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Donna Mctavish - One of the best experts on this subject based on the ideXlab platform.
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Alendronate
Drugs, 1997Co-Authors: Wendy Jeal, Lee B. Barradell, Donna MctavishAbstract:Synopsis Alendronate is an aminobisphosphonate which appears to attenuate, rather than completely inhibiting bone turnover, by suppressing the activity of osteoclasts. Clinical trials have established that 10 mg/day orally administered alendronate is the optimum dosage. Despite its poor bioavailability after oral administration, alendronate is highly effective at preventing bone loss associated with the absence of endogenous estrogen. A sustained increase in bone mass was observed during alendronate therapy without accelerated loss after withdrawal of the drug. Increased bone mass was associated with a reduction in the risk and rate of occurrence of vertebral fractures. A recent study demonstrated a 47% reduction in the risk of developing new radiographic vertebral fractures over 3 years in women with low bone mass and pre-existing vertebral fractures. There have been few direct comparisons in clinical trials. However, when compared with calcium or low dosages of salmon calcitonin (Salcatonin) therapy in women with postmenopausal osteoporosis, alendronate induced a sustained increase in bone mass during therapy that was not seen with the comparator. In clinical trials alendronate was generally well tolerated when taken as recommended. Adverse events tended to be transient and usually associated with the upper gastrointestinal tract; the most common events included abdominal pain, nausea, dyspepsia, constipation and diarrhoea, which are also common with other bisphosphonates. Of potential concern are the small number of reports of patients developing oesophageal ulcération; however, this adverse event was attributed to noncompliance with the manufacturer’s recommendations for administration of the drug. In addition, alendronate has not been associated with osteomalacia. Studies are still required to establish the long term efficacy of alendronate, particularly with regard to other available therapies. Although estrogen replacement therapy is generally considered the treatment of choice for the management of postmenopausal osteoporosis, many women are unable or unwilling to receive estrogens on a long term basis. Thus, alendronate, with its demonstrated beneficial effects and its good tolerability profile (when taken as recommended), is a promising alternative treatment option for the management of postmenopausal osteoporosis. Pharmacodynamic Properties Animal studies have indicated that at concentrations which elicit a physiological response, alendronate adsorbs to exposed bone surfaces and prevents the resorptive activity of osteoclasts without injuring them. Alendronate increases bone strength in ovariectomised rats but the effect on bone stiffness is inconclusive. Nevertheless, the potential effects of alendronate on bone metabolism in the absence of estrogen have been demonstrated. In postmenopausal women, biochemical markers of bone resorption were dose-dependently decreased 3 weeks after the initiation of alendronate (5 to 40 mg/day) and were reduced by at least 47% after 3 months. Similar decreases in markers of bone formation were observed 6 to 9 months after initiation of therapy. The depressed levels of all markers were maintained for the duration of therapy. Alendronate attenuated the increased level of bone turnover observed in postmenopausal women to within 1 standard deviation of that observed in premenopausal women. In preclinical trials, alendronate showed a marked, dose-dependent efficacy in preventing osteoporosis related to non—weight bearing and immobilisation. Pharmacokinetic Properties The bioavailability of alendronate after oral administration is less than 1% and is reduced by the presence of food and divalent ions, such as calcium, in the stomach; an increase in gastric pH effects an increase in bioavailability. Alendronate is rapidly distributed from plasma; over 95% is cleared 6 hours after intravenous infusion, with the remainder being undetectable after a further 6 hours. Elimination of alendronate appears to be exclusively via the urine in a multiphasic manner. Clinical studies have estimated a 10-year elimination half-life, suggesting a prolonged sequestration of the drug within bone tissue. Alendronate has a high specific affinity for actively metabolising bone tissue, and to date, no metabolites have been identified. The latter may be a reflection of the stability of the drug. Therapeutic Use in Postmenopausal Osteoporosis In several large clinical studies in postmenopausal women with osteoporosis, alendronate (usually 5 to 20 mg/day) increased bone mineral density (BMD); effects were sustained over a period of 2 to 3 years during continued administration of the drug and for up to 12 months after discontinuation of treatment. For example, alendronate 10 mg/day for 3 years increased BMD in the lumbar spine 6.8 to 9.6% compared with decreases of approximately 0.7% noted in placebo recipients. There is evidence that both cortical and trabecular bone tissue are affected, suggesting that observed total bone mass increases of up to 1.6% with alendronate 10 mg/day were not merely the result of bone mineral redistribution. In studies that monitored fracture rate, daily administration of alendronate 5 to 20mg compared with placebo prevented the rate of development of new vertebral fractures. A consistent but nonsignificant dose-related decrease in the risk of fractures was observed which was independent of age and the presence of existing fractures. Alendronate also reduced the severity of fractures which occurred. Pooled data from 5 studies of 2 to 3 years’ duration indicate that the relative risk rate and cumulative proportion of non-vertebral fractures were linear over time with placebo, but reduced in alendronate recipients. In addition, results from the Fracture Intervention Trial demonstrated a significant 47% decrease in the risk of developing new radiographic vertebral fractures in postmenopausel women with low bone mass and pre-existing vertebral fractures who received alendronate for 3 years compared with placebo recipients. There have been few direct comparisons in clinical trials. However, when compared with calcium or low dosages of salmon calcitonin therapy in women with postmenopausal osteoporosis, alendronate induced a sustained increase in bone mass during therapy that was not seen with the comparator. Tolerability Alendronate 5 to 20 mg/day was generally well tolerated in clinical trials. The most commonly reported adverse events included abdominal pain, nausea, dyspepsia, constipation and diarrhoea which were reported in 3 to 7% of patients. However, there were no statistically significant differences between the frequency of adverse events reported by alendronate or placebo recipients. In addition, the incidence of adverse events does not appear to be dose related over this range. Patient withdrawals due to therapy-related adverse events were generally low for both alendronate 5 to 20 mg/day (1.9 to 7.4%) and placebo (2 to 6.8%) recipients; events associated with the upper gastrointestinal tract were the most common reason for withdrawal. Subsequent to marketing, a small number of patients (less than 1%) have developed oesophageal ulcération after taking alendronate. This adverse event has generally been attributed to noncompliance with the manufacturer’s administration recommendations. Dosage and Administration The recommended daily oral dosage of alendronate is 10mg. To help improve bioavailability, the tablet should be taken on waking after an overnight fast, with a full glass of water (not mineral water), no less than 30 (preferably 60) minutes prior to eating or drinking. Patients should also avoid lying down for at least 30 minutes immediately after taking the tablet to avoid potential irritation of the upper gastrointestinal mucosa. Dosage adjustments are not necessary for elderly patients or patients with mild to moderate renal insufficiency.
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Alendronate. A review of its pharmacological properties and therapeutic efficacy in postmenopausal osteoporosis.
Drugs, 1997Co-Authors: Wendy Jeal, Lee B. Barradell, Donna MctavishAbstract:Alendronate is an aminobisphosphonate which appears to attenuate, rather than completely inhibiting bone turnover, by suppressing the activity of osteoclasts. Clinical trials have established that 10 mg/day orally administered alendronate is the optimum dosage. Despite its poor bioavailability after oral administration, alendronate is highly effective at preventing bone loss associated with the absence of endogenous estrogen. A sustained increase in bone mass was observed during alendronate therapy without accelerated loss after withdrawal of the drug. Increased bone mass was associated with a reduction in the risk and rate of occurrence of vertebral fractures. A recent study demonstrated a 47% reduction in the risk of developing new radiographic vertebral fractures over 3 years in women with low bone mass and pre-existing vertebral fractures. There have been few direct comparisons in clinical trials. However, when compared with calcium or low dosages of salmon calcitonin (Salcatonin) therapy in women with postmenopausal osteoporosis, alendronate induced a sustained increase in bone mass during therapy that was not seen with the comparator. In clinical trials alendronate was generally well tolerated when taken as recommended. Adverse events tended to be transient and usually associated with the upper gastrointestinal tract; the most common events included abdominal pain, nausea, dyspepsia, constipation and diarrhoea, which are also common with other bisphosphonates. Of potential concern are the small number of reports of patients developing oesophageal ulceration; however, this adverse event was attributed to noncompliance with the manufacturer's recommendations for administration of the drug. In addition, alendronate has not been associated with osteomalacia. Studies are still required to establish the long term efficacy of alendronate, particularly with regard to other available therapies. Although estrogen replacement therapy is generally considered the treatment of choice for the management of postmenopausal osteoporosis, many women are unable or unwilling to receive estrogens on a long term basis. Thus, alendronate, with its demonstrated beneficial effects and its good tolerability profile (when taken as recommended), is a promising alternative treatment option for the management of postmenopausal osteoporosis.
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Intranasal Salcatonin (Salmon Calcitonin)
Drugs & Aging, 1996Co-Authors: Greg L. Plosker, Donna MctavishAbstract:Synopsis Osteoporosis is a common problem among postmenopausal women and is associated with significant morbidity, mortality and costs primarily resulting from osteoporotic fractures. Salcatonin (salmon calcitonin) inhibits osteoclastic bone resorption and is approximately 40 to 50 times more potent than human calcitonin. In most randomised trials in which intranasal Salcatonin (usually 50 to 200 IU/day plus oral calcium supplements) was administered for 1 to 5 years to postmenopausal women for prevention of osteoporosis, bone mineral density or content of the lumbar spine increased by approximately 1 to 3% from baseline. In contrast, postmenopausal women receiving only oral calcium supplements typically had reductions in bone mineral density or content of about 3 to 6%. The difference between treatment groups was statistically significant in essentially all studies. Although changes in bone mineral density or content were broadly similar in studies of postmenopausal women with established osteoporosis to those in postmenopausal women receiving therapy for prevention of the disease, studies in women with established osteoporosis did not usually demonstrate statistically significant differences between treatment groups. Also in postmenopausal women with established osteoporosis, intranasal Salcatonin reduced pain and/or analgesic consumption in some trials and, in a limited number of studies of relatively short duration (i.e. ≤2 years), the incidence of osteoporotic fractures. A large multicentre 5-year study with adequate statistical power to confirm the effect of intranasal Salcatonin on reducing osteoporotic fracture rates in postmenopausal women is currently under way. The intranasal formulation of Salcatonin offers a more convenient and better tolerated alternative to the parenteral formulation of the drug which is administered by regular subcutaneous or intramuscular injections. Adverse events associated with the intranasal formulation are generally mild and transient, usually involving local reactions such as nasal discomfort, rhinorrhoea or rhinitis. Thus, for postmenopausal women unable or unwilling to tolerate long term hormone replacement therapy, intranasal Salcatonin is an attractive alternative for the management of osteoporosis. Pharmacodynamic Properties Salcatonin (salmon calcitonin) is approximately 40 to 50 times more potent than human calcitonin, an endogenous hormone intimately involved in calcium homeostasis. Studies in humans demonstrated that single-dose intranasal administration of Salcatonin 50 to 400IU reduced bone resorption and increased urinary excretion of calcium, phosphate and sodium. The mechanism of action of Salcatonin mimics the physiological action of human calcitonin. Inhibition of bone resorption by Salcatonin depends on binding of the drug to specific calcitonin receptors on osteoclasts. Once binding occurs, Salcatonin reduces the recruitment and activity of these bone-resorbing cells. The effect of Salcatonin on bone formation has been shown in experimental models and in clinical trials of postmenopausal women. Putative bone-forming effects may be related, in small part, to a direct anabolic action of the drug on osteoblast-line cells, although further research is needed to clarify this issue. A number of mechanisms have been suggested to account for the analgesic action of Salcatonin in patients with skeletal disorders. These include increased plasma β-endorphin levels, effects on central serotonergic or monoaminergic pathways, modification of intracellular calcium levels in the CNS and, perhaps the most likely mechanism, a direct central effect via specific receptors. The analgesic action appears to be independent of the effect on osteoclastic bone resorption. Although antibody formation against human calcitonin is rare during long term administration of the hormone, approximately 40 to 70% of patients receiving long term therapy with intranasal or parenteral Salcatonin produce antibodies specific for Salcatonin. The clinical significance of these antibodies is unclear; however, clinical trials have generally shown sustained long term efficacy of intranasal Salcatonin despite specific antibody formation in a significant proportion of postmenopausal women with osteoporosis. Pharmacokinetic Properties Peak plasma Salcatonin concentrations are achieved 31 to 39 minutes after intra-nasal administration and are dose-related. Although bioavailability of intranasal Salcatonin is approximately 3% of that for intramuscular Salcatonin, plasma drug concentrations are typically more sustained following intranasal than parenteral administration. The intranasal formulation provides approximately 25 to 50% of the biological activity of the same parenterally administered dose. Salcatonin appears to distribute extensively into extravascular tissue sites. Elimination half-life has been calculated to be 43 minutes. Therapeutic Use In most randomised studies in which intranasal Salcatonin (usually 50 to 200 IU/day) plus oral calcium supplements were administered for 1 to 5 years to recently postmenopausal women for prevention of osteoporosis, bone mineral density or content of the lumbar spine increased by approximately 1 to 3% from baseline compared with reductions of about 3 to 6% among women receiving oral calcium supplements only. These trials consistently demonstrated statistically significant differences between Salcatonin and control treatment groups for changes in vertebral bone mineral density and, in a small number of studies, similar results were shown for changes in forearm bone mineral content. A long term evaluation of a relatively low dose intermittent intranasal Salcatonin regimen (50 IU/day for 5 days/week) demonstrated a statistically significant difference in favour of Salcatonin plus calcium over calcium alone in bone mineral density of lumbar vertebrae after 6 months which was maintained for the entire duration of the 5-year study. In most trials, attenuation of bone loss by Salcatonin was accompanied by reductions in biochemical markers of bone résorption. Both cyclical regimens of intranasal Salcatonin 100 or 200 IU/day (which involved interruption of therapy every other month for 18 months) and continuous administration of the drug at the same dosages (all regimens with oral calcium supplements) increased bone mineral content of the lumbar spine by approximately 4 to 5% from baseline in postmenopausal women with a high rate of bone turnover. Peak increases in bone mineral content occurred somewhat earlier and tended to be slightly higher among women receiving continuous therapy. In general, intranasal administration of Salcatonin produced broadly similar effects on bone mineral density or content in postmenopausal women with established osteoporosis to those in postmenopausal women receiving the drug for prevention of the disease; however, statistically significant differences between treatment groups were usually not demonstrated. Randomised studies in postmenopausal women with established osteoporosis receiving intranasal Salcatonin 50, 100 or 200 IU/day for 1 to 2 years have demonstrated a dose-related response with respect to changes in bone mineral density or content. Results of a large 2-year trial comparing intranasal Salcatonin 100 IU/day with oral alendronate 10 or 20 mg/day (all with oral calcium supplements) demonstrated a somewhat greater effect of the bisphosphonate than Salcatonin on increasing bone mineral density of the lumbar spine in postmenopausal women with established osteoporosis. However, the dosage of intranasal Salcatonin used in the trial was only half the recommended dosage, and Salcatonin was not administered under a double-blind protocol. Importantly, both parenteral and intranasal Salcatonin have been shown to decrease fracture rates in this patient population, although this has been documented in only a limited number of trials. In a study of 164 elderly postmeno-pausal women with “moderate” osteoporosis, those who received intranasal Salcatonin 50, 100 or 200 IU/day plus calcium supplements for 2 years had a statistically significant reduction in fracture rate to approximately one-third that of women who received calcium supplements only. In another randomised study of 88 postmenopausal women with established osteoporosis, cyclical treatment with intranasal Salcatonin 100 IU/day plus oral calcium supplements (for 2 consecutive weeks followed by 2 weeks without therapy) for 1 year resulted in a statistically significant reduction in the rate of new vertebral fractures compared with calcium alone. These studies were of relatively short duration, and the effect of long term intranasal Salcatonin on osteoporotic fracture rates is currently under investigation in a much larger 5-year study of more than 1200 postmenopausal women. Intranasal Salcatonin has also been associated with improvement in pain and/or reductions in analgesic consumption in some studies of postmenopausal women with established osteoporosis. Tolerability In general, adverse events associated with intranasal administration of Salcatonin are relatively mild and tend to occur in less than 10% of patients. The most frequently reported adverse events are local transient reactions such as stinging or tingling of the nasal passage, sneezing, rhinitis, rhinorrhoea and nasal mucosal erythema which lead to discontinuation of therapy in about 4% of patients. In a comparative trial, primarily in patients with Paget’s disease, 10% of patients receiving subcutaneously administered Salcatonin discontinued therapy because of adverse events compared with 4% of those receiving the drug by intranasal administration. Dosage and Administration The recommended intranasal dosage of Salcatonin for the management of established osteoporosis is 200IU once daily. In clinical trials, postmenopausal women received intranasal Salcatonin dosages ranging from 50 to 400 IU/day as a single daily dose or in 2 divided doses for the prevention or treatment of osteoporosis. In virtually all clinical studies with intranasal Salcatonin, patients also received oral calcium supplements. It is not clear whether cyclical regimens of intranasal Salcatonin plus oral calcium supplements (e.g. 1 month of therapy followed by no drug treatment for 1 month and repeated in a cyclical fashion) have any clinically significant advantages over continuous treatment.
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Intranasal Salcatonin (salmon calcitonin). A review of its pharmacological properties and role in the management of postmenopausal osteoporosis.
Drugs & aging, 1996Co-Authors: Greg L. Plosker, Donna MctavishAbstract:Synopsis Osteoporosis is a common problem among postmenopausal women and is associated with significant morbidity, mortality and costs primarily resulting from osteoporotic fractures. Salcatonin (salmon calcitonin) inhibits osteoclastic bone resorption and is approximately 40 to 50 times more potent than human calcitonin. In most randomised trials in which intranasal Salcatonin (usually 50 to 200 IU/day plus oral calcium supplements) was administered for 1 to 5 years to postmenopausal women for prevention of osteoporosis, bone mineral density or content of the lumbar spine increased by approximately 1 to 3% from baseline. In contrast, postmenopausal women receiving only oral calcium supplements typically had reductions in bone mineral density or content of about 3 to 6%. The difference between treatment groups was statistically significant in essentially all studies. Although changes in bone mineral density or content were broadly similar in studies of postmenopausal women with established osteoporosis to those in postmenopausal women receiving therapy for prevention of the disease, studies in women with established osteoporosis did not usually demonstrate statistically significant differences between treatment groups. Also in postmenopausal women with established osteoporosis, intranasal Salcatonin reduced pain and/or analgesic consumption in some trials and, in a limited number of studies of relatively short duration (i.e. ≤2 years), the incidence of osteoporotic fractures. A large multicentre 5-year study with adequate statistical power to confirm the effect of intranasal Salcatonin on reducing osteoporotic fracture rates in postmenopausal women is currently under way. The intranasal formulation of Salcatonin offers a more convenient and better tolerated alternative to the parenteral formulation of the drug which is administered by regular subcutaneous or intramuscular injections. Adverse events associated with the intranasal formulation are generally mild and transient, usually involving local reactions such as nasal discomfort, rhinorrhoea or rhinitis. Thus, for postmenopausal women unable or unwilling to tolerate long term hormone replacement therapy, intranasal Salcatonin is an attractive alternative for the management of osteoporosis.
Greg L. Plosker - One of the best experts on this subject based on the ideXlab platform.
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Intranasal Salcatonin (Salmon Calcitonin)
Drugs & Aging, 1996Co-Authors: Greg L. Plosker, Donna MctavishAbstract:Synopsis Osteoporosis is a common problem among postmenopausal women and is associated with significant morbidity, mortality and costs primarily resulting from osteoporotic fractures. Salcatonin (salmon calcitonin) inhibits osteoclastic bone resorption and is approximately 40 to 50 times more potent than human calcitonin. In most randomised trials in which intranasal Salcatonin (usually 50 to 200 IU/day plus oral calcium supplements) was administered for 1 to 5 years to postmenopausal women for prevention of osteoporosis, bone mineral density or content of the lumbar spine increased by approximately 1 to 3% from baseline. In contrast, postmenopausal women receiving only oral calcium supplements typically had reductions in bone mineral density or content of about 3 to 6%. The difference between treatment groups was statistically significant in essentially all studies. Although changes in bone mineral density or content were broadly similar in studies of postmenopausal women with established osteoporosis to those in postmenopausal women receiving therapy for prevention of the disease, studies in women with established osteoporosis did not usually demonstrate statistically significant differences between treatment groups. Also in postmenopausal women with established osteoporosis, intranasal Salcatonin reduced pain and/or analgesic consumption in some trials and, in a limited number of studies of relatively short duration (i.e. ≤2 years), the incidence of osteoporotic fractures. A large multicentre 5-year study with adequate statistical power to confirm the effect of intranasal Salcatonin on reducing osteoporotic fracture rates in postmenopausal women is currently under way. The intranasal formulation of Salcatonin offers a more convenient and better tolerated alternative to the parenteral formulation of the drug which is administered by regular subcutaneous or intramuscular injections. Adverse events associated with the intranasal formulation are generally mild and transient, usually involving local reactions such as nasal discomfort, rhinorrhoea or rhinitis. Thus, for postmenopausal women unable or unwilling to tolerate long term hormone replacement therapy, intranasal Salcatonin is an attractive alternative for the management of osteoporosis. Pharmacodynamic Properties Salcatonin (salmon calcitonin) is approximately 40 to 50 times more potent than human calcitonin, an endogenous hormone intimately involved in calcium homeostasis. Studies in humans demonstrated that single-dose intranasal administration of Salcatonin 50 to 400IU reduced bone resorption and increased urinary excretion of calcium, phosphate and sodium. The mechanism of action of Salcatonin mimics the physiological action of human calcitonin. Inhibition of bone resorption by Salcatonin depends on binding of the drug to specific calcitonin receptors on osteoclasts. Once binding occurs, Salcatonin reduces the recruitment and activity of these bone-resorbing cells. The effect of Salcatonin on bone formation has been shown in experimental models and in clinical trials of postmenopausal women. Putative bone-forming effects may be related, in small part, to a direct anabolic action of the drug on osteoblast-line cells, although further research is needed to clarify this issue. A number of mechanisms have been suggested to account for the analgesic action of Salcatonin in patients with skeletal disorders. These include increased plasma β-endorphin levels, effects on central serotonergic or monoaminergic pathways, modification of intracellular calcium levels in the CNS and, perhaps the most likely mechanism, a direct central effect via specific receptors. The analgesic action appears to be independent of the effect on osteoclastic bone resorption. Although antibody formation against human calcitonin is rare during long term administration of the hormone, approximately 40 to 70% of patients receiving long term therapy with intranasal or parenteral Salcatonin produce antibodies specific for Salcatonin. The clinical significance of these antibodies is unclear; however, clinical trials have generally shown sustained long term efficacy of intranasal Salcatonin despite specific antibody formation in a significant proportion of postmenopausal women with osteoporosis. Pharmacokinetic Properties Peak plasma Salcatonin concentrations are achieved 31 to 39 minutes after intra-nasal administration and are dose-related. Although bioavailability of intranasal Salcatonin is approximately 3% of that for intramuscular Salcatonin, plasma drug concentrations are typically more sustained following intranasal than parenteral administration. The intranasal formulation provides approximately 25 to 50% of the biological activity of the same parenterally administered dose. Salcatonin appears to distribute extensively into extravascular tissue sites. Elimination half-life has been calculated to be 43 minutes. Therapeutic Use In most randomised studies in which intranasal Salcatonin (usually 50 to 200 IU/day) plus oral calcium supplements were administered for 1 to 5 years to recently postmenopausal women for prevention of osteoporosis, bone mineral density or content of the lumbar spine increased by approximately 1 to 3% from baseline compared with reductions of about 3 to 6% among women receiving oral calcium supplements only. These trials consistently demonstrated statistically significant differences between Salcatonin and control treatment groups for changes in vertebral bone mineral density and, in a small number of studies, similar results were shown for changes in forearm bone mineral content. A long term evaluation of a relatively low dose intermittent intranasal Salcatonin regimen (50 IU/day for 5 days/week) demonstrated a statistically significant difference in favour of Salcatonin plus calcium over calcium alone in bone mineral density of lumbar vertebrae after 6 months which was maintained for the entire duration of the 5-year study. In most trials, attenuation of bone loss by Salcatonin was accompanied by reductions in biochemical markers of bone résorption. Both cyclical regimens of intranasal Salcatonin 100 or 200 IU/day (which involved interruption of therapy every other month for 18 months) and continuous administration of the drug at the same dosages (all regimens with oral calcium supplements) increased bone mineral content of the lumbar spine by approximately 4 to 5% from baseline in postmenopausal women with a high rate of bone turnover. Peak increases in bone mineral content occurred somewhat earlier and tended to be slightly higher among women receiving continuous therapy. In general, intranasal administration of Salcatonin produced broadly similar effects on bone mineral density or content in postmenopausal women with established osteoporosis to those in postmenopausal women receiving the drug for prevention of the disease; however, statistically significant differences between treatment groups were usually not demonstrated. Randomised studies in postmenopausal women with established osteoporosis receiving intranasal Salcatonin 50, 100 or 200 IU/day for 1 to 2 years have demonstrated a dose-related response with respect to changes in bone mineral density or content. Results of a large 2-year trial comparing intranasal Salcatonin 100 IU/day with oral alendronate 10 or 20 mg/day (all with oral calcium supplements) demonstrated a somewhat greater effect of the bisphosphonate than Salcatonin on increasing bone mineral density of the lumbar spine in postmenopausal women with established osteoporosis. However, the dosage of intranasal Salcatonin used in the trial was only half the recommended dosage, and Salcatonin was not administered under a double-blind protocol. Importantly, both parenteral and intranasal Salcatonin have been shown to decrease fracture rates in this patient population, although this has been documented in only a limited number of trials. In a study of 164 elderly postmeno-pausal women with “moderate” osteoporosis, those who received intranasal Salcatonin 50, 100 or 200 IU/day plus calcium supplements for 2 years had a statistically significant reduction in fracture rate to approximately one-third that of women who received calcium supplements only. In another randomised study of 88 postmenopausal women with established osteoporosis, cyclical treatment with intranasal Salcatonin 100 IU/day plus oral calcium supplements (for 2 consecutive weeks followed by 2 weeks without therapy) for 1 year resulted in a statistically significant reduction in the rate of new vertebral fractures compared with calcium alone. These studies were of relatively short duration, and the effect of long term intranasal Salcatonin on osteoporotic fracture rates is currently under investigation in a much larger 5-year study of more than 1200 postmenopausal women. Intranasal Salcatonin has also been associated with improvement in pain and/or reductions in analgesic consumption in some studies of postmenopausal women with established osteoporosis. Tolerability In general, adverse events associated with intranasal administration of Salcatonin are relatively mild and tend to occur in less than 10% of patients. The most frequently reported adverse events are local transient reactions such as stinging or tingling of the nasal passage, sneezing, rhinitis, rhinorrhoea and nasal mucosal erythema which lead to discontinuation of therapy in about 4% of patients. In a comparative trial, primarily in patients with Paget’s disease, 10% of patients receiving subcutaneously administered Salcatonin discontinued therapy because of adverse events compared with 4% of those receiving the drug by intranasal administration. Dosage and Administration The recommended intranasal dosage of Salcatonin for the management of established osteoporosis is 200IU once daily. In clinical trials, postmenopausal women received intranasal Salcatonin dosages ranging from 50 to 400 IU/day as a single daily dose or in 2 divided doses for the prevention or treatment of osteoporosis. In virtually all clinical studies with intranasal Salcatonin, patients also received oral calcium supplements. It is not clear whether cyclical regimens of intranasal Salcatonin plus oral calcium supplements (e.g. 1 month of therapy followed by no drug treatment for 1 month and repeated in a cyclical fashion) have any clinically significant advantages over continuous treatment.
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Intranasal Salcatonin (salmon calcitonin). A review of its pharmacological properties and role in the management of postmenopausal osteoporosis.
Drugs & aging, 1996Co-Authors: Greg L. Plosker, Donna MctavishAbstract:Synopsis Osteoporosis is a common problem among postmenopausal women and is associated with significant morbidity, mortality and costs primarily resulting from osteoporotic fractures. Salcatonin (salmon calcitonin) inhibits osteoclastic bone resorption and is approximately 40 to 50 times more potent than human calcitonin. In most randomised trials in which intranasal Salcatonin (usually 50 to 200 IU/day plus oral calcium supplements) was administered for 1 to 5 years to postmenopausal women for prevention of osteoporosis, bone mineral density or content of the lumbar spine increased by approximately 1 to 3% from baseline. In contrast, postmenopausal women receiving only oral calcium supplements typically had reductions in bone mineral density or content of about 3 to 6%. The difference between treatment groups was statistically significant in essentially all studies. Although changes in bone mineral density or content were broadly similar in studies of postmenopausal women with established osteoporosis to those in postmenopausal women receiving therapy for prevention of the disease, studies in women with established osteoporosis did not usually demonstrate statistically significant differences between treatment groups. Also in postmenopausal women with established osteoporosis, intranasal Salcatonin reduced pain and/or analgesic consumption in some trials and, in a limited number of studies of relatively short duration (i.e. ≤2 years), the incidence of osteoporotic fractures. A large multicentre 5-year study with adequate statistical power to confirm the effect of intranasal Salcatonin on reducing osteoporotic fracture rates in postmenopausal women is currently under way. The intranasal formulation of Salcatonin offers a more convenient and better tolerated alternative to the parenteral formulation of the drug which is administered by regular subcutaneous or intramuscular injections. Adverse events associated with the intranasal formulation are generally mild and transient, usually involving local reactions such as nasal discomfort, rhinorrhoea or rhinitis. Thus, for postmenopausal women unable or unwilling to tolerate long term hormone replacement therapy, intranasal Salcatonin is an attractive alternative for the management of osteoporosis.
Jean-yves Reginster - One of the best experts on this subject based on the ideXlab platform.
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Efficacy and Tolerability of Calcitonin in the Prevention and Treatment of Osteoporosis
BioDrugs, 1998Co-Authors: Véronique Halkin, Jean-yves ReginsterAbstract:Calcitonin in general, and, more specifically, salmon calcitonin (Salcatonin), has been known for 30 years to be a specific inhibitor of bone resorption. Studies have confirmed its efficacy in metabolic bone diseases characterised by excessive bone resorption, such as osteoporosis. Most randomised studies in which Salcatonin and oral calcium were administered for 1 to 5 years to recently postmenopausal women for the prevention of osteoporosis have shown that bone mineral density or bone content of the lumbar spine increased significantly, compared with a reduction among women receiving calcium only. Prospective studies have shown that Salcatonin is effective in the treatment of established osteoporosis, reducing significantly the relative risk of new vertebral fractures. The benefits of Salcatonin nasal spray therapy were observed in the majority of women studied, and it has been shown to be an effective alternative for osteoporotic women more than 5 years postmenopausal who refuse estrogens, or for whom estrogens are contraindicated. Finally, in established osteoporosis, nasal calcitonin possesses a potent analgesic effect. The well-demonstrated effects of nasal calcitonin permit it to be considered a well tolerated and efficient approach for prevention and treatment of postmenopausal osteoporosis.
Chen Lulin - One of the best experts on this subject based on the ideXlab platform.
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Clinical observiation on calcitonin in management of osteoporosis
Chinese Journal of Osteoporosis, 2006Co-Authors: Chen LulinAbstract:Objective To study the influence of calcitonin on bone mineral density (BMD) in osteoporotic patients. Methods Totally, 198 osteoporotic patients were divided into two groups. Patients in Group Ⅰ(n=92) were given oral calcium (600mg+Vit D_3 125U,QD) and those in Group Ⅱ (n=102) were given oral calcium and calcitonin (Salcatonin 50 IU, IM, QD×14 d, then QOD×28 d, finally twice a week to the end of the course with the same dose of oral cacium and Vit D_3). Subgroups were divided according the courses of treatment, ie. 3 months and 6 months. The BMD of lumbar vertebra 2-4 and neck of left femur were measured by duel-energy X-ray absorptiometry before and after the treatment. Results Patients in Group Ⅱ had quicker and more effective pain relief than those in Group Ⅰ and the BMD was much more increased at both 3 and 6 months after the treatment than that of Group Ⅰ.The BMD at the 6 months was higher than that at the 3 months (P0.01). The effect of the treatment on the lumbar vertebra was better than that of the femur neck. Conclusions Calcitonin is effective in management of osteoporosis and patients would obtain more benefit with relatively longer courses.
Zhang Huixi - One of the best experts on this subject based on the ideXlab platform.
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preparation of mpeg plga porous microspheres and their adsorption to Salcatonin
The Chinese Journal of Process Engineering, 2013Co-Authors: Zhang HuixiAbstract:Relatively uniform size porous methoxy poly(ethylene glycol-L-lactic-co-glycolic acid)(mPEG-PLGA) microspheres were successfully prepared by premix membrane emulsification with solvent evaporate method. The effects of Salcatonin concentration, salt concentration, pH value, adsorption temperature and time, and properties of microspheres on the adsorption capacity of Salcatonin were investigated. The results showed that the adsorption capacity of porous microspheres reached 48.9 mg/g under the conditions of 1.0mg/mL Salcatonin concentration, pH value 7.4 of phosphate buffer, 0.2 mol/L NaCl concentration, 14 ℃ adsorption temperature and 8 h adsorption time. In addition, the adsorption capacity increased with the increase of specific surface area.
