 
  • 20-50% women - arthralgia
  • Joint symptoms most often develop within the first 3 months on therapy and peak at 6 months
  • Typically affect the fingers, hands, wrists, elbows, shoulders, knees and ankles.
Figure 2. Occurence of 5 types of pain syndrome over the 1-year study period. The data shown for each visit are the numbers of patients developing a specific pain syndrome
Figure 2. Occurence of 5 types of pain syndrome over the 1-year study period. The data shown for each visit are the numbers of patients developing a specific pain syndrome








AIA complications
  • Pain → discontinuation of AI in up to 20% of patients.
AIA treatment(1,3-5,9-11,13)
AIA complications
  • Pain → discontinuation of AI in up to 20% of patients.
AIA treatment(1,3-5,9-11,13)
n Definitive therapy for AI-induced arthralgias has not been developed.
1) Patient education
  • patients uncertain which healthcare professional address the AIs side effects. 
  • advise patients: AIA is common; can be managed by drug therapy and lifestyle changes
⇒ Adherence to AI therapy.
2) Pain assessment
Women on AI should undergo pain assessments for at least 1 year.

3) Nonpharmacologic
  • Lifestyle changes: 
 physical activity (including weight bearing exercise)
 reducing or stopping smoking
 weight loss.
  • Yoga may be effective; needs verification in further trials.
  • Acupuncture may reduce pain from joint symptoms and improve functioning and well-being.
4) Calcium and vitamin D supplements
n Vitamin D levels should be measured routinely and optimized throughout the patient,s lifetime. 
n Women,s Health Initiative Observational Study:
 31% increased risk of fracture in women with vs. those without breast cancer
 5-fold increased risk of vertebral compression fractures in women with breast cancer with or without bony metastases.

5) Omega-3 fatty acids
  • Anti-inflammatory effects 
  • Placebo-controlled trial:
 3.3 g Omega-3-fatty acids, 249 women on AIs with severe pain (≥5/10) and/or stiffness
 60% improvement observed in the group randomized to Omega-3
 similar reduction was seen in the placebo (soybean/corn oil) arm.
6) Pharmacologic
  • NSAIDs (ibuprofen) or a COX2 inhibitor - recommended as first-line treatment
  • APAP
  • Anticonvulsants: gabapentin, pregabalin
  • Opioids
  • Duloxetine:
  1.  single-arm, open-label phase 2 study:
  2.  29 women with breast cancer with new or worsening pain with AI
  3.  21 women (72.4%) achieved at least 30% decrease in average pain
  • Bisphosphonates:
 May prevent AI-related joint symptoms
 ASCO recommends bisphosphonate therapy for all women undergoing adjuvant therapy for breast cancer with T score <-2.5
  • Prednisolone, short course, low-dose:
  1.  small, non-randomized trial of 27 patients
  2.  5 mg of prednisolone daily for 1 week
  3.  67% of patients reported immediate relief in joint pain
  4.  63% still reporting improvement at 1 month
  • Consider switching to tamoxifen if symptoms cannot be managed - Tamoxifen + Cymbalta (CYP2D6)!
  • Stop therapy for 6 to 8 weeks to ensure the AI is the cause of the symptoms prior to switching.  
Figure 3. Pharmacologic options for the amelioration of pain in early breast cancer patients with symptoms of athralgia
Figure 3. Pharmacologic options for the amelioration of pain in early breast cancer patients with symptoms of athralgia
Figure 4. Potential interventions for athralgia
Figure 3. Pharmacologic options for the amelioration of pain in early breast cancer patients with symptoms of athralgia
Figure 5. Potential treatments for myalgias and arthralgias caused by cancer
Figure 4. Potential interventions for athralgia
Figure 5. Potential treatments for myalgias and arthralgias caused by cancer
Figure 5. Potential treatments for myalgias and arthralgias caused by cancer
Figure 6. The management of arthralgias in cancer patients
Figure 6. The management of arthralgias in cancer patients