Administration Of Synthetic Salmon Calcitonin Research Articles

Effects of synthetic salmon calcitonin on C cells of the thyroid.

The effects of long-term administration of synthetic salmon calcitonin (TZ-CT) on thyroid C cells of rats were evaluated immunohistochemically and electron microscopically. Low dose (0.075, 0.75 and 7.5 IU/kg/day) administration caused no significant changes in the C cell population, whereas high doses (30 and 120 IU/kg/day) caused C cell suppression. The area ratio of C cells to total cells in the thyroid was measured on sections immunoperoxidase stained for calcitonin. The average C cell ratio was compared among the experimental groups. This morphometric analysis of the high-dose and control groups confirmed the differences in C cell populations statistically (30 IU/kg vs. control, p less than or equal to 0.05; 120 IU/kg vs. control, p less than or equal to 0.05). The suppressive effect of TZ-CT on C cells was reversible after cessation of administration for one month. Electron microscopic examination on the C cells in the high-dose groups revealed no particular ultrastructural differences. These results may suggest a negative feedback mechanism on C cells by exogenous CT.

Effects of the acute subcutaneous administration of synthetic salmon calcitonin in tumoral calcinosis.

We examined the effects of the acute administration of salmon calcitonin on phosphate metabolism in tumoral calcinosis. On two different days, 200 MRC U of the synthetic hormone were administered sc to a 38-year-old patient, either as twice daily 100 MRC U injections, or as a continuous sc infusion via a portable pump. Both ways of calcitonin administration elicited a phosphaturic effect and a lowering of serum phosphate level comparable with that observed after an iv infusion of calcitonin. 1,25 dihydroxyvitamin D level, which was in the normal range during a control study, increased after calcitonin administration. In our patient, long term therapy with diet, a phosphate-binding agent and calcitonin prevented the occurrence of new ectopic calcifications. Owing to its phosphaturic activity, synthetic salmon calcitonin may be a useful adjunct to diet and aluminium-containing antacids in long-term management of tumoral calcinosis.

Treatment of Paget's Disease of Bone with Salmon Calcitonin Nasal Spray

Subcutaneous daily or bidaily administration of synthetic salmon calcitonin is an effective form of therapy for Paget's disease, but the requirement for parenteral injection deters geriatric patients from using the drug. This study compares a new intranasal preparation of salmon calcitonin to subcutaneous drug in 18 patients with Paget's disease using two different protocols. In the first protocol, 15 patients not previously treated with salmon calcitonin were given the agent for 3 months by either the intranasal or subcutaneous route. Seven patients treated with intranasal calcitonin had a mean fall in the serum alkaline phosphatase of 33% over a 3-month period compared to a fall of 40% in the subcutaneously treated group; the difference between the two treatment groups was not statistically significant. In the second protocol, three patients previously stabilized on subcutaneous calcitonin were switched to the nasal spray with no subsequent change in alkaline phosphatase values during 6 months of treatment. These results demonstrate that intranasal salmon calcitonin is effective in lowering the serum alkaline phosphatase in Paget's disease. Ease of administration and patient acceptance make intranasal calcitonin a reasonable alternative for geriatric patients.

Therapy of osteogenesis imperfecta with synthetic salmon calcitonin

We evaluated the long-term use of synthetic salmon calcitonin in the management of osteogenesis imperfecta tarda and congenita. Forty-eight children, ranging in age from 6 months to 15 years, and two young adults, received synthetic salmon calcitonin 2 MRC units/kg three days a week and a daily oral calcium supplement of 230 to 345 mg. The annual fracture rate was decreased during calcitonin therapy as compared to the period preceding therapy. There was an increase in the ability of the patient to stand and move and in the subjective feeling of strength in the lower extremities during calcitonin therapy. There was also a significant improvement in radiographic bone density, as determined by the method of photodensitometry, in patients under 5 years of age. Long-term administration of synthetic salmon calcitonin may be beneficial to young children with osteogenesis imperfecta.

836 CALCITONIN THERAPY IN OSTEOGENESIS IMPERFECTA

We have previously shown increased skeletal turnover in 0.1. with resorption being more accelerated than bone accretion. Calcitonin, through its ability to inhibit skeletal resorption, might be useful in the treatment of 0.1. Twenty-five patients with 0.1. tarda and 25 with 0.1. congenita received synthetic salmon calcitonin (SSC) 2 MRC units/kg 1.M. three times a week, for periods of 6 to 48 months. In O.I.T. the fracture rate decreased from 2.7 before calcitonin to 0.5/yr/patient during calcitonin; in O.I.C. from 3.6 to 0.8/yr/patient. Therapy was discontinued in 3 patients because of persistent vomiting and in one because of an allergic skin reaction. X-rays of the left hand with the same control metal wedge were taken every 3 months. Bone density was measured by a photodensitometer connected to a LINC-8 computer, and corrected for changes between X-rays and compared to normals for age and sex. 38/50 studies were successfully terminated. Calcitonin significantly increased bone density in the 0-5 year age range when compared with normal rates. SSC appears to be more effective in increasing bone density during the first year of therapy. Antibodies to SSC were found in 6 patients treated with SSC, at titers of 1:10 to 1:600. There was no increase in plasma iPTH concentrations during SSC administration. These data suggest that long term SSC therapy reduces fracture-rate and increases bone density in young children with 0.1. (Supported by NIH Grant RR-318).

Effects of implantation of the ultimobranchial glands and the administration of synthetic salmon calcitonin on serum Ca concentrations in ultimobranchialectomized bullfrog tadpoles

Serum Ca concentrations in ultimobranchialectomized bullfrog tadpoles increased markedly in a high Ca environment. However, tadpoles implanted with the ultimobranchial glands of bullfrog tadpoles, or of Rana nigromaculata, showed no changes in serum Ca levels. The administration of synthetic salmon calcitonin (5 MRC units per individual) to the ultimobranchialectomized tadpoles partially suppressed the acute rise of serum Ca concentrations in a high Ca environment.

Effects of calcitonin and ultimobranchialectomy (UBX) on calcium and bone metabolism in the eel, Anguilla anguilla L.

Prolonged administration of synthetic salmon calcitonin (SCT) to immature female silver eels, maintained in sea water, provoked a decrease of the serum calcium concentration and an increase of both the osteoblastic apposition and of the degree of mineralization of the intercellular matrix in the vertebral bone. The osteoclastic resorption and osteocytic osteolysis were not significantly affected, however the osteoclastic index was reduced. The ultimobranchial body, site of CT secretion, was cauterized in immature female silver eels maintained in Ca++ rich tap water. This operation resulted in a rise in serum calcium levels with a maximal response after two weeks. After UBX, the vertebral bone osteoblastic apposition stopped completely but the osteoclastic resorption was not modified. The degree of osteocytic osteolysis did not vary. We also observed a significant decrease in the degree of mineralization of the bone organic matrix. The observations made after UBX confirm those obtained after exogenous CT treatment. SCT administered preventively to immature female eels (maintained in sea water), before experimental maturation, inhibited, at least partially, the acute osteoclastic resorption and completely inhibited the bone demineralization induced by carp pituitary extract. The increase of osteocytic ostelysis, usually observed, did not appear.

Paget's disease of the bone: observations after cessation of long-term synthetic salmon calcitonin treatment.

Thirteen patients with Paget's disease of the bone were treated with subcutaneous injections of synthetic salmon calcitonin (SCT) for a mean period of 22 months at doses of 50-100 MCR units daily or 3 times a week. They manifested symptomatic improvement and significant reductions in serum alkaline phosphatase and urinary hydroxyproline excretion during SCT administration. Following discontinuation of SCT, symptomatic improvement was maintained in 10 patients for up to one year, whereas a recurrence of symptoms was seen in only 3 patients. The serum alkaline phosphatase generally showed a return toward pretreatment values 6 months after discontinuation of SCT, whereas urinary hydroxyproline remained depressed for up to a year.

Effect of calcitonin on DNA synthesis in experimental wounds.

3H-thymidine incorporation and intracellular distribution in epidermal cells and fibroblasts of scar tissue from wounded rabbits were studied following synthetic salmon calcitonin administration. Both scintillation counting and electron microscopic autoradiography revealed a marked increase in 3H-thymidine incorporation within nuclear dense chromatin of epidermal and fibroblasts cells, mainly in 2-day wounded rabbits and at 2.5 hr. Then, 3H-thymidine uptake decreased moderately. These findings demonstrate an important role of calcitonin on DNA synthesis.

Paradoxical effect of salmon calcitonin on serum calcium: studies in intact and thyroparathyroidectomized men and dogs.

Total serum calcium of normal men, a hypoparathyroid man, two thyroparathyroidectomized men, and intact and thyroparathyroidectomized dogs were studied at multiple intervals following the acute administration of synthetic salmon calcitonin. Calcitonin produced marked fluctuations in serum calcium in one normal man and a biphasic hypocalcaemic response in another. In four of five intact dogs, calcitonin caused absolute or relative hypercalcaemia. In contrast, administration of calcitonin to thyroparathyroidectomized dogs caused a hypocalcaemia with less fluctuations and with no periods of hypercalcaemia. It is possible that some of the paradoxical responses of serum calcium induced by exogenous calcitonin are due to overcompensation by parathyroid hormone. However, other mechanisms may be involved. Our findings indicate that when the disturbing influence is sufficiently great, the control of serum calcium is not as well modulated as previously suspected. In addition, our findings of paradoxically hypercalcaemic responses to calcitonin indicates that the pathophysiologic interpretation of serum calcium at any single moment in time following the administration of this hormone to either intact or thyroparathyroidectomized men or dogs is a precarious endeavour.

Metabolic effects of synthetic salmon calcitonin in Paget's disease of bone

The initial effects of synthetic salmon calcitonin (SCT) given as a single subcutaneous injection of 50 or 100 MRC units daily or three times a week were studied in ten patients with Paget's disease of bone. Positive shifts in calcium balance and/or a decrease in the rate of radiocalcium tumover were prominent effects in nine patients. Serum alkaline phosphatase did not change significantly and urinary total hydroxproline excretion decreased an average of 20% during the initial 28 days of SCT administration. A comparison of the combined radiocalcium turnover and calcium balance data indicated effective inhibition of bone resorption in eight of ten patients. The changes in skeletal metabolism were similar with the smallest dose employed, 50 MRC units three times a week compared to the largest dose, 100 MRC units daily. Significant natriuresis and a reduction in the degree of positive sodium balance were observed in three patients. These data are compatible with other studies indicating that SCT is more potent in the human than porcine calcitonin, by approximately 20-fold on a molar basis, and 50 MRC units of SCT three times a week appears to be an effective dose in initiating treatment of Paget's disease.

Effect of Synthetic Salmon Calcitonin on Iodine Metabolism in Rabbits

SummaryLong-term administration of synthetic salmon calcitonin to rabbits markedly decreases the radioiodine (131I) uptake in the thyroid gland as well as in the plasma. Protein-bound iodine and thyroxine serum levels are also decreased. In contrast, the renal iodine clearance is much increased in calcitonin-treated rabbits as compared to controls or to vehicle alone. This ioduric effect of salmon calcitonin can explain its role in goiter induction.This study was supported in part by NIH-General Grant, and Detroit General Research Corporation. We thank the Armour Pharmaceutical Company for the kind supply of synthetic salmon calcitonin used in this study.