calcitonin and Hypercalcemia

Despite being approved by the Food and Drug Administration for over 30 years, calcitonin salmon has seen a dramatic increase in acquisition cost over the last few years. Being commonly used for the treatment of hypercalcemia of malignancy, health systems must implement stewardship strategies in order to curtail usage. This review is intended to provide a background on calcitonin usage for hypercalcemia of malignancy and associated strategies to ensure appropriateness of utilization within health systems.

Topics: Calcitonin; Calcium-Regulating Hormones and Agents; Drug Costs; Drug Utilization Review; Humans; Hypercalcemia

Calcitonin (CT) inhibits osteoclast-mediated bone resorption and is being used to treat Paget's disease of bone, hypercalcemia of malignancy and postmenopausal osteoporosis. The formation of antibodies against heterologuous calcitonins like salmon calcitonin (sCT) is common and occurs in 40-70% of the patients treated for more than 4 months. Not all of these patients, however, develop a secondary resistance to sCT, therefore the clinical significance of sCT antibodies is discussed controversially. In vivo and in vitro approaches demonstrate a neutralizing effect in 35 to 60% of the patient sera with antibodies against sCT. These neutralizing antibodies appear to explain most cases of clinically relevant secondary resistance to sCT treatment, which occurs in 25-45% of the patients after treatment periods of 6 months and longer. A positive treatment response to human CT after development of secondary resistance to sCT proves the diagnosis of antibody related resistance. Few cases develop secondary resistance in the absence of sCT binding antibodies, the mechanism of this phenomenon is unclear. Antibody related resistance is a significant problem in long term treatment with sCT. Especially in conditions like postmenopausal osteoporosis, where no readily accessable marker of treatment response is available, the development of sCT antibodies and their possible neutralizing effect has to be considered.

Topics: Animals; Antibodies; Calcitonin; Drug Resistance; Female; Humans; Hypercalcemia; Neoplasms; Osteitis Deformans; Osteoporosis, Postmenopausal

Recent information on the pathophysiology and treatment of hypercalcemia of malignancy is reviewed, and the roles of two new agents, gallium nitrate and pamidronate, are discussed. Current evidence suggests that parathyroid hormone-related protein is the most important mediator of humoral hypercalcemia of malignancy. In patients with local osteolytic hypercalcemia, cytokines have been implicated as mediators. Effective treatment of hypercalcemia of malignancy may improve patients' quality of life, although an episode of hypercalcemia is a poor prognostic indicator for survival. Gallium nitrate is more effective than salmon calcitonin and possibly more effective than etidronate in the treatment of hypercalcemia of malignancy. The primary adverse effect of gallium nitrate is nephrotoxicity, and its use must be avoided in patients who have renal dysfunction or who are receiving nephrotoxic drugs. Pamidronate is more effective than etidronate in the treatment of hypercalcemia of malignancy and can be administered as a single i.v. dose. The adverse effects of pamidronate include mild fever, hypocalcemia, and hypophosphatemia. Compared with gallium nitrate, pamidronate offers a more convenient dosing regimen, is less frequently associated with nephrotoxicity, and is less expensive. Single i.v. doses of either pamidronate or plicamycin effectively lower serum calcium levels and are reasonable choices for maintenance therapy. Gallium nitrate and pamidronate may be slightly more effective than previously available agents for initial treatment of hypercalcemia. Pamidronate currently offers the best combination of effectiveness, ease of administration, and a low rate of adverse effects.

Topics: Animals; Antineoplastic Agents; Calcitonin; Diphosphonates; Etidronic Acid; Gallium; Humans; Hypercalcemia; Neoplasm Proteins; Neoplasms; Neoplasms, Experimental; Pamidronate; Parathyroid Hormone-Related Protein; Proteins; Treatment Outcome

Salmon calcitonin has been used for the management of acute hypercalcemia for the past several years. Unlike other hypocalcemic agents, it is effective within 2 hours after first dosing. This pharmacologic agent shows peak effect at 24-48 hours and has a duration of action of 4-7 days in most cases. Its effectiveness may diminish thereafter despite continuous administration (the so-called "escape phenomenon"). Salmon calcitonin has been shown to be effective in the management of acute hypercalcemia due to a variety of causes, and, because of its low toxicity profile, it may be administered to patients with congestive heart failure or azotemia. Salmon calcitonin is also an analgesic agent in patients with pain associated with bone metastases and may be used in conjunction with other hypocalcemic agents such as mithramycin, the bisphosphonates, or gallium nitrate to prolong the clinical response to more than 1 week. Salmon calcitonin is therefore effective and safe in the management of acute hypercalcemia.

Topics: Adrenal Cortex Hormones; Calcitonin; Calcium; Diphosphonates; Gallium; Humans; Hypercalcemia; Pamidronate; Plicamycin

The treatment of hypercalcaemia with low-dose salcatonin (100 U/d), administered either as a single intramuscular bolus or as a continuous intravenous infusion for five days, was examined in two groups of 10 patients with primary hyperparathyroidism, in a randomized open parallel study. Both the peak (0.31 +/- 0.035 mmol/L v 0.13 +/- 0.034 mmol/L) and overall (0.073 +/- 0.016 mmol/L v 0.018 +/- 0.016 mmol/L) hypocalcaemic responses were greater in the infusion group. The peak reduction in serum calcium occurred on day 2 of treatment after which there was a progressive attenuation of response. All the differences between the two methods of administration wer due to renal rather than bony effects of salcatonin. Possible causes of progressive resistance to treatment included reductions in sodium excretion and serum phosphate. It is concluded that low-dose salcatonin administered as a continuous infusion was more effective than the same dose given as a bolus. The kidney played a pivotal role both in the cause of the hypercalcaemia and in the response to treatment, including the rapid development of resistance which limits the use of salmon calcitonin in primary hyperparathyroidism to short-term reduction of serum calcium.

Topics: Alkaline Phosphatase; Calcitonin; Calcium; Creatinine; Humans; Hypercalcemia; Hyperparathyroidism; Infusions, Intravenous; Injections, Intramuscular; Parathyroid Hormone; Phosphates; Random Allocation

Pharmacotherapy towards hypercalcemia treatment mainly caused by osteoporosis and bone tumor is an effective method to regulate in vivo calcium equilibrium. As a clinical therapeutic peptide, salmon calcitonin (sCT) is considered as a quick-acting medicine but it is limited by the short half-life. To address this challenge, we designed an injectable thermo-sensitive hydrogel based on hydroxypropyl chitin (HPCH) and incorporated the complex of sCT and hyaluronic acid (HA) (sCT-HA) with high association efficiency up to 96.84 ± 7.25%. This composite hydrogel showed a tunable biodegradable property. In vitro sCT release profiles revealed that this hydrogel can achieve long-term sustained sCT release (28 days) with considerable structure stability. The cellular study illustrated outstanding compatibility and osteoconductive potential of this multi-component hydrogel according to the higher ALP activity (2.10-fold), calcium expression (2.30-fold) and extracellular calcium deposition (1.10-fold) compared to that of the sCT group. In vivo sCT release confirmed that this hydrogel system realized sustained sCT release and a continuous hypocalcemic effect for as long as 28 days, and there were no inflammation and immune responses according to the histological evaluations (H&E and IgG staining). These findings demonstrate that this osteoconductive hydrogel system can provide a promising method for therapy of bone related disease.

Topics: Animals; Calcitonin; Calcium; Cell Line; Chitin; Drug Liberation; Female; Hyaluronic Acid; Hydrogels; Hypercalcemia; Mice; Osteogenesis; Rats, Sprague-Dawley

The common pathological characteristic of osteoporosis and hypercalcemia is the disorder of calcium homeostasis. Currently, salmon calcitonin (sCT), a clinical regenerative medicine, is an attractive chioice to regulate calcium metabolism for alleviation of osteoporosis and hypercalcemia. Unfortunately, serum sCT is quickly cleared in vivo, leading to its short half-life. Here, we designed a versatile hydrogel, based on salmon calcitonin-oxidized calcium alginate (sCT-OCA) conjugate and hydroxypropyl chitin (HPCH). The release profile showed that sCT could be released from HPCH hydrogels loaded with sCT-OCA conjugate (sCT-OCA-HPCH) for at least 28 days with conformation stability. The cellular test demonstrated that the biocompatible sCT-OCA-HPCH, compared with sCT formulation, had capacity in up-regulating alkaline phosphatase activity (∼63% increase) and promoting calcium to deposit into extracellular matrix (∼42% increase). These results indicated that thermosensitive sCT-OCA-HPCH hydrogel herein is a versatile platform for many applications such as calcium metabolism regulation, osteoporosis treatment, and hypercalcemia therapy.

Topics: Bone Density Conservation Agents; Calcitonin; Humans; Hydrogels; Hypercalcemia

A patient with extremely high calcium level of 23.9 mg/dL (5.97 mmol/L) was admitted to our department unconscious with pathological ECG recording, demonstrating shortening of QT interval. The patient was treated by fluid resuscitation, bisphosphonates, salmon calcitonin and steroids. Haemodialysis with low calcium bath had been promptly provided with improvement of consciousness and calcium level. ECG changes disappeared. Subsequent investigations revealed hyperparathyroidism and a large parathyroid adenoma was then surgically removed. Extreme and rapid calcium elevation (parathyroid crisis) is rarely seen in primary hyperparathyroidism and usually is distinctive for malignancy. In the context of acute kidney injury and refractory hypercalcaemia with life-threatening complications (coma, ECG changes with impending danger of arrhythmia), haemodialysis may effectively decrease calcium levels. It should be pointed out that dialysis is an efficient method of treatment of refractory hypercalcaemia, parathyroid crisis, but it is rarely used due to its invasive nature.

Topics: Adenoma; Aged; Bone Density Conservation Agents; Calcitonin; Dexamethasone; Diphosphonates; Fluid Therapy; Glucocorticoids; Humans; Hypercalcemia; Male; Pamidronate; Parathyroid Neoplasms; Prednisone; Renal Dialysis; Severity of Illness Index; Tomography, X-Ray Computed

Topics: Calcitonin; Humans; Hypercalcemia; In Situ Hybridization, Fluorescence; Williams Syndrome

As primary hyperparathyroidism affects mainly middle-aged and elderly women, it is an infrequent finding during gestation and breastfeeding. To date, less than 200 pregnant patients with primary hyperparathyroidism diagnosed during pregnancy have been described. Like in other disorders of the parathyroid gland, the recognition of primary hyperparathyroidism during pregnancy and lactation may be difficult, as clinical symptoms are not specific, while laboratory findings may be masked by some typical pregnancy-induced changes in calcium and phosphate homeostasis. If remains untreated, the disease may result in serious clinical implications for the mother and fetus. Most authors consider surgery within the second trimester of pregnancy as the treatment of choice in this group of patients.. In our paper, we discuss the case of a 35-year-old female with a history of recurrent acute pancreatitis and recurrent abortions. As the patient declined surgery, conservative management with calcitonin was started and continued throughout the rest of pregnancy, and led to giving birth to the infant whose only health problem was transient hypocalcemia.. The described case shows that conservative management, if started respectively early and conducted on the basis of a patient's condition, may effectively reduce increased perinatal and maternal morbidity and mortality in pregnant women declining surgery.

Topics: Abortion, Habitual; Adenoma; Adult; Calcitonin; Calcium Gluconate; Female; Humans; Hypercalcemia; Hyperparathyroidism; Infant, Newborn; Pancreatitis; Parathyroid Neoplasms; Pregnancy; Pregnancy Complications; Recurrence

Oral delivery of salmon calcitonin (sCT) to rats via a recombinant Saccharomyces cerevisiae was assessed. A synthetic sCT gene was cloned and expressed in S. cerevisiae yAGA2-sCT. Recombinant salmon calcitonin (rsCT) expression was detected by flow cytometry. The resorption activity of osteoclasts was inhibited by 3 x 10(-6 )M rsCT. Oral administration of 5 g lyophilized yAGA2-sCT/kg to hypercalcemic rats decreased serum calcium from 2.8 +/- 0.02-2.7 +/- 0.02 mM.

Topics: Administration, Oral; Animals; Bone Resorption; Calcitonin; Calcium; Cattle; Flow Cytometry; Gene Expression; Genetic Vectors; Hypercalcemia; Male; Rats; Rats, Wistar; Recombinant Proteins; Saccharomyces cerevisiae

Calcitonin is currently used to treat hypercalcemia of many clinical types. However, we encountered a woman who suffered severe hypercalcemia and status epilepticus, both of which developed 8 days after the administration of salmon calcitonin for the treatment of breast cancer. When the patient first presented her serum calcium level was 15.5mg/dl, intact parathyroid hormone level 118 pg/ml, calcitonin <2 pg/ml, magnesium 1.2mg/dl, and phosphate 1mg/dl. Her serum calcium level returned to the reference range within 48 h after correction. At follow-up no hypercalcemia had developed, although the patient had received no further treatment for her breast cancer and multiple metastases were subsequently detected. Her hypercalcemia is ascribed to exogenous calcitonin supplementation. These conflicting events may be due to functionally heterogeneous calcitonin receptors or to activation of 1 alpha-hydroxylase by exogenous calcitonin.

Topics: Bone Neoplasms; Breast Neoplasms; Calcitonin; Female; Humans; Hypercalcemia; Middle Aged; Osteoporosis; Status Epilepticus

To determine whether pamidronate disodium can reduce vitamin D3-induced hypercalcemia in dogs and whether combination treatment with calcitonin is more effective than treatment with pamidronate alone.. 20 clinically normal male Beagles.. All dogs were given 8 mg of cholecalciferol (CCF)/kg of body weight once orally, then were assigned randomly to 4 groups of 5 dogs each. Dogs were given 0.9% NaCl solution IV (group 1), calcitonin SC and 0.9% NaCl solution IV (group 2), pamidronate and 0.9% NaCl solution IV (group 3), or a combination of all 3 agents (group 4). Dogs were observed for 28 days, and serial blood and urine samples were collected for determination of serum biochemical, electrolyte, and 25(OH)D3 values, CBC, and urine mineral excretion. Samples of kidney, stomach, lung, aorta, liver, duodenum, and brain were evaluated by light microscopy and quantitative mineral analysis.. Two dogs in group 1 were euthanatized 4 days after CCF administration because of severe clinical signs of disease. Dogs in group 3 lost less weight and had significantly lower serum phosphorus, total and ionized calcium, and urinary zinc concentrations, compared with dogs in group 1. On day 4, serum urea nitrogen concentration was significantly lower in dogs of groups 3 and 4, compared with dogs in group 1. Mild to moderate mineralization of kidneys and stomach were observed in the 2 group-1 dogs euthanatized on day 4.. Pamidronate administration effectively prevents CCF-induced hypercalcemia and mineralization of soft tissues.. Pamidronate is a potentially useful antidote against CCF toxicosis in dogs.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Blood Chemical Analysis; Calcitonin; Cholecalciferol; Creatinine; Diphosphonates; Dog Diseases; Dogs; Hypercalcemia; Ion-Selective Electrodes; Kidney Cortex; Male; Pamidronate; Radioimmunoassay; Random Allocation; Urea; Zinc

Topics: Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Calcitonin; Carcinoma, Lobular; Female; Humans; Hypercalcemia; Middle Aged; Palliative Care; Paraneoplastic Syndromes; Radiotherapy Dosage

Topics: Adult; Antineoplastic Agents; Breast Neoplasms; Calcitonin; Female; Fluid Therapy; Gallium; Humans; Hypercalcemia

Serum bone Gla protein (BGP) and alkaline phosphatase (AP) activity were compared for the assessment of skeletal status in 11 normal pregnant women, 12 normal women on days 3 and 13 of the menstrual cycle, five postmenopausal women before and after 1 month of treatment with ethinyl estradiol (20 micrograms/day), five patients with cancer and hypercalcemia during treatment with calcitonin, and one patient with Paget disease during treatment with Plicamycin. BGP and AP correlated with each other only in the pregnant women. In all other circumstances, there was no correlation between these two serum osteoblast products. Furthermore, there were conditions in which the two measurements became discordant. These studies demonstrate that BGP and AP commonly are dissociated when used as measurements of skeletal status. Although both are osteoblast products, BGP and AP probably reflect different aspects of osteoblast differentiation and function.

Topics: Adult; Alkaline Phosphatase; Calcitonin; Carcinoma, Squamous Cell; Ethinyl Estradiol; Female; Humans; Hypercalcemia; Lung Neoplasms; Middle Aged; Multiple Myeloma; Osteocalcin; Postmenopause; Pregnancy

Topics: Aged; Bronchial Neoplasms; Calcitonin; Carcinoma, Squamous Cell; Diphosphonates; Drug Therapy, Combination; Humans; Hypercalcemia; Male

Topics: Bone Diseases; Calcitonin; Calcium; Female; Humans; Hypercalcemia; Male; Osteitis Deformans; Osteoporosis, Postmenopausal

Topics: Administration, Intranasal; Calcitonin; Calcium; Circadian Rhythm; Dose-Response Relationship, Drug; Drug Evaluation; Humans; Hypercalcemia; Neoplasms; Time Factors

A 3 year old girl presented with malignant osteopetrosis, which was treated by allogeneic bone marrow transplantation. Successful engraftment was complicated by prolonged hypercalcaemia, which was controlled by a combination of a bisphosphonate, phosphate infusions, vigorous resalination, and salmon calcitonin. She was alive and well 16 months after the transplant.

Topics: Bone Marrow Transplantation; Calcitonin; Child, Preschool; Diphosphonates; Female; Humans; Hypercalcemia; Osteopetrosis; Pamidronate; Phosphates; Postoperative Complications

Calcitonin was used in conjunction with saline diuresis, furosemide, and prednisone in treatment of a dog that consumed a rodenticide that contained cholecalciferol and has been touted as safe for nontarget species. This report shows that the rodenticide is toxic to dogs and that salmon calcitonin is a useful treatment for the often refractory hypercalcemia induced by vitamin D toxicosis.

Topics: Animals; Calcifediol; Calcitonin; Cholecalciferol; Combined Modality Therapy; Dog Diseases; Dogs; Fluid Therapy; Hypercalcemia; Male; Rodenticides

Seventeen patients with malignant hypercalcemia were treated with a combination of a single dose of 3-amino 1-hydroxypropylidene-1-bisphosphonate (APD [also known as AHPrBP or palmidronate disodium]) and salmon calcitonin given as suppositories for 3 days. To assess whether such a combined short treatment has a significant benefit leading to earlier normalization of the plasma calcium level than does APD alone, 17 additional patients matched for the type of tumor, initial plasma calcium level, urinary hydroxyproline level, and the dose of APD served as controls. All patients receiving the combination of calcitonin and APD achieved normalization of the plasma calcium level within 9 days, with a decrease from 3.22 +/- 0.90 mmol/L (mean +/- SEM) to 2.29 +/- 0.03 mmol/L. In the group receiving APD alone, the plasma calcium level normalized in only 14 of 17 patients by day 9. In the group receiving calcitonin and APD, the drop in the plasma calcium level occurred more rapidly, and the plasma calcium values were lower from days 2 to 4. This advantage was explained by the calciuric effect of calcitonin, as reflected by a significant decrease in the notional setting of renal reabsorption of calcium, reaching 2.16 +/- 0.06 mmol/L compared with 2.34 +/- 0.06 mmol/L in the group receiving APD alone. There were no side effects of both treatments, in particular neither flushing nor nausea induced by the suppositories of calcitonin. Clinical Improvement occurred after 2 days in the group receiving the combined treatment. In conclusion, the combined treatment is rapidly effective and safe in the treatment of patients with hypercalcemia, particularly when the notional setting of renal tubular reabsorption of calcium is increased and a rapid correction of the plasma calcium level is needed.

Topics: Aged; Calcitonin; Diphosphonates; Drug Therapy, Combination; Female; Fluid Therapy; Humans; Hypercalcemia; Male; Middle Aged; Neoplasms; Pamidronate; Suppositories; Time Factors

Some patients treated for the hypercalcaemia of malignancy develop renal tubular resistance to the effects of calcitonin which is independent of concurrent changes in sodium excretion. This type of resistance can be overcome by the addition of corticosteroids. In other patients apparent renal resistance to calcitonin is a consequence of reduced sodium excretion and is unaffected by corticosteroids.

Topics: Aged; Calcitonin; Calcium; Dexamethasone; Drug Synergism; Drug Therapy, Combination; Female; Humans; Hypercalcemia; Kidney Tubules; Male; Middle Aged; Neoplasms; Prednisolone; Time Factors

A 14 week old female infant who presented with a mesoblastic nephroma was found to be hypercalcaemic. This was corrected prior to removal of the tumour and serum calcium concentrations remained within the normal range postoperatively. Hypercalcaemia is a life threatening complication of mesoblastic nephromas and should be investigated in all cases.

Topics: Calcitonin; Calcium; Female; Humans; Hypercalcemia; Infant; Kidney Neoplasms; Nephrectomy; Vincristine; Wilms Tumor

Topics: Adenoma; Adult; Aged; Calcitonin; Calcium; Female; Fluorescent Antibody Technique; Humans; Hypercalcemia; Hyperparathyroidism; Hyperplasia; In Vitro Techniques; Kidney Failure, Chronic; Luminescent Measurements; Male; Middle Aged; Parathyroid Glands; Parathyroid Hormone; Parathyroid Neoplasms

Topics: Calcitonin; Calcium; Diagnosis, Differential; Edetic Acid; Humans; Hypercalcemia; Hyperparathyroidism; Hypocalcemia; Parathyroid Hormone; Reference Values

The authors compared the effect of synthetic salmon calcitonin and synthetic somatostatin (SRIF) and hypercalcaemia on an oral glucose tolerance test (OGTT) in healthy subjects in relation to changes of insulin (IRI), somatotrophin (HGH) and cortisol levels. Calcitonin--100 U--in an intravenous infusion in the course of OGTT markedly altered the pattern of the blood sugar curve and of IRI levels. After the initial retardation of the rise of the blood sugar and IRI levels during the 15th and 30th min, the values of both variables increased parallel during the 120th and 180th min, as compared with the control examination after saline. SRIF--500 micrograms--administered in an intravenous infusion altered the pattern of the blood sugar and IRI curves in a similar way as calcitonin, however during the 120th and 180th minute when the blood sugar levels rose significantly the IRI levels did not rise. The curve of HGH levels on infusion with calcitonin displayed a typical three-phase course, as during the control OGTT. During infusion of SRIF the HGH levels were insignificantly but constantly reduced during the first 60 mins. of the OGTT and thus the typical three-phase shape of the curve was impaired. Calcitonin significantly raised the cortisol levels throughout the OGTT, while SRIF caused their slight decline during the 120th min. Hypercalcaemia induced by infusion of 13.3 mg Ca/kg body weight did not alter significantly the blood levels of glucose, IRI and HGH, but caused a significant rise of the cortisol level throughout the OGTT.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Blood Glucose; Calcitonin; Calcium; Female; Glucose Tolerance Test; Growth Hormone; Humans; Hydrocortisone; Hypercalcemia; Insulin; Kinetics; Male; Somatostatin

Although calcitonin is a natural, nontoxic, and rapid inhibitor of bone resorption, its use in the treatment of hypercalcemia is limited because of its transient efficacy and the need for repeated parenteral administration. In normal subjects, suppositories of calcitonin have been shown to be biologically active. Peak plasma concentrations of salmon calcitonin after rectal administration in six normal subjects were similar to those measured after parenteral administration. To evaluate the efficacy of calcitonin suppositories in disease states, 10 patients with moderate hypercalcemia due to malignancy were treated with salmon calcitonin, administered as suppositories containing 300 MRC units, three times a day for seven days. The mean plasma calcium level decreased significantly from 2.96 +/- 0.09 mmol/liter to 2.57 +/- 0.09 after one week (p less than 0.005) and rose again after discontinuation of treatment to 2.86 +/- 0.09 mmol/liter one week later. Urinary calcium and hydroxyproline values decreased during treatment and rose after discontinuation of treatment. The plasma calcium level decreased rapidly in six patients, becoming normal in five; three patients showed only a partial response, and one patient had no response at all. No side effects were observed, and clinical improvement was noted in nine of the 10 patients. Little or no response was observed in patients with extremely high urinary calcium or, to a lesser extent, high hydroxyproline excretion. There was a significant negative correlation between the maximal decrease in plasma calcium concentration and initial urinary calcium excretion (r -0.78, p less than 0.01). Thus, salmon calcitonin administered by the rectal route appears to be an easy, safe, and effective treatment of moderate hypercalcemia without apparent side effects.

Topics: Administration, Rectal; Aged; Calcitonin; Female; Humans; Hypercalcemia; Male; Middle Aged; Neoplasms; Suppositories

Hypocalcemia induced by salmon calcitonin (SCT) was evaluated in 125 patients with multiple myeloma (MM) and compared with 20 normal individuals (NCs) and 20 individuals with monoclonal gammopathy of undetermined significance (MGUS). It is now well documented that the maximum hypocalcemia (M delta CA) induced in man by SCT is related to the prevailing rate of osteoclastic resorption. In patients with MGUS, the level of M delta CA was normal. Conversely, the M delta CA was significantly abnormal in patients with MM (P less than .0001 for differences between NC/MGUS patients) and was correlated with (1) initial calcium levels (P less than .001), (2) the extent of lytic bone lesions (LBLs) (P less than .01), and (3) the myeloma cell mass (P less than .001) plus disease activity. The M delta CA was found to be of predictive value for new LBLs with or without hypercalcemia and to have dramatic influence on the survival of patients with MM. We conclude that the SCT-induced hypocalcemia test is of significant importance in the evaluation of the instantaneous rate of bone resorption and in the prognosis of patients with MM.

Topics: Adult; Aged; Bone Diseases; Calcitonin; Calcium; Female; Humans; Hypercalcemia; Hypocalcemia; Male; Middle Aged; Multiple Myeloma; Neoplasm Staging; Osteoclasts; Prognosis; Radiography; Radionuclide Imaging

The hypocalcaemic response to salmon calcitonin was separated into its renal and skeletal components during the treatment of 21 patients with severe hypercalcaemia complicating malignant disease. Inhibition of renal tubular calcium reabsorption by calcitonin may induce a rapid fall in serum calcium. The magnitude of this response depends in part upon the correction of volume depletion which is a common feature of hypercalcaemia from any cause. The adequacy of rehydration can be assessed from the relationship between serum calcium and the calcium excretion rate expressed in mumol/l glomerular filtrate (CaE). Not all patients show a good renal response to calcitonin and this may reflect secretions by the primary tumour of substances which inhibit the renal tubular actions of calcitonin. The response to rehydration may identify such patients and this has obvious practical implications for the choice of treatment.

Topics: Adult; Aged; Calcitonin; Calcium; Female; Glomerular Filtration Rate; Humans; Hypercalcemia; Kidney; Male; Middle Aged; Neoplasms

Topics: Calcitonin; Humans; Hypercalcemia; Neoplasms