Is inhaled calcitonin (calcitonin) effective for managing vertebral fracture pain?

Intranasal Calcitonin for Vertebral Fracture Pain

Intranasal calcitonin at 200 IU daily is effective for acute pain from osteoporotic vertebral compression fractures and should be initiated within 5 days of fracture onset for a 4-week course, but it has no proven benefit for chronic vertebral fracture pain beyond 4-6 months. 1, 2, 3

Acute Vertebral Fracture Pain (< 6 months)

Dosing and Administration

• Administer 200 IU daily as nasal spray for 4 weeks as the primary regimen 1, 2
• Alternative: 100 IU subcutaneously or intramuscularly every other day if nasal route is not tolerated 1, 2
• Initiate treatment within 0-5 days after fracture or symptom onset for optimal analgesic effect 1, 2
• Always provide concurrent calcium supplementation (at least 1000 mg elemental calcium daily) and vitamin D (400 IU daily) 1, 2, 4

Evidence for Acute Pain Relief

• Meta-analysis of 13 trials (n=589) demonstrated significant pain reduction at rest by week 1 (mean difference = -3.39,95% CI = -4.02 to -2.76), with continued improvement through 4 weeks 3
• Pain reduction with mobility was even more pronounced at 4 weeks (SMD = -5.99,95% CI = -6.78 to -5.19) 3
• Thirteen of fourteen double-blind, placebo-controlled trials showed statistically significant improvement in pain or function 5
• The American Geriatrics Society recognizes calcitonin as helpful for pain from post-osteoporotic vertebral compression fractures 6

Chronic Vertebral Fracture Pain (> 6 months)

Calcitonin is NOT recommended for chronic vertebral fracture pain, as there is no convincing evidence of benefit for fractures older than 6 months 3

• At 6 months, there was no statistical difference in pain at rest between calcitonin and placebo groups 3
• Only a small, statistically significant difference existed with mobility at 6 months (SMD = 0.49,95% CI = -0.85 to -0.13), which is clinically marginal 3

Patient Selection Criteria

Appropriate Candidates

• Postmenopausal women greater than 5 years postmenopause with acute vertebral compression fractures 1, 4
• Patients who refuse, cannot tolerate, or have contraindications to bisphosphonates or estrogens 1, 4
• Patients with impaired renal function who cannot take bisphosphonates 7
• Older women with painful acute vertebral fractures requiring rapid pain relief 7

Monitoring Requirements

• Assess serum calcium and phosphorus levels periodically, as calcitonin can alter these values 6, 2
• Monitor bone mineral density (BMD) yearly while on treatment 2
• If BMD falls >4% per year for two successive years, switch to another agent 2

Side Effects and Safety

Common Side Effects

• Mild and generally well-tolerated 1, 3, 5
• Nausea and gastrointestinal disturbances (most common) 6, 3, 5
• Mild dizziness 1, 2
• Flushing 3
• Altered serum calcium and phosphorus levels 6, 2

Contraindications

• Allergy to calcitonin-salmon or synthetic calcitonin-salmon 1
• Hypersensitivity reactions are rare but constitute absolute contraindication 2

Clinical Context and Limitations

Important Caveats

• Calcitonin's vertebral fracture efficacy is less robust than bisphosphonates (alendronate, risedronate) but similar to raloxifene 7
• No demonstrated reduction in hip fracture risk 7
• The FDA label indicates calcitonin should be reserved for patients who refuse or cannot tolerate other treatments 4
• Bioavailability of nasal spray is only 3-5% compared to intramuscular administration, but this is sufficient for clinical effect 4

Procedural Alternatives

• The American Society of Anesthesiologists strongly recommends considering minimally invasive spinal procedures (vertebroplasty, kyphoplasty) for vertebral compression fracture pain as these provide effective relief for 6-12 months 6
• For multifocal bone pain in cancer patients, bisphosphonates and denosumab are preferred over calcitonin 2

Practical Algorithm

For acute vertebral compression fracture pain:

1. Confirm fracture is < 5 days old
2. Start calcitonin 200 IU nasal spray daily + calcium 1000 mg + vitamin D 400 IU
3. Continue for 4 weeks
4. Reassess pain at 1-2 weeks (expect significant improvement)
5. If inadequate response or pain persists beyond 4-6 weeks, consider vertebroplasty/kyphoplasty or transition to bisphosphonates

For chronic vertebral fracture pain (> 6 months):

• Do not use calcitonin
• Consider bisphosphonates, NSAIDs, or interventional procedures instead