Tools for Practice


#96 Calcitonin withdrawal: Now what for acute vertebral fractures?


CLINICAL QUESTION
Is there any medication (other than traditional analgesia) that works for bone pain resulting from osteoporotic vertebral compression fractures (OVCF)?

BOTTOM LINE
Calcitonin had weak evidence of moderate effectiveness for acute OVCF pain but was withdrawn over cancer risks. Although the evidence is very poor, bisphosphonates appear to have similar effect on acute pain reduction and are useful in secondary fracture prevention


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EVIDENCE
As of October 1, 2013, Synthetic Calcitonin (Salmon) nasal spray will be withdrawn from the Canadian Market.1 Despite being on the market since 1975 (in the U.S.), only recently has a meta-analysis of 17 Randomized Controlled Trials (RCTs) concluded that calcitonin is associated with an increased risk of overall malignancy with a Number Needed to Harm (NNH) of 63.2
  • A systematic review of five RCTs (246 patients) demonstrated that calcitonin was effective in reduction of OVCF pain compared to placebo with a mean difference (MD) of 3.4 on a 10 point visual analogue scale (VAS) at one week.3
  • Two small studies examining bisphosphonates for pain.
    • One direct comparison RCT: 27 women, IV pamidronate or IV calcitonin x 1 dose4
      • Day 4: both groups had statistically significant improvement in pain on VAS scale:
        • • Pamidronate ~1.1 (baseline 5.9)
        • • Calcitonin ~2.3 (baseline 6.3)
      • ▪ Day 30: Pamidronate ~2.3cm, Calcitonin ~3.1cm
        • No statistically significant difference in pain scores, functional disability or analgesic use
    • o RCT 32 women, IV pamidronate versus placebo (baseline ~7.6)5
      • After one week, those taking pamidronate had significantly decreased pain with standing (MD ~2.3) but not in supine pain (MD ~1.1)
Context:
  • The minimum clinically significant change in patient’s pain severity measured with a 10-cm VAS is 1.3 cm.6
  • • Approximately 60% of patients with OVCF who are conservatively managed will have adequate resolution of pain within three months.7
  • For secondary prevention, bisphosphonates are beneficial in prevention of vertebral (NNT 9-60) and non-vertebral fractures (NNT 20-68).8
  • Bisphosphonates (oral and IV) have also demonstrated benefit in metastatic bone pain.9
  • There is no evidence of superiority of one bisphosphonate over another in acute pain management.
updated by evan sehn on march 8 2017
September 23, 2013

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Author(s):

  • Christina Korownyk MD CCFP
  • David Ross MD CCFP

1. Recalls and safety alerts. Website. Health Canada. Available from: http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2013/34783a-eng.php

2. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Dr ugs/ReproductiveHealthDrugsAdvisoryCommittee/UCM343748.pdf

3. Knopp-Sihota JA, Newburn-Cook CV, Homik J. Osteoporosis Int. 2012; 23(1):17-38.

4. Laroche M, Cantogrel S, Jamard B, Clin Rheumatol. 2006; 25(5):683-6.

5. Armingeat T, Brondino R, Pham T, et al. Osteoporos Int. 2006; 17:1659-65.

6. Todd KH, Funk KG, Funk JP, Bonacci R. Ann Emerg Med. 1996 Apr; 27(4):485-9.

7. Venmans A, Klazen CA, Lohle PN, et al. AJNR Am J Neuroradiol. 2012; 33:519-21.

8. McClung M, Harris ST, Miller PD, et al. Am J Med. 2013; 126(1):13-20.

9. Wong R, Wiffen PJ. Cochrane Database Syst Rev. 2002; (2):CD002068.

Authors do not have any conflicts of interest to declare.