Calcitonin is a hormone that lowers calcium levels in the blood. It can be used orally, via nasal spray or via injections for osteoporosis, Paget’s disease, and hypercalcemia (elevated calcium levels). Read more about the uses and side effects of calcitonin.
Disclaimer: Calcitonin is a prescription medication that should only be used by a doctor’s prescription. By writing this post, we are not recommending the use of calcitonin. This post provides an overview of the scientific literature on this drug. Speak with your doctor about your medications and call your doctor for medical advice about side effects.
What Is Calcitonin?
Calcitonin is a peptide hormone produced in the thyroid gland by parafollicular cells (also called C-cells). It is produced from procalcitonin, a larger peptide, that is in turn controlled by the calcitonin gene (CALCA). Calcitonin helps maintain calcium blood levels. If calcium levels are too high, then this hormone reduces them .
The hormone is produced in response to:
- High calcium levels in the blood .
- Gastrin, a peptide hormone produced in the stomach, which triggers the release of stomach acid to digest food .
Scientists consider calcitonin has the following function:
- Reducing osteoclast activity and bone loss. Osteoclasts are bone cells that break down bone tissue. This releases calcium into the bloodstream. By preventing osteoclast activity, calcitonin preserves bone density and decreases the levels of calcium in the blood [1, 4, 5].
- Decreasing the reuptake of calcium in the kidneys, hence increasing the elimination of calcium through the urine .
Calcitonin produces effects by binding to the calcitonin receptor (CALCR) found in the bones, in the kidney, and regions of the brain .
Calcitonin is used to treat osteoporosis in postmenopausal women, Paget’s disease of bone, and hypercalcemia (elevated calcium levels). Research suggests that calcitonin may reduce the risk of fractures, however, its fracture reduction efficacy has not been demonstrated in large-scale studies [4, 8, 9].
In general, a normal calcitonin value is less than 10 pg/mL.
Women have lower calcitonin levels than men, due to lower production [10, 2].
Levels in women increase in pregnancy and breastfeeding [11, 10].
In postmenopausal women on estrogen treatment, levels may be higher [12, 2].
Adults have lower levels than infants and children [13, 14, 2].
Depending on age and gender, the following normal levels of calcitonin have been proposed :
- <40 pg/L in children under 6 months of age
- <15 pg/L in children between 6 months and 3 years of age
- <5 pg/L for women (adults)
- <12 pg/L for men (adults)
Levels may slightly differ between laboratories.
Levels may also decrease with age and increase in chronic kidney disease, although the mechanism is still unclear .
Interestingly, some people with very low (removal of the thyroid) or very high calcitonin levels show no adverse effects related to calcium balance and have no other medical issues [11, 16].
Lab results are commonly shown as a set of values known as a “reference range”, which is sometimes referred to as a “normal range”. A reference range includes the upper and lower limits of a lab test based on a group of otherwise healthy people.
Your healthcare provider will compare your lab test results with reference values to see if any of your results fall outside the range of expected values. By doing so, you and your healthcare provider can gain clues to help identify possible conditions or diseases.
Remember that some lab-to-lab variability occurs due to differences in equipment, techniques, and chemicals used. Don’t panic if your result is slightly out of range – as long as it’s in the normal range based on the laboratory that did the testing, your value is normal.
However, it’s important to remember that a normal test doesn’t mean a particular medical condition is absent. Your doctor will interpret your results in conjunction with your medical history and other test results.
But remember that a single test isn’t enough to make a diagnosis. Your doctor will interpret this test, taking into account your medical history and other tests. A result that is slightly low/high may not be of medical significance, as this test often varies from day to day and from person to person.
High Levels & Thyroid Cancer
Elevated levels of calcitonin may indicate thyroid cancer (medullary cancer of the thyroid), the most common cause of high blood calcitonin .
However, high levels can also be due to:
- Lung cancer
- Kidney disease
- Drugs for acid reflux
Speak to your doctor if your calcitonin levels are high. He or she will ensure you get an accurate diagnosis and treatment.
Medullary thyroid carcinoma is a form of thyroid cancer that originates from thyroid C-cells, which produce calcitonin. This cancer triggers the production of calcitonin [17, 18].
According to some studies, levels higher than 60 pg/ml can indicate medullary thyroid carcinoma, whereas if the levels are between the cutoff range and 60 pg/ml, it could indicate C-cell hyperplasia (a genetic defect of the thyroid gland) .
In a clinical trial of 54 patients who were surgically treated for medullary thyroid carcinoma, those with calcitonin levels higher than 1 ng/ml (measured within 1 month after surgery) had a higher risk of cancer reappearing compared to those with lower levels .
Levels greater than 2 ng/ml after surgery were associated with lower cancer survival rate. However, levels measured before the surgery had no predictive effect on survival or disease recurrence .
Injections, tablets, or nasal spray, have been used to treat several conditions.
1) Osteoporosis in Postmenopausal Women
Calcitonin is indicated for treating osteoporosis in postmenopausal women when alternative treatments (estrogen products) are not suitable [21, 22, 23].
It is also safe to use in postmenopausal women who have both osteoporosis and chronic asthma .
In a clinical study (DB-RCT) of 1,255 postmenopausal women with osteoporosis, calcitonin nasal spray lowered the risk of spinal fractures compared to placebo, while increasing spine bone density .
In a study (DB-RCT) of 28 men with osteoporosis, calcitonin nasal spray increased bone density by 7% and decreased bone turnover more effectively than the placebo .
Clinical trials have shown that calcitonin maintains the bone mass in the lower back (but not in the femoral neck) by 3% higher compared to placebo. Its protective effect against bone mass loss was higher when patients received corticosteroids for more than 3 months .
Similarly, calcitonin nasal spray prevented bone loss in the lower back and resulted in a 1% decrease in bone density compared to 5% with placebo .
In a study (DB-RCT) of 90 healthy women, nasal calcitonin prevented the deterioration of the bones in the lower leg (tibia) and forearm (distal radius) .
However, its ability to reduce fracture risk has not been demonstrated. In a study (DB-RCT) of 4,665 postmenopausal women with osteoporosis showed that calcitonin did not prevent spinal or non-spinal fractures [23, 30].
Acute Pain in Osteoporosis
According to the evidence, calcitonin relieves acute but not chronic pain in osteoporosis. In a systematic review including 774 patients with osteoporosis, this hormone significantly reduced pain and/or improved daily function .
In another systematic review including 246 patients with osteoporosis, calcitonin therapy effectively reduced acute pain (in all functions including resting, sitting, standing, and walking) within one week after treatment .
A meta-analysis including 589 patients with spinal bone fractures due to osteoporosis showed that calcitonin relieved the acute pain of recent fractures but had no effect on chronic pain and older fractures .
Similarly, in 110 women with osteoporosis, calcitonin nasal spray did not have any effect on chronic pain and daily activities, irrespective of previous fractures or non-specific back pain .
Scientists hypothesize calcitonin may block pain in osteoporosis by [35, 36]:
- Decreasing serotonin transporters (SLC6A4), but increasing serotonin receptors (HTR1A).
- Altering the sodium channel transcription, which controls the excitability of nerves.
2) Paget’s Disease of Bone
Calcitonin is indicated for treating symptomatic Paget’s disease of bone when alternative treatments are not suitable .
Paget’s disease is a chronic condition that causes over-the-top breakdown and formation of bone tissue, which results in large, deformed, weak bones, and pain. It is common among older people and affects one or more bones .
In patients with Paget’s disease, the levels of the protein alkaline phosphatase are elevated and indicate the severity of the disease. Calcitonin reduces the activity of alkaline phosphatase, relieves bone pain, and increases bone blood vessels, which is vital for bone formation .
In a clinical study of 18 patients with Paget’s disease, both calcitonin nasal spray and injections lowered alkaline phosphatase levels .
Calcitonin is indicated for the treatment of hypercalcemia (elevated blood calcium levels). It has been used for this indication for many years [23, 40, 2].
In a randomized study of 40 patients, calcitonin injections effectively treated hypercalcemia within first 24 hours of treatment .
In 12 patients with acute hypercalcemia, this hormone reduced calcium levels and improved their clinical condition. However, it was less effective for malignant conditions .
Calcitonin lowers blood calcium levels by preventing bone-resorbing osteoclasts (bone cells) that release calcium from bones into the blood and by increasing calcium loss through the urine. Its effects can be seen within the first 6 hours of dosing .
For treatment of hypercalcemia (elevated calcium levels), it should be administered via injections as the nasal spray is not effective. Calcitonin serves as the first line of treatment .
Possibly Effective for:
Acute Phantom Limb Pain
People missing a limb, usually after an amputation, often experience pain where the limb used to be, a phenomenon known as “phantom limb pain” .
Limited research points to calcitonin as a potentially promising therapy, though the evidence is mixed. Large-scale studies are needed before the safety and efficacy of calcitonin in people with acute phantom limb pain is determined.
In a study (DB-RCT) of 21 patients with major amputations, a week after the first calcitonin treatment, 90% of the patients reported that their pain decreased by 50% or more, 76% of the patients were pain-free, and 71% of the patients never reported phantom limb pain again. A year later with calcitonin treatment, 8 out of the 13 surviving patients reported more than 75% pain relief .
A small clinical trial of 10 people with phantom limb pain showed that in 9 of them calcitonin immediately relieved pain symptoms .
On the contrary, a trial (DB-RCT) of 20 patients with chronic phantom limb pain showed that ketamine and not calcitonin was effective in pain relief and the combination of ketamine and calcitonin was less effective than ketamine alone .
Thus, calcitonin is likely not effective for chronic phantom limb pain.
Total Hip Replacement Pain
In an open clinical trial of 37 middle-aged women who had undergone total hip replacement, calcitonin nasal spray together with calcium and vitamin D supplements resulted in less dependence on assistance from others and less fear of falls. Furthermore, calcitonin decreased further bone density loss, relieved pain, and accelerated the repair of hip fractures .
Similar results were seen in a clinical study of 75 women after their total hip replacement, as calcitonin nasal spray significantly decreased pain, bone density loss, and bone turnover. It also decreased the risk of falls and fractures and accelerated hip repair .
Further clinical trials are needed to establish the safety and efficacy of calcitonin for total hip replacement pain.
Likely Ineffective for:
Lumbar Spinal Stenosis
Lumbar spinal stenosis is a chronic disease which causes narrowing of the spinal canal in the lower back, known as the lumbar area by an overgrown bone or bone tissue .
A meta-analysis concluded that calcitonin is not effective in increasing the walking distance or relieving the pain among patients with lumbar spinal stenosis .
Six more clinical trials showed that calcitonin injections were not more effective in pain relief than placebo or paracetamol (Tylenol). Moreover, some people complained about feelings of sickness or developed a rash .
In two DB-RCTs of 40 and 55 people with lumbar spinal stenosis, calcitonin nasal spray had no effect on the condition [54, 55].
On the contrary, a clinical trial of 90 patients with lumbar spinal stenosis showed that calcitonin nasal spray decreased the symptoms of the disease more effectively than an anti-epileptic drug (gabapentin) and the placebo .
Studies suggest that calcitonin acts on both osteoclasts (bone cells) and chondrocytes (cartilage cells), indicating that its mechanism may be helpful for osteoarthritis .
However, two clinical trials of 2,026 patients with osteoarthritis showed that it had no significant therapeutic effect .
Possibly Ineffective for:
Bipolar disorder or manic-depressive disorder is characterized by abnormal shifts in mood, energy, and activity levels. Mania is a phase of bipolar disorder during which the patient feels increased optimism, euphoria, and hyperactivity .
Double-blind trials conducted in the early 1980s showed that calcitonin injections decreased irritability, euphoria, and hyperactivity in mania patients. Although these results were promising, there were no follow-up studies .
Some scientists thought that calcitonin may stabilize the nerve function and prevent calcium signaling. According to this still unproven theory, calcitonin may assist the function of serotonin while opposing the function of dopamine. Both neurotransmitters have been associated with bipolar disorders .
However, a more recent clinical trial showed that calcitonin had no effect on 46 adults with treatment-resistant mania .
Insufficient Evidence for:
Bone Pain in Bone Metastasis
In a study of 20 patients with bone metastases, calcitonin injections decreased pain significantly compared to placebo .
In another clinical trial of 23 patients with multiple myeloma, calcitonin nasal spray together with calcium increased bone volume, cortical bone (the hard exterior of the bones) thickness, osteoid (the organic component of the bone) thickness and volume .
Large-scale clinical trials are lacking.
Jaw Tumor Recurrence
There is insufficient evidence about the effects of calcitonin on jaw tumor recurrence.
Giant cell lesions of the jaws (central giant cell granuloma) is a benign condition of the jaws and is more common among women and people aged between 20 and 40 .
In a double-blind clinical trial of 24 patients who had surgery for their central giant cell granuloma, calcitonin nasal spray decreased the risk of recurrence compared to placebo in both upper and lower jaws .
In a small study of 5 patients with giant cell lesions of the jaws, calcitonin decreased the lesions and there was no reappearance of the condition. Large-scale trials are warranted .
Types of Calcitonin
Nasal Spray (Miacalcin)
There are two calcitonin peptide drugs approved in the US, human and salmon calcitonin. Salmon calcitonin is more therapeutically effective than the human calcitonin .
Salmon calcitonin is the only marketed drug. It is FDA-approved and available in two forms [68, 69]:
- Injections (Calcitonin Salmon Injection)
- Nasal spray (known as Miacalcin)
The nasal spray is indicated for bone loss in women with osteoporosis. Women should make sure to get enough vitamin D and calcium when using Miacalcin. Your doctor may recommend supplements if your dietary intake is not enough .
Which Form Is More Effective?
In a double-blind study of 204 patients with spine fracture, calcitonin injections had the same pain-relief results as the nasal spray .
However, a systematic review including 246 patients with osteoporosis shows injections were more effective in decreasing acute pain than nasal sprays .
In another study (DB-RCT) in 565 women with osteoporosis, oral calcitonin caused a greater increase in hip, lower back, and total bone density and a larger decrease in bone loss markers compared to the nasal spray and placebo, while being equally safe and tolerable .
In patients with hypercalcemia (elevated calcium levels), the nasal spray was not effective whereas the injections lowered the calcium levels in the blood .
In patients with Paget’s disease, injections were more effective than the nasal spray .
For hypercalcemia, only the injections should be used.
Calcitonin is also being developed as tablets that are resistant to stomach acid. They suspect that water, food intake, and time of use may play an important role in the effectiveness of oral calcitonin. Taking the calcitonin tablet with 50 – 200 ml water, in the evening, 4 hours after eating and 1 hour before the next meal maximize its therapeutic effect [75, 76].
Calcitonin Side Effects & Precautions
This list does not cover all possible side effects. Contact your doctor or pharmacist if you notice any other side effects.
Call your doctor for medical advice about side effects. In the US, you may report side effects to the FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch. In Canada, you may report side effects to Health Canada at 1-866-234-2345.
Side Effects List
Calcitonin may cause gut-related side effects including [77, 72, 58]:
- Loose stools
- Stomach pain
- Dyspepsia (impaired digestion)
The following side effects have also been reported :
- Injection site inflammation
- Flushing of the face and hands
- Increased urination at night
- Eye pain
Calcitonin & Cancer Risk
The effects of calcitonin on cancer risk is still an area of research. However, a meta-analysis of 21 clinical trials suggested an increased risk of overall malignancies in calcitonin-salmon-treated patients .
In a study of 28,222 women with osteoporosis, calcitonin significantly elevated the risk of liver cancer but reduced the risk of breast cancer. However, the risk of liver cancer was higher only among the high-dose users .
A study of 9,995 patients with osteoporosis showed that calcitonin is correlated with a higher risk of cancer compared to bisphosphonates and selective estrogen receptor modulators (SERMs), both drugs used for osteoporosis .
However, a different review suggested that calcitonin does not cause or increase tumors and that there is no causal relationship between this hormone and cancer .
Warning: In Europe, calcitonin is not recommended for osteoporosis due to the risk of cancer. It is only recommended for short-term use for Paget’s disease, hypercalcemia, and acute bone loss.
In the US, the FDA recommends calcitonin for osteoporosis only if no other treatment is suitable. Patients should discuss the benefits and risks ratio with their doctors in detail before starting treatment [81, 82].
Calcitonin reduces lithium levels in the blood, as calcitonin increases the amount of lithium flushed with the urine. The dose of lithium may require adjustment .
Calcitonin vs. Parathyroid Hormone and Calcitriol
Parathyroid Hormone and Calcitonin
Parathyroid hormone is a hormone produced in the parathyroid gland, which is behind the thyroid gland. Its function is to increase calcium levels when they are too low. It triggers the release of calcium from bones to the blood, decreases the loss of calcium in the urine, and increases calcium absorption from food .
Basically, it has the opposite effect of calcitonin.
Both hormones are responsible for maintaining healthy levels of calcium in the blood and are used to treat osteoporosis. More research is needed to potentially discover a combination therapy .
Calcitonin and Calcitriol
Calcitriol is another molecule that acts in opposition to calcitonin. Calcitriol (1α,25-dihydroxyvitamin D3) is a by-product of vitamin D and is produced in the kidneys. Parathyroid hormone, low calcium, and low phosphate levels trigger its production .
Calcitriol increases calcium levels in the blood and can slow the progression of chronic kidney disease and decrease protein levels in the urine .
However, high levels of calcitriol can cause hypercalcemia (elevated calcium levels) .
The main function of calcitriol is to increase the uptake absorption of calcium from the gut. It also works together with parathyroid hormone .
In patients with medullary thyroid cancer, calcitriol reduces the production of calcitonin .
Calcitonin gene (CALCA)
The calcitonin-related polypeptide alpha gene (CALCA) produces three peptide hormones: calcitonin, calcitonin gene-related peptide, and katacalcin .
Some studies have linked having at least one C variant (CC or CT) in rs3781719 with an elevated risk of essential hypertension (high blood pressure) .
Genetic variations (706G>T, and 778C>T) have been correlated with osteoarthritis [92, 93].
Non-SNP genetic variations (microdeletion) may be related to increased risk of osteoporosis and lower bone density .
Also, other genetic variations in this gene (number of repeats) may be associated with bipolar disorder, though much more research is needed .
Calcitonin receptor (CALCR)
CALCR gene produces a G protein-coupled receptor that binds calcitonin .
The variant T in this SNP has been associated with kidney stones in one study .
Two meta-analyses suggested that the C variant is associated with increased bone density in the lumbar spine [98, 99].
Women with two T variants had decreased bone density and increased risk of osteoporosis, whereas the C variant was associated with increased bone density and lower risk of bone fractures [100, 101].
According to another study, the C variant was linked with reduced risk of fluorosis (bone disease induced by very high levels of fluoride in the bones) .
The T variant was associated with kidney stones risk [103, 104].