Calcitonin deficiency has been implicated in the pathogenesis of accelerated bone loss, especially in postmenopausal osteoporosis. To investigate this issue, we studied 25 patients with untreated postmenopausal osteoporosis, 14 age-matched and sex-matched healthy controls (spinal bone mineral density greater than or equal to age-specific and sex-specific mean), and 5 women who had undergone total thyroidectomy. Each subject received an intravenous infusion of 2 mg of elemental calcium per kilogram of body weight over 5 minutes, to test the C-cell secretory reserve. We measured calcitonin by radioimmunoassay in whole plasma and in silica-cartridge extracts of plasma, the latter method providing greatly improved sensitivity and specificity for monomeric calcitonin. Basal immunoreactive calcitonin concentrations, whether measured in whole plasma or in extracts, were significantly higher in the subjects with osteoporosis (P less than 0.01) than in the healthy controls. The calcitonin secretory reserve, as assessed by calcium stimulation, was normal in the osteoporotic group but virtually absent in the thyroidectomy group. We conclude that postmenopausal osteoporosis is not associated with and does not result from calcitonin deficiency. On the contrary, excessive skeletal calcium release may stimulate calcitonin secretion in patients with the disorder.

An acute increase in serum calcium stimulates calcitonin (CT) secretion, but the effects of chronic hypercalcemia are controversial. Histopathological studies have shown C-cell hyperplasia in primary hyperparathyroidism (1 degree HPT), although circulating levels of CT have been variously reported to be normal, elevated, or depressed. We reexamined this relationship using CT RIA in conjunction with a silica extraction technique that conveys improved sensitivity and specificity for monomeric CT. Nine men and seven women with surgically documented 1 degree HPT were studied preoperatively before and after a short calcium infusion (2 mg Ca/kg, for 5 min), as were 72 normal men and 76 normal women. Basal whole plasma immunoreactive CT and silica-extractable CT concentrations in 1 degree HPT were indistinguishable from normal, regardless of sex. In addition, the whole plasma and silica-extractable CT responses to calcium stimulation were normal or blunted in patients with 1 degree HPT. We conclude that hypercalcemia resulting from 1 degree HPT is not associated with augmented CT secretion in response to an iv calcium infusion.

Some data suggest that human calcitonin (CT) secretion is lower in women than in men, decreases with age and the menopause, and is absent in thyroidectomized persons. To further explore CT secretory physiology, we have studied basal and calcium-stimulated plasma immunoreactive CT (iCT) and silica-extractable monomeric CT concentrations in 148 healthy volunteers and 33 patients with a history of thyroid damage (total or subtotal thyroidectomy, radioiodine treatment for thyrotoxicosis). Both whole-plasma iCT and extractable CT levels were lower basally and after calcium infusion in women than in men, basal levels being reduced about 50% and calcium-stimulated values about 75% from those of male subjects. There were no significant changes in basal iCT or extractable CT concentrations with age, and CT secretory capacity (CT response to calcium infusion) likewise did not change with age. Infusion of monomeric CT to constant concentration in 27 persons permitted estimates of CT metabolic clearance rates (MCRs) and secretion rates (SRs). Calculated MCRs of about 9 ml/min.kg-1 (persons aged 21-30 yr) and 6 ml/min.kg-1 (persons aged 54-70 yr) were in good agreement with published data, and did not differ between the sexes. SRs were dependent upon the assay method used to estimate basal plasma CT concentrations, being highest when whole-plasma iCT values were used. Based on estimates of plasma monomeric CT from the silica extraction procedure, the SR of CT was 59 +/- 6 (SE) ng/d.kg-1 in men, and 22 +/- 3 ng/d.kg-1 in women. Thyroid damage reduced, but did not abolish, apparent CT immunoreactivity, even in silica extracts of plasma. However, all subsets of thyroid-damaged patients had absent-to-markedly-impaired CT secretion in response to calcium infusion. We conclude that CT secretion is substantially lower both basally and after stimulation in women than in men, and that this difference in CT immunoreactivity probably reflects differences in circulating CT bioactivity. The sex difference in plasma CT concentrations probably results from lower rates of CT secretion in women, not increased MCR. There is no age-related decrease of plasma CT concentrations (or CT secretory reserve), calling into question the concept that a progressive deficiency of CT is partly responsible for age-related ("senile") osteoporosis. Surgical or radiation damage to the thyroid gland commonly abolishes C-cell response to calcium; such CT-deficient patients form a population suitable for determining whether or not reduced CT secretion can impair skeletal homeostasis.

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Estrogen (E) therapy and administration of oral contraceptives (OC) reportedly increase plasma calcitonin (CT) concentrations in women, effects said to mediate in part the beneficial actions of E on bone. To further examine this theory, we tested the effects of three cycles of OC therapy in 12 young women, comparing them to 10 healthy women before and after three normal menstrual cycles. We also determined the effects of 3 months of E therapy (ethinyl estradiol, 20 micrograms/day, 25 of 30 days) in 14 healthy postmenopausal women, using a crossover design (studied after 3 months with and 3 months without E). We determined CT by radioimmunoassay (antiserum G-1701) in whole plasma (iCT) and silica cartridge extracts of plasma (exCT) after overnight fasting, after calcium (Ca) infusion (2 mg Ca/kg over 5 minutes), and during a normal day at 0800, 1200, 1700, and 2000 h. In no control study was there a significant diurnal change in iCT or exCT, and neither OC nor E therapy altered this. Similarly, OC administration did not affect basal CT levels or the normal iCT and exCT responses to Ca infusion. E therapy induced expected changes in serum Ca, phosphorus, and alkaline phosphatase and urinary Ca and cAMP excretion; basal and diurnal plasma exCT levels were decreased significantly, consonant with the decrement in serum Ca. E did not alter normal iCT and exCT responses to Ca infusion. Thus, administration of either OC or E has no stimulatory effect on CT secretion, which suggests that the beneficial actions of E on bone are not mediated through CT-induced inhibition of bone resorption.(ABSTRACT TRUNCATED AT 250 WORDS)