Intranasal Calcitonin Research Articles

Comparison of Alendronate and Intranasal Calcitonin for Treatment of Osteoporosis in Postmenopausal Women

Both alendronate and calcitonin, the latter administered intranasally, reportedly increase bone mineral density (BMD) and reduce bone turnover, but alendronate seems to be somewhat more effective. This study directly and prospectively compared these treatments in 299 women with an average age of 64 years who were at least 5 years postmenopausal. BMD was monitored at the lumbar spine and femoral neck and trochanter by dual-energy x-ray absorptiometry during 12 months of treatment with 10 mg of alendronate, a matching placebo, or open-label intranasal calcitonin in a daily dose of 200 IU. Serum bone-specific alkaline phosphatase (BSAP) and urinary N-telopeptide of type I collagen adjusted for urinary creatinine (NTx) were measured as markers of bone formation and resorption, respectively. BMD at both the lumbar spine and trochanter increased significantly more in patients given alendronate than in those given calcitonin (Fig. 1). The effect of alendronate significantly exceeded that in placebo patients at all sites. Both serum BSAP and urinary NTx decreased substantially more in alendronate-treated patients than in those given calcitonin or placebo at all intervals (Fig. 2). Adverse events in general and serious complications were noted in similar proportions of all groups. Effects on the upper gastrointestinal tract were more prevalent with alendronate therapy than with calcitonin therapy but were nearly as frequent in patients given the alendronate placebo. Findings in this double-blind randomized study indicate that alendronate was more effective than intranasal calcitonin in promoting increased BMD in postmenopausal women. It suppressed bone turnover more than did calcitonin during 1 year of treatment.Fig. 1: BMD. Mean percent change (±SE) in BMD of the lumbar spine, hip trochanter, and femoral neck with 10 mg of alendronate (ALN, ○), 200 IU of intranasal calcitonin (CT, ▵), and placebo tablet (PBO, □) over 12 months. P values for between-group comparisons are presented.Fig. 2: Biochemical markers of bone turnover. Mean percent change from baseline and SE in BSAP and NTx with 10 mg of alendronate (ALN, ○), 200 IU of intranasal calcitonin (CT, ▵), and placebo tablet (PBO, □) over 12 months. P values for between-group comparisons are presented.J Clin Endocrinol Metab 2000;85:1783–1788

Comparison of Alendronate and Intranasal Calcitonin for Treatment of Osteoporosis in Postmenopausal Women*

This study compared the effects of oral alendronate and intranasal calcitonin for treatment of osteoporosis in postmenopausal women. Women at least 5 yr postmenopause (n = 299) were randomized to either 10 mg alendronate, matching alendronate placebo, or open-label intranasal calcitonin 200 IU daily for 12 months. Hip and spine bone mineral density (BMD) and markers of bone turnover were measured, and safety and tolerability were assessed. Alendronate produced greater increases in BMD than calcitonin at 12 months at the lumbar spine (5.16% vs. 1.18%; P < 0.001), trochanter (4.73% vs. 0.47%; P < 0.001), and femoral neck (2.78% vs. 0.58%; P < 0.001). Changes in BMD with calcitonin were greater than with placebo at the femoral neck, but were not different from placebo at either the trochanter or lumbar spine. Greater decreases in bone turnover were seen with alendronate than with calcitonin (serum bone-specific alkaline phosphatase, 43% vs. 9%, P < 0.001; urinary N-telopeptide, 62% vs. 11%, P < 0.001). Similar percentages of patients in each group reported an adverse experience during the study. We conclude that, in postmenopausal women with osteoporosis, 12 months of therapy with alendronate produced significantly greater increases in BMD of the hip and spine and greater decreases in bone turnover than intranasal calcitonin.

Comparison of Alendronate and Intranasal Calcitonin for Treatment of Osteoporosis in Postmenopausal Women

Comparison of Alendronate and Intranasal Calcitonin for Treatment of Osteoporosis in Postmenopausal Women

Efecto de dosis bajas de calcitonina sobre la remodelación ósea en mujeres postmenopáusicas con alto recambio

Calcitonin is specially indicated for the treatment of osteoporosis in women that cannot receive estrogen replacement therapy or that have a high bone turnover rate. To study the effects of low intranasal calcitonin doses on bone remodeling in postmenopausal women with a high bone turnover. Forty one healthy women aged 56 +/- 6 years old, with a mean lapse after menopause of 7.6 +/- 6.5 years and with a high bone turnover rate, evidenced by an urinary hydroxyproline (mg/dl)/creatinine (g/dl) ratio of 52.4 +/- 7.2, were studied. They were randomly assigned to receive 100 or 50 U/calcitonin thrice a week during 3 months or to a control group that received placebo. All received 500 mg/day calcium carbonate. Urinary hydroxyproline/creatinine ratio was measured a 0, 15, 30, 60 and 90 days. Plasma bone fraction of alkanine phosphatases was measured at 0, 30 and 90 days. Initial urinary hydroxyproline/creatinine ratio and plasma bone fraction of alkanine phosphatases were similar in all study groups and there was no change in these parameters during the study period. Intranasal calcitonin in doses of 100 U thrice a week or less, does not modify accelerated bone turnover in postmenopausal women.

Great news for brittle bones

Results of a much-anticipated comparison of 2 competing osteoporosis therapies show a significant advantage for Merck & Co.’s bisphosphonate agent alendronic acid [‘Fosamax’] over Novartis’ intranasal calcitonin [‘Miacalcin’] in postmenopausal women with osteoporosis. Treatment with alendronic acid led to greater increases in bone mineral density (BMD) in the spine, femoral neck and trochanter, compared with calcitonin. The agents had similar tolerability; in addition, the incidence of adverse events in both active therapy groups was similar to that seen in placebo recipients, as reported at the 81st Annual Meeting of the Endocrine Society [San Diego, US; June 1999].

Diagnosis and management of osteoporosis in postmenopausal women: Clinical guidelines

The authors, all physicians involved in clinical research on bone and practicing clinicians, propose practical guidelines for identifying persons with osteoporosis or those at high risk of developing the disease and for managing patients who may benefit from therapy. These guidelines are based on an analysis of peer-reviewed articles published before November 1998. A flowchart of women who might benefit from treatment is provided, including clinical presentation (recent fracture of the spine, hip, or other bone or no fracture; risk factors for Osteoporosis); relevant investigations (bone mineral density measurement and laboratory tests required for the differential diagnosis); and therapeutic management (general measures such as calcium and vitamin D supplementation and specific pharmacologic interventions such as estrogen, bisphosphonates, intranasal calcitonin, raloxifene, fluoride salts, and other compounds that have been assessed in randomized clinical trials). The strongest evidence for antifracture efficacy (reduction of vertebral and nonvertebral fracture risk) was observed with alendronate.

What can we learn from bone biology for the treatment for osteoporosis?

There does not exist an entirely satsifactory drug for patients with established osteoporosis. No currently available drug is either universally acceptable or leads to substantial formation of new bone. Moreover, in spite of the recent introduction of newer bisphosphonates, intranasal calcitonin and estrogen-related compounds, there is still room for new preventive treatments for bone loss associated with the menopause and hormone withdrawal. There is an even greater need for acceptable and efficacious therapies for patients with established osteoporosis who have severe bone deficits. This is the reason that the pharmaceutical industry is now spending billions of dollars in a search for better modalities of treatment than those currently available. Specific problems can be found with all existing therapies, and drugs under development. The task that confronts the industry in identifying new therapies is particularly difficult. Although bringing a new drug to the market is very expensive in any pharmaceutical arena, it is particularly so in osteoporosis. This is because the Food and Drug Administration in the United States and many other regulatory agencies require evidence of beneficial effects on fracture rates. This problem is compounded somewhat by the expense involved in clinical studies in osteoporosis (requiring large numbers of patients from multiple centers), and the decline in research and development budgets associated with reduced profits due to managed care and price controls on drugs in some countries. Establishing practice guidelines for osteoporosis may also limit the use of drugs, particularly those that are expensive, or require treatment in many patients to see benefits in one. In the European Community, price controls on drugs already exist in many countries. A pharmaceutical company entering this field must consider the size of the therapeutic market, as well as the competition. For example, the bisphosphonate market is likely to be shared by a number of similar compounds during the next decade, and the same appears likely for estrogenrelated compounds. The lag time between discovery of a new lead for osteoporosis and the introduction of a new drug in the clinic may be 10–15 years. This certainly seems to have been the experience with resorption inhibitors such as alendronate and raloxifene. This means that there must be an enormous investment by the pharmaceutical company, possibly in the order of $500 million in today’s dollars, so that the eventual market must be substantial to accommodate this risk.

Calcitonin in phantom limb pain.

PLP is a challenging disorder that is often difficult to treat. Like all other types of pain, PLP is a tremendous source of morbidity and should be treated aggressively. Though evidence is very limited, one or two doses of intravenous salmon calcitonin 200 IU may be an effective treatment. The minor adverse effects reported in the literature would seem to indicate the relative safety of this regimen; however, clinicians should be aware of the rare but severe hypersensitivity reactions that can occur with salmon calcitonin. Intranasal calcitonin appears to be similar in efficacy to the parenteral formulation, at least in pain associated with vertebral crush fractures. Long-term studies using intranasal calcitonin for relief of PLP are warranted given the ease of administration of this dosage form.

THE EFFECT OF DIFFERENT DOSES OF CALCITONIN ON BONE MINERAL DENSITY AND FRACTURE RISK IN POSTMENOPAUSAL OSTEOPOROSIS

SUMMARY A total of 107 patients were included in the study to determine the effects of different doses of intranasal calcitonin on bone mineral density and fracture risk in postmenopausal osteoporosis. Patients were randomly divided into three groups. All three groups were given 1000 mg/day calcium and vitamin D in adequate doses. Two of the groups, the exception being the placebo group, were also given either 50 IU or 100 IU of calcitonin. The data of 81 patients who completed the 24 months of regular study treatment and controls were evaluated. When compared, both of the calcitonin groups were superior to the placebo group regarding increase in bone mineral density and decrease in fracture rate.

The morbidity of bone disease in thalassemia.

As thalassemia patients age, bone disease becomes a serious cause of morbidity. The frequency and type of bone disease is affected by the underlying type of thalassemia and its treatment. Problems include rickets, scoliosis, spinal deformities, nerve compression, fractures and severe osteoporosis. In early stages, patients may be asymptomatic but can present with back pain, a limp, dyspnea, neurological emergencies, or sudden fractures. The etiologies are often multifactorial, culminating with increased bone resorption and remodeling. They include hormonal deficiency, bone marrow expansion, nutritional deficiency, or desferal toxicity. Particular risk factors include older patients, low baseline hemoglobin, delayed puberty, hormonal failure, and high iron stores. Nutritional deficiencies may further compound the patient's risk for bone disease. Increasing evidence suggests that these complications and their associated long-term morbidity can be prevented if an annual screening is done, followed by long-term intervention. Patients treated with amino biphosphonates inhibit bone resorption and may demonstrate rapid healing. Intra-nasal calcitonin has also been successful in treating osteopenia. Early use of estrogen and testosterone appears to markedly lower the risk for selective patients. Both transfused and non-transfused patients should be educated about risk factors and early symptoms. All patients should be screened annually for bone disease. Once adolescence occurs, annual testing in selected cases should include bone density studies with X-ray absorptiometry.

Calcium potentiates the effect of estrogen and calcitonin on bone mass: review and analysis

We reviewed published clinical trials that measured bone mass of postmenopausal women from at least one skeletal site to evaluate whether calcium supplementation influenced the efficacy of estrogens and intranasal calcitonin on bone mass change. We compared results of the administration of oral estrogen or nasal calcitonin in conjuction with additional calcium intake either through diet or supplements compared with those of estrogen or calcitonin alone. Of the 31 published estrogen trials analyzed, 20 modified the diet or used a calcium supplement (total 1183 mg/d) and 11 did not (total 563 mg/d). The mean increase in bone mass of the lumbar spine when estrogen was given alone was 1.3%/y (n = 5) compared with 3.3%/y when estrogen was given in conjunction with calcium (n = 14; P = 0.01). The mean increase in bone mass of the femoral neck with estrogen alone (n = 3) was only 0.9%/y compared with 2.4%/y when calcium was given with estrogen (n = 6; P = 0.04). Similarly, forearm bone mass increased 0.4%/y with estrogen alone (n = 7) compared with 2.1%/y when estrogen was given with calcium (n = 12; P = 0.04). Similar results were found when weighted means were calculated. Of the seven published trials evaluating the effects of 200 IU nasal salmon calcitonin, six also used calcium supplements (total 1466 mg/d) whereas one used calcitonin alone (total 627 mg/d). Bone mass of the lumbar spine increased 2.1% with calcitonin plus calcium supplementation compared with -0.2%/y with calcitonin alone. These results suggest that a high calcium intake potentiates the positive effect of estrogen on bone mass at all skeletal sites and perhaps that of calcitonin on bone mass of the spine.

Changes in prolactin levels with the menopause: The effects of estrogen/androgen and calcitonin treatment

Prolactin levels were evaluated over a 2-year period in three groups of postmenopausal women: group A consisted of 35 untreated women distributed according to time since the menopause; group B consisted of 17 women on a combined estrogen/androgen preparation (Gynodian depot®) intramuscularly at monthly intervals; and group C consisted of 12 women on 100 units of salmon calcitonin intranasally on alternate days and 1500 mg calcium daily. The control group (group D) consisted of 11 healthy premenopausal women. Serum prolactin, estradiol, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were measured at the onset and at 6-month intervals over 24 months. Mean serum prolactin concentrations decreased significantly during the second postmenopausal year in untreated women (p = 0.0001 and p = 0.0000after 18and 24 months, respectively) when compared to either the levels in premenopausal women or those at the beginning of the menopause (p = 0.0007). Neither combined estrogen/ androgen nor calcitonin therapy significantly influenced prolactin levels which were similar throughout the observed period. In the group on a combined estrogen/androgen preparation, physiological estradiol concentrations together with a suppression of gonadotropins during the first 6 months of therapy were achieved. In women treated with intranasal salmon calcitonin, estradiol, FSH and LH levels were unchanged.Our results show that prolactin levels decrease significantly during the second year of the menopause. Neither combined estrogen/androgen, nor salmon calcitonin therapy had any effect on serum prolactin concentrations in postmenopausal women.

Intranasal salmon calcitonin for the prevention and treatment of postmenopausal osteoporosis

In a randomized, double-blind, placebo-controlled trial, we have studied the effects of intranasal salmon calcitonin (SCT) on bone mineral density (BMD) and biochemical markers of bone turnover over a period of 2 years. Our study comprised 117 Caucasian postmenopausal women, otherwise healthy apart from reduced bone density. They received either intranasal synthetic SCT (200 IU either three times weekly or daily) or placebo. Compared with placebo, daily intranasal calcitonin resulted in no significant bone loss in the lumbar spine, as assessed by dual photon absorptiometry, over the 2-year study period (P < 0.02). In this group, women more than 5 years postmenopause, with the lowest baseline bone mass, showed the greatest response to this treatment, with a total increase placebo in lumbar spine BMD of 3.1%. Significant spinal bone loss (P < 0.005) occurred in women receiving either placebo or thrice-weekly calcitonin. Although the rates of bone loss in the proximal femur were not significantly different in the three groups, there were differences over time. Whereas bone loss in the daily calcitonin group was insignificant, women who received placebo or thrice-weekly calcitonin experienced significant bone loss (P < 0. 001). No significant changes in biochemical markers were observed in any group. Therapy was well tolerated and there were no significant treatment-related adverse events. We conclude that intranasal SCT 200 IU daily is effective and safe for the prevention of bone loss in postmenopausal women with reduced bone mass.

The Effect of Intranasal Salmon Calcitonin on Postmenopausal Bone Turnover as Assessed by Biochemical Markers: Evidence of Maximal Effect After 8 Weeks of Continuous Treatment

The Effect of Intranasal Salmon Calcitonin on Postmenopausal Bone Turnover as Assessed by Biochemical Markers: Evidence of Maximal Effect After 8 Weeks of Continuous Treatment

L-thyroxine suppressive therapy and bone density in postmenopausal women—The effect of calcium supplementation and intranasal calcitonin

L-thyroxine suppressive therapy and bone density in postmenopausal women—The effect of calcium supplementation and intranasal calcitonin

Different therapeutic regimens of intranasal salmon calcitonin in postmenapousal osteoporosis

Different therapeutic regimens of intranasal salmon calcitonin in postmenapousal osteoporosis

Effects of oral alendronate and intranasal salmon calcitonin on bone mass and biochemical markers of bone turnover in postmenopausal women with osteoporosis

The main objective of this study was to determine the effect of daily oral alendronate treatment on bone mass in post-menopausal women affected by osteoporosis. The efficacy of intranasal salmon calcitonin was also examined. Nine centers in Italy enrolled 286 postmenopausal women between the ages of 48 and 76 with spinal bone mineral density ⩾ 2 SD below adult mean peak in the two-year, double-blind, randomized, placebo-controlled trial. Patients were randomized to one of four treatment arms: double-blind placebo, alendronate 10 mg/day, alendronate 20 mg/day, or open-label intranasal salmon calcitonin 100 IU/day; all patients received 500 mg Ca ++ supplements. Bone mass was measured by dual-energy x-ray absorptiometry every six months for two years. Patients who received alendronate 10 or 20 mg experienced significant increases in bone mass at all sites measured. At the end of the second year, the mean percent changes, for alendronate 10 and 20 mg relative to placebo, were 5.2% and 7.3% at the lumbar spine, 3.8% and 4.6% at the femoral neck, and 7.1% and 7.5% at the trochanter, respectively. In contrast, intranasal salmon calcitonin failed to increase bone mineral mass significantly at any site. Both alendronate doses significantly decreased serum alkaline phosphatase, serum osteocalcin, and urinary pyridinolines, markers of bone turnover, whereas placebo and intranasal calcitonin did not. Alendronate was generally well tolerated and no serious adverse events were attributed to its use. In conclusion, alendronate increased bone mass at the spine and hip, decreased bone turnover, and was generally well tolerated at doses up to 20 mg daily for two years. Intranasal salmon calcitonin 100 IU/day did not differ from placebo, and was ineffective in reducing bone turnover or increasing bone mass. ( Bone 17:383–390; 1995)

The Prevention of Osteoporosis-State of the Art 1995

RésuméIl conviendra à l’avenir de concentrer notre attention sur les moyens possibles de prévenir et de traiter l’ostéoporose. Toutefois, toute mesure de prévention ou de traitement doit nécessairement être précédée d’un diagnostic et il est par conséquent essentiel que toutes les possibilités de diagnostic soient optimisées et utilisées. Pour la prévention et le traitement de l’ostéoporose chez les femmes ménopausées, l’hormonothérapie substitutive est la méthode de choix. Par ailleurs, on peut maintenant, dans de nombreux pays, recourir à l’administration intranasale de calcitonine, ce qui procure aux clinicians une plus grande gamme d’options thérapeutiques. Les analogues d’oestrogène et les biphosphonates font actuellement l’objet de recherches; on peut espérer qu’ils nous procureront également d’autres solutions de prévention et de traitement de l’ostéoporose.

Intranasal calcitonin keeps steroid-induced bone loss at bay

Intranasal calcitonin keeps steroid-induced bone loss at bay

CALCITONINS AND OSTEOPOROSIS

SUMMARY Calcitonin, a polypeptide hormone secreted by the parafollicular C cells of the thyroid gland, lowers serum calcium by decreasing bone resorption and tubular calcium reabsorption. An analgesic action, possibly mediated via β‐endorphins, is also evident. Parenteral calcitonin has been shown to stabilise and increase indices of cortical and trabecular bone mass and total body calcium when administered to patients with established osteoporosis. The routine use of this route of administration has been limited by poor patient compliance and tolerability. An intranasal preparation of calcitonin provided a more convenient means of administration. Several clinical trials have shown that intranasal calcitonin is effective and well tolerated both in prevention of postmenopausal bone loss and in established osteoporosis. Calcitonin therapy is particularly indicated for patients with high‐turnover osteoporosis where results show a net gain of bone mineral in the axial skeleton and a slowing of bone loss in the appendicular bones. Due to receptor downregulation a resistance to the hormone may occur after 12‐18 months of continuous treatment. This resistance can be avoided and delayed by the cyclical or discontinued administration of the hormone. Further research is needed to confirm longer‐term efficacy and effects on fracture rate.