Synthetic human calcitonin in refractory Paget's disease of bone

Fourteen patients with symptomatic and active Paget's disease of bone who had demonstrated resistance to parenteral synthetic salmon calcitonin, oral disodium etidronate, or both in combination were treated with parenteral synthetic human calcitonin. Eleven patients (79%) demonstrated clinical and chemical improvement for up to five years. Two patients received additional benefit with combined synthetic human calcitonin and etidronate disodium.     

Effects of synthetic salmon calcitonin in patients with Paget's disease of bone

Sixteen patients with symptomatic, metabolically active Paget's disease of bone received a single daily injection of synthetic salmon calcitonin for 3 to 20 months (average, 9 months). Elevations of serum alkaline phosphatase or urinary hydroxyproline levels were reduced in 14 of 16 patients and became normal in 4 of 16. Chemical evidence of resistance to calcitonin developed in 2 of 16 patients and may have correlated with phosphate depletion. Oral phosphate therapy appeared to improve the response to calcitonin. Bone pain caused directly by Paget's disease was ameliorated in 12 of 13 patients, but pain resulting from skeletal deformity or mechanical stress was not alleviated. No significant side effects of calcitonin therapy were noted. Salmon calcitonin is effective in the treatment of selected patients with Paget's disease of bone.     

Response of Paget's disease to human calcitonin in patients resistant to porcine calcitonin

Eleven patients with Paget's disease of bone, treated intermittently for 2-4 years with porcine calcitonin (pCT) and clinically resistant to pCT [no modifications of serum alkaline phosphatase (ALP) and urinary hydroxyproline ( uHOP ) during pCT administration] were treated with 0.5-0.25 mg/day of human calcitonin (hCT) for 3-6 months. Nine of our patients showed biochemical improvement during the first 2 months of treatment, with reduction in ALP and uHOP . In one patient with slightly increased ALP and uHOP , and in another one during the second treatment course, hCT treatment did not modify the biochemical indices of bone disease. However all patients, including those with biochemical resistance, experienced a remarkable diminution of bone pain, which had not been observed during previous pCT treatment courses. Therefore, hCT appears to be indicated for therapeutic use in patients who are resistant to foreign calcitonins.     

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.     

Formation of antibodies to synthetic human calcitonin during treatment of Paget's disease

Low-titre antibodies to synthetic human calcitonin (hCT) were detected in a 69-year-old woman suffering from Paget's disease who was treated for 16 months with hCT and the diphosphonate EHDP. Levels of antibody were highest between 10 and 18 months after commencement of therapy, slowly decreased after completion of treatment and were later no longer measurable. There was no immunological response to a single re-injection of hCT 14 months after discontinuation of therapy. Formation of antibodies to hCT in man is a very rare event, this being the first recorded case of an immune response to synthetic human calcitonin, whereas synthetic salmon calcitonin induces an immune response in a high percentage (up to 78%) of the patients treated with this hormone.     

Effect of acute administration of salmon and human calcitonin on blood urate and renal excretion of uric acid in patients with Paget's disease of bone

The sc injection of salmon calcitonin (CT) (100 MRC U) or human CT (50 MRC U) to Pagetic patients reduces the plasma urate concentration and increases the renal excretion of uric acid. This effect is independent of the natriuretic, phosphaturic, or glycosuric actions of CT and is not due to the transient increment of the glomerular filtration rate noted after CT administration. Our results suggest that the hypouricemia observed during CT treatment is related, at least in part to a direct action on the renal handling of uric acid.     

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.     

Osteolytic Paget's bone disease in a young man. Rapid healing with human calcitonin therapy

Paget's bone disease is rare in young adults. Severe osteolytic Paget's bone disease in a 28-year-old man was found to respond, clinically, biochemically, and radiographically, within one month to daily subcutaneous injections of 0.5 mg of synthetic human calcitonin. After two years of therapy, he remains asymptomatic and has no biochemical evidence of Paget's bone disease while receiving injections three times a week. Despite aggressive disease, young patients may rapidly demonstrate the same beneficial response to synthetic human calcitonin therapy as has been observed in middle-aged or elderly patients with Paget's bone disease.     

On the treatment of the osteodystrophia deformans (Paget's disease) with synthetic salmon calcitonin (author's transl)

Sixteen patients with Paget's disease of bone aged from 51 to 80 years was treated daily with 20 micrograms (equivalent to 80 MRCU) synthetic salmon calcitonin. Fourteen patients was observed on a long time. In all cases was observed significant reductions in increased serum alkaline phosphatase. The urinary hydroxyproline excretion was also decreased. Other laboratory dates as serum calcium, serum phosphorus, serum acide phosphatase, urinary calcium and phosphorus excretion was not significantly influenced by the therapy. The treatment produced a clear remission of pain. After treatment of 6 months the dose was reduced (2 or 3 injections subcutaneously of 20 micrograms salmon calcitonin weekly). There was observed a recurrence of pain and an increase of serum alkaline phosphatase, but not until the pretreatment values. These results confirm the effectiveness of calcitonin treatment in Paget's disease of bone.     

Treatment of Paget's disease of bone with synthetic human calcitonin: biochemical and roentgenologic changes

The roentgenologic and biochemical changes observed in 28 adults with Paget's disease, during treatment with synthetic human Calcitonin for 15 months to 4 years, are described. Treatment resulted in biochemical improvement in all patients and in roentgenologic regression in seven patients. The importance of measuring morphologic as well as biochemical variables is discussed.     

Side effects of synthetic salmon calcitonin given by intranasal spray compared with intramuscular injection

Side effects are the most frequent reason for discontinuing treatment with Calcitonin. Having been assessed in a previous report that the intranasal administration of Synthetic Salmon Calcitonin (SSCT) is as effective as its intramuscular administration, the aim of this work was to investigate the side-effects of intranasal administration of SSCT in patients who are known to show intolerance after intramuscular administration of the drug. The results show that intranasal administration of SSCT does not give rise to side-effects even in patients known to be intolerant to SSCT by the intramuscular route.     

Human calcitonin in the treatment of symptomatic Paget's disease

We evaluated the effect of a 6 months trial with synthetic human calcitonin in 10 symptomatic patients with polyosseous Paget's disease of bone. All patients reported a distinct clinical improvement which correlated with a significant decrease of alkaline phosphatase in the plasma and hydroxyproline and calcium excretion in the urine. Though no changes in skeletal x-rays were observed, the bone lesions showed a significant decrease of activity in tho bone scintigrams. Histologically there was a marked decrease of bone turn-over calcitonin therapy. No patient revealed the formation of autoantibodies against exogenous calcitonin after treatment.     

The treatment of osteoporosis in patients with rheumatoid arthritis receiving glucocorticoids: a comparison of alendronate and intranasal salmon calcitonin

Objective The purpose of this study was to assess the effects of alendronate and intranasal salmon calcitonin (sCT) treatments on bone mineral density and bone turnover in postmenopausal osteoporotic women with rheumatoid arthritis (RA) receiving low-dose glucocorticoids.Methods Fifty osteoporotic postmenopausal women with RA, who had been treated with low-dose corticosteroids for at least 6 months, were randomized to receive alendronate 10 mg/day or sCT 200 IU/day for a period of 24 months. All patients received calcium supplementation 1,000 mg and vitamin D 400 IU daily. Bone mineral density (BMD) of the lumbar spine, femoral neck, and trochanter was measured annually using dual-energy X-ray absorptiometry. Bone metabolism measurements included urinary deoxypyridinoline (DPD), serum bone alkaline phosphatase (BAP), and serum osteocalcin (OC).Results Over 2 years, the lumbar spine (4.34%, P <0.001), femoral neck (2.52%, P <0.05), and trochanteric (1.29%, P <0.05) BMD in the alendronate group increased significantly. The sCT treatment increased lumbar spine BMD (1.75%, P <0.05), whereas a significant bone loss occurred at the femoral neck at month 24 (–3.76%, P <0.01). A nonsignificant decrease in the trochanteric region was observed in the sCT group (–0.81%). The difference between the groups with respect to the femoral neck and trochanteric BMD was statistically significant ( P <0.001and P <0.05, respectively). The decreases in urinary DPD (–21.87%, P <0.001), serum BAP (–10.60%, P <0.01), and OC (–19.59%, P <0.05) values were statistically significant in the alendronate group, whereas nonsignificant decreases were observed in the sCT group (–5.77%, –1.96%, and –4.31%, respectively). A significant difference was found in the DPD and BAP levels between the two treatment groups in favor of the alendronate group at all time points ( P =0.001 and P <0.05, respectively).Conclusion The results of this study demonstrated that alendronate treatment produced significantly greater increases in the femoral neck BMD and greater decreases in bone turnover than intranasal sCT in RA patients receiving low dose glucocorticoids.     

Influence of pharmacological doses of calcitonin on serum osteocalcin concentration in patients with Paget's disease of the bone

The effect of continuous infusion of calcitonin on serum osteocalcin concentration was studied in 14 patients with Paget's disease. In all patients serum osteocalcin was initially increased. Within 24 h calcitonin gradually reduced serum osteocalcin, a marker of osteoblastic activity. This means that inhibition of the function of the osteoclasts by calcitonin results in an inhibition of the osteoblasts within 24 h in patients with Paget's disease.     

Paget's disease of bone in patients with gout

In a study designed to evaluate the radionuclide images in patients with gout, six (23%) of the 26 patients had clear evidence of Paget's disease of bone by technetium Tc 99m medronate imaging. A reference population consisting of 333 technetium Tc 99m medronate bone scans ordered for other reasons was reviewed, and only seven scans (2.1%) were found to have evidence of Paget's disease. This difference was found to be highly significant. All cases of Paget's disease were confirmed by independent radiologic evaluation. We conclude that there is a significant association between Paget's disease and gout, the basis for which is not yet known.     

Alternate calcitonin and etidronate disodium therapy for Paget's bone disease

The efficacy of salmon calcitonin and etidronate disodium was compared in the therapy of Paget's bone disease in 37 patients. Nineteen patients received etidronate for six months with a mean alkaline phosphatase reduction to 53% of initial values. Bone scintophotographs improved in 12 and were unchanged in seven. Symptoms improved in 11 subjects, were unchanged in seven, and worsened in one. Twelve of these patients were then treated with calcitonin for six months with continued improvement in alkaline phosphatase values to 36% of initial values. All bone scintophotographs improved compared with initial studies. Seven patients continued to improve symptomatically; five described no change. Eighteen individuals were treated initially with calcitonin for six months. During therapy, the alkaline phosphatase level fell to 76% of initial values. Bone scintophotographs were worse in two patients, did not change in seven, and improved in nine. Eleven patients reported improvement in symptoms and seven reported no change. Seventeen of these patients were then treated with etidronate for six months with a decrease in alkaline phosphatase levels to 64% of initial values. Compared with initial tests, bone scintophotographs were worse in three with no change in five and improvement in nine. Symptomatically, three patients reported improvement; four noted no change, and ten reported increasing pain. Although the reason for the poor response to initial calcitonin therapy and/or subsequent etidronate therapy is not apparent, we have concluded that patients fare better when treated with an etidronate calcitonin sequence when compared with those treated with a calcitonin/etidronate sequence.