Calcitonin Injection

Number: 0803


Aetna considers calcitonin-salmon injection (Miacalcin injection) medically necessary for treatment of the following conditions:

  • Hypercalcemia
  • Individuals who present with an osteoporotic spinal compression fracture on imaging with correlating clinical signs and symptoms suggesting an acute injury (0 to 5 days after identifiable event or onset of symptoms) and who are neurologically intact.  (Note: Calcitonin treatment is considered medically necessary for 4 weeks for this indication).
  • Paget’s disease of bone (osteitis deformans)

Aetna considers calcitonin-salmon injection experimental and investigational for all other indications including the following (not an all-inclusive list) because its effectiveness for these indications has not been established:

  • Intraarticular injection for joint inflammation
  • Prevention and treatment of glucocorticoid-induced osteoporosis
  • Prevention and treatment of post-menopausal osteoporosis
  • Prevention and treatment of osteoarthritis
  • Prevention of osteoporosis including after organ or bone marrow transplantation
  • Treatment of Behcet's disease
  • Treatment of bone pain due to malignancy
  • Treatment of complex regional pain syndrome
  • Treatment of diabetic neuropathy
  • Treatment of lumbar facet joint osteoarthritis
  • Treatment of osteogenic sarcoma
  • Treatment of phantom limb pain
  • Treatment of regional migratory osteoporosis
  • Treatment of renal osteodystrophy
  • Treatment of rheumatoid arthritis
  • Treatment of spinal stenosis
  • Treatment of transient osteoporosis.

For Miacalcin (calcitonin-salmon) nasal spray, see pharmacy CPB on Bone Disease/Calcium Regulator Agents. 

Dosing Recommendations

The recommended dose of Miacalcin injection for treatment of symptomatic Paget's disease of bone is 100 International Units (0.5 mL) per day.

The recommended starting dose of Miacalcin injection for early treatment of hypercalcemia is 4 International Units/kg body weight every 12 hours by subcutaneous or intramuscular injection. The FDA-approved labeling for Micalcin states that, if the response to this dose is not satisfactory after one or two days, the dose may be increased to 8 International Units/kg every 12 hours. If the response remains unsatisfactory after two more days, the dose may be further increased to a maximum of 8 International Units/kg every 6 hours.

The recommended dose of Miacalcin injection for treatment of postmenopausal osteoporosis in women greater than 5 years postmenopause is 100 International Units (0.5 mL) per day administered subcutaneously or intramuscularly. The FDA-approved labeling states that the minimum effective dose of Miacalcin injection for the prevention of vertebral bone mineral density loss has not been established. Patients who use Miacalcin injection for treatment of postmenopausal osteoporosis should receive adequate calcium (at least 1000 mg elemental calcium per day) and vitamin D (at least 400 International Units per day).

The recommended dose of Miacalcin (calcitonin-salmon) nasal spray in post-menopausal osteoporotic females is 1 spray (200 I.U.) per day administered intra-nasally, alternating nostrils daily.


The National Osteoporosis Foundation Consensus Development Conference (2003) defined osteoporosis as a disease characterized by low bone mass and micro-architectural deterioration of bone tissue, leading to enhanced bone fragility and increased risk of hip, spine, and wrist fractures.  Osteoporosis is the most common bone disease in humans.  Approximately 10 million Americans (80 % of them women) suffer from osteoporosis.  For post-menopausal women, age, Asian or Hispanic heritage, cortisone use, family or personal history of fracture, as well as smoking have been associated with significantly increased likelihood of osteoporosis; while African American heritage, estrogen or diuretic use, exercise, as well as higher body mass index (BMI) have been associated with significantly decreased likelihood of osteoporosis (Siris et al, 2001).  Furthermore, Wu and colleagues (2002) reported that any fracture (unrelated to motor vehicle accidents) sustained between the ages of 20 and 50 years is associated with increased risk of fractures after the age of 50 years in women.  Although osteoporosis is usually considered a disease of women, up to 20 % of vertebral fractures and 30 % of hip fractures occur in men.  Risk factors for osteoporotic fractures in men include corticosteroid therapy, diseases that predispose to low bone mass, high alcohol consumption, low BMI, physical inactivity, and smoking (Eastell et al, 1998).  However, the exact mechanism of bone loss remains unknown in primary male osteoporosis (Legrand et al, 2001).

Calcitonin is a 32-amino acid peptide hormone secreted by the para-follicular cells of the thyroid gland in mammals and by the ultimo-branchial gland of birds and fishes.  Its direct actions on the osteoclast are responsible for its physiological effects as a hypocalcemic agent and a potent inhibitor of bone resorption.  

Per the Prescribing Information, calcitonin-salmon injection (Miacalcin injection) is indicated for the treatment of post-menopausal osteoporosis in women greater than 5 years post-menopause.

A joint meeting of the FDA's Reproductive Health Drugs and the Drug Safety Committee and its Risk Management Advisory Committee concluded that calcitonin salmon should no longer be used by women because there is little evidence it works and it may actually increase the risk of cancer. The committee members voted 12-9 that the risks of calcitonin exceed the benefits when used to treat osteoporosis. The combined FDA advisory panel also voted 20-1 that companies developing biotech versions of the salmon hormone must conduct trials to substantiate that their calcitonin products reduce the risk of fracture. The committees' concerns about safety and efficacy were based on data detailed in a that FDA reviewers released as background material for the meeting. The briefing document stated: "Intervention to reduce the risk of fracture is the standard for treatment of postmenopausal osteoporosis. Despite three fracture trials conducted, there remain significant questions regarding calcitonin salmon’s effectiveness in reducing fractures in postmenopausal women. This lack of effectiveness when combined with the potential for a cancer risk associated with calcitonin salmon therapy raises concerns about the overall risk and benefit assessment for calcitonin salmon products in the treatment of postmenopausal osteoporosis.

In 2012, the European Medicines Agency recommended against using calcitonin salmon long-term, after a research review showed a slight higher increase of cancer among patients who had used the drug for an extensive length of time to treat osteoporosis. Health Canada issued a statement warning of an increased risk of cancer with long-term use of calcitonin salmon products.

Lewiecki (2009) stated that adequate intake of calcium and vitamin D is recommended as baseline therapy for osteoporosis prevention and treatment.  Available pharmacological agents for the management of post-menopausal osteoporosis include oral bisphosphonates, which are generally considered first-line therapy for patients with osteoporosis, but their use may be limited by gastrointestinal side effects.  Other agents include calcitonin-salmon, hormone therapy, human recombinant parathyroid hormone (PTH) teriparatide (1-34 PTH), the selective estrogen-receptor modulator (SERM) raloxifene, and strontium ranelate, and rank ligand inhibitors (e.g., denosumab).  Emerging therapies for post-menopausal osteoporosis include novel SERMs (e.g., arzoxifene, bazedoxifene, lasofoxifene, ospemifene).

Calcitonin's role as a therapeutic option for glucocorticoid-induced osteoporosis (GIO) has not been established.  Reviews on GIO did not mention calcitonin as a treatment option.  De Nijs (2008) stated that pharmacotherapy for prevention of GIO is needed depending on the age and gender of the patient and sometimes BMI at the start of treatment, dosage of glucocorticoid, and expected duration of glucocorticoid treatment.  Bisphosphonates seem to be the first choice of pharmacological intervention for prevention and treatment of GIO.  There is no evidence that one specific bisphosphonate is superior to another bisphosphonate due to a lack of head-to-head studies on GIO.  Calcium and vitamin D3 supplementation are considered as important support for prevention and treatment of GIO.  Silverman and Lane (2009) noted that bone loss that accompanies glucocorticoid use is rapid, and early treatment with bone-sparing agents can prevent bone loss and reduce fracture risk.  Several randomized controlled clinical trials have found prevention and treatment of GIO with bisphosphonates, and recently the treatment of GIO with teriparatide, to be effective.  Compston (2010) stated that bisphosphonates are the front-line choice for prevention of fracture in glucocorticoid-treated patients, with teriparatide as the second-line option; calcium and vitamin D supplements should be co-prescribed in the majority of individuals.  Future guidelines for the management of GIO should include recently approved interventions (e.g., teriparatide and zoledronate). 

Furthermore, the Spanish Society of Internal Medicine's guidelines for the prevention and treatment of GIO (Sosa Henríquez et al, 2008) stated that treatment must be prescribed to any patient who is receiving glucocorticoids or is going to receive them at doses greater than 7.5 mg/day for more than 3 months and 5 mg/day if the patient is a post-menopausal woman or has suffered from previous fragility fractures.  Alendronate and risedronate are the mainstays for the management of patients with GIO, accompanied with calcium and vitamin D supplements; in very ill patients, PTH can be used.

Calcitonin has also been reported to be beneficial in the treatment of Paget’s disease of the bone (osteitis deformans) and hypercalcemia.  Paget disease of the bone is a disorder of uncertain etiology characterized by abnormal and accelerated bone formation and resorption in one or more bones.  In most patients, only small areas of bone are involved, and the disease is asymptomatic.  In a small number of patients, however, the abnormal bone may lead to bone deformity, cranial and spinal nerve entrapment, or spinal cord compression.  Furthermore, the increased vascularity of the abnormal bone may result in high-output congestive heart failure.  The effectiveness of calcitonin has been shown mainly in patients with moderate-to-severe disease characterized by polyostotic involvement with elevated serum alkaline phosphatase and urinary hydroxyproline excretion.  Whyte (2006) noted that medications for Paget's disease include various bisphosphonates and calcitonin-salmon injection.  The use of latter for Paget's disease has been largely supplanted by the use of the former, although treatment with calcitonin-salmon remains an option if bisphosphonates are not tolerated or contraindicated.  Furthermore, Saura (2007) stated that according to the Japanese guidelines for diagnosis and management of Paget's disease of the bone, calcitonin and etidronate are approved therapeutic agents for this condition and surgery is indicated for associated orthopedic problems (e.g., bone deformity, malignant soft-tissue tumor, osteosarcoma, and unstable fractures) in these patients.

Calcitonin injection has also been demonstrated to reduce elevated serum calcium of patients with carcinoma, multiple myeloma or primary hyper-parathyroidism.  In a review on drugs used in pediatric bone and calcium disorders, Cheung (2009) noted that hypercalcemia is treated initially with hyperhydration and diuretics, but may require more specific treatment with either bisphosphonates or calcitonin.  Several newer drugs have either recently been introduced or are under consideration.  These include bone morphogenic protein 2, calcimimetics (cinacalcet), calciolytic drugs, cathepsin K inhibitor, rank ligand inhibitors (denusomab and osteoprotegerin), and sclerostin.

Assadi (2009) stated that primary hyperparathyroidism and malignancy are responsible for greater than 90 % of all cases of hypercalcemia.  Compared with the hypercalcemia of malignancy, hyperparathyroidism tends to be associated with lower serum calcium levels (less than 12 mg/dL) and a longer duration of hypercalcemia (more than 6 months).  The hypercalcemic symptoms are usually fewer and subtle. Hyperparathyroidism tends to cause kidney calculi, hyperchloremic metabolic acidosis, and the characteristics of metabolic bone disease osteitis fibrosa cystica, but no anemia.  In contrast, hypercalcemia of malignancy is typically rapid in onset, with higher serum calcium levels, and more severe symptoms.  Patients so affected show marked anemia, but they never have kidney calculi or metabolic acidosis.  Parathyroid hormone assay is the most useful test for differentiating hyperparathyroidism from malignancy and other causes of hypercalcemia.  In hyperparathyroidism, serum PTH levels will be elevated.  In other cases, high serum calcium concentration usually results in suppression of PTH.  Treatment of hypercalcemia should commence with hydration; loop diuretics may be needed in patients with renal insufficiency or heart failure to prevent fluid over-load.  Calcitonin is administered for the immediate short-term management of severe symptomatic hypercalcemia.  For long-term control of severe or symptomatic hypercalcemia, the addition of bisphosphonates is typically required.  Among intravenous bisphosphonates, pamidronate and zoledronic acid are the agents of choice.

Calcitonin is also being used in the treatment of various conditions/diseases/disorders such as Behcet's disease, bone pain, complex regional pain syndrome, diabetic neuropathy, osteoarthritis, osteogenic sarcoma, renal osteodystrophy, and spinal stenosis, as well as prevention of osteoporosis following organ and bone marrow transplantations.  However, its effectiveness for these indications has not been established.

Calcitonin has been employed, however without much success, in the treatment of osteogenic sarcoma and renal osteodystrophy (AHFS, 2001).  In a Cochrane review, Martinez-Zapata et al (2006) evaluated the effectiveness of calcitonin in controlling metastatic bone pain and reducing bone complications (fractures, hypercalcemia, and nerve compression) in patients with bone metastases.  Electronic searches were performed in Medline (1966 to 2005), Embase (1974 to 2005), the Cochrane Central Register of Controlled Trials (Issue 2, 2005), specialized registers of the Cochrane Cancer Network and of the Cochrane Pain, Palliative and Supportive Care Group.  Registers of clinical trials in progress were also searched.  Studies were included if they were randomized, double-blind, clinical trials of patients with metastatic bone pain, treated with calcitonin, where the major outcome measure was pain, assessed at 4 weeks or longer.  Study selection and data extraction were performed by 2 independent review authors.  Only 2 studies (n = 90) were eligible for inclusion in the review and therefore meta-analysis of the data was not possible.  Intention-to-treat analysis was performed by imputing all missing values as adverse outcomes.  Of the 2 small studies included in the review, 1 study showed a non-significant effect of calcitonin in the number of patients with total pain reduction (relative risk [RR] 2.50; 95 % confidence interval [CI]: 0.55 to 11.41).  The second study provided no evidence that calcitonin reduced analgesia consumption (RR 1.05; 95 % CI: 0.90 to 1.21) in patients with painful bone metastases.  There was no evidence that calcitonin was effective in controlling complications due to bone metastases; and for improving quality of life or patients' survival.  Although not statistically significant, a greater number of adverse effects were observed in the groups given calcitonin in the 2 included studies (RR 3.35, (5 % CI: 0.72 to 15.66).  The authors concluded that the limited evidence currently available does not support the use of calcitonin to control pain from bone metastases.

In a review on diabetic neuropathy, Vinik (1999) stated that no definitive treatment is available for painful diabetic neuropathy.  Several medications have been used, among them antiepileptic drugs, calcitonin, dextromethorphan, local anesthetics, non-steroidal anti-inflammatory drugs, phenothiazines, and tricyclic antidepressants.  Moreover, calcitonin was not mentioned as a therapeutic option in recent reviews on management of neuropathic pain.  Gilron and colleagues (2006) noted that pharmacotherapy includes gabapentin, mixed serotonin-norepinephrine reuptake inhibitors, opioids, pregabalin, topical lidocaine, tramadol, and tricyclic antidepressants.  Baron (2009) stated that the medical management of neuropathic pain consists of 5 main classes of oral medication (anticonvulsants with calcium-modulating actions, anticonvulsants with sodium-blocking action, antidepressants with reuptake blocking effect, opioids, and tramadol) and several categories of topical medications for patients with cutaneous allodynia and hyperalgesia (e.g., capsaicin and local anesthetics).

Vranken (2009) stated that while many options are available for relieving neuropathic pain, there is no consensus on the most appropriate therapy.  However, recommendations can be proposed for first-line, second-line, and third-line pharmacotherapies based on the level of evidence for the different treatment strategies.  Beside opioids, the available therapies shown to be effective in managing neuropathic pain include anticonvulsants, antidepressants, ketamine, and topical treatments (e.g., capsaicin and lidocaine patch).  Tricyclic antidepressants are often the first drugs selected to alleviate neuropathic pain (first-line pharmacological treatment).  Although they are very effective in reducing pain in several neuropathic pain disorders, treatment may be compromised by their side effects.  In patients with a history of cardiovascular disorders, glaucoma, and urine retention, gabapentine and pregabalin are emerging as first-line treatment for neuropathic pain.  In addition these anti-epileptic drugs have a favorable safety profile with minimal concerns regarding drug interactions and showing no interference with hepatic enzymes.  Despite the many treatment options available for relieving neuropathic pain, the most appropriate treatment strategy is only able to reduce pain in 70 % of these patients.  In the remaining patients, combination therapies using 2 or more analgesics with different mechanisms of action may also offer adequate pain relief.  Although combination treatment is clinical practice and may result in greater pain relief, trials regarding different combinations of analgesics are lacking.  Additionally, 10 % of patients still experience intractable pain and are refractory to all forms of pharmacotherapy.  If medical treatments fail, invasive therapies such as intrathecal drug administration and neurosurgical interventions may be considered.

Karsdal et al (2007) noted that several lines of evidence suggest direct anabolic effects of calcitonin on articular chondrocytes, resulting in increased proteoglycan synthesis, which may prove calcitonin to be beneficial for the prevention and treatment of osteoarthritis.  Chesnut et al (2008) noted that calcitonin-salmon demonstrates clinical utility in the treatment of such metabolic bone diseases as osteoporosis and Paget's disease, and potentially in the treatment of osteoarthritis.  In a review on non-surgical treatment of osteoarthritis of large joints, Wagner (2009) listed bisphosphonates, calcitonin, and interleukin-1 antagonists as experimental drugs for this condition.

The Institute for Clinical Systems Improvement's guideline on diagnosis and treatment of osteoporosis (ICSI, 2008) stated that studies demonstrate that standard calcium and vitamin D supplementation, with or without calcitonin, are unable to prevent osteoporosis following organ or bone marrow transplantation.  Palmer et al (2005) evaluated the evidence available to guide targeted treatment to reduce bone disease in transplant recipients.  The Cochrane CENTRAL Registry, Medline, and Embase were searched for randomized trials of interventions for bone disease after renal transplantation.  Data were extracted on acute graft rejection, adverse events, bone mineral density (BMD) by means of dual-energy X-ray absorptiometry, and fracture.  Analysis was performed with a random-effects model, and all results are expressed as RR with 95 % CIs.  A total of 23 eligible trials (n = 1,209) were identified.  No trial found a reduction in risk for fracture.  Bisphosphonates (7 trials; n = 268; weighted mean difference [WMD], 7.66; 95 % CI: 4.82 to 10.50), vitamin D analogs (2 trials; n = 51; WMD, 6.13; 95 % CI: 4.97 to 7.29), and calcitonin (1 trial; n = 31; WMD, 5.00; 95 % CI: 0.88 to 9.12) favorably affected the percentage of change in BMD at the lumbar spine compared with no treatment.  Bisphosphonates (4 trials; n = 149; WMD, 7.18; 95 % CI: 6.22 to 8.13) and vitamin D analogs (2 trials; n = 51; WMD, 3.73; 95 % CI: 2.71 to 4.75), but not calcitonin (1 trial; n = 31; WMD, -0.30; 95 % CI: -5.00 to 4.40), had a favorable effect on BMD measured at the femoral neck compared with no treatment.  The incidence of reported toxicity was low.  The authors concluded that the trials were inadequately powered to show a reduction in risk for fracture.  Bisphosphonates and vitamin D have a beneficial effect on BMD at the lumbar spine and femoral neck.  With increasing survival after renal transplantation, this study emphasized the importance of randomized controlled trial (RCT) evidence of interventions of bone disease after renal transplantation.

In a randomized, single-blind study, Sahin et al (2009) compared the effectiveness of physical therapy alone and in combination with calcitonin in patients with neurogenic claudication (NC).  Patients with lumbar spinal canal stenosis who were diagnosed by clinical findings and magnetic resonance imaging and having NC were included.  They were observed for 8 weeks and evaluated before and after treatment.  Patients were randomized between the calcitonin-salmon 200 U/day + physical therapy (n = 23; group 1) and paracetamol 1,500 mg/day + physical therapy (n = 22; group 2) treatment groups.  Both groups received the same physical therapy (hot pack + interferential current + short wave diathermy) and exercise protocol.  The association of various clinical and functional parameters was assessed statistically by using paired and unpaired t-tests, Chi-square test and McNemar's test; p < 0.05 indicated statistical significance.  Mean ages of the patients were 57.6 +/- 11.2 years and 2 54.5 +/- 10.6 years for group 1 and group 2, respectively.  Before treatment, there were no significant differences between groups with respect to age, BMI, spinal axial diameter, visual analog scale (VAS), spinal mobility, functional status and walking distance (p > 0.05).  After 8 weeks of treatment, both groups benefited significantly with respect to VAS, functional status and walking distance (p < 0.001).  There was no statistically significant difference between groups (p > 0.05).  The authors concluded that in patients with lumbar spinal stenosis who received 8 weeks of treatment, concomitant use of calcitonin with physical therapy and exercise did not have any beneficial effect on the patient's pain, functional status, lumbar mobility and walking distance.

In a systematic review, Coronado-Zarco and colleagues (2009) examined the effectiveness of calcitonin on the treatment of NC in patients with lumbar spinal stenosis.  These investigators performed a search on electronic databases that included Medline and Embase; they recovered 10 original articles, of which only 4 fulfilled the RCT criteria.  These articles were reviewed independently by 6 reviewers to extract data and their quality scored by the criteria of Cochrane Handbook (with maximum score of 1.00 and minimum score of 0.33).  Score quality vary in the 4 articles.  Due to the great heterogenicity observed (doses, duration and frequency of calcitonin, outcome measurements, sample sizes, and selection criteria), these researchers were unable to perform a meta-analysis.  Only 1 of these studies found favorable results for the use of calcitonin compared with placebo; of the 3 remaining trials, none found significant evidence between drug therapy and placebo.  The authors concluded that the present data suggest that calcitonin administration in the treatment for NC has no benefit in patients with lumbar spinal stenosis.  Furthermore, the North American Spine Society's guideline on diagnosis and treatment of degenerative lumbar spinal stenosis (2007) stated that there is little evidence that pharmacotherapies, including intramuscular calcitonin, intranasal calcitonin, intravenous lipo-prostaglandin E1, or methyl-cobalamin provides long-term benefit in patients with lumbar spinal stenosis.

Qin and associates (2009) noted that the treatment of Behcet's disease, a chronic, multi-system inflammatory disorder, continues to be a major therapeutic challenge.  Exogenous calcitonin is thought to cross the blood-brain barrier and to accumulate slowly in the brain, inducing analgesia once sufficient receptors are occupied.  Since calcitonin could antagonize resorptive and analgesic activity by competitively binding to calcitonin receptor and has been considered as a specific antagonist, these researchers postulated that the calcitonin could function as a novel agent to inhibit Behcet's disease.

Tran and associates (2010) reviewed the evidence derived from RCTs pertaining to the treatment of complex regional pain syndrome.  The search criteria yielded 41 RCTs with a mean of 31.7 subjects per study.  Blinded assessment and sample size justification were provided in 70.7 % and 19.5 % of RCTs, respectively.  Only bisphosphonates appear to offer clear benefits for patients with complex regional pain syndrome.  Improvement has been reported with dimethyl sulfoxide, epidural clonidine, intrathecal baclofen, motor imagery programs, spinal cord stimulation, and steroids, but further trials are required.  The available evidence does not support the use of calcitonin, vasodilators, or sympatholytic and neuromodulative intravenous regional blockade.  Clear benefits have not been reported with gabapentin, mannitol, occupational/physical therapy, and lumbar/stellate sympathetic blocks.

The American Academy of Orthopaedic Surgeons' guideline on the treatment of symptomatic osteoporotic spinal compression fractures (AAOS, 2010) recommended that patients who present with an osteoporotic spinal compression fracture on imaging with correlating clinical signs and symptoms suggesting an acute injury (0 to 5 days after identifiable event or onset of symptoms) and who are neurologically intact be treated with calcitonin for 4 weeks.

In a randomized, placebo-controlled, double-blind trial, Pappa et al (2011) examined the safety and effectiveness of intra-nasal calcitonin in improving BMD in young patients with inflammatory bowel disease (IBD) and defined additional factors that impact bone mineral accrual.  A total of 63 subjects, aged 8 to 21 years, with a spinal BMD Z-score less than or equal to -1.0 S.D. measured by dual energy X-ray absorptiometry were included in this study.  Subjects were randomized to 200 IU intra-nasal calcitonin (n = 31) or placebo (n = 32) daily.  All received age-appropriate calcium and vitamin D supplementation.  Subsequent BMD measurements were obtained at 9 and 18 months.  Intra-nasal calcitonin was well-tolerated.  Adverse event frequency was similar in both treatment groups, and such events were primarily minor, reversible, and limited to the upper respiratory tract.  The BMD Z-score change documented at screening and 9 months and screening and 18 months did not differ between the 2 therapeutic arms.  In participants with Crohn's disease, the spinal BMD Z-score improved between screening and 9 months (change in spine BMD Z-score (ΔZSBMD)(9-0)) in the calcitonin group (ΔZSBMD(9-0)(calcitonin) = 0.21 (0.37), ΔZSBMD(9-0)(placebo) = -0.15 (0.5), p = 0.02); however, this was only a secondary subgroup analysis.  Bone mineral accrual rate during the trial did not lead to normalization of BMD Z-score in this cohort.  Factors favoring higher bone mineral accrual rate were lower baseline BMD and higher baseline body mass index Z-score, improvement in height Z-score, higher serum albumin, hematocrit and iron concentration, and more hours of weekly weight-bearing activity.  Factors associated with lower bone mineral accrual rate were more severe disease -- as indicated by elevated inflammatory markers, need for surgery, hospitalization, and the use of immunomodulators -- and higher daily caffeine intake.  The authors concluded that intra-nasal calcitonin is well-tolerated but does not offer a long-term advantage in youth with IBD and decreased BMD.  Bone mineral accrual rate remains compromised in youth with IBD and low BMD raising concerns for long-term bone health outcomes.  Improvement in nutritional status, catch-up linear growth, control of inflammation, increase in weight-bearing activity, and lower daily caffeine intake may be helpful in restoring bone density in children with IBD and low BMD.

In a case-report, Turek and Wigton (2012) described the use of calcitonin to relieve severe, treatment-refractory phantom limb pain (PLP).  After an above-knee leg amputation, a 29-year old pregnant woman (at 8 weeks gestation) reported severe PLP (consistent scores of 9 or 10 on a 10-point pain severity scale).  The pain persisted for more than 2 weeks and was not relieved by multiple regimens of opioid and non-opioid medications, including extremely high doses of intravenous fentanyl.  On post-amputation day 16, a 30-min intravenous infusion of 200 IU of calcitonin (salmon) was administered; the woman reported transient excruciating pain during the final 5 mins of the infusion.  There was little overall change in her pain status over the next 3 days.  On post-infusion day 4, the patient reported reductions in the frequency and severity of PLP episodes, and a trend of improved PLP symptom control was noted over the next 48 hours, allowing the pain management team to begin tapering some medication dosages and thus reduce the woman's overall narcotic exposure.  The patient was discharged to a nursing facility several weeks later with relatively stable pain (scores of less than7) on a regimen of carbamazepine, gabapentin, and oxycodone.  She eventually delivered a healthy full-term baby.  The authors concluded that reduction in the frequency of PLP attacks and a lessening of pain intensity were observed after administration of calcitonin (salmon) by intravenous infusion in a pregnant patient. Calcitonin therapy was not associated with any apparent long-term adverse effects to the patient or infant.  This finding from a single case study needs to be validated by well-designed studies.

Calcitonin Salmon Nasal Spray

Overgaard et al (1995) performed a sub-analysis of results from a randomized, double-blind, placebo-controlled, parallel-group, 2-year study to evaluate the response of individual patients to therapy with 200 IU/day calcitonin salmon nasal spray compared with placebo in post-menopausal women who had low bone mass. All patients received 500 mg/day of oral supplemental calcium.  A response to therapy was defined as an increase from baseline in lumbar vertebral BMD, measured by use of dual-energy x-ray absorptiometry, at the end of 2 years of treatment.  Of 41 valid completers (i.e., patients who met the entry criteria, were compliant with the protocol, and completed the study) treated with calcitonin salmon nasal spray, 31 (76 %) responded positively to treatment.  Of 40 valid completers who received placebo, 25 (63 %) lost bone mass (p = 0.001 between groups).  The relative risk of bone loss for patients receiving calcitonin salmon nasal spray was 0.19 (95 % CI: 0.07 to 0.50), representing an 81 % risk reduction.  The authors concluded that this sub-analysis demonstrated that the benefits of calcitonin salmon nasal spray therapy were seen in the majority of women studied.  They stated that calcitonin salmon nasal spray represented an effective therapeutic alternative for osteoporotic women more than 5 years post-menopause who reject or cannot tolerate estrogens or for whom estrogens are contraindicated.

Plosker and McTavish (1996) stated that intra-nasal salcatonin (salmon calcitonin) inhibits osteoclastic bone resorption and is approximately 40 to 50 times more potent than human calcitonin. In most randomized trials in which intra-nasal salcatonin (usually 50 to 200 IU/day plus oral calcium supplements) was administered for 1 to 5 years to post-menopausal women for prevention of osteoporosis, BMD or content of the lumbar spine increased by approximately 1 to 3 % from baseline.  In contrast, post-menopausal women receiving only oral calcium supplements typically had reductions in BMD or content of about 3 to 6 %.  The difference between treatment groups was statistically significant in essentially all studies.  Although changes in BMD or content were broadly similar in studies of post-menopausal women with established osteoporosis to those in post-menopausal women receiving therapy for prevention of the disease, studies in women with established osteoporosis did not usually demonstrated statistically significant differences between treatment groups.  Also in post-menopausal women with established osteoporosis, intra-nasal salcatonin reduced pain and/or analgesic consumption in some trials and, in a limited number of studies of relatively short duration (i.e., less than or equal to 2 years), the incidence of osteoporotic fractures.  A large multi-center 5-year study with adequate statistical power to confirm the effect of intra-nasal salcatonin on reducing osteoporotic fracture rates in post-menopausal women is currently under way.  The intra-nasal formulation of salcatonin offered a more convenient and better tolerated alternative to the parenteral formulation of the drug which is administered by regular subcutaneous or intra-muscular injections.  Adverse events associated with the intra-nasal formulation are generally mild and transient, usually involving local reactions such as nasal discomfort, rhinorrhea or rhinitis.  The authors concluded that for post-menopausal women unable or unwilling to tolerate long-term hormone replacement therapy, intra-nasal salcatonin is an attractive alternative for the management of osteoporosis.

In a 1-year, prospective, open, RCT, Kaskani and colleagues (2005) examined the effect of intermittent administration of 200 IU intra-nasal salmon calcitonin and 1alpha(OH) vitamin D3 [1alpha(OH)D3] on BMD of the lumbar spine and hip as well as on the markers of bone metabolism in women with post-menopausal osteoporosis. A total of 102 randomly recruited women received either 200 IU intra-nasal salmon calcitonin (Miacalcic nasal 200) daily, 1 month on-1 month off, 0.25 mug 1alpha(OH)D3, and 500 mg elemental calcium continuously (n = 57 women) or only 0.25 mug 1alpha(OH)D3 and 500 mg calcium (n = 45 women) for a period of 1 year; BMD of the lumbar spine and hip plus biochemical markers reflecting calcium (Ca) metabolism and bone turnover [serum Ca, serum phosphorus, intact parathyroid hormone (iPTH), total and bone-specific alkaline phosphatase, osteocalcin levels, 24-h urinary Ca, morning fasting urinary Ca/creatinine, and Pyrilinks-D/creatinine ratio] were measured at the beginning of the study before treatment and after 6 and 12 months of treatment.  Baseline characteristics of participants, including age, BMI, lumbar and hip BMD, and biochemical markers were similar between the 2 groups.  A total of 91 patients completed the study (50 in the salmon calcitonin nasal spray group and 41 in the other group).  Lumbar BMD increased significantly in the salmon calcitonin group from baseline (3.0 %, p = 0.005) and in comparison to the non-calcitonin-treated group (p = 0.009).  The salmon calcitonin group also had a significant increase in femoral neck BMD compared with baseline values (3.1 %, p = 0.0005) and in comparison to the non-calcitonin-treated group (p = 0.0005) in Ward's triangle BMD (2.9 % from baseline values, p = 0.009) and in comparison to the non-calcitonin-treated group (p = 0.005) in trochanteric BMD (3.4 % from baseline values, p = 0.007) and in comparison to the non-calcitonin-treated group (p = 0.01).  Urinary Ca/creatinine and Pyrilinks-D/creatinine levels were significantly decreased from baseline in the salmon calcitonin-treated group (-6.1 and -6.3 %, respectively, p = 0.001).  Bone-specific alkaline phosphatase levels were also significantly decreased from baseline in the salmon calcitonin-treated group (-3.6 %, p = 0.003).  In the same group, a significant decrease in iPTH serum levels compared to baseline values (-2.5 %, p = 0.005) and in comparison to the non-calcitonin-treated group (p = 0.005) was noted.  The authors concluded that 1-year intermittent treatment with 200 IU intra-nasal salmon calcitonin and low doses of 1alpha(OH)D3 produced a significant effect on bone turnover and BMD in post-menopausal women with osteoporosis.

Per the Prescribing Information, Miacalcin (calcitonin-salmon) nasal spray is indicated for the treatment of post-menopausal osteoporosis in females greater than 5 years post-menopause with low bone mass relative to healthy premenopausal females.  Miacalcin nasal spray should be reserved for patients who refuse or cannot tolerate estrogens or in whom estrogens are contraindicated.  Use of Miacalcin nasal spray is recommended in conjunction with an adequate calcium (at least 1,000 mg elemental calcium per day) and vitamin D (400 I.U. per day) intake to retard the progressive loss of bone mass.

Regional Migratory Osteoporosis

Regional migratory osteoporosis (RMO) is a migrating arthralgia of the weight-bearing joints of the lower limb that mainly affects middle-aged men.  Its etiology is unknown.  Aguilera and colleagues (1994) reported 2 cases of RMO.  One was a 41-year old man, with the classical form, presenting with successive episodes of painful osteoporosis lasting for 5 months at the hip, knee and distal epiphysis of the right metatarsophalangeal joints.  The second case was a 40-year old woman presenting with an unusual disseminated form, lasting for 30 months, with successive and simultaneous episodes of poly-articular and costal painful osteoporosis.  An increased bone fraction of serum alkaline phosphatases and urine hydroxyproline/creatinine and calcium/creatinine ratios were detected.  Imaging showed localized peri-articular or costal osteoporosis.  Bone biopsies disclosed a severe osteopenia with accelerated bone reabsorption.  Bone scintigraphy precociously detected location, migration and evolution of lesions.  Patients were treated with subcutaneous calcitonin, 100 U/day during 1 month and on alternative days posteriorly; this treatment alleviated pain but did not prevent the appearance of new crisis.  The authors concluded that these findings suggested that regional migratory osteoporosis presentation may range from oligo-articular to disseminated forms and that calcitonin has a precocious and persistent analgesic effect.

Straten and associates (2009) reported the first case of RMO in a patient with ankylosing spondylitis (AS).  This middle-aged man suffered from an acute onset of knee pain that increased on weight-bearing, followed by ankle pain.  The diagnosis of RMO was confirmed using magnetic resonance imaging (MRI), after exclusion of other causes of knee pain.  MRI revealed a large area of bone marrow edema without a zone of demarcation or subchondral fracture with a demonstration of shifting marrow edema on the follow-up MRI scan from the medial femur condyl to the tibia plateau lateral and then to the distal tibia epiphysis.  Treatment with the bisphosphonate ibandronate, however, was unsuccessful.  RMO is characterized clinically by migrating arthralgia of the weight-bearing joints of the lower limbs, mainly in middle-aged men.  Although the etiology is unknown, the pathophysiology of RMO appeared to be closely related to transient osteoporosis of the hip (TOH), which has been considered a reversible stage of avascular necrosis of the hip (AVN).  There is no causal treatment for RMO.  Avoidance of weight-bearing and use of analgesics are effective in reducing symptoms.  The combination of RMO and AS yielded diagnostic difficulties, as the clinical picture and the marrow edema seen on MRI could be attributed to several AS-related causes such as enthesitis, early stadium of arthritis, osteonecrosis, or sterile osteomyelitis.

Transient Osteoporosis

Samdani and associates (1998) noted that transient osteoporosis associated with pregnancy is a rare, self-limiting skeletal disorder, the origin of which remains unclear.  These researchers reported the case of a 36-year old Japanese woman who developed pain in the left hip, groin, and knee in the seventh month of pregnancy.  The pain gradually worsened and prevented weight-bearing.  The hip and knee pain progressed to bilateral involvement and persisted after an emergent cesarean section at 35 weeks.  Radiographs after delivery revealed gross osteopenia of both the femoral heads, left distal femur, and proximal tibia, consistent with transient osteoporosis associated with pregnancy.  The patient remained mostly wheelchair-dependent because of severe hip and knee pain.  Several weeks later, the patient was started on alendronate, which provided dramatic relief of hip and knee pain.  The patient's ambulatory function subsequently improved dramatically as a result of pain relief and assistance with gait training.  The authors stated that this case was unique for several reasons:
  1. it is rare for transient osteoporosis associated with pregnancy to involve both hip joints, and it rarely involves the knee,
  2. this is the first reported case of pain management of transient osteoporosis associated with pregnancy being successfully treated with an anti-resorptive agent, and
  3. the use of alendronate in transient osteoporosis associated with pregnancy may help shorten disability by providing pain relief and decreasing the fracture risk associated with this disease.

Arayssi and colleagues (2003) stated that TOH is a rare clinical disorder of unknown etiology characterized by hip pain and functional disability that resolve spontaneously in 6 to 24 months.  These investigators reported 2 patients with TOH during pregnancy who had rapid resolution of their illness with the use of calcitonin.  They reviewed the literature on TOH with special emphasis on its treatment.  A Medline search of studies published from 1966 to 2002 was performed to review the therapeutic options for TOH and their effect on the natural history of the disease.  These 2 patients developed hip pain during pregnancy with classical changes of TOH on MRI.  Both patients received calcitonin, 1 during pregnancy and 1 post-partum with resolution of their symptoms within 6 to 9 weeks.  Previous reports in the literature of treatment of TOH showed that anti-resorptive agents (bisphosphonates and calcitonin) had shortened the duration of the illness compared with the natural history of the disease.  The authors concluded that TOH is an under-recognized entity associated with pain and disability; and the use of anti-resorptive agents may be of help in reducing the duration of the disease.

Laktasic-Zerjavic and co-workers (2007) reported on a case of TOH during pregnancy that was rapidly resolved with the use of calcitonin.  An accurate diagnosis was made 2 months after the onset of symptoms (4 weeks post-partum) based on findings in the form of bone marrow edema of the right hip by MRI.  The patient received calcitonin for 8 weeks and the beneficial effect was observed after 3 weeks of therapy with full resolution of symptoms after 8 weeks of therapy (4 months after onset of symptoms).  The authors suggested that the use of calcitonin may be considered as a therapeutic intervention to shorten the disease duration.

Intraarticular Injection for Joint Inflammation

Sladek and colleagues (2018) noted that polyelectrolyte nanoparticle constructs (NPs) comprising salmon calcitonin (sCT), chitosan (CS), and hyaluronic acid (HA) were previously established as having anti-inflammatory potential when injected via the intra-articular (i.a.) route to a mouse model.  These researchers attempted to translate the formulation to a large animal model, the lipopolysaccharide (LPS)-stimulated equine model of joint inflammation.  The objective was to manufacture under aseptic conditions to produce sterile pyrogen-free NPs, to confirm physicochemical characteristics, and to test toxicity and efficacy in a pilot study.  Polyelectrolyte nanoparticle constructs dispersions were successfully formulated using pharmaceutical-grade source materials and were aseptically manufactured under GMP-simulated conditions in a grade A modular aseptic processing work-station.  The NP formulation had no detectable pathogen or endotoxin contamination; NPs were then tested versus a lactated Ringer's solution control following single i.a. injections to the radio-carpal joints of 2 groups of 4 horses pre-treated with LPS, followed by arthrocentesis at set intervals over 1 week.  There was no evidence of treatment-related toxicity over the period.  While there were no differences between clinical read-outs of the NP and the control, 2 synovial fluid-derived biomarkers associated with cartilage turnover revealed a beneficial effect of NPs.  The authors concluded that  NPs comprising well-known materials were manufactured for an equine i.a.-injectable pilot study and yielded no NP-attributable toxicity.  Evidence of NP-associated benefit at the level of secondary end-points was detected as a result of decreases in synovial fluid inflammatory biomarkers. 

Lumbar Facet Joint Osteoarthritis

Guo and colleagues (2019) examined the effects of sCT and celecoxib (CLX) on cartilage, subchondral bone and tactile allodynia in a rat model of lumbar facet joint (FJ) osteo-arthritis (OA).  A total of 40 male Sprague-Dawley rats (3-month old) were randomly divided into 4 groups: 30 received surgical collagenase (type II) injections in the right L3 to L6 facet joints followed by 8 weeks of treatment with normal saline, CLX or sCT, and the other 10 received sham surgery.  Tactile allodynia, changes of cartilage and subchondral bone of the L4 to L5 FJs, and serum biomarkers were analyzed for all rats.  Both sCT and CLX ameliorated cartilage lesions, significantly increased aggrecan expression and decreased caspase-3 expression.  sCT also decreased the expression of a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS-4).  According to the micro-computed tomography (micro-CT) analysis, sCT significantly improved micro-architecture parameters of subchondral bone and micro-CT score; and inhibited articular process hypertrophy.  CLX showed better anti-hyperalgesic effects than sCT on days 3 and 7 post-operatively despite no statistical differences, whereas sCT possessed better analgesic effects than CLX on days 42 and 56.  In addition, the sCT treatment reduced the elevated cartilage oligomeric matrix protein (COMP) concentration in rats injected with collagenase (type II).  The authors concluded that both sCT and CLX exerted preventive effects on FJ OA caused by collagenase (type II), but sCT showed more protective effects, especially on maintaining cartilage metabolism, restraining the deterioration of the subchondral bone microarchitecture and tactile allodynia, and reducing serum COMP concentrations.

Rheumatoid Arthritis

Katri and colleagues (2019) noted that pain is a debilitating symptom of rheumatoid arthritis (RA), caused by joint inflammation and cartilage and bone destruction.  Non-steroidal anti-inflammatory drugs (NSAIDs) are used to treat pain and inflammation in RA, but are not disease-modifying and do not prevent joint destruction when administered alone.  KBPs (Key Bioscience peptides) are synthetic peptides based on sCT and are expected to inhibit bone resorption and to be chondro-protective.  These investigators examined if combining a standard of care NSAID (naproxen) with a KBP resulted in improvement in pain scores, as well as disease activity and structural damage in a rat model of RA.  Collagen-induced arthritis (CIA) was induced in 40 female Lewis rats by immunization with porcine type II collagen; 10 rats were given sham injections.  CIA rats were treated with KBP and/or naproxen.  Health scores and joint scores were evaluated daily.  Mechanical and cold allodynia tests and burrowing tests were used to assess pain-like behaviors.  Blood samples were collected for biomarker testing, and paws were collected for histology and micro-CT.  Naproxen monotherapy increased the time until humane end-points was reached, and improved health score, pain assessments, and trabecular thickness, while KBP monotherapy did not result in improvements.  Combination therapy had improved efficacy over naproxen monotherapy; combination therapy resulted in improved health scores, and importantly reduced mechanical and cold allodynia assessment.  Furthermore, protection of articular cartilage structure and preservation of bone structure and bone volume were also observed.  The authors concluded that the findings of this study showed that combining KBP and naproxen may be a relevant therapeutic strategy for RA, resulting in improvements to the overall health, pain, inflammation, and joint structure.

Metastatic Bone Pain

Jain and Chatterjee (2020) stated that injection calcitonin is a natural hormone inhibiting osteoclastic bone resorption have been used as an analgesic to control bone metastasis pain or pain due to osteoporosis or fracture.  In a randomized, double-blind, placebo-controlled study, these researchers determined the role of injection Salmon Calcitonin therapy to control refractory pain caused due to bone metastasis arising from cancer breast, lung, prostate or kidney.  All patients had received palliative radiotherapy and were suffering unsatisfactory pain relief on NSAIDs and tab morphine.  Fourteen days of calcitonin injection or placebo injections were administered in 23 patients initially as high dose induction dose (800 IU per day subcutaneous [SC]) followed 200 IU SC once-daily.  Patients were assessed for pain intensity and quality of life (QOL) on EORTC QLQ-30 questionnaire 6 hourly for 2 days and on seventh and 30th day.  Any incidence of hypercalcemia, bone fracture, nerve root and bone marrow compression were also noted.  This study found a significant reduction in pain after SC calcitonin injection therapy at 14 and 30 days' assessment.  No patients in the study group needed rescue analgesia after 18 hours.  There was a statistically significant difference in rescue analgesics needed between the groups during 2 days hospitalization.  Global health as well as physical and social well-being was better at 30 and 90 days in the study group as compared to control group, however it could not reach a statistical significance which may be attributed to the small sample size of the study.  Moreover, these researchers stated that the findings of this randomized, double-blind trial should be considered as a pilot study for conducting a large, double-blind RCT on injection calcitonin for metastatic bone pain, which may show its exact effectiveness to control pain in refractory clinical settings.

Table: CPT Codes / HCPCS Codes / ICD-10 Codes
Code Code Description

Information in the [brackets] below has been added for clarification purposes.   Codes requiring a 7th character are represented by "+":

CPT codes related to the CPB:

20610 Arthrocentesis, aspiration and/or injection, major joint or bursa (eg, shoulder, hip, knee, subacromial bursa); without ultrasound guidance
20611 Arthrocentesis, aspiration and/or injection, major joint or bursa (eg, shoulder, hip, knee, subacromial bursa); with ultrasound guidance, with permanent recording and reporting
96372 Therapeutic, prophylactic, or diagnostic injection; subcutaneous or intramuscular

HCPCS codes covered if selection criteria are met:

J0630 Injection, calcitonin (salmon), up to 400 units

ICD-10 codes covered if selection criteria are met:

E83.52 Hypercalcemia
M80.08x+ Age-related osteoporosis with current pathological fracture, vertebra(e)
M80.88x+ Other osteoporosis with current pathological fracture, vertebra(e)
M88.0 - M88.9 Osteitis deformans [Paget's disease of bone]

ICD-10 codes not covered for indications listed in the CPB (not an all inclusive list):

C40.00 - C40.32 Malignant neoplasm of bone and articular cartilage of limbs
C41.0 - C41.9 Malignant neoplasm of bone and articular cartilage of other and unspecified limbs
E10.40 - E10.43 Type 1 diabetes mellitus with neurological complications [neuropathy]
E11.40 - E11.43 Type 2 diabetes mellitus with neurological complications [neuropathy]
G89.3 Neoplasm related pain (acute) (chronic)
G90.50 - G90.59 Complex regional pain syndrome I
M05.00 - M14.89 Inflammatory polyarthropathies
M15.0 - M19.93 Osteoarthritis
M35.2 Behcet's disease
M46.86 Other specified inflammatory spondylopathies, lumbar region [lumbar facet joint osteoarthritis]
M46.96 Unspecified inflammatory spondylopathy, lumbar region [lumbar facet joint osteoarthritis]
M47.16 Other spondylosis with myelopathy, lumbar region [lumbar facet joint osteoarthritis]
M47.26 Other spondylosis with radiculopathy, lumbar region [lumbar facet joint osteoarthritis]
M47.816 Spondylosis without myelopathy or radiculopathy, lumbar region [lumbar facet joint osteoarthritis]
M47.896 Other spondylosis, lumbar region [lumbar facet joint osteoarthritis]
M48.00 - M48.08 Spinal stenosis
M81.0 Age-related osteoporosis without current pathological fracture [postmenopausal]
M81.8 Other osteoporosis without current pathological fracture [glucocorticoid-induced osteoporosis] [regional migratory osteoporosis and transient osteoporosis]
N25.0 Renal osteodystrophy
Z94.0 - Z94.9 Transplanted organ and tissue status

The above policy is based on the following references:

  1. Aguilera S, Cortes C, Martínez V. Migratory regional osteoporosis. Effect of treatment with calcitonin. Report of 2 cases. Rev Med Chil. 1994;122(9):1045-1051.
  2. American Academy of Orthopaedic Surgeons (AAOS). The treatment of symptomatic osteoporotic spinal compression fractures. Rosemont, IL: AAOS; September 24, 2010.
  3. Arayssi TK, Tawbi HA, Usta IM, Hourani MH. Calcitonin in the treatment of transient osteoporosis of the hip. Semin Arthritis Rheum. 2003;32(6):388-397.
  4. Assadi F. Hypercalcemia: An evidence-based approach to clinical cases. Iran J Kidney Dis. 2009;3(2):71-79.
  5. Baron R. Neuropathic pain: A clinical perspective. Handb Exp Pharmacol. 2009;(194):3-30.
  6. Chesnut CH 3rd, Azria M, Silverman S, et al. Salmon calcitonin: A review of current and future therapeutic indications. Osteoporos Int. 2008;19(4):479-491.
  7. Cheung M. Drugs used in paediatric bone and calcium disorders. Endocr Dev. 2009;16:218-232.
  8. Clarke T. FDA panel advises calcitonin salmon not be used for osteoporosis. Reuters News, March 5, 2013.
  9. Compston J. Management of glucocorticoid-induced osteoporosis. Nat Rev Rheumatol. 2010;6(2):82-88.
  10. Coronado-Zarco R, Cruz-Medina E, Arellano-Hernández A, et al. Effectiveness of calcitonin in intermittent claudication treatment of patients with lumbar spinal stenosis: A systematic review. Spine. 2009;34(22):E818-E822.
  11. De Nijs RN. Glucocorticoid-induced osteoporosis: A review on pathophysiology and treatment options. Minerva Med. 2008;99(1):23-43.
  12. Dimai HP, Pietschmann P, Resch H, et al; Austrian Society for Bone and Mineral Research (AuSBMR). Austrian guidance for the pharmacological treatment of osteoporosis in postmenopausal women -- update 2009. Wien Med Wochenschr Suppl. 2009;(122):1-34.
  13. Eastell R, Boyle IT, Compston J, et al. Management of male osteoporosis: Report of the UK Consensus Group. QJM. 1998;91(2):71-92.
  14. European Medicines Agency. European Medicines Agency recommends limiting long-term use of calcitonin medicines. Intranasal formulation for osteoporosis treatment to be withdrawn; new restriction to indication for injectable use in Paget's disease. Press Release. London, UK: EMA; July 20, 2012.
  15. Gilron I, Watson CP, Cahill CM, Moulin DE. Neuropathic pain: A practical guide for the clinician. CMAJ. 2006;175(3):265-275.
  16. Gou Y, Tian F, Dai M, et al. Salmon calcitonin exerts better preventive effects than celecoxib on lumbar facet joint degeneration and long-term tactile allodynia in rats. Bone. 2019;127:17-25.
  17. Health Canada. Calcitonin-containing drugs: Health Canada assessing potential cancer risk with long-term use. Information Update. Identification number:RA-15044. Ottawa, ON: Government of Canada; July 31, 2012.
  18. Institute for Clinical Systems Improvement (ICSI). Diagnosis and treatment of osteoporosis. Bloomington, MN: Institute for Clinical Systems Improvement (ICSI); September, 2008.
  19. Jain PN, Chatterjee A. A randomized placebo-controlled trial evaluating the analgesic effect of salmon calcitonin in refractory bone metastasis pain. Indian J Palliat Care. 2020;26(1):4-8.
  20. Joffe HV. Calcitonin salmon for the treatment of postmenopausal osteoporosis. Joint Meeting of the Advisory Committee for Reproductive Health Drugs and the Drug Safety and Risk Management Advisory Committee. Silver Spring, MD: U.S. Food and Drug Administration, Center for Drug Evaluation and Research; March 5, 2013. 
  21. Karsdal MA, Sondergaard BC, Arnold M, Christiansen C. Calcitonin affects both bone and cartilage: A dual action treatment for osteoarthritis? Ann N Y Acad Sci. 2007;1117:181-195.
  22. Kaskani E, Lyritis GP, Kosmidis C, et al. Effect of intermittent administration of 200 IU intranasal salmon calcitonin and low doses of 1alpha(OH) vitamin D3 on bone mineral density of the lumbar spine and hip region and biochemical bone markers in women with postmenopausal osteoporosis: A pilot study. Clin Rheumatol. 2005;24(3):232-238.
  23. Katri A, Dąbrowska A, Löfvall H, et al. Combining naproxen and a dual amylin and calcitonin receptor agonist improves pain and structural outcomes in the collagen-induced arthritis rat model. Arthritis Res Ther. 2019;21(1):68. 
  24. Laktasic-Zerjavic N, Curkovic B, Babic-Naglic D, et al. Transient osteoporosis of the hip in pregnancy. Successful treatment with calcitonin: A case report. Z Rheumatol. 2007;66(6):510-5133.
  25. Legrand E, Hedde C, Gallois Y, et al. Osteoporosis in men: A potential role for the sex hormone binding globulin. Bone. 2001;29(1):90-95.
  26. Lewiecki EM. Current and emerging pharmacologic therapies for the management of postmenopausal osteoporosis. J Womens Health (Larchmt). 2009;18(10):1615-1626.
  27. Lipp L, Sharma D, Banerjee A, Singh J. Controlled delivery of salmon calcitonin using thermosensitive triblock copolymer depot for treatment of osteoporosis. ACS Omega. 2019;4(1):1157-1166.
  28. Martinez-Zapata MJ, Roqué M, Alonso-Coello P, Català E. Calcitonin for metastatic bone pain. Cochrane Database Syst Rev. 2006;(3):CD003223.
  29. National Osteoporosis Foundation (NOF). Physician’s guide to prevention and treatment of osteoporosis. Washington, DC: NOF; 2003. 
  30. No authors listed. Calcitonin. AHFS Drug Information. 2001. American Society of Health-System Pharmacists. 2001, pp. 3051-3053.
  31. North American Menopause Society. Management of osteoporosis in postmenopausal women: 2006 position statement of The North American Menopause Society. Menopause. 2006;13(3):340-367.
  32. North American Spine Society. Diagnosis and treatment of degenerative lumbar spinal stenosis. Burr Ridge, IL: North American Spine Society (NASS); January, 2007. 
  33. Overgaard K, Lindsay R, Christiansen C. Patient responsiveness to calcitonin salmon nasal spray: A subanalysis of a 2-year study. Clin Ther. 1995;17(4):680-685.
  34. Palmer SC, Strippoli GF, McGregor DO. Interventions for preventing bone disease in kidney transplant recipients: A systematic review of randomized controlled trials. Am J Kidney Dis. 2005;45(4):638-649.
  35. Pappa HM, Saslowsky TM, Filip-Dhima R, et al. Efficacy and harms of nasal calcitonin in improving bone density in young patients with inflammatory bowel disease: A randomized, placebo-controlled, double-blind trial. Am J Gastroenterol. 2011;106(8):1527-1543.
  36. Plosker GL, McTavish D. Intranasal salcatonin (salmon calcitonin). A review of its pharmacological properties and role in the management of postmenopausal osteoporosis. Drugs Aging. 1996;8(5):378-400.
  37. Qin H, Cai J, Xu H, Gong Y. Inhibition of Behcet's disease by calcitonin. Med Hypotheses. 2009;73(1):24-26.
  38. Sahin F, Yilmaz F, Kotevoglu N, Kuran B. The efficacy of physical therapy and physical therapy plus calcitonin in the treatment of lumbar spinal stenosis. Yonsei Med J. 2009;50(5):683-688.
  39. Samdani A, Lachmann E, Nagler W. Transient osteoporosis of the hip during pregnancy: a case report. Am J Phys Med Rehabil. 1998;77(2):153-156.
  40. Saura R. Paget's disease of bone. Clin Calcium. 2007;17(11):1769-1772.
  41. Silverman SL, Lane NE. Glucocorticoid-induced osteoporosis. Curr Osteoporos Rep. 2009;7(1):23-26.
  42. Siris ES, Miller PD, Barrett-Connor E, et al. Identification and fracture outcomes of undiagnosed low bone mineral density in postmenopausal women: Results from the National Osteoporosis Risk Assessment. JAMA. 2001;286(22):2815-2822.
  43. Sladek S, Kearney C, Crean D, et al. Intra-articular delivery of a nanocomplex comprising salmon calcitonin, hyaluronic acid, and chitosan using an equine model of joint inflammation. Drug Deliv Transl Res. 2018;8(5):1421-1435.
  44. Sosa Henríquez M, Díaz Curiel M, Díez Pérez A, et al; Sociedad Española de Medicina Interna. Guide for the prevention and treatment of glucocorticoid-induced osteoporosis of the Spanish Society of Internal Medicine.  Rev Clin Esp. 2008;208(1):33-45.
  45. Straten VH, Franssen MJ, den Broeder AA, et al. Regional migratory osteoporosis in a patient with ankylosing spondylitis. Scand J Rheumatol. 2009;38(1):63-65. 
  46. Tran de QH, Duong S, Bertini P, Finlayson RJ. Treatment of complex regional pain syndrome: A review of the evidence. Can J Anaesth. 2010;57(2):149-166.
  47. Turek T, Wigton A. Calcitonin for phantom limb pain in a pregnant woman. Am J Health Syst Pharm. 2012;69(24):2149-2152.
  48. U.S. Food and Drug Administration, Center for Drug Evaluation and Research. Background Document for Meeting of Advisory Committee for Reproductive Health Drugs and Drug Safety and Risk Management Advisory Committee. Silver Spring, MD: FDA; March 5, 2013.
  49. Vinik AI. Diabetic neuropathy: Pathogenesis and therapy. Am J Med. 1999;107(2B):17S-26S.
  50. Vranken JH. Mechanisms and treatment of neuropathic pain. Cent Nerv Syst Agents Med Chem. 2009;9(1):71-78.
  51. Wagner E. Non-surgical treatment of osteoarthritis of large joints - new aspects. Wien Med Wochenschr. 2009;159(3-4):76-86.
  52. Whyte MP. Clinical practice. Paget's disease of bone. N Engl J Med. 2006;355(6):593-600.
  53. Wu F, Mason B, Horne A, et al. Fractures between the ages of 20 and 50 years increase women's risk of subsequent fractures. Arch Intern Med. 2002;162(1):33-36.