Nasal Calcitonin Research Articles

Corticosteroid-induced bone loss. Prevention and management.

Osteoporosis is one of the most serious adverse effects experienced by patients receiving long term corticosteroid therapy. Bone loss occurs soon after corticosteroid therapy is initiated and results from a complex mechanism involving osteoblastic suppression and increased bone resorption. There are a number of factors that may increase the risk of corticosteroid-induced osteoporosis [smoking, excessive alcohol (ethanol) consumption, amenorrhoea, relative immobilisation, chronic obstructive pulmonary disease, inflammatory bowel disease, hypogonadism in men, organ transplantation]. The initial assessment of patients about to start taking corticosteroids should include measurement of spinal bone density, urinary calcium level and plasma calcifediol (25-hydroxycholecalciferol) level; serum testosterone levels should also be measured when hypogonadism is suspected. Many different drugs have been used to prevent osteoporosis in patients receiving long-term corticosteroid therapy, including thiazide diuretics, cholecalciferol (vitamin D) metabolites, bisphosphonates, calcitonin, fluoride, estrogens, anabolic steroids and progesterone. At present, however, published studies have failed to demonstrate a reduction in the rate of fracture using different preventive pharmacological therapies in patients being treated with corticosteroids on a continuous basis. Among the drugs studied, bisphosphonates (pamidronic acid and etidronic acid) and calcitonin appear to be effective in increasing bone density. Cholecalciferol preparations have been reported to be effective in some, but not all, studies. Limited data have shown positive results with thiazide diuretics, estrogen, progesterone and nandrolone. When treating patients with corticosteroids, the lowest effective dose should be used, with topical corticosteroids used whenever possible. Auranofin may be considered in patients with corticosteroid-dependent asthma. Patients should take as much physical activity as possible, maintain an adequate daily intake of calcium (1000 mg/day0 and cholecalciferol (400 to 800 U/day), stop smoking and avoid excessive alcohol intake. It is important to detect and treat hypogonadism in men, if present, and to replace gonadal hormones in postmenopausal women or amenorrhoeic premenopausal women, and to detect and correct cholecalciferol deficiency. A thiazide diuretic should be considered if hypercalciuria is present (urinary calcium excretion in excess of 4 mg/kg/day). High-risk patients and those with established osteoporosis should be treated with bisphosphonates (cyclical etidronic acid or intravenous pamidronic acid), nasal calcitonin, or calcifediol or calcitriol. Patients receiving cholecalciferol preparations should be carefully monitored for hypercalciuria and hypecalcaemia.

P019 Use of nasal calcitonin in severe osteoporotic post menopausal women: Metabolic action, bone density fluctuations, possible prevention of future fractures

P019 Use of nasal calcitonin in severe osteoporotic post menopausal women: Metabolic action, bone density fluctuations, possible prevention of future fractures

Enhancement of nasal salmon calcitonin absorption by lauroylcarnitine chloride in rats.

We investigated optimum formulation characteristics in the nasal absorption of salmon calcitonin (sCT) by incorporation of acylcarnitines. Nasal sCT formulations were administered to anesthetized rats. Plasma calcium level was measured and pharmacological bioavailability (P.bioav) was calculated. Nasal sCT absorption was significantly enhanced by carnitines with acyl groups of 12 or more carbon atoms. Enhancement by lauroylcarnitine chloride (LCC) was observed at its critical micelle concentration and reached a plateau at the concentration of 0.1 percent. Optimal absorption was achieved at a molar ratio of LCC to sCT of 5:1. Enhancement was not influenced by osmolarity and maximum enhancement was obtained at pHs 3.1 and 4.0. The 12-carbon LCC was the strongest enhancer among acylcarnitines. Micelle formation played a key role in this enhancement effect.

Effect of nasal calcitonin on pain in osteoporotic patients with vertebral fractures

Effect of nasal calcitonin on pain in osteoporotic patients with vertebral fractures

Effect of nasal calcitonin on bone density and vertebral deformity in rheumatoid arthritis patients treated with steroids

Effect of nasal calcitonin on bone density and vertebral deformity in rheumatoid arthritis patients treated with steroids

Calcitonin for prevention and treatment of postmenopausal osteoporosis.

Prolonged calcitonin administration (intramuscular, subcutaneous, or intranasal) can prevent postmenopausal trabecular bone loss. Nasal administration constitutes a particularly attractive option for women who cannot tolerate or benefit from estrogen replacement therapy. The optimal schedule of administration still has to be precised, but 100 U/day of nasal calcitonin, combined with calcium supplements, can currently be recommended. Interrupted regimens are maybe favourable. Calcitonin can also prevent further bone loss in established osteoporosis particularly if bone turnover is increased. The anti-fracture efficacy of calcitonin is suggested by different types of studies but has not been formally demonstrated. Lastly, its analgesic efficacy in cases of painful vertebral compression fractures has been demonstrated in controlled studies.

A double-blind, placebo-controlled, dose-finding trial of intermittent nasal salmon calcitonin for prevention of postmenopausal lumbar spine bone loss

Nasal administration of salmon calcitonin (SCT) has been suggested for preventing trabecular bone loss during the first years following the menopause, but no conclusive evidence has appeared about the minimal effective dose. Since nasal calcitonin is highly expensive, it makes sense to define this dose. We performed a double-blind, placebo-controlled, randomized, single-center study with a 3-arm parallel-group design. The subjects were 251 healthy women who had experienced natural menopause within the past 6 to 72 months and were not affected by any diseases or treatments that interfere with calcium metabolism. They were randomly allocated in groups of 6 to receive intranasal SCT 50 IU (n = 84), SCT 200 IU (n = 84), or placebo (n = 83). All treatments were given on 5 consecutive days per week. Statistical analysis was based on two populations: intention-to-treat (IT) and valid completers (VC). The main assessments performed were bone mineral density of the lumbar spine (LSBMD) and biochemical parameters reflecting bone turnover (serum alkaline phosphatase, urinary calcium/creatinine, and hydroxyproline/creatinine ratios). Changes over the treatment period were comparable in the IT and VC populations. In the group receiving the placebo, LSBMD decreased from baseline to end point by a mean of 6.28% (95% confidence interval [CI] -7.69 to -4.89) in the IT population and 6.98% (95% CI -8.86 to -5.11) in the VC population (P = 0.0001, end LSBMD versus baseline LSBMD). LSBMD increased slightly with the 50-IU/d dose of SCT, by 0.82% (95% CI -0.26 to 1.89) in the IT population, and 0.51% (95% CI -0.69 to 1.72) in the VC (P = NS, versus baseline). Subjects who received SCT 200 IU/d experienced significant increases of 2.03% (95% CI 0.92 to 3.15) in the IT population and 2.26% (95% CI 1.01 to 3.51) in the VC (both P = 0.001). The difference between the evolution of the combined groups receiving nasal SCT and the group treated with the placebo was highly significant (P = 0.0001). No significant changes were recorded in biochemical parameters reflecting bone turnover. SCT 50 IU/d administered nasally and intermittently appears to prevent lumbar bone loss in nonobese early postmenopausal women.

Prevention of further bone mass loss by nasal calcitonin in patients on long term glucocorticoid therapy for asthma: a two year follow up study.

Injectable calcitonin is effective in reducing spinal bone loss in steroid-dependent asthma but side effects are frequent. In contrast, a nasal spray presentation has been shown to be effective and well tolerated in involutional osteoporosis. To test the efficacy of nasal calcitonin a two year prospective trial was conducted in 44 steroid-dependent asthmatic patients. All patients received a calcium supplement of 1000 mg and were allocated randomly into two groups treated with either salmon calcitonin nasal spray (200 IU every other day, n = 22) or calcium alone (n = 22) for two years. All patients completed the first year of the study. Five patients in each group dropped out during the second year. In the calcitonin group one patient developed generalised pruritus and four lost steroid dependence, and in the calcium alone group five were no longer dependent on steroids. The efficacy of treatment was evaluated as follows: bone turnover assessed by biochemical markers, bone loss assessed by serial measurement of lumbar spine density, and rates of bone fractures. The bone mass in the calcitonin group increased by 2.7% in the first year while in the group receiving calcium alone it decreased by 2.8%; this difference was significant. Calcitonin prevented more bone loss during the second year while the calcium alone group continued losing bone mass (-7.8%). The difference between means was 0.1077 (95% CI 0.0381 to 0.1773). Three new fractures occurred in both groups. No changes in biochemical parameters were detected in either group. Calcitonin given intranasally increased spinal bone mass during the first year of treatment and maintained bone mass in a steady state during the second year. These results suggest that calcitonin may be a useful agent to prevent steroid-induced osteoporosis. However, the lack of effect of calcitonin on the rate of vertebral fractures does not permit its recommendation for routine use in preventing steroid-induced osteoporosis.

Calcitonin for prevention and treatment of osteoporosis

There appears to be a consensus that 100 IU/day of nasally administered salmon calcitonin may prevent trabecular bone loss during the first years of the menopause. Strong evidence exists that half that dose may also be sufficient to prevent trabecular bone loss and that higher doses (≥200 IU/day) induce a significant increase in spinal bone mineral content. Calcium supplements should be systemically administered when calcitonin is given, particularly at high doses. Rectal calcitonin seems also to be an efficient alternative in prevention of trabecular bone loss. Further studies are required to evaluate the effect of calcitonin in prevention of cortical bone loss. In established osteoporosis calcitonin may prevent further bone loss at trabecular and cortical sites. A similar benefit is obtained following parenteral or nasal administration of the drug. Long-term administration of nasal salmon calcitonin induces a significant dose-dependent gain of bone at the lumbar spine, whereas discontinuous therapy with a ratio of 1:2 or 2:3 between the treatment and nontreatment periods is the best regimen for cortical bone. Epidemiological, retrospective, and prospective studies provide a convergent network of evidence that calcitonin administration in osteoporosis contributes to reduce significantly the frequency of subsequent fractures, both in the spine and in the hip. Finally, in established osteoporosis, nasal calcitonin possesses a potent analgesic effect, reduces the duration of bed confinement, and decreases the number of concomitant analgesic medications. The well-demonstrated effects of nasal calcitonin permit it to be considered as a highly rational solution for the prevention and the treatment of postmenopausal osteoporosis.

Acute effects of nasal salmon calcitonin on calcium and bone metabolism

Effects of a single dose of 200 IU of nasal salmon calcitonin (SCT) on calcium metabolism and biochemical markers of bone turnover were investigated in 12 healthy male volunteers in a randomized, placebo-controlled, cross-over design. The nasal spray was given in the morning, and subsequently blood and urine samples were collected for 26 hours. There was a significant decrease in serum ionized calcium with a nadir 4 hours after administration of nasal SCT accompanied by a significant increase in serum parathyroid hormone (P = 0.01) and serum calcitriol (P = 0.04). Nasal SCT did not reduce urinary hydroxyproline/creatinine. Urinary deoxypyridinoline/creatinine was lowered significantly 2 hours after administration of nasal SCT and throughout the first 24 hours, but remained unchanged for the last 2 hours. On a 24-hour basis, urinary deoxypyridinoline/creatinine decreased from 14.1 (3.5) nmol/mmol to 11.7 (3.2) nmol/mmol after nasal SCT (P = 0.04). Nasal SCT did not change the serum levels of alkaline phosphatase, osteocalcin, and the carboxyterminal propeptide of type 1 procollagen. The results indicate that nasal SCT given as a single dose provokes a modest decrease in bone resorption lasting several hours, but leaves bone formation unaffected.

Effects of continuous and cyclic nasal calcitonin administration in ovariectomized women

The aim of the present study was to assess the effects of continuous and cyclic salmon calcitonin (sCT) administration in the prevention of the rapid bone loss that follows ovariectomy in humans. Patients who had undergone bilateral ovariectomy 10–30 days previously received either calcium supplementation alone (500 mg/day, n = 12) or such supplementation together with nasal sCT (200 IU/day) according to a continuous ( n = 20) or a cyclic (3 months on, 1 month off) regimen ( n = 16) for 2 years. In the calciumonly-treated subjects urinary hydroxyproline excretion, serum alkaline phosphatase and plasma bone Gla protein levels showed a substantial increase ( P < 0.01) 6 months after surgery, while radial bone density was found to have decreased significantly ( P < 0.01). The patterns of biochemical markers in the sCT-treated groups indicated that nasal sCT can positively uncouple the two bone remodelling processes without inducing any significant change in radial bone density over a 2-year period. No differences were observed between the two sCT-treated groups. These results demonstrate that the rapid bone loss that follows ovariectomy can be prevented by either cyclic or continuous nasal sCT administration. Thus, cyclic nasal sCT represents an attractive alternative for the prevention of osteoporosis in postmenopausal women with contraindications to oestrogen replacement therapy.

Nasal deformation with nasal calcitonin

Nasal deformation with nasal calcitonin

Acute changes in bone resorptive and formative markers after nasal salmon calcitonin

Acute changes in bone resorptive and formative markers after nasal salmon calcitonin

Nasal salmon calcitonin in the treatment of postmenopausal osteoporosis

Nasal salmon calcitonin in the treatment of postmenopausal osteoporosis

91271981 Circulating levels of calciotropic hormones during treatment with nasal salmon calcitonin

91271981 Circulating levels of calciotropic hormones during treatment with nasal salmon calcitonin

Basic study on the effect of nasally administered salmon calcitonin preparation on the nasal ciliary epithelium.

Nasal administration of drugs is an administration method which is worthy of attention. In such therapy, local administration should not damage the nasal mucous membranes. In the present study, we conducted an investigation by the tissue culture test method of the functional and morphological effects of new nasal calcitonin preparation, which is being developed as a nasal spray agent for osteoporosis, on the nasal ciliary epithelium. The nasal septal mucous membranes of C3H-strain mice were used, and 5 types of nasal calcitonin preparations with a microcrystalline cellulose base and additives added were used. The various drugs were added to nasal mucous membrane slices in RPMI-1640 culture medium; ciliary activity before addition and 0.5, 2, and 4 hr after was electrophotometrically measured; and morphological observation was then carried out by SEM. In the various additive groups, virtually no effect on ciliary activity was observed, and the same results were obtained when 3 and 9 times the estimated clinical spray dosage was added. Moreover, in morphological observation by SEM, in the various additive groups, no morphological changes in samples of nasal ciliary specimens were observed after 4 hr of culturing at the maximum administered dosage (9 times the estimated clinical spray dosage). Based on these findings, it was concluded that the series of calcitonin preparations with various additives had no hazardous effect on the nasal ciliary epithelium.

The use of nasal calcitonin spray in the treatment of hypercalcaemia of malignancy

The use of nasal calcitonin spray in the treatment of hypercalcaemia of malignancy

Nasal calcitonin preserves bone mineral content in children with steroid-induced osteoporosis

Nasal calcitonin preserves bone mineral content in children with steroid-induced osteoporosis

Use of nasally administered salmon calcitonin in preventing bone loss

This article reviews several of our studies in which we evaluated the effect of nasal salmon calcitonin in preventing bone loss in normal women just after menopause. In the first study, after treatment with nasal salmon calcitonin, bone loss stopped and, in fact, actually increased slightly. In contrast, the placebo group continued to lose bone mass. On the other hand, bone mass in the forearm, which has more cortical bone, showed no change in response to nasal salmon calcitonin. The effect of salmon calcitonin nasal spray in women with established osteoporosis has also been studied. In one study, bone mass in the forearm was constant in the group receiving nasal salmon calcitonin plus calcium, whereas bone mass in the placebo plus calcium group decreased by roughly 2%. Similarly, patients in the group without any treatment also lost 2%. The effect of nasal salmon calcitonin is probably the result of a reduction in the bone resorption to a level seen in premenopausal females. When women were divided according to their baseline bone turnover or initial bone mass, the women with the highest turnover level (assessed by alkaline phosphatase or fasting urinary hydroxyproline) or the lowest bone mass were the group with the greatest increase in bone mass. In conclusion, treatment with salmon calcitonin nasal spray in patients with established osteoporosis stops bone loss, normalizes bone turnover, and causes no subjective or objective side effects.

THE USE OF NASAL CALCITONIN IN THE TREATMENT OF POST-TRAUMATIC ALGODYSTROPHY

Calcitonin is widely used in the treatment of algodystrophy but a major disadvantage is the need for its parenteral administration. For this reason, we evaluated the effect of 400 iu of nasal calcitonin in the treatment of post-traumatic algodystrophy in a prospective randomized double-blind study. We found no demonstrable effect on the clinical or skeletal progression of the disorder using sensitive methods of measuring the response to treatment. There was, however, a small but significant hypocalcaemic response in the treatment group despite no change in the other indices of bone turnover. Possible reasons for this lack of clinical and skeletal effect are discussed.