Picture source: Wikipedia
Calcitonin is a polypeptide hormone that participates in calcium and phosphorous metabolism. It controls calcium level in the blood by opposing the effect of the parathyroid hormone through its actions on osteoclasts. Salmon calcitonin is the form of calcitonin used clinically. The two major advantages of salmon calcitonin are:
- It resembles human calcitonin but is more potent.
- In animal studies it is shown not to be teratogenic or embryotoxic due to salmon calcitonin inability to cross the placental barrier.
Commercially it is produced by recombinant DNA methods and because it is a relatively short 32-amino acid linear polypeptide it is also amenable to be manufactured by peptide synthesis. Since its discovery by Copp and Cheney (Nature, 1962) it has been available in parenteral formulation since the early 1970's and the nasal spray formulation became available in the mid 1980's. Nasal spray is currently the most commonly used formulation and is available in the US
European Medicines Agency's RecommendationThe European Medicines Agency (Agency) is the European Union's counterpart of US Food and Drug Administration Agency. Like the US FDA, this agency is responsible for ensuring that the public safety is protected and the approved drugs for specific indications are effective. In their 19 July 2012 publication, it was recommended that the is a small increased risk of cancer with the long term use of calcitonin be discontinued. Following an internal review, the Agency recommends short term use (presumably for 6-12 weeks or less) for the following three conditions:
- Paget's disease not responding to alternative treatments;
- Acute bone loss due to sudden immobilization as in patients with recent osteoporotic fractures and
- Hypercalcemia caused by cancer.
The Agency further recommends that calcitonin no longer be used for the treatment of osteoporosis, presumably this recommendation pertains to the long term use of calcitonin. What is surprising is the recommendation that calcitonin in the form of nasal spray no longer be available. The only available formulation of calcitonin will then be either for subcutaneous injection or for intravenous infusion. This will create an inconvenience barrier to continued long term use of calcitonin. The product information for calcitonin will also need to be revised to conform with the current recommendations. The recommendations are pending approval by the European Commission. There are two issues with the Agency's document namely what constitute short-term treatment and what role does calcitonin play in the treatment of vertebral compression fracture secondary to osteoporosis. In the Agency's document, even under the restricted recommended uses of calcitonin, the "treatment should be given for the shortest possible time using the smallest effective dose." It goes without saying that such treatment principle applies to any medication that has potential side effects. Agency's lack of clear definition of short-term treatment appears to be based on the believe that the potential for long-term use of calcitonin will be balanced by the inconvenience factor associated with the parental administration when nasal spray is no longer available. In an article by Robert Lowes in Medscape News (Orthopedic), he conjectured that a reasonable treatment time frame would be 4 weeks for treatment of acute bone loss secondary to sudden immobilization and no more than 3 months to treat Paget's disease. The treatment of hypercalcemia related to cancer is less clearcut given the unknown effect of the calcitonin on the existing malignancy.
American Academy of Orthopedic Surgeons' Clinical Practice Guidelines
The second issue relates to the use calcitonin in the treatment of symptomatic osteoporotic spinal compression fractures appears not be have been dealt with by the Agency's report. Calcitonin for pain relief in acute osteoporotic vertebral body compression fracture has been use for over 15 years and there are clinical evidence to suggest the efficacy of such treatment. The American Academy of Orthopedic Surgeon in September 2010 issued a clinical practice guideline and evidence report on the treatment of osteoporotic spinal compression fractures. Of the 11 recommended practice guidelines, use of calcitonin for 4 weeks was the only one that has moderate evidence confirming its efficacy. The rest of the 10 therapeutic modalities are not supported by available evidence to be effective. The recommendation is quoted here for convenience of the readers and for more detail readers are encouraged to review the original source:
"We suggest patients who present with an osteoporotic spinal compression fracture on imaging with correlating clinical signs and symptoms suggesting an acute injury (0-5 days after identifiable event or onset of symptoms) and who are neurologically intact be treated with calcitonin for 4 weeks.
Strength of Recommendation: Moderate"
In my opinion should the Agency's recommendations be accepted by the European Commission, then a large number of EU patients who would otherwise benefit from the short-term calcitonin treatment for pain control of acute osteoporotic spinal compression fracture would either be inconvenienced or possibly may not even have this treatment option available. I would urge the European Medicines Agency to supplement their review to include evidence put forth by the Work Group on Clinical Practice Guideline, American Academy of Orthopedic Surgeons.
Full Text of the document from European Medicines Agency is available free from here.