Clinical application of calcitonin: Calcitonin is mainly used in diseases with increased bone resorption such as osteoporosis, deformational osteitis, cancerous hypercalcemia, etc. 1, prevention of postmenopausal osteoporosis: Calcitonin (CT) injection has the effect of slowing down bone loss in women with estrogen deficiency in the early postmenopausal period. In recently postmenopausal women, the application of calcitonin subcutaneously (20 units, twice weekly) has been shown to have a utility equivalent to estrogen in maintaining vertebral bone mineral content. A similar effect was obtained in post-ovariectomized patients given CT injections. Calcitonin inhalation, whether administered continuously or intermittently, has been shown to prevent vertebral bone loss in postmenopausal women. CT inhalation has also been shown to reduce rapid bone loss in post-ovariectomized women. In patients within 30 days of bilateral oophorectomy, both continuous and intermittent (3 months of continuous use and 1 month of discontinuation) administration of inhalation (200 IU/day) were successful in preventing rapid bone loss. However, no such effectiveness has also been reported. In women with early menopause with low bone mass or osteoporosis with low bone turnover rate, the results of calcitonin’s effect on bone density are inconsistent, and there is also a lack of information on the prevention of bone loss in the hip, so to date the US FDA has not made the prevention of early menopausal bone loss an indication for calcitonin. 2, treatment of postmenopausal osteoporosis Application of calcitonin (CT) injection 100 IU/day intramuscularly or subcutaneously for the treatment of osteoporosis, or 100 IU/day, every other day intramuscularly on the vertebral body, the femoral stem at BMD increased significantly compared to the placebo group. Intermittent small low volume CT subcutaneous injections (50 IU, every other day) for one year were also observed to increase vertebral BMC in women with osteoporosis associated with high conversion, with no such effect in patients with normal conversion. Salmon calcitonin nasal aspirate (NSCT), 200 IU/day for new vertebral fractures, was observed for 5 years and was effective in reducing the rate of new vertebral fractures compared to the control group, whereas the group using the lower dose of 100 IU/day had no effect in reducing the rate of vertebral fractures but had utility in reducing the rate of non-vertebral fractures. There is a lack of prospective studies on the role of CT inhalation agents in reducing hip fracture rates. Improvement in bone strength and reduction in fracture rate is not only a factor of bone mass, but also the involvement of non-bone mass factors of bone strength. In clinical practice, it has been observed that the efficacy of antiresorptive agents is related to the severity of osteoporosis, with women with lower BMD gaining greater bone mass than women with higher osteoporosis, similar to the results of the alendronate study for the prevention of osteoporotic fractures. The effectiveness of CT in preventing bone loss was mainly seen in women with long menopause (up to 3.1% difference compared to control), but not in women with short menopause and high BMD; secondly, the efficacy of the antiresorptive drug was also related to the bone turnover status, and if salmon was injected subcutaneously every other day in postmenopausal osteoporosis patients with high bone turnover status, the effect of the drug on vertebral BMD was reduced. In patients with postmenopausal osteoporosis with high bone turnover, subcutaneous injections of salmon calcitonin on alternate days can result in a significant increase in vertebral BMD, while patients with normal bone turnover do not have this change. Thus, the evaluation of the effectiveness of osteoporosis control drugs is not limited to the assessment of a single factor. 3. Glucocorticoid osteoporosis (GCHOP): In patients with chronic obstructive pulmonary disease who applied GCH, the salmon calcitonin 100 IU/day subcutaneous injection group was controlled with the non-medicated group to observe radial BMD, showing a certain effect. In asthmatic patients with long-term GCH, controlled observation by calcitonin injections (3 times a week) for one year showed an effect of increasing vertebral BMD, but with a high rate of shedding due to side effects and poor compliance. Application of CT nasal aspirate against GCHOP: In patients with active rheumatoid arthritis applying low doses of prednisolone (mean dose 8.7% mg/day), application of 100 IU/day showed a protective effect on proximal femoral BMD, the long-term effect is not yet certain. combination of CT and GCH started simultaneously prevents bone loss: in sarcoma patients treated with GCH, salmon CT nasal aspirate with The osteoprotective effect was significant when used intermittently with injections. 4. Other types of osteoporosis: estrogen-dependent bone loss after oophorectomy: salmon calcitonin injection (100 IU/every other day) or the use of NSCT (200 IU/day x 3 months, 3 months off) immediately after surgery can significantly retard rapid bone loss, but neither is as effective as estrogen supplementation. Braking or wasting osteoporosis: application of NSCT 200IU twice a day in bedridden patients showed some effect. Rheumatoid arthritis: Calcitonin is effective in preventing rapid bone loss. Multiple myeloma: NSCT 200IU/day has been shown to improve cancellous and cortical bone BMD, reduce bone turnover rate and blood calcium, but there is a lack of experience with long-term treatment. CT may also have the effect of accelerating bone healing, and individual clinical experience also suggests that it is effective for osteogenesis imperfecta. 5, analgesic effect: For patients with osteoporosis and other diseases with increased bone resorption such as deformational osteitis, calcitonin injectable form or nasal aspiration form has significant analgesic effect, especially for acute vertebral fractures, and also reported to apply to pain caused by non-skeletal tissue, such as neuralgia, migraine, mild lumbar stenosis, pain due to limited bone metastases, etc. Multiple mechanisms to explain the analgesic mechanism of CT may be related to the release of endorphins in vivo; inhibition of prostaglandin E2 synthesis; alteration of serotonergic receptor expression levels affecting nociceptive signal afferents, etc. Long-term treatment with SCT and ECT can produce antibodies. The presence of low titers of antibodies does not affect the efficacy, while high levels of antibodies reduce the efficacy of CT, but cannot therefore be used as a cause of CT resistance. (C) application method 1, the choice of patients with osteoporosis: the following patients can be preferred to calcitonin nasal aspirate: for elderly women with low bone mass, no longer suitable for estrogen supplementation therapy, especially for patients with poor gastrointestinal tolerance to bisphosphonate drugs, NSCT is the best choice; patients suffering from multiple diseases, the need to take a variety of drugs, and oral bisphosphonates malabsorption; not suitable for estrogen Supplementary therapy and bisphosphonates in patients with glucocorticoid osteoporosis; male patients with osteoporosis and other mineralization disorders. 2, the type of preparation: currently there are people (HCT), pigs (PCT), salmon (SCT) and eel (ECT) calcitonin four, the current clinical do not use PCT. various CT has different biological activity, SCT>ECT>HCT. SCT has an injection (50IU/sticks) and nasal aspirate (200IU/drops) two, salmon calcitonin nasal aspirate than the injectable form has many Advantages, less side effects, easy to be accepted by patients, but its absorption rate is lower than that of the injectable, the bioavailability is estimated to be 20-40% of the injectable. ECT: At present, the supply is only injectable (10IU/stem, 20IU/stem). 3, the route of administration (1) calcitonin nasal aspirate: single nasal aspirate CT50-400IU can obtain rapid biological effects, a nasal aspirate 200IU required to achieve the utility of 30-80IU injection, the intensity ratio of the two is roughly 1:2.8-1:3.5. nasal aspirate 200IU each time, once a day, can also be used intermittently such as every other day or use 3 months stop 3 months, can be used continuously for several years. Continuous use for several years. (2) Calcitonin injection: salmon CT 50IU/branch for intramuscular or subcutaneous injection, daily or every other day, also can be injected twice a week, depending on the therapeutic effect. Eel CT 10, 20IU/stem, 20IU per week. (3) Calcitonin rectal suppository: currently not available in China. Oral formulation is currently only completed phase II clinical trials. 4, calcitonin resistance problem: resistance can be in 3 types: (1) primary or resistance type: injected therapeutic dose or dose up to 100-500IU/day without any clinical response, less common. (2) Secondary resistant type: also known as delayed desensitization state, rebound phenomenon or steal phenomenon, seen in patients with osteoporosis receiving long-term CT treatment and losing therapeutic response after 3-9 months of CT application. (3) Flat segment response type: The beginning phase of treatment shows obvious efficacy, and no further improvement with continued treatment. There are various mechanisms that cause resistance to calcitonin, including possible degradation of the used calcitonin in vitro, reduction of cells with functional receptors or diminished or lost affinity of these cells for CT, blocking of CT receptors on cells by inactive fragments of CT or its inactives, uncoupling of adenylyl cyclase, loss of phosphorylation state, loss of differentiation of CT to pre-osteoblastic cells of bone tissue, anti-CT osteoclast generation, the formation of anti-CT antibodies and other factors. 5, the problem of adverse drug effects Receiving CT treatment about 30-60% of patients due to drug-induced symptoms of different nature, in the long-term treatment process about 5-15% of patients interrupt treatment due to drug side effects, the most common reaction to the injectable form is facial congestion, injection site tingling, more common when applying HCT (about 6%), the incidence is significantly higher than SCT; the phenomenon of polyuria accounted for about 10-15% of treated 10-15% of patients, headache and nausea <10%; nasal aspirate side effects are significantly less than injections, except for facial flushing, a few patients can cause side effects of nasal irritation and rhinitis symptoms. Although there is no report of anaphylaxis, calcitonin is a polypeptide substance and should be used with caution for allergic patients. Anti-allergic drugs taken 20-30 minutes before injection can relieve skin symptoms caused by CT. To reduce gastrointestinal side effects such as nausea, injections can be given 4-5 hours after meals or at bedtime. Among many effective drugs against osteoporosis, calcitonin is a good choice for the treatment of osteoporosis due to its safety, ease of use especially for inhalation.