Calcitonin Deficiency Research Articles

Calcitonin, the forgotten hormone: does it deserve to be forgotten?

Calcitonin is a 32 amino acid hormone secreted by the C-cells of the thyroid gland. Calcitonin has been preserved during the transition from ocean-based life to land dwellers and is phylogenetically older than parathyroid hormone. Calcitonin secretion is stimulated by increases in the serum calcium concentration and calcitonin protects against the development of hypercalcemia. Calcitonin is also stimulated by gastrointestinal hormones such as gastrin. This has led to the unproven hypothesis that postprandial calcitonin stimulation could play a role in the deposition of calcium and phosphate in bone after feeding. However, no bone or other abnormalities have been described in states of calcitonin deficiency or excess except for diarrhea in a few patients with medullary thyroid carcinoma. Calcitonin is known to stimulate renal 1,25 (OH)2 vitamin D (1,25D) production at a site in the proximal tubule different from parathyroid hormone and hypophosphatemia. During pregnancy and lactation, both calcitonin and 1,25D are increased. The increases in calcitonin and 1,25D may be important in the transfer of maternal calcium to the fetus/infant and in the prevention and recovery of maternal bone loss. Calcitonin has an immediate effect on decreasing osteoclast activity and has been used for treatment of hypercalcemia. Recent studies in the calcitonin gene knockout mouse have shown increases in bone mass and bone formation. This last result together with the presence of calcitonin receptors on the osteocyte suggests that calcitonin could possibly affect osteocyte products which affect bone formation. In summary, a precise role for calcitonin remains elusive more than 50 years after its discovery.

Response of Bone Mineral Density to Physical Exercises after Thyroidectomy

Introduction: Thyroidectomy could be associated with bone loss because of an endogenous excess of thyroxin, over enthusiastic thyroid replacement therapy following surgery, deregulation of bone resorption as consequence of calcitonin deficiency or some combination of these factors. The aim was to investigate the effect of weight bearing exercises on Improving bone mineral density in post thyroidectomy patients suffering from osteoporosis. Subjects and methods: Thirty osteoporotic patients were assigned randomly into two equal groups; their ages ranged from 20-45 years. The study group received weight bearing exercises program in addition to routine medical treatment. Control group received medical treatment only. Study group received two sessions per week for two successful months. The data were collected before and after the same period of treatment for both groups. Evaluation procedures were carried out to evaluate the bone mineral density using Dual Energy X-ray Absorptiometry. Results: Post treatment both groups showed a variant improvement in bone mineral density, but a significant improvement difference was recorded between the two groups in favor of the study group. Percentage of improvement of bone mineral density in the study group was 10.69%, while it was 2.8% in the control group. Conclusion: Weight bearing exercises were considered to be an effective modality for improving bone mineral density in subjects suffering from osteoporosis following thyroidectomy.

Calcitonin Deficiency in Mice Progressively Results in High Bone Turnover

Although the pharmacological action of calcitonin (CT) as an inhibitor of bone resorption is well established, there is still some controversy regarding its physiological function. Unexpectedly, Calca-deficient mice lacking CT and alpha-calcitonin gene-related peptide (alphaCGRP) were described to have a high bone mass phenotype caused by increased bone formation with normal bone resorption. Here we show that these mice develop a phenotype of high bone turnover with age, suggesting that CT is a physiological inhibitor of bone remodeling. The absence of significant changes in bone mineral density caused by decline or overproduction of CT in humans has raised the question, whether the pharmacological action of CT as an inhibitor of bone resorption is also of physiological relevance. To study the physiological role of mammalian CT, we have analyzed the age-dependent bone phenotype of two mouse models, one lacking CT and alphaCGRP (Calca-/-), the other one lacking only alphaCGRP (alphaCGRP-/-). Bones from wildtype, Calca-/- -mice and alphaCGRP-/- -mice were analyzed at the ages of 6, 12 and 18 months using undecalcified histology. Differences of bone remodeling were quantified by static and dynamic histomorphometry as well as by measuring the urinary collagen degradation products. To rule out secondary mechanisms underlying the observed phenotype, we determined serum concentrations of relevant hormones using commercially available antibody-based detection kits. Whereas alphaCGRP-/- -mice display an osteopenia at all ages analyzed, the Calca-/- -mice develop a phenotype of high bone turnover with age. Histomorphometric analysis performed at the age of 12 months revealed significant increases of bone formation and bone resorption specifically in the Calca-/- -mice. This severe phenotype that can result in hyperostotic lesions, can not be explained by obvious endocrine abnormalities other than the absence of CT. In addition to the previously described increase of bone formation in the Calca-deficient mice, we have observed that there is also an increase of bone resorption with age. This suggests that CT has a dual action as an inhibitor of bone remodeling, which may explain why alterations of CT serum levels in humans do not result in major changes of bone mineral density.

Antiepileptic Drugs and Bone Disease

Numerous studies have provided evidence of an association between antiepileptic drugs (AEDs) and adverse effects. Manifestations of bone disease in persons treated with AEDs include rickets, osteomalacia, osteoporosis, and fracture. There exists pathological and radiographic evidence of bone disease in persons with epilepsy treated with AEDs. As well, numerous biochemical abnormalities have been described including hypocalcemia, hypophosphatemia, reduced levels of biologically active vitamin D metabolites, hyperparathyroidism, and accelerated bone turnover, as measured by markers of bone formation and bone resorption. The AEDs most commonly reported as affecting bone include inducers of the cytochrome P450 enzyme system (phenytoin, phenobarbital, primidone, carbamazepine). In addition, there is growing evidence to suggest that valproate, an enzyme inhibitor, also affects bone. Limited data exists regarding the newer AEDs. Several mechanisms for AED-associated bone disease have been proposed, but no single mechanisms adequately addresses all the reported findings. Reported mechanisms include hepatic induction of the cytochrome P450 enzyme system leading to increased catabolism of vitamin, impaired absorption of calcium, inhibition of response to parathyroid hormone, hyperparathyroidism, impaired bone resorption and formation, vitamin K deficiency, and calcitonin deficiency. Few studies have evaluated the effect of treatment in bone disease associated with AEDs.

Impact of congenital calcitonin deficiency due to dysgenetic hypothyroidism on bone mineral density.

The objective of the present study was to determine the effect of chronic calcitonin deficiency on bone mass development. The results of 11 patients with thyroid dysgenesis (TD) were compared to those of 17 normal individuals (C) and of 9 patients with other forms of hypothyroidism (OH): 4 with hypothyroidism due to inborn errors of thyroid hormone synthesis and 5 with Hashimoto's thyroiditis. The subjects received an intravenous calcium stimulus and blood was collected for the determination of ionized calcium (Ca2+), calcitonin, and intact parathyroid hormone. Bone mineral density (BMD) was determined by dual-energy X-ray absorptiometry. After calcium administration the levels of Ca2+ in the two groups of hypothyroidism were significantly higher than in the normal control group (10 min after starting calcium infusion: C=1.29 +/- 0.08 vs TD=1.34 +/- 0.03 vs OH=1.34 +/- 0.02 mmol/l; P<0.05), and only the TD group showed no calcitonin response (5 min after starting calcium infusion: C = 27.9 5.8 vs TD = 6.6 0.3 vs OH = 43.0 13.4 ng/l). BMD values did not differ significantly between groups (L2-L4: C=1.116 +/- 0.02 vs TD=1.109 +/- 0.03 vs OH=1.050 +/- 0.04 g/cm2). These results indicate that early deficiency of calcitonin secretion has no detrimental effect on bone mass development. Furthermore, the increased calcitonin secretion observed in patients with inborn errors of thyroid hormone biosynthesis does not confer any advantage in terms of BMD.

Blood concentrations and secretory capacity of calcitonin in blood in osteoporosis

The deficiency of calcitonin, CT, which has an inhibitory effect of bone resorption might be related to the pathogenesis of osteoporosis. Therefore, in this paper, in regard to the sex difference, the changes with aging, and the comparison with patients with osteoporosis and normal controls, the basal value and the secretion capacity of CT concentrations in the blood, and the metabolic clearance rate, MCR, and the production rate, PR, of CT have been reviewed.

Calcitonin deficiency in early stages of chronic autoimmune thyroiditis.

Although calcitonin (Ct) deficiency has been described in chronic autoimmune thyroiditis (CAT) it is unclear at what stage in the disease it develops. We have analysed the Ct secretory responses of patients in two different evolutionary stages of CAT, namely the goitrous and atrophic phases. We studied the Ct response to combined calcium (2 mg/kg) and pentagastrin (0.5 microgram/kg) intravenous infusion in 27 patients with CAT and 30 normal adult controls. The cases were divided into two groups. The first comprised eleven women with CAT and goitrous subclinical hypothyroidism (GH), aged 28.6 +/- 10.1 years--at diagnosis they had increased thyroid autoantibody titres and cytological features compatible with stages 1 and 2 of Hashimoto's thyroiditis. The second comprised 16 females with CAT and an atrophic thyroid confirmed by ultrasound scan, aged 38.0 +/- 9.2 years--these patients were severely hypothyroid at diagnosis and were termed AH (atrophic hypothyroidism). Both groups (GH and AH) received replacement doses of thyroxine sufficient to restore euthyroidism for at least six months before the stimulation tests. Control group (C) consisted of 20 healthy women (A), aged 30.0 +/- 9.6 years, and 10 healthy men (B), aged 34.7 +/- 8.0 years. Serum Ct was measured by IRMA. The Ct secretory response was related to thyroid size and cytological data, when available. Basal Ct concentrations in groups GH (0.08 ng/l, median) and AH (0.07 ng/l, median) were significantly lower than those of female controls (0.58 ng/l, median). Stimulated Ct peak values in groups GH (0.08 ng/l, median) and AH (0.19 ng/l, median) were significantly lower than those of female controls (13.61 ng/l, median). Also, both basal (2.72 ng/l, median) and stimulated Ct levels (35.73 ng/l, median) in male controls were significantly higher than in female controls given already. A positive correlation between the Ct secretory reserve and thyroid dimensions, evaluated by ultrasound scan, was found only in patients with thyroid atrophy (AH; rs = 0.61, P < 0.05). We have found low basal and stimulated calcitonin values in patients with chronic autoimmune thyroiditis and thyroid enlargement, which represents an early phase of chronic autoimmune thyroiditis. Our data have also confirmed previous findings of deficient calcitonin secretion in advanced stages of chronic autoimmune thyroiditis in which thyroid atrophy is usually found. These findings may be associated with C-cell destruction following progressive, nonspecific follicular cell damage caused by lymphocytic infiltration and fibrosis of the gland.

Fractures after thyroidectomy in men: a population-based cohort study.

Bone mass is purportedly reduced by an endogenous or exogenous excess of thyroid hormone or, perhaps, by calcitonin deficiency. Patients who have undergone thyroidectomy could be subject to all of these effects, yet their practical implications in terms of fracture risk are poorly defined. Interpretation is further hampered by the focus on women, where results may be influenced by involutional osteoporosis. Consequently, we assessed the potential for fractures among the 136 Rochester, Minnesota men who underwent thyroidectomy between 1935 and 1979, relative to a group of age-matched control men from the community. With 2194 person-years of follow-up in each group, survival free of any fracture of vertebra, proximal humerus, distal forearm, pelvis, or proximal femur was similar in the two groups (p = 0.23), and the relative risk of any of these fractures for thyroidectomized patients versus their controls was increased only 1.5-fold (95% CI, 0.7-3.2). The difference was entirely accounted for by a statistically significant excess of proximal femur fractures in the men with thyroidectomy. Risk factors for fractures among men with thyroidectomy included greater age at surgery, greater extent of surgery, and the presence of risk factors for secondary osteoporosis. Thus, thyroidectomy, performed mainly for adenoma or goiter, seems to have little overall influence on the risk of age-related fractures in men. However, the association with hip fractures requires further evaluation.

The changes of the calcitonin reserve function in patients with primary osteoporosis

In order to study the role of calcitonin (CT) in osteoporosis, the calcium loading calcitonin stimulated test (calcium element 3 mg/kg body weight, i.v., 10 min) was used to investigate calcitonin reserve function in 21 women with osteoporosis. The sesults were compared with those in 48 healthy women and 7 women with osteopenia. After calcium infusion, there was no significant difference in the basal CT, the peak CT value, the CT increase range, and the area under the curve (AUC) between pre- and post-menopausal healthy women. In patients with primary osteoporosis, the four parameters were significantly lower than those in normal controls, and the CT peak value and increase range were lower than those in patients with osteopenia. In the osteopenia group, the basal CT value and its AUC were lower than those in the age-matched control group, but no difference was found in the peak CT value and the increase range between the two groups. The results showed no evident effect of menopause on calcitonin reserve function, but suggested a possible relationship between the decrease of CT reserve function and osteoporosis in patients with osteoporosis. Calcitonin deficiency has something to do with the development of osteoporosis.

Evolution of the pathogenesis of postmenopausal bone loss.

At a time when the investigation of bone diseases appears to be on the threshold of a new era, it is appropriate to pause and contemplate past and present thinking on the etiology of postmenopausal osteoporosis. This brief review traces the evolution of ideas on the nature of the pathogenesis of this disease from Albright's hypoosteoblastic hypothesis through other hypotheses that include disturbance in osteoclasia, negative calcium balance, disturbance of calcium homeostatic control mechanisms, increased skeletal sensitivity to parathyroid hormone, deficiency of calcitriol and calcitonin, altered activities of growth factors and cytokines, alterations in the local regulation of osteoclastogenesis, and changes in mechanical usage set points.

Bone Density and Mineral Metabolism in Thyroidectomized Patients Treated with Long-Term l-Thyroxine

1. A decreased bone mass has been reported in patients with endogenous hyperthyroidism, but the effect on bone density and mineral metabolism of thyroxine administration in thyroidectomized patients is still controversial. To further contribute to this debate, we studied 25 women thyroidectomized for thyroid cancer on long-term treatment with thyroid-stimulating hormone-suppressive doses of L-thyroxine. Twenty-one sex- and age-matched normal subjects were also studied as a control group. 2. The bone density of the spine and serum calcitonin, calcitriol and parathyroid hormone concentrations were not different when the whole patient group was compared with the control subjects, nor when the patients and control subjects were compared according to their menopausal status. However, post-menopausal thyroidectomized patients showed significantly lower bone mass (P < 0.001) than premenopausal patients. 3. L-Thyroxine-treated patients showed significantly higher levels of bone alkaline phosphatase and urine hydroxyproline excretion than control subjects (P < 0.003 and P < 0.001, respectively). These differences were still present when patients and control subjects were analysed according to their menopausal status. However, bone alkaline phosphatase was significantly higher in postmenopausal than in premenopausal women only in L-thyroxine-treated patients (P < 0.05). In postmenopausal L-thyroxine-treated patients a negative correlation between time since menopause and bone mass (P < 0.05) and a positive correlation between bone alkaline phosphatase and hydroxyproline excretion (P < 0.03) were also found.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of long-and short-term corticosteroids on plasma calcitonin and parathyroid hormone levels

The role of calcitonin and parathyroid hormone (PTH) in corticosteroid-induced osteoporosis is controversial. We therefore measured plasma calcitonin and PTH levels in 34 adults receiving chronic pharmacological corticosteroids for obstructive airways disease, and in controls matched for age, sex, menopause, and disease. In addition, the acute effect of a 7-day course of 15 mg prednisolone daily on fasting and calcium-stimulated calcitonin was studied in 10 normal male volunteers. There was no difference in calcitonin and PTH levels in the corticosteroid-treated patients when compared with controls. The corrected serum calcium was significantly higher in the steroid-treated patients (patients mean 2.40 (SEM 0.01) mmol/liter; controls mean 2.33 (SEM 0.01) mmol/liter; P < 0.001). The short course of corticosteroids in volunteers did not alter basal or stimulated calcitonin, PTH, or calcium levels. These results suggest that neither calcitonin deficiency nor PTH excess is a feature of corticosteroid-induced osteoporosis.

Effect of 131I treatment on the calcitonin response to calcium infusion in hyperthyroid patients.

The objective was to evaluate the effect of 131I treatment for hyperthyroidism on calcitonin secretion by thyroid C-cells. Determination of basal calcitonin levels and calcitonin secretory reserve before and after 131I administration. Seventeen hyperthyroid patients (15 female, two male) were studied before, and 2 months after 131I treatment, and 12 of these patients were restudied 8 months after 131I treatment. Calcitonin response was assessed by measuring basal and post calcium infusion calcitonin levels. Basal TSH, T3, and T4 levels were also determined at each study. The rise of plasma calcium resulted in statistically significant increase of plasma calcitonin levels before 131I treatment (10.9 +/- 2.4 pmol/l), while this response was significantly diminished 2 and 8 months after treatment (2.6 +/- 0.7 and 1.6 +/- 0.3 pmol/l, respectively). No correlation was found between the calcitonin response and age or plasma TSH. Our results demonstrate that 131I treatment for hyperthyroidism may seriously damage thyroid C-cells and cause calcitonin deficiency.

Assessment of thyroidal "C" cell secretion in osteoporotic girls with Turner's syndrome. Basal and calcium-stimulated levels of total calcitonin, extractable calcitonin and katakalcin.

Osteoporosis is a common finding in Turner's syndrome. To test the hypothesis that calcitonin deficiency may contribute to bone mineral loss in Turner's syndrome, we studied basal and calcium-stimulated (2 mg/kg body weight in 5 min) levels of total calcitonin, extractable calcitonin and katacalcin in 15 girls with Turner's syndrome and osteoporosis. Fifteen age-matched healthy girls were studied as controls. Both basal calcitonin (total and extractable) and katacalcin values were not significantly different in patients with Turner's syndrome in comparison with those of the controls. The calcium stimulation test showed a similar "C" cell secretory reserve in both groups. The calculation of delta CT/delta iCa of total and extractable calcitonin and delta KC/delta iCa, which accounts for individual variations in serum ionized calcium increases, did not show any significant difference between girls with Turner's syndrome and controls. We conclude that calcitonin deficiency is not a causative factor of osteoporosis in girls with Turner's syndrome and that in this syndrome long-life estrogen deficiency does not impair "C" cell secretory activity.

Effect of calcitonin deficiency on bone density and bone turnover in totally thyroidectomized patients

To investigate the influence of calcitonin deficiency on bone turnover and density we studied 25 premenopausal female and 12 male patients (age 23 to 49 years) who had undergone total thyroidectomy for differentiated thyroid cancer 1 to 15 years previously. Basal and calcium stimulated extractable calcitonin, representing the monomeric, biologically active form of the hormone, was lacking or markedly decreased in all patients. There was a relative increase of urine hydroxyproline excretion (an index of osteoclastic bone degradation) in relation to serum osteocalcin (an index of osteoblastic bone formation) indicating an imbalance of bone turnover with a tendency to increased degradation in all patients. Total and trabecular bone density, measured with quantitative computed tomography at the distal forearm were significantly decreased in the male and normal in the female patients, without a relation to the duration of the calcitonin deficiency. The study indicates that patients with calcitonin deficiency, suppressive thyroid hormone treatment, or both may have a higher risk of increased bone degradation and osteopenia. Whether the effect is more due to calcitonin deficiency or thyroid hormone therapy, cannot be concluded from this study design. The fact that only the male patients had a decreased bone density may be due to a lower parathyroid activity in our female patients and the greater thyroidectomy-induced decrement of monomeric calcitonin in our male patients compared with male controls.

Calcitonin secretion in children with insulin-dependent diabetes mellitus

To test the hypothesis that calcitonin (CT) deficiency may contribute to bone mineral loss in insulin-dependent diabetes mellitus (IDDM), we studied basal and calcium stimulated (2 mg/kg body wt. in 5 min) CT levels in 15 children with IDDM and osteopenia. Ten age-sex matched healthy children were studied as controls. Since extractable CT (exCT) allows more sensitive and specific measurement of CT monomer, we measured both total serum CT (tCT) and exCT. Diabetic children had slightly but significantly (P less than 0.05) higher basal levels of both tCT (24.5 +/- 7.1 ng/l) and exCT (5.6 +/- 1.6 ng/l) than controls (tCT: 18.7 +/- 5.4 ng/l; exCT: 4.3 +/- 1.2 ng/l). Calcium stimulation test pointed out significant increase (P less than 0.001) of tCT and exCT in both groups with peak values not significantly different in IDDM in respect to controls. However, diabetic children showed a reduced CT reserve evidenced by a lower peak/basal ratio (diabetics: tCT 1.68, exCT 1.84; controls: tCT 2.49, exCT 2.88) and by a more rapid decrease in CT levels. We conclude that CT deficiency is not a causative factor of diabetic osteopenia. The slightly higher basal CT values suggest that an increased bone reabsorption may be operative in IDDM and it stimulates CT secretion. This chronic "C" cell stimulation may induce the reduction in CT reserve observed employing the calcium infusion test.

Bone mass in totally thyroidectomized patients. Role of calcitonin deficiency and exogenous thyroid treatment

Calcitonin has an uncertain role in the preservation of bone mass. Since surgical thyroidectomy abolishes the calcitonin secretion in response to calcium, the bone mineral density at the radius shaft and lumbar spine was measured in 60 patients (5 men, 16 premenopausal, 34 postmenopausal euparathyroid and 5 postmenopausal hypoparathyroid women) who had undergone near total thyroidectomy for thyroid cancer 8.4 +/- 0.7 years before the study. All patients were maintained on suppressive doses of thyroid hormones. Bone mineral density values of the radius shaft (expressed as Z-score) of 34 postmenopausal euparathyroid women was significantly below the normal average (mean +/- SEM = -0.59 +/- 0.2; p = 0.01). Bone mineral density of the lumbar spine was also below the normal average although the difference only approached statistical significance (-0.36 +/- 0.2; 0.05 less than p less than 0.1). The bone mineral density of neither the radius nor the spine differed from normal levels in the premenopausal women and the postmenopausal hypoparathyroid women. Unexpectedly, the bone mineral density of the spine was significantly increased in the 5 thyroidectomized men. The results indicate that thyroidectomized women have a diminished bone mass after the menopause only if parathyroid function is normal. Since the patients were receiving thyroid hormone at suppressive doses, the present study is not able to separate the relative contributions of calcitonin deficit and exogenous thyroid on bone mass loss.

Characterization of the calcitonin/CGRP gene in Williams syndrome

We have investigated the possibility of mutations in the calcitonin/calcitonin gene related peptide (CGRP) gene in children with Williams syndrome. Involvement of the calcitonin/CGRP gene in Williams syndrome is postulated on the basis that Williams syndrome children often have infantile hypercalcemia and deficient expression of calcitonin, a hormone that lowers serum calcium levels. To test the hypothesis that mutations in the calcitonin/CGRP gene might be responsible for the reduced calcitonin levels, we examined the calcitonin/CGRP gene structure in Williams syndrome children. Analysis of white blood cell DNA by Southern blot hybridizations in 5 individuals did not show any detectable large deletions or rearrangements in the calcitonin/CGRP gene locus. The possibility of small deletions or point mutations within the exon encoding the mature calcitonin hormone is unlikely based on ribonuclease protection assays with patient DNA amplified by the polymerase chain reaction (PCR) technique. These findings suggest that the calcitonin deficiency might be due either to mutations elsewhere in the gene or to defects in the cellular machinery needed for calcitonin synthesis and/or secretion.

Bone mineral density in postmenopausal women treated with L-thyroxine

<h3>PURPOSE:</h3> To determine if bone mineral density is decreased in postmenopausal women treated with 1-thyroxine, and, if any decrease is observed, whether it is related to overtreatment with thyroid hormone, to deficiency of calcitonin, or to other factors. <h3>PATIENTS AND METHODS:</h3> The study consisted of 19 postmenopausal women between 50 and 75 years of age treated with 1-thyroxine for 5 years or longer, and 19 matching control subjects with no thyroid disease. Bone mineral density of the spine and hip was measured by dual-photon absorptiometry. Plasma calcitonin concentrations and serum thyroid hormone levels were determined by radioimmunoassays. <h3>RESULTS:</h3> The 1-thyroxine-treated women had lower bone density in the lumbar spine (1.013 g/cm² [95% confidence interval, 0.945 to 1.081] versus 1.134 g/cm² [1.026 to 1.242], p=0.043); in the femoral neck (0.736 g/cm² [0.694 to 0.778] versus 0.809 g/cm² [0.747 to 0.872], p=0.040); in Ward's triangle (0.576 g/cm² [0.530 to 0.623] versus 0.694 g/cm² [0.617 to 0.770], p=0.011); and in the trochanteric area (0.626 g/cm² [0.581 to 0.672] versus 0.722 g/cm² [0.651 to 0.794], p=0.027). The maximal increase in calcitonin following calcium infusion was 1.37 ng/L (95% confidence interval, −0.44 to 3.17) in the 1-thyroxine-treated patients versus 18.8 ng/L (95% confidence interval, 10.0 to 27.5) in normal women, p <0.001. The average dose of 1-thyroxine was 120 μg/day; 16 of the 19 patients had normal serum thyroxine levels. However, TSH levels were low in 13 of the 19, suggesting that 1-thyroxine treatment was supraphysiologic. Seven of the 19 patients had a history of hyperthyroidism in the distant past; these patients, considered separately, had significantly reduced bone density in the hip. The other 12 patients, considered separately, did not have a statistically significant loss of bone density. <h3>CONCLUSIONS:</h3> Long-term 1-thyroxine therapy is associated with decreased density of the spine and hip. Since subclinical hyperthyroidism, decreased calcitonin responsiveness, and a history of hyperthyroidism were demonstrated in some or all of these patients, these factors must be considered as possible causes of the decreased bone density.

Calcitonin secretion in idiopathic renal stone formers

Several studies demonstrated a reduction in bone mineral content (BMC) in idiopathic renal stone formers (RSF). We found this reduction in association with a chronic low-calcium diet. Low calcium intake could theoretically result in calcitonin deficiency, responsible for increased bone resorption. This hypothesis was tested in 22 male RSF eating a low-calcium diet (350 +/- 72 SD mg/day) for 2 years or more, who showed a significant reduction in their BMC. When compared to 15 normal male subjects eating a free diet, RSF showed increases in serum alkaline phosphatase activity and fasting urinary excretion of hydroxyproline and calcium, suggesting increased bone turnover. Plasma calcitonin levels were measured by radioimmunoassay following an extraction-concentration technique (exCT). Basal plasma exCT levels were higher (P less than 0.005) in RSF (4.1 +/- 0.8 SEM pg/ml) than in normal subjects (2.8 +/- 0.4). Following a 5 minute infusion of 2 mg elemental calcium per kg, levels of plasma exCT tended to increase more, although not significantly, in RSF (51.3 +/- 9.4 pg/ml) than in normal subjects (36.6 +/- 9.7). The CT secretory response, taking into account changes in serum calcium concentration (delta exCT/delta Ca), was higher (P less than 0.05) in RSF (50.0 +/- 10.0) than in normal subjects (25.6 +/- 6.6). Our study thus demonstrates that RSF chronically fed a low-calcium diet have increased basal plasma CT levels and increased CT cells responsiveness. CT deficiency cannot therefore be considered a cause for the low BMC associated with a chronic low-calcium diet in RSF.