What are the pain symptoms associated with Bisphosphonate (bone resorption inhibitor) therapy?

From the Guidelines

Bisphosphonates are recommended for patients with pain due to osteolytic disease and as an adjunctive treatment for patients receiving radiation therapy, analgesics, or surgical intervention to stabilize fractures or impending fractures, as they have been shown to decrease pain and bone-related complications, improve performance status, and preserve quality of life in patients with multiple myeloma and other bone diseases 1.

Key Points

• Bisphosphonates can cause several pain-related symptoms, including bone, joint, or muscle pain, which typically begins within days to months after starting treatment 1.
• The most common pain symptom is bone pain, which can range from mild to severe and may affect various parts of the body 1.
• Some patients experience acute-phase reactions within the first 3 days of treatment, particularly with intravenous bisphosphonates like zoledronic acid, causing flu-like symptoms including fever, muscle aches, and joint pain 1.
• Rarely, bisphosphonates can cause severe jaw pain from osteonecrosis of the jaw, particularly in patients undergoing dental procedures while on these medications 1.
• Another rare but serious side effect is atypical femur fractures, which may present as dull, aching thigh pain weeks or months before an actual fracture occurs 1.

Management of Bisphosphonate-Related Pain

• Pain management typically involves over-the-counter pain relievers like acetaminophen or NSAIDs, and in some cases, temporary dose adjustment or medication change may be necessary 1.
• Patients who experience persistent or severe pain while taking bisphosphonates should contact their healthcare provider immediately 1.
• Bisphosphonates should be used in conjunction with calcium and vitamin D supplementation to minimize the risk of hypocalcemia and other side effects 1.

Recommendations

• The NCCN Guidelines for multiple myeloma recommend bisphosphonates or denosumab for all patients receiving therapy for symptomatic multiple myeloma regardless of documented bone disease 1.
• The frequency of dosing (monthly vs every 3 months) would depend on the individual patient criteria and response to therapy 1.
• Patients who are on bisphosphonates should have their renal function monitored and undergo a dental examination before starting bisphosphonate therapy and should be monitored for osteonecrosis of the jaw 1.

From the Research

Bisphosphate Pain Symptoms

• Bisphosphonates have been studied for their potential in treating pain, particularly chronic pain, with some evidence suggesting clinical efficacy in chronic pain states 2.
• However, the mechanisms underlying the analgesic effects of bisphosphonates are still not fully understood 2.
• Severe and sometimes incapacitating muscle, joint, and bone pain can occur in patients taking bisphosphonates, especially those treated for osteoporosis, with an incidence of 2-5% 3.
• Bisphosphonates have been used to treat complex regional pain syndrome, with some studies suggesting that bone tissue involvement in the early pathophysiological steps of the disease may play a role in the efficacy of bisphosphonates 4.

Treatment of Bisphosphate-Related Pain

• Discontinuation of bisphosphonate therapy may be considered in patients experiencing musculoskeletal pain, as it may represent a better option than escalation of analgesic therapy 3.
• Other treatments, such as nonsteroidal anti-inflammatory drugs, acetaminophen, gabapentin, and pregabalin, may be used to manage pain in conditions like hidradenitis suppurativa, but no studies exist specifically for pain control in this condition 5.
• The combined use of gabapentin and pregabalin may be considered for pain control, as they have been shown to have a synergistic effect without significant pharmacokinetic interactions 6.