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.     

Effects of salmon calcitonin suppositories on bone mass and turnover in established osteoporosis

The objective of this study was to test the efficacy and safety of salmon calcitonin (sCT) suppository in postmenopausal women with previous hip fractures as an inhibitory agent of bone loss. The study was a single blind, randomized, and placebo-controlled trial comparing three parallel groups of patients. Fifty-four healthy women were randomly allocated to 1 year's treatment with either sCT 100 IU/6 times a week, 200 IU/3 times a week, or placebo/6 times a week. All groups received a calcium supplement of 500 mg daily. Fifteen patients left the study before its end, six of those due to adverse events, such as abdominal and rectal pain, nausea, headache, and diarrhea. Bone mineral density of the spine and the femoral neck was measured every 26 weeks, and biochemical markers of bone turnover were measured at baseline and week 12, 26, and 52. There were no significant changes in bone mineral density in the spine and in the hip in any of the treatment groups. No significant changes were observed in serum alkaline phosphatase, serum osteocalcin, urine hydroxyproline, and urine pyridinoline or deoxypyridinoline. Conclusively, we did not observe any significant effect on bone metabolism in women with postmenopausal osteoporosis after 1 year of treatment with sCT suppositories at the doses used.     

Effect of intranasal salmon calcitonin therapy on bone mass and bone turnover in early postmenopausal women: A dose-response study

We examine the dose-related effect of intranasal salmon calcitonin (sCT) on the early postmenopausal bone loss and bone turnover; a 2-year, prospective, randomized, double-blind, placebo-controlled study was carried out with 134 healthy women who had passed a natural menopause within 6 months to 3 years. The women were allocated randomly to 2 years of treatment with either 100, 200, or 400 IU of sCT given intranasally or placebo. All groups received a calcium supplement of 500 mg. Twenty-one women left the study before its end and 91 complied with the study criteria throughout. Bone mineral content/density of the distal forearm and lumbar spine and biochemical parameters of bone turnover were measured. Although the measurements after 24 months revealed no significant difference between groups in bone mineral density of the lumbar spine, the average changes over time revealed prevention of bone loss in the groups treated with 200 and 400 IU of sCT (0.2 to-0.6%) and declines of 0.8-1.7% in the groups treated with 100 IU of sCT and placebo (P<0.05–0.01; within-group testing). There was no dose-related response to sCT but there was a significant difference between the pooled groups treated with 200 plus 400 IU of sCT versus the 100 IU sCT and placebo-treated groups (P=0.030–0.005). The same difference between groups was seen for biochemical parameters of bone turnover (P=0.022–0.003). The biochemical parameters of bone turnover revealed decreases of 10–20% (P<0.001; within group testing) in the groups treated with the two highest sCT doses. It was concluded that nasal sCT in doses of 200 and 400 IU has some effect in women soon after the menopause—preventing the bone loss in the spine throughout the first year of therapy and lowering the bone turnover. It may be used as an alternative to hormone replacement when estrogens are contraindicated. The present data indicate that discontinuous strategies should be preferred.     

The effect of high-dose salmon calcitonin on bone mineral metabolism in the normal rat

Summary The paucity of information on the effect of long-term high-dose salmon calcitonin administration on normal bone mineral metabolism and histology prompted an investigation of the influence of high-dose synthetic calcitonin in the rat. Serum ionized calcium, osteocalcin or BGP (bone gla protein), and immunoreactive PTH were measured serially during calcitonin administration and bone histomorphometry analyzed at 6 weeks (after sacrifice). Daily injections of salmon calcitonin, 0.4 IU/100 g (group B) and 2 IU/100 g (group C), resulted in significant hypocalcemia at 4 hours for both experimental groups (P<0.004). Serium iPTH was significantly higher over the study period for both groups administered calcitonin. Serum BGP levels were significantly lower than controls during the study in group C (P<0.002) and to a lesser extent in group B (P<0.05). In group C, bone histomorphometry revealed increased resorption (onteoclast count), decreased trabecular bone volume, and decreased double-labeled tetracycline surface (bone formation). In group B an increase in osteoclast count but no alteration in bone formation was observed. To assess the role of PTH in the above findings, high-dose calcitonin was administered to parathyroidectomized rats. All of the above changes in bone histomorphometry were not observed in this group of animals. In conclusion, high doses of calcitonin promote hypocalcemia, secondary hyperparathyroidism, and osteoclastosis in the normal rat in a dose-dependent manner with very high-dose calcitonin impairing bone formation.     

Prevention of bone loss in early nonsurgical and nonosteoporotic high turnover patients with salmon calcitonin: The role of biochemical bone markers in monitoring high turnover patients under calcitonin treatment

Annual bone loss rate was estimated in a group of randomly selected 150 nonsurgical and nonosteoporotic early postmenopausal women, 42–56 years, with the use of the mathematical equation proposed by Christiansen et al. (OSTEOTREND-R) [1]. Fifty-six women were characterized as high turnover patients (estimated annual bone loss more than 2.7%). These high turnover patients were included in a double-blind, placebo-controlled clinical study. Patients were divided into two groups of 28 women each. The first group of patients received 100 IU of salmon calcitonin intranasally daily for 1 year and the second group intranasal spray of placebo daily. Blood and urine biochemical parameters as well as bone mineral content of the spine and proximal forearm were determined initially and at the end of 6 and 12 months. No other side effects were noted apart from discomfort of nasal mucosa in two patients (one in each group). The group of calcitonin-treated patients showed a dramatic decrease in bone loss rate as estimated with the use of biochemical bone markers at the end of 6 and 12 months (3.7% versus 0.8% and 0.0% at the end of 6 and 12 months, respectively, P<0.001) whereas in the placebo group, bone loss rate remained unchanged (4.2% versus 4.1% and 4.3% at the end of 6 and 12 months, respectively). The calcitonintreated patients showed a significant increase in bone mineral content of spine and proximal forearm (P<0.001 at the end of 6 and 12 months, respectively). On the other hand, a significant decrease in all measurement sites appeared in the placebo group. In conclusion, our results showed that nasal salmon calcitonin administration can prevent the increased postmenorpausal bone loss in selected high bone turnover patients. The predicted annual bone loss rate, as estimated with the combination of biochemical bone markers, is useful in monitoring the responsiveness of high turnover patients to calcitonin at short intervals.     

Ineffectiveness of calcitonin on a local-disuse osteoporosis in the sheep: A histomorphometric study

Local immobilization is a good model for studying disuse-induced bone loss and to appreciate the effects of drugs, especially preventive action of antiresorptive therapy. In fact, increased osteoclastic activity is the main point of such a bone loss. The effect of salmon calcitonin was investigated on immobilization-induced osteoporosis in the sheep. Twenty-four nonovariectomized, adult, female, Welsh mountain sheep were submitted, by an external fixator procedure, to hock joint immobilization from the tibia to the the metatarsus for 12 weeks. The sheep were randomized into two groups receiving either an injection of placebo or salmon calcitonin (100 IU) three times per week, for 12 weeks. Histomorphometric analysis was performed on pre-and posttherapeutic transiliac bone biopsies, and on immobilized (left) and nonimmobilized calcanei removed after sacrifice. Results showed a 29% significant decrease of cancellous bone volume in the placebo group due to a significant reduced trabecular thickness when we compared immobilized versus nonimmobilized calcaneus. This structural adaptation appeared to be the consequence of an overall increased bone turnover. In the calcitonin group, same changes were observed, with a 23% reduction of bone mass in the immobilized calcaneus. By comparing calcitonin with placebo groups in both left and right calcanei, no difference was found. On the other hand, a significant increase of mineralization parameters in the iliac crest was only observed in the calcitonin group. In conclusion, salmon calcitonin, at a dose of 100 IU/day three times a week, was ineffective in preventing local disuse osteoporosis in this sheep model.This work was presented as a poster at the annual meeting of the American Society for Bone and Mineral Research, in Tampa, Florida, 1993.     

A phase 3 trial of the efficacy and safety of oral recombinant calcitonin: the Oral Calcitonin in Postmenopausal Osteoporosis (ORACAL) trial

The Oral Calcitonin in Postmenopausal Osteoporosis (ORACAL) study was a randomized, double‐blind, double‐dummy, active‐ and placebo‐controlled, multiple‐dose, phase 3 study to assess the efficacy and safety of oral recombinant calcitonin for treatment of postmenopausal osteoporosis. A total of 565 women age 46 to 86 (mean 66.5) years were randomized (4:3:2) to receive oral recombinant salmon calcitonin (rsCT) tablets (0.2 mg/d) plus placebo nasal spray, synthetic salmon calcitonin (ssCT) nasal spray (200 IU/d) plus placebo tablets, or placebo (placebo tablets plus placebo nasal spray), respectively for 48 weeks. All women received calcium (≥1000 mg/d) and vitamin D (800 IU/d). Women randomized to oral rsCT had a mean ± SD percent increase from baseline in lumbar spine bone mineral density (BMD) (1.5% ± 3.2%) that was greater than those randomized to ssCT nasal spray (0.78% ± 2.9%) or placebo (0.5% ± 3.2%). Lumbar spine BMD change in those receiving nasal calcitonin did not differ from placebo. Oral rsCT treatment also resulted in greater improvements in trochanteric and total proximal femur BMD than ssCT nasal spray. Reductions in bone resorption markers with oral rsCT were greater than those observed in ssCT nasal spray or placebo recipients. Approximately 80% of subjects in each treatment group experienced an adverse event, the majority of which were mild or moderate in intensity. Gastrointestinal system adverse events were reported by nearly one‐half of women in all treatment groups and were the principal reason for premature withdrawals. Less than 10% of women experienced a serious adverse event and no deaths occurred. Overall, oral rsCT was superior to nasal ssCT and placebo for increasing BMD and reducing bone turnover. Oral rsCT was safe and as well tolerated as ssCT nasal spray or placebo. Oral calcitonin may provide an additional treatment alternative for women with postmenopausal osteoporosis. © 2012 American Society for Bone and Mineral Research.     

Long-term treatment of established osteoporosis with intranasal calcitonin

We examined the long-term effects of intranasal administration of salmon calcitonin on bone and calcium metabolism in women with established osteoporosis (forearm fracture). Over a period of 5 years, 14 women received discontinuous calcitonin (200 IU) plus calcium (500 mg) daily for 3 years or 4 years. To allow assessment of the optimum duration of therapy, patients in whom treatment had been for shorter intervals were also included. At the end of the first 2 years, a group receiving placebo had lost significantly more bone from their spines and forearms than the group receiving calcitonin in the first year (P<0.01). In the 14 women who completed a further 3 years on calcitonin, the bone mineral contents of the spines increased continually. Bone loss in the forearm was arrested for 1 year. Treatment lasting for about 2 years prevented bone loss in both areas. Treatment for 3 years resulted in net gains in spinal bone but no further benefits in relation to forearms. Biochemical parameters of bone turnover (serum alkaline phosphatase levels, plasma bone Gla protein levels, and fasting urinary hydroxy-proline/creatinine levels) exhibited similar declines irrespective of the duration of treatment. It is concluded that longterm intranasal treatment with calcitonin produced net gains in spinal bone and that optimum response in forearms was achieved using discontinuous therapy. The ratio between periods with and without treatment was between 1∶2 and 2∶3.     

Effect of Salmon Calcitonin on Femoral Bone Quality in Adult Ovariectomized Ewes

The aim of this study was to evaluate the effect of intermittent calcitonin on femoral bone quality in adult ewes from the time of ovariectomy. Six months after the start of the experiment, bone density measurements and mechanical testing (torsion and resonant frequency analysis of the diaphysis and compression of an excised trabecular bone cylinder from the femoral neck) were performed in sham-control and ovariectomized (OVX) ewes treated with placebo or salmon calcitonin (50 or 100 units, 3 times/week). Crystallinity of bone was evaluated by measuring X-ray diffraction line broadening. After OVX, a nonsignificant bone loss was found at all measured sites in the femur (−3 to −9%) together with a decreased biomechanical competence in the trabecular bone (compressive strain −28%, P < 0.05). Treatment with salmon calcitonin, 50 or 100 IU subcutaneously three times a week from the time of ovariectomy, resulted in a significant dose-dependent preservation of bone strength in the trabecular bone of the femoral neck compared with OVX. No adverse effects of calcitonin were observed on bone crystal composition as assessed by diffractiometry. We conclude that in adult ewes intermittent calcitonin treatment from the time of OVX was associated with a significant preservation of cancellous bone strength and strain in trabecular bone of the femoral neck, without affecting crystalline properties of bone. Received: 20 October 1995 / Accepted: 19 February 1996     

The effect of different doses of nasal salmon calcitonin on plasma cyclic AMP and serum ionized calcium

Summary To investigate the effect of low doses of intranasal salmon calcitonin on plasma cyclic AMP (cAMP) and serum ionized calcium, 40 healthy postmenopausal women were randomized to receive a single dose of either placebo or 50, 100, or 200 IU of salmon calcitonin as a nasal spray. Blood samples were collected throughout an 8-hour period. None of the doses could provoke detectable hypocalcemia, whereas 100 and 200 IU of salmon calcitonin were associated with an increase in plasma cAMP after 15 minutes. Measurable plasma levels of salmon calcitonin were demonstrated in all active treatment groups, and the calculated areas under the curves showed a dose-dependent increase.     

Effect of calcitonin on bone histomorphometry and bone metabolism in rheumatoid arthritis

Summary Twenty-four women (mean age±SD 49±13 years) with classical or definite rheumatoid arthritis (disease duration 15±8 years) were treated with synthetic salmon calcitonin (SCT) nasal spray 200 IU three times a week for 3 months. Bone biopsies from the iliac crest were taken before and after SCT treatment. Histomorphometrical quantification of undecalcified bone sections was made using the manual point-counting method. SCT decreased the resorption surface of trabecular bone (ES/BS) significantly (P< 0.001). There was also a significant increase (P< 0.05) in trabecular bone volume (BV/TV) after 3 months of treatment, whereas no statistically significant changes were found in osteoid parameters. There were no significant changes in biochemical analyses of bone metabolism. We conclude that SCT might be useful in the prevention of bone loss in RA.     

A new biochemical marker of bone resorption for follow-up on treatment with nasal salmon calcitonin

In a double-blind, placebo-controlled, randomized group comparison, new and specific biochemical markers for bone resorption as follow-up parameters on the therapeutic response to nasal salmon calcitonin (sCT) were evaluated. Evaluation took place at an outpatient clinic where osteoporosis was being researched. The subjects included 208 women aged 68–72 treated for 2 years with either 50 IU, 100 IU, or 200 IU of nasal sCT or placebo; all groups received a daily calcium supplementation of 500 mg. Only 164 women fulfilled the study as valid completers. Markers were applied to frozen urine samples of a previously published intervention study of a new fasting urinary (fU) biochemical marker for bone resorption (CrossLaps^TM, ELISA) and the urinary excretion of cross-links (pyridinoline and deoxypyridinoline) was measured, all corrected for creatinine. Bone mineral density of the lumbar spine and rates of vertebral and peripheral fractures were measured after 2 years of treatment. The creatinine corrected urinary pyridinoline, deoxypyridinoline, and CrossLaps showed maximum decreases of 10–43% (95% confidence interval-29.5% to 9.6% and -75.1% to 9.3%;P < 0.01-0.001) after 6–9 months, after which the response leveled off. A significant difference among the four treatment groups was seen in fU CrossLaps(P < 0.01). The changes in spinal bone mass were significantly related to the decreases in fU CrossLaps: women with the highest response in spinal bone mass had decreases in fU CrossLaps of 44% (-83.5% to 7.4%) and women without response of 5% (-57.6% to 99.9%)P 0.001). In women who fractured during the 2-year period, fU CrossLaps remained unchanged, whereas decreases of 30% (-75.1% to 44.7%) were seen in women who did not fracture(P = 0.002). The results suggest that biochemical markers can be used to determine the optimum treatment regimen of nasal sCT. The response of the new marker, fU CrossLaps, significantly reflects the responses in bone mass of the spine and fracture rates.     

Effects of calcitonin on the biomechanics,histopathology, and radiography of callus formation in rats

Background This study was designed to examine the effect of salmon calcitonin on fracture repair. Methods A transverse middiaphyseal fracture of the right tibia was surgically induced, and stabilized by an intramedullary Kirschner wire. Eighty male Wistar rats were arbitrarily assigned to four groups of 20 animals each. Groups I and II were the controls and did not receive any medication but did receive placebo injections. The other two groups received 5 IU/kg/day salmon calcitonin intramuscularly for 6 weeks (Group III) or for 10 weeks (Group IV) postoperatively. The formation and healing of the bones were determined by radiographic and histopathological analyses and by biomechanical tests. Results In radiographic examinations, there were no statistically significant differences between groups I and III at week 6 or between groups II and IV at week 10. However, the histopathological evaluation scores were higher in the calcitonin group at the early stage (6 weeks) of fracture healing, which indicates a more mature callus formation (P < 0.05). The values for maximum torsional moment during fracture were higher in the calcitonin group in both stages of fracture healing (P < 0.01). Conclusions This study could have two important clinical implications. (1) Higher scores for the histopathological evaluation and a greater resistance to moment force applied at an early stage (week 6) of fracture healing imply that calcitonin intake might enable us to allow earlier mobilization and weight-bearing in clinical cases with rigid fixation. (2) At a late stage of fracture healing (week 10), the significantly better (P < 0.0001) results obtained in the biomechanical parameters used might imply that calcitonin intake could enable us to perform early implant removal, and strongly suggest that the strength and quality of the callus formation could be improved by administering calcitonin following a fracture.     

鲑鱼降钙素喷鼻剂临床试验分析

目的 观察国产鲑鱼降钙素喷鼻剂的有效性、安全性和顺应性。方法采用多中心,随机对照开放实验设计。选择年龄55-70岁,患骨质疏松伴骨痛的患者141例,随机分组。对照组(72例):肌注法给药,每日1次,50IU;研究组(69例):喷鼻法给药,每日每鼻孔1次.100IU。疗程12周。治疗前后分别用标尺评分方法测定疼痛程度、血ca、碱性磷酸酶(ALP)及空腹晨尿脱氧吡啶并啉与肌酐的比值(DPD/cr)。结果 治疗后两组患者的主客观疼痛评分与治疗前比较下降差异有显著性(P<0.001),两组之间比较差异无显著性(P>0.05)。两组之间主客观疼痛的总有效率比较差异无显著性(P>0.05),尿脱氧吡啶并啉与肌酐的比值均下降,差异有显著性(P<0.01)。血碱性磷酸酶均下降,差异有显著性(P<0.05),两组问比较差异无显著性(P>0.05)。不良反应发生率喷鼻剂组14.5％,注射剂组38.8％,两组间比较差异有显著性(P<0.001),但两组均无严重不良反应发生。结论 国产喷鼻鲑鱼降钙素与其注射剂一样能明显缓解骨质疏松性疼痛,抑制体内的破骨活动,其不良反应的发生率明显低于注射剂,有良好的顺应性。     

Neurogenic claudication and root claudication treated with calcitonin. A double-blind trial

Forty-two patients with either neurogenic claudication or unilateral root claudication were analyzed in a double-blind comparison of salmon calcitonin (SCT) and placebo, receiving either 100 IU SCT or 1 ml saline four times a week for 8 weeks. Five of 20 SCT and one of 22 placebo patients were classified as responders. There was no statistically significant difference between the treatment groups in the proportion of responders. Seven of eighteen of the placebo group who later received salmon calcitonin improved their walking distance. The authors have not established that this is an organic response.     

Effect of different doses of nasal salmon calcitonin on bone mass

Summary Forty postmenopausal women with a former Colles' fracture were enrolled in a 1-year study to determine the dose-effect relationship of nasal salmon calcitonin (SCT) on bone mass. They were randomized to receive either placebo, 50, 100, or 200 IU per day of SCT given as a nasal spray. The rate of change in the bone mineral content of the lumbar spine was 0.7, 0.2, 1.1, and 2.0 gHA per year, respectively, and the rate of change in the bone mineral content in the forearm was −0.4, −0.1, 0.0, and −0.1 AU per year, respectively. The rate of change in the bone mineral content of the lumbar spine in patients receiving 200 IU of SCT per day differed significantly from zero (P<0.01). Except for one patient, who experienced intolerable nausea, no systemic side effects were observed. Seven patients withdrew, two patients from nasal intolerance to the spray. These preliminary data suggest that SCT given by the nasal route has a positive and dose-dependent effect on spinal bone mass, but affects forearm bone mass only minimally.     

Bone loss during gonadotropin releasing hormone agonist treatment and use of nasal calcitonin

Gonadotropin releasing hormone (GnRH) agonists have shown to be effective in the treatment of several sex-hormone-dependent conditions. However, their use could be limited by the bone loss they induce. To evaluate the use of nasal salmon calcitonin (sCT) in preventing this bone loss, 40 patients with endometriosis were treated for 6 months with triptoreline (3.75 mg monthly) and calcium (1 g daily), and randomized in three groups — placebo, sCT 100 IU daily and sCT 200 IU daily — in a prospective double-masked study. Dual-energy X-ray absorptiometry and biochemical parameters were used to evaluate the benefit of the treatment. At baseline, there were no statistically significant differences between the groups. After 6 months, estradiol and biochemical markers of bone metabolism were at postmenopausal levels, with no difference between the groups. There was no difference in bone loss in the three groups, at all sites. Mean lumbar bone loss was 4.01±2.59% (mean±SD) in this population. In this study dosages of 100 IU and 200 IU daily of nasal sCT were insufficient to prevent bone loss during GnRH agonist treatment.     

An effective regimen of intranasal salmon calcitonin in early postmenopausal bone loss

Summary In order to devise a convenient and effective therapeutic regimen of intranasal salmon calcitonin (sCT) for the treatment of early postmenopausal bone loss, we studied the effects of a 1-year course of sCT nasal spray on vertebral mineral content (VMC), assessed by dual photon densitometry, and bone turnover in 21 early postmenopausal osteoporotic women. Subjects enrolled in the study had a value above the normal average of at least one index of bone turnover: whole body retention (WBR) of ^99mTc-methylenedichloro-bisphosphonate (^99mTc-MDP), serum bone gla protein (BGP), urinary hydroxyproline/creatinine excretion (HOP/Cr). After baseline evaluation, patients were randomized for treatment with either sCT (200 IU every other day) or plabebo. Treatment with sCT significantly increased VMC by 2.7±0.9% at 6 months, and 3.3±0.8% at 1 year, whereas a progressive decline was observed in the placebo group (-2.6±0.5%, and -3.5±0.5% after 6 and 12 months, respectively). These changes were associated with a progressive and significant reduction of all parameters of bone turnover in the sCT-treated patients, whereas no changes were detected in the control group during the study period. The differences between the two groups were significant after 1 year for VMC, BGP, and WBR (P<0.05, one-way analysis of variance). Thus, 200 IU intranasal sCT administered on alternate days is adequate to stop the fast bone loss occurring early after the menopause in women with high bone turnover rates. This therapeutical modality represents an important addition to the available pharmacologic spectrum for the prevention and treatment of postmenopausal osteoporosis.     

Nandrolone decanoate and intranasal calcitonin as therapy in established osteoporosis

This study used a randomized, 2 × 2 factorial design to evaluate over 2 years the effect of intranasal salmon calcitonin and intramuscular nandrolone decanoate on bone mass in elderly women with established osteoporosis. The study was double masked in relation to calcitonin and open in relation to nandrolone decanoate. One hundred and twenty-three women aged 60–88 years who had sustained a previous osteoporotic fracture, or had osteopenia, were recruited through an outpatient clinic. Women were assigned to one of four groups: (1) daily placebo nasal spray, (2) 400 IU intranasal calcitonin daily, (3) 20 intramuscular injections of 50 mg nandrolone decanoate (given as two courses of 10 injections) plus placebo nasal spray, or (4) 20 injections of 50 mg nandrolone decanoate plus 400 IU intranasal calcitonin daily. All subjects received 1000 mg calcium supplementation daily. Outcomes measured included changes in bone mineral density (BMD) at the lumbar spine, as measured by dual-energy quantitative computed tomography (DEQCT), in BMD of the proximal femur, and BMD and bone mineral content (BMC) of the lumbar spine and forearm, as measured by dual-energy X-ray absorptiometry (DXA). Significant positive changes from baseline in DXA BMC at the lumbar spine were observed over 2 years in the calcitonin group (5.0±1.9%, mean ± SE) and in the nandrolone deconate group (4.7±1.9%) but not in the placebo group (1.1±2.2%) or the combined therapy group (0.7±1.8%). Modelling based on the 2×2 factorial design revealed that nandrolone decanoate was associated with a 3.8±1.8% (p<0.05) gain in DXA BMD at the proximal femur. Modelling also revealed that calcitonin treatment was associated with a loss of 11.5±4.7% in DEQCT BMD at the lumbar spine and a loss of 3.7±1.8% in DXA BMD at the proximal femur (p<0.05). There was in vivo antagonism between the two medications of 7.9±3.9% for DXA BMC at the lumbar spine. Both agents caused positive changes from baseline in lumbar spine BMC. Nandrolone decanoate had beneficial effects on BMD at the proximal femur. This dose of intranasal calcitonin was associated with deleterious effects on trabecular BMD at the lumbar spine and total BMD at the proximal femur. There may be significant clinical antagonism between these two medications.     

The effects of calcitonin on acute bone loss after pertrochanteric fractures. A prospective, randomised trial

We investigated the effect of calcitonin in the prevention of acute bone loss after a pertrochanteric fracture and its ability to reduce the incidence of further fractures in the same patient. Fifty women aged between 70 and 80 years who had a pertrochanteric fracture of the hip were randomly allocated to group A (200 IU of nasal salmon calcitonin daily for three months) or group B (placebo). Patients in group A showed a significantly higher level of total alkaline phosphatase and osteocalcin on the 15th day after injury and a significantly higher level of bone alkaline phosphatase on the 90th day after surgery. These patients also had significantly lower levels of urinary C-telopeptide (CrossLaps) on the 15th, 45th and 90th days after injury and lower levels of urinary hydroxyproline on the 15th and 45th days after injury. Patients in group A had significantly higher bone mineral density at all recorded sites except the greater trochanter at three months and one year after operation. After a four-year period of clinical observation, five patients (24%) in group B sustained a new fracture, in four of whom (20%) it was of the contralateral hip. Our findings show that calcitonin reduces acute bone loss in patients with pertrochanteric fractures and may prevent the occurrence of new fractures of the contralateral hip in the elderly.