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). However, it is often accompanied by stomach side effects and increased risk of cancer. Read more about the benefits and side effects of calcitonin.
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 produced 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 the stomach acid to digest food .
- Reducing the osteoclast activity and bone loss. Osteoclasts are bone cells that break down bone tissue. This releases calcium into the bloodstream. By preventing the 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 .
Due to its pain-relieving effects and its ability to reduce the risk of fractures, it can be used as a treatment for hypercalcemia (elevated calcium levels) and bone diseases, such as osteoporosis and Paget’s disease [4, 8, 9].
Normal levels of calcitonin are :
<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 .
High Calcitonin May Indicate Thyroid Cancer
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 more or less effectively.
1) Calcitonin Helps Osteoporosis
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, another study (DB-RCT) of 4,665 postmenopausal women with osteoporosis showed that calcitonin did not prevent spinal or non-spinal fractures .
2) Calcitonin Relieves Pain
- Decreasing serotonin transporters (SLC6A4), but increasing serotonin receptors (HTR1A).
- Altering the sodium channel transcription, which controls the excitability of nerves.
Calcitonin Treats 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 .
Calcitonin May Relieve 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” .
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 may be effective with acute phantom limb pain but not with chronic phantom limb pain.
Calcitonin Helps Relieve 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 .
Calcitonin Reduces Bone Pain in Bone Metastasis
In a study of 20 patients with bone metastases, calcitonin injections decreased pain significantly compared to placebo .
It was also effective against bone lesions.
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 .
3) Calcitonin Helps with Jaw Tumor
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 significantly the risk of recurrence compared to placebo both in upper and lower jaws .
In a small study of 5 patients with giant cell lesions of the jaws, calcitonin significantly decreased the lesions and there was no reappearance of the condition .
4) Calcitonin Helps with Paget’s Disease
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 .
5) Calcitonin Can Treat Severe Hypercalcemia
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 .
Calcitonin May Not Work 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 .
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 it could be used as a treatment for osteoarthritis .
However, two clinical trials of 2,026 patients with osteoarthritis showed that it had no significant therapeutic effect .
In rats with induced osteoarthritis, calcitonin injections slowed the progression of the disease, reduced pain, and increased chondrocyte numbers .
Bipolar disorder or manic-depressive disorder is a brain dysfunction characterized by abnormal shifts in mood, energy, and activity levels. Mania is a phase of the 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 .
Calcitonin stabilizes the nerve function and prevents calcium signaling. It assists the function of serotonin while opposing the function of dopamine, both neurotransmitters associated with bipolar disorders .
However, a more recent clinical trial showed that calcitonin had no effect on 46 adults with treatment-resistant mania .
There are two calcitonin peptide drugs approved in the US, human and salmon calcitonin. Salmon calcitonin is more therapeutically effective than the human calcitonin .
It is also being developed as tablets .
Water, food intake, and time of use 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 .
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 .
Side Effects of Calcitonin
1) Calcitonin May Cause Adverse Stomach and Skin Effects
It can also cause skin irritations such as :
- Hot flashes
2) Calcitonin May Increase Cancer Risk
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 meta-analysis 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.
Calcitonin reduces lithium levels in the blood. Patients in lithium therapy need to adjust their treatment if they are also taking this hormone .
Calcitonin gene (CALCA)
The calcitonin-related polypeptide alpha gene (CALCA) produces three peptide hormones: calcitonin, calcitonin gene-related peptide, and katacalcin .
Non-SNP genetic variations (microdeletion) are 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 .
Calcitonin receptor (CALCR)
CALCR gene produces a G protein-coupled receptor that binds calcitonin .
The variant T in this SNP increases the risk of kidney stones .
The C variant reduces the risk of fluorosis (bone disease induced by very high levels of fluoride in the bones) .
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 discover a combination therapy .
Calcitonin and Calcitriol
This is another molecule that acts in opposition to calcitonin.
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 .