calcitonin and Bone-Neoplasms

We undertook a prospective, nonrandomized study with the objective to evaluate the efficacy of salmon calcitonin (sCT) in controlling pain secondary to bone metastases. Our study population consisted of 45 cancer patients with bone metastases (26 men) with a mean age of 64 years (range, 48-70) who had completed chemotherapy, hormonal therapy and radiation therapy at least 30 days prior to enrollment in the study, and had intractable pain despite the use of common analgesics (acetaminophen, nonsteroidal anti-inflammatory agents, opioids) and bisphosphonates. The study medication was a 300-IU dose of sCT administered intravenously daily for 5 consecutive days and repeated every two weeks until no response was noticeable. The analgesic efficacy of sCT was evaluated by means of Huskisson's visual analogue scale and Keele's pain scale; the daily consumption of analgesic drugs and performance status were also monitored. None of the patients managed to completely discontinue the use of other analgesics, but 5 patients (11% of the total number) had an analgesic response that lasted 4 weeks and less than 5% of the patients continued to respond for 6 weeks. No significant side effects were observed. Our data show that intravenous calcitonin administered in a relatively high dose has a very limited therapeutic potential as an adjuvant analgesic for a short period of time in selected cancer patients with bone metastases.

Topics: Aged; Analgesics; Bone and Bones; Bone Neoplasms; Calcitonin; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Neoplasm Metastasis; Pain, Intractable; Palliative Care; Prospective Studies; Time Factors

This prospective nonrandomized trial was performed to evaluate the efficacy of salmon calcitonin (sCT) in controlling pain related to bone metastasis in cancer patients and the relation of sCT's analgesic efficacy with beta-endorphin blood levels. The study group consisted of 22 cancer patients with bone metastases (male 13 and female 9, age range 38-77 years). Pain control was first achieved by continuous subcutaneous (s.c.) morphine administration. The next increase in pain was managed with continuous s.c. administration of 400 IU/day sCT. Beta-endorphin blood levels were measured before and during sCT administration. The first measurement was taken before sCT administration; subsequent measurement occurred at 12, 24, and 48 hours and 7 days after the commencement of treatment. Pain scores were monitored by a visual analogue scale. A complete blood count and a biochemical screening profile were taken before the administration of calcitonin and also on the seventh and the fifteenth day of the administration. The results showed a satisfactory analgesic effect. The mean pain score before the calcitonin administration was 4.43 and the score on the seventh day was 1.17. The gradual reduction of pain score was associated with an increase in beta-endorphin blood levels (increase to 147.2% of baseline on the seventh treatment day). In three cases, no satisfactory analgesic effect was obtained and pain control was achieved by increasing the continuous s.c. morphine dosage. No significant side effects were observed. These data suggest that sCT in high doses may be a useful adjuvant analgesic when combined with low doses of morphine in continuous s.c. administration for the management of metastatic bone pain.

Topics: Adult; Aged; Analgesics; beta-Endorphin; Bone Neoplasms; Calcitonin; Dose-Response Relationship, Drug; Female; Humans; Injections, Subcutaneous; Male; Middle Aged; Pain; Prospective Studies

Salmon calcitonin 100 MRCU/day or a saline placebo were given in daily injections for at least three months to 49 patients with bone metastases from breast cancer in a randomized double-blind trial. All patients were normocalcemic, and most patients had stable or regressing disease at start of trial. No improvement in general performance or bone pain was detected as measured by a visual analogue scale, the daily duration of pain or consumption of analgetic drugs. Calcitonin had no effect on disease progression as judged by bone scans and radiographs. Calcitonin therapy did not affect serum calcium, alkaline phosphatase, bone gla-protein, or the urinary excretion of calcium and hydroxyproline. Serum phosphate and magnesium decreased significantly during calcitonin treatment (p = 0.01, and 0.00005, respectively). It was concluded that salmon calcitonin in this dosage has no discernible effect on skeletal pain, general performance, bone metabolism or disease progression in patients with breast cancer metastatic to bone. A significant decrease in serum phosphate and magnesium probably indicated an effect of calcitonin on the renal excretion of these ions.

Topics: Bone Neoplasms; Breast Neoplasms; Calcitonin; Clinical Trials as Topic; Double-Blind Method; Electrolytes; Female; Humans; Pain; Random Allocation

The effects of salmon calcitonin administered 100 IU i.m. daily for 30 consecutive days were evaluated in patients with painful bone metastasis secondary to different types of solid cancer. The results were compared with placebo-receiving patients. In the 22 patients treated with calcitonin a significant reduction ( p less than 0.001) was observed in the severity of bone pain. Significant reductions were also encountered in the serum alkaline phosphatase (p less than 0.02) and urinary hydroxyproline excretion values (p less than 0.05) in calcitonin-treated patients, indicating an inhibition of bone destruction. It is concluded that salmon calcitonin has an important place in the treatment of patients with metastatic bone lesions both as a potent analgesic and as an effective inhibitor of bone destruction.

Topics: Adult; Aged; Alkaline Phosphatase; Bone Neoplasms; Calcitonin; Calcium; Female; Follow-Up Studies; Humans; Hydroxyproline; Male; Middle Aged; Pain; Time Factors

Topics: Analgesics; Bone Neoplasms; Calcitonin; Clinical Trials as Topic; Female; Humans; Male; Palliative Care

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

Human calcitonin (hCT) has been reported to have a less hypocalcemizing effect on rats and to have a lower binding affinity for the receptor of mouse osteoclasts than salmon CT(sCT). In this study we comparatively examined the effect of hCT and sCT on osteoclastic bone-resorbing activity of unfractionated cells obtained from human giant cell tumor of bone and from rabbit and mouse long bones. We found that hCT had the same inhibitory effect as sCT on the bone-resorbing activity of human and rabbit osteoclastic cells, but a different one on that of mouse cells. These results indicate that the activity of drugs should be assayed using human cells if possible.

Topics: Animals; Bone Neoplasms; Bone Resorption; Calcitonin; Cell Fractionation; Giant Cells; Humans; Mice; Microscopy, Electron; Osteoclasts; Rabbits; Species Specificity; Tumor Cells, Cultured

We report here a case of primary osteoclastoma that despite possessing HLA-DR-positive status and 'functional' calcitonin receptors, exhibited aggressive in vitro and in vivo bone resorptive activity. In the osteoclast bone slice assay employing scanning electron microscopy, the giant cell-mediated bone resorption was uninhibited by salmon calcitonin (10 nM) and significantly inhibited by raised extracellular calcium (20 mM). In Fura-2AM based microspectrofluorimetric assays, the presence of the 'functional' calcitonin receptors was ascertained by a rise in intracellular calcium induced by calcitonin and high extracellular calcium. These findings provide evidence for a hitherto unrecognized subtype of giant cells that have HLA-DR-positive status, exhibit avid bone resorptive activity, but remain insensitive to calcitonin despite possessing calcitonin receptors.

Topics: Adult; Analgesics; Bone Neoplasms; Bone Resorption; Calcitonin; Calcium; Giant Cell Tumor of Bone; HLA-DR Antigens; Humans; Immunohistochemistry; Microscopy, Electron, Scanning; Receptors, Calcitonin; Spectrometry, Fluorescence; Tumor Cells, Cultured

Authors have administered between 1984--87 in 30 patients with bone metastasis weekly 3 X 100 iu Miacalcic injections to relieve pain. The literature dealing with the pain relieving effect of calcitonin is summarized and their own results are assessed from more viewpoints. The use of Miacalcic injection is suggested as it was found a modern and very effective palliative medicine for pain relieving.

Topics: Analgesics; Bone Neoplasms; Calcitonin; Humans; Pain, Intractable; Palliative Care; Postoperative Care

Topics: Aged; Aged, 80 and over; Bone Neoplasms; Calcitonin; Humans; Male; Middle Aged; Palliative Care; Pilot Projects; Prostatic Neoplasms

The analgesic effect of salmon calcitonin (Calcitonina-Sandoz) was evaluated in an open study of thirty-four patients with bone metastases of a lung cancer. Two different administration protocols were used: eighteen subjects received sCT 400 IU/day for three consecutive days, while the remaining sixteen were given sCT 200 IU/day for six consecutive days. In both protocols salmon calcitonin was diluted in saline and infused intravenously in one hour. Bone, visceral and neuritic pain were evaluated by means of Huskisson's visual analog scale and Keele's pain scale. The analgesic efficacy of salmon calcitonin was also evaluated on the basis of daily consumption of analgesic drugs. Salmon calcitonin proved of extreme efficacy in the treatment of intractable pain from advanced malignancy. A higher and earlier analgesic activity was observed with sCT at the 400 IU daily dosage.

Topics: Bone Neoplasms; Calcitonin; Drug Administration Schedule; Female; Humans; Lung Neoplasms; Male; Middle Aged; Pain, Intractable

Topics: Adult; Aged; Bone and Bones; Bone Neoplasms; Calcitonin; Female; Humans; Male; Middle Aged; Pain; Pain Measurement; Radionuclide Imaging

Clinical details are given of 8 patients who complained of severe pain from metastatic bone disease or from multiple myeloma. Four of the patients were included in a double-blind pilot trial designed to compare the effectiveness of salmon calcitonin (200 i.u. intramuscularly) and placebo given twice daily for 4 days. Two of these patients experienced pain relief and were found to have been given salmon calcitonin; the other 2 had no pain relief and had been given placebo. The other 4 of the 8 patients were treated with salmon calcitonin and also had relief of their pain. It would appear, therefore, that salmon calcitonin may be dramatically effective in the treatment of intractable pain from advanced malignancy and its use warrants further study.

Topics: Bone Neoplasms; Calcitonin; Double-Blind Method; Female; Humans; Male; Multiple Myeloma; Pain, Intractable; Pilot Projects

Bone Gla protein (BGP) was measured in the plasma by radioimmunoassay (RIA) during treatment of 59 patients with bone diseases including Paget's disease (N = 9), primary hyperparathyroidism (N = 25), chronic renal failure (N = 20), and cancer involving bone (N = 5). Plasma BGP was increased above normal in all patients. BGP decreased in the patients with Paget's disease following the acute and chronic administration of salmon calcitonin. Plasma BGP was higher in women then in men with primary hyperparathyroidism. Following parathyroidectomy, BGP decreased in both sexes but the decrease was significant in women only. Plasma BGP was increased in patients with renal osteodystrophy and did not change after hemodialysis. In the patients with bone cancer, plasma BGP decreased during treatment of the attendant hypercalcemia with salmon calcitonin. Although plasma BGP and serum alkaline phosphatase (AP) levels were generally correlated in these studies, there were examples of dissociation between the two. The measurement of plasma BGP appears to provide a specific index of bone metabolism that may in some circumstances be more sensitive than serum alkaline phosphatase measurement. However, further studies are necessary to establish the clinical value of plasma BGP measurement by RIA in the management of patients with bone diseases.

Topics: Alkaline Phosphatase; Bone and Bones; Bone Diseases; Bone Neoplasms; Calcitonin; Calcium-Binding Proteins; Chronic Kidney Disease-Mineral and Bone Disorder; Female; Humans; Hyperparathyroidism; Male; Osteitis Deformans; Osteocalcin; Parathyroid Glands; Radioimmunoassay; Renal Dialysis; Vitamin K