A randomized trial of nasal spray salmon calcitonin in men with idiopathic osteoporosis: effects on bone mineral density and bone markers.

In a 12-month 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. Twenty-eight men with idiopathic osteoporosis aged 27-74 years (mean, 52.4 years) were randomized to receive either nasal SCT (200 IU) or a nasal placebo daily for a period of 1 year. All the men received a daily supplement of 0.5 g of calcium. The men who received SCT had a mean (+/-SEM) increase in BMD of 7.1 +/- 1.7% at the lumbar spine. In contrast, the men who received the placebo had an increase of 2.4 +/- 1.5% (p > 0.05) for the comparison with baseline. The increase in lumbar BMD in the calcitonin group was significantly greater than that in the placebo group (p < 0.05). There were no significant changes in the femoral neck, trochanter, or Ward's triangle relative to both baseline and placebo after 12 months. Treatment with nasal SCT resulted in a significantly pronounced suppression of bone resorption markers (urinary deoxypyridinoline [DPD], type I cross-linked N-telopeptide [NTX], and type I cross-linked C-telopeptide [CTX]) and to a lesser extent in bone formation markers (serum bone-specific alkaline phosphatase [BALP], osteocalcin [OC], serum C-terminal procollagen type I extension peptides [PICP], and serum N-termnal procollagen type I extension peptides [PINP]), whereas the placebo did not. Therapy was tolerated well and there were no treatment-related adverse events. We conclude that intranasal SCT (200 IU daily) is safe and effective in increasing lumbar BMD and reducing bone turnover in men with idiopathic osteoporosis.     

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。     

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.     

Effect of long-term calcitonin administration on steroid-induced osteoporosis after cardiac transplantation.

BACKGROUND: Early, rapid bone loss and fractures after cardiac transplantation are well-documented complications of steroid administration; therefore, we undertook this study on the effects of long-term calcitonin on steroid-induced osteoporosis. METHODS: Twenty-three heart transplant recipients on maintenance immunosuppression with cyclosporine, mycophenolate mofetil and prednisone were retrospectively studied. All patients received long-term prophylactic treatment with elemental calcium and vitamin D. Twelve (52.2%) patients also received long-term intranasal salmon calcitonin, whereas 11 (47.8%) received none. Bone mineral density and vertebral fractures were assessed at yearly intervals. Statistical comparisons between each group's bone loss during the first year and in the early (1 to 3 years), intermediate (4 to 6 years) and late (7+ years) post-transplantation periods were done. RESULTS: Lumbar spine bone loss was significant during the early follow-up period in the group not receiving calcitonin (0.744 +/- 0.114 g/cm(2) vs 0.978 +/- 0.094 g/cm(2) [p = 0.002]). The calcitonin group showed bone mineral density (BMD) levels within normal average values throughout the study period. BMD increased in the no-calcitonin group during the intermediate (4 to 6 years) and late (7+ years) follow-up periods, with values approaching normal average and no significant difference between the 2 groups (0.988 +/- 0.184 g/cm(2) vs 0.982 +/- 0.088 g/cm(2) [p = 0.944] and 0.89 +/- 0.09 g/cm(2) vs 1.048 +/- 0.239 g/cm(2) [p = 0.474], respectively). CONCLUSIONS: Prophylactic treatment with intranasal salmon calcitonin prevents rapid bone loss associated with high-dose steroids early after cardiac transplantation. Long-term administration does not seem warranted in re-establishing BMD.     

Teriparatide vs. calcitonin in the treatment of Asian postmenopausal women with established osteoporosis

This study compared the clinical efficacy, safety, and tolerability of daily subcutaneous injections of teriparatide and salmon calcitonin in the treatment of postmenopausal women with established osteoporosis in Taiwan. This 6-month, multicenter, randomized, controlled study enrolled 63 women with established osteoporosis. They were randomized to receive either teriparatide 20 μg or calcitonin 100 IU daily in an open-label fashion. Lumber spine, femoral neck, total hip bone mineral density (BMD), and biochemical markers of bone turnover were measured, and adverse events and tolerability were recorded. The results at 6 months showed that patients using teriparatide had larger mean increases in spinal BMD than those who used calcitonin (4.5% vs. 0.1%), but the BMD changes in these two groups at the femoral neck and the total hip were not significant. There were also larger mean increases in bone markers in the teriparatide group than in the calcitonin group (bone specific alkaline phosphatase 142% vs. 37%; osteocalcin 154% vs. 23%). We conclude that teriparatide has more positive effects on bone formation than salmon calcitonin, as shown by the larger increments of lumbar spine BMD and bone formation markers, and caused only mild adverse events and no significant change in liver, kidney or hematological parameters. Compared with the published global results, teriparatide seems to be equally effective and safe to use in this Asian population.     

Management of male osteoporosis

The objective of this study was to evaluate the efficacy of treatments for male osteoporosis selected based on the cause of the disease. METHODS: Sixty-three men with osteoporosis (T-score at the lumbar spine and/or femoral neck lower than -2.5) with a mean age of 53+/-11 years were studied. Forty-three (68.3%) had a history of fracturing without trauma (vertebral fractures, 37 patients, 57%). Treatments were as follows: idiopathic osteoporosis: calcium and vitamin D supplements (N = 10) or cyclical etidronate for 2 weeks followed by calcium and vitamin D supplements for 76 days (N = 29); moderate idiopathic phosphate diabetes: calcitriol and phosphate (N = 15); idiopathic hypercalciuria: hydrochlorothiazide (N = 6); and hypogonadism: testosterone (N = 3). RESULTS: Percentage change in bone mineral density (mean +/- standard error of the mean) after 18 months: calcium and vitamin D (lumbar spine: 0.6+/-2; femoral neck: 2.2+/-2.2); etidronate (lumbar spine: 3.6+/-1.4*; femoral neck: 0.5+/-1); calcitriol (lumbar spine: 7.0+/-3.5*; femoral neck: 0.0+/-1.4); thiazide diuretic (lumbar spine: 1+/-3.2; femoral neck: -2.3+/-3.7); and testosterone (lumbar spine: 6.8+/-6.4; femoral neck: 2.5+/-2.7), where *P < 0.05 versus baseline. Gastrointestinal side effects occurred in three patients (4.8%), including two on calcitriol-phosphate therapy and one on etidronate therapy. Of the six (9.5%) patients who experienced incident fractures, four were on etidronate, one on calcitriol-phosphate, and one on calcium-vitamin D. No patients discontinued their treatment because of side effects. CONCLUSION: Etidronate and the combination of calcitriol-phosphate produce a significant increase in lumbar spine bone mass in men with idiopathic osteoporosis or moderate idiopathic phosphate diabetes.     

Prevention of corticosteroid-induced osteoporosis with salmon calcitonin in sarcoid patients

Summary The aim of this study was to evaluate the usefulness of salmon calcitonin (sCT) in preventing corticosteroid-induced osteoporosis. Three groups of patients with sarcoidosis requiring long-term steroid therapy were followed for 2 years with yearly evaluations of vertebral cancellous mineral content (VCMC) by quantitative computed tomography. The first group (n=18) was treated with intramuscular (i.m.) sCT for the 2-year study period; the second (n=11) with i.m. sCT for the first 4 months and then with sCT nasal spray for 20 months; the third (n=35) received no sCT. We observed a large mineral loss in the third group but a very slight drop of VCMC in the two groups receiving sCT. SCT nasal spray was better tolerated and as effective as i.m. injections. The action of sCT appeared extremely useful, especially in the first year of steroid therapy when corticosteroid-induced mineral loss was maximal. We conclude that sCT nasal spray is a good tool for preventing corticosteroid-induced osteoporosis.     

Prevention of further bone mass loss by nasal calcitonin in patients on long term glucocorticoid therapy for asthma: a two year follow up study.

BACKGROUND--Injectable calcitonin is effective in reducing spinal bone loss in steroid-dependent asthma but side effects are frequent. In contrast, a nasal spray presentation has been shown to be effective and well tolerated in involutional osteoporosis. To test the efficacy of nasal calcitonin a two year prospective trial was conducted in 44 steroid-dependent asthmatic patients. METHODS--All patients received a calcium supplement of 1000 mg and were allocated randomly into two groups treated with either salmon calcitonin nasal spray (200 IU every other day, n = 22) or calcium alone (n = 22) for two years. All patients completed the first year of the study. Five patients in each group dropped out during the second year. In the calcitonin group one patient developed generalised pruritus and four lost steroid dependence, and in the calcium alone group five were no longer dependent on steroids. The efficacy of treatment was evaluated as follows: bone turnover assessed by biochemical markers, bone loss assessed by serial measurement of lumbar spine density, and rates of bone fractures. RESULTS--The bone mass in the calcitonin group increased by 2.7% in the first year while in the group receiving calcium alone it decreased by 2.8%; this difference was significant. Calcitonin prevented more bone loss during the second year while the calcium alone group continued losing bone mass (-7.8%). The difference between means was 0.1077 (95% CI 0.0381 to 0.1773). Three new fractures occurred in both groups. No changes in biochemical parameters were detected in either group. CONCLUSIONS--Calcitonin given intranasally increased spinal bone mass during the first year of treatment and maintained bone mass in a steady state during the second year. These results suggest that calcitonin may be a useful agent to prevent steroid-induced osteoporosis. However, the lack of effect of calcitonin on the rate of vertebral fractures does not permit its recommendation for routine use in preventing steroid-induced osteoporosis.     

鲑鱼降钙素在骨质疏松性椎体压缩骨折椎体后凸成形术后的应用

目的观察鲑鱼降钙素对骨质疏松性椎体压缩骨折行椎体后凸成形术后骨密度及腰背痛症状的改善情况。方法将行椎体后凸成形术后的骨质疏松性椎体压缩骨折患者79例分成两组,鲑鱼降钙素组44例,予以鲑鱼降钙素肌肉注射,术后每天1次100IU,连用3 d后,改为50 IU隔天1次,连用1个月,间歇1个月后再重复,共半年,同时加服维D2磷葡钙;对照组35例,单纯口服维D2磷葡钙,疗程半年。两组治疗前后均测定腰1～腰4椎体及股骨颈骨密度(BMD);并观察患者腰背痛的情况。结果:鲑鱼降钙素组有6例因肌注降钙素出现面部潮红和皮肤瘙痒等反应停止疗程,其余38例和对照组35例得到了随访。鲑鱼降钙素组腰椎及股骨颈BMD较治疗前明显升高(P<0.01),对照组各部位骨密度较治疗前无明显改变(P>0.01)。鲑鱼降钙素组没有病例再次出现腰背痛,而对照组在半年内有7例再次出现腰背痛,经腰椎MRI证实发生其他节段的椎体压缩骨折。结论:鲑鱼降钙素与钙剂联合治疗行椎体后凸成形术后的骨质疏松性椎体压缩骨折患者,可以提高患者的骨量,降低再骨折的风险。     

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.     

A randomized controlled trial of salmon calcitonin to prevent bone loss in corticosteroid-treated temporal arteritis and polymyalgia rheumatica

Patients treated with high-dose or long-term corticosteroids are at risk of accelerated osteoporosis and spontaneous vertebral and traumatic fractures. To assess the efficacy of salmon calcitonin in preventing corticosteroid-induced osteoporosis, 48 patients with newly diagnosed polymyalgia rheumatica, temporal arteritis, and other vasculitides were enrolled in a 2-year, double-blind, randomized, controlled trial. Patients were randomized to receive subcutaneous injections t.i.w. of either 100 IU of salmon calcitonin (25 patients) or placebo (23 patients). After 2 years, 19 and 21 patients, respectively, were evaluable. All patients also received supplemental calcium carbonate (1500 mg daily in divided doses) and vitamin D₃ (400 IU daily). Baseline and serial radiologic assessments included dual-energy X-ray absorptiometry (DXA) of the lumbar spine and hip, and spine radiographs to detect vertebral fractures. There were no significant baseline differences between the two study groups. The mean within-subject percentage change in DXA lumbar spine density in the two groups over the 2-year period of the study was only −0.1% (calcitonin plus calcium) versus −0.2% (placebo plus calcium) a nonsignificant difference despite the high mean cumulative corticosteroid doses of 5371 mg and 4680 mg, respectively (NS). The incidence of vertebral fracture was 12.5% (calcitonin plus calcium: 11%, versus placebo plus calcium: 14%, NS), with four fractures in the first year and one fracture in the second year. Higher cumulative corticosteroid dose was associated with a greater loss in bone density. In rheumatic disease patients starting high-dose, long-term corticosteroids, salmon calcitonin with calcium and vitamin D₃ provided no greater bone preservation than that observed with calcium and vitamin D₃ alone. Deceased. This report is dedicated to Patricia Schwartzberg, R.N., who gave life to the study, and without whom it could not have been accomplished.     

Salmon calcitonin in the prevention of bone loss at perimenopause

The objective of this study was to determine whether intranasal salmon calcitonin prevents physiological bone loss at perimenopause. A double-blind study of 120 perimenopausal women without present or past disease or medication that could affect bone metabolism were studied. The subjects were randomized in two groups and provided with nasal spray bottles containing either placebo (excipient only) or active compound (excipient plus 50 international units (IU) salmon calcitonin per dose). Subjects took one puff from the nasal spray in each nostril every morning. All subjects took one soluble tablet of calcium (1000 mg) per day. Serum biochemistry, dual-energy X-ray absorptiometry of lumbar spine and proximal femur, quantitative computed tomography of lumbar spine, and single photon attenuation of forearm were used to evaluate bone mineral density (BMD). There were no differences in demographic characteristics or hormone status at entry. No fractures were recorded during the study period. Serum calcium increased and serum dihydroxyvitamin D and osteocalcin decreased in both groups. There was no difference in biochemical parameters between the groups. The BMD of upper femur did not change during the study, but it was decreased in the lumbar spine in both groups. The mineral content of distal radius increased in both groups. In conclusion, nasal salmon calcitonin, 100 IU daily, has no protective effect on bone mass and does not modify bone metabolism at perimenopause.     

Comparison of calcitonin versus calcitonin + resistance exercise as prophylaxis for osteoporosis in heart transplant recipients

BACKGROUND: Rapid bone loss occurs early after heart transplantation. There is no standard therapeutic intervention to prevent osteoporosis in heart transplant recipients (HTR). The purpose of this study was to determine the effectiveness of a regimen combining the antiresorptive properties of nasal calcitonin with the osteogenic stimulus of resistance exercise. METHODS: Eighteen candidates for heart transplantation were randomly assigned either to a group that received calcitonin and participated in 6 months of resistance exercise (n=10) or to a group that received only calcitonin (n=8). Calcitonin therapy (200 IU daily for 8 months) was initiated 48 hr after transplantation. Resistance exercise was initiated 2 months after transplantation. Bone mineral density (BMD) of the total body, femur neck, and lumbar vertebra (L2-3) were assessed before, and at 2 and 8 months after transplantation. RESULTS: Total body and femur neck BMD did not decrease (P>or=0.05) below pretransplantation values at 2 months after transplantation in either group. BMD of the lumbar spine was significantly (P相似文献   

Randomised placebo-controlled trial on the effectiveness of nasal salmon calcitonin in the treatment of lumbar spinal stenosis

This is a double blind randomised controlled trial to assess the effectiveness of nasal salmon calcitonin in the treatment of lumbar spinal stenosis. The trial compared the outcome of salmon calcitonin nasal spray to placebo nasal spray in patients with MRI confirmed lumbar spinal stenosis. Lumbar spinal stenosis is one of the commonest conditions encountered by spine surgeons. It more frequently affects elderly patients and lumbar decompression has been used to treat the condition with variable success. Non operative measures have been investigated, but their success ranges from 15% to 43% in patients followed up for 1–5 years (Simotas in Clin Orthop 1(384):153–161, 2001). Salmon calcitonin injections have been investigated in previous trials and may have a treatment effect. Nasal salmon calcitonin has become available and if effective would have advantages over injections. Forty patients with symptoms of neurogenic claudication and MRI proven lumbar spinal stenosis were randomly assigned either nasal salmon calcitonin or placebo nasal spray to use for 4 weeks. This was followed by a ‘washout’ period of 6 weeks, and subsequent treatment with 6 weeks of nasal salmon calcitonin. Standard spine outcome measures including Oswestry disability index (ODI), low back outcome score, visual analogue score and shuttle walking test were administered at baseline, 4, 10 and 16 weeks. Twenty patients received nasal salmon calcitonin and twenty patients received placebo nasal spray. At 4 weeks post treatment there was no statistically significant difference in the outcome measures between the two groups. The change in ODI was a mean 1.3 points for the calcitonin group and 0.6 points for the placebo group (P = 0.51), the mean change in visual analogue score for leg pain was 10 mm in the calcitonin group and 0 mm in the placebo group (P = 0.51). There was no significant difference in walking distance between the two groups, with a mean improvement in walking distance of 21 m in the calcitonin group and 8 m in the placebo group (P = 0.78). At the end of the trial the ODI had improved by a mean of 3.7 points in the calcitonin group and 3.8 points in the placebo group (P = 0.44). This randomised placebo controlled trial has not shown any treatment effect in patients with lumbar spinal stenosis treated with nasal salmon calcitonin.     

Equivalence of Nasal Spray and Subcutaneous Formulations of Salmon Calcitonin

The aim of this study was to assess the efficacy and safety of nasal spray and subcutaneous formulations of salmon calcitonin. Two-hundred-four patients, 27 males and 177 females, aged 72 years on average, with a recent, painful, vertebral crush fracture were given either 50 IU/day of subcutaneous salmon calcitonin (SCSCT, 102 patients) or 200 IU/day of intranasal salmon calcitonin (INSCT, 102 patients) for 30 consecutive days, according to a double-blind, double-placebo design. The two-sided 95% confidence interval of the difference between the two formulations for the pain on D30 assessed by Huskisson's Visual Analogue Scale (VAS) [−5.3 mm, 7.9 mm] was included in the [−10 mm, 10 mm] reference interval. Equivalence of the two formulations, was demonstrated. At the end of the study, the 95% confidence intervals of VAS of both treatment groups were included in the [0 mm, 30 mm] interval, which is considered to be clinically pertinent. Relief was obtained in less than 10 days for more than 50% of patients. The urinary hydroxyproline/creatinine and calcium/creatinine ratios remained constant between D1 and D30 with both formulations. General safety was comparable between the two formulations. Local safety of INSCT was similar to that of its placebo. Received: 13 August 1996 / Accepted: 31 December 1996     

Therapy of Male Osteoporosis with Parathyroid Hormone

Definable causes of male osteoporosis account for only about 60% of the osteoporotic population. Those for whom no etiology is readily apparent are said to have primary or idiopathic male osteoporosis. In these individuals, histomorphometric studies indicate that this is a disorder that is more typically characterized by low turnover. Although antiresorptive agents such as alendronate have been shown to increase bone mass in men, the rationale for an anabolic agent that can stimulate bone formation is clear. The most attractive anabolic agent at this time is parathyroid hormone (PTH) administered in low dosage and intermittently. Such regimens in experimental animals have been associated with marked gains in bone mass. Slovik et al. showed that parathyroid hormone can increase vertebral bone mass in men with idiopathic osteoporosis. We have conducted the first controlled, randomized, double-blind study of PTH in men with idiopathic osteoporosis. Twenty-three men, 30-68 years old (50 +/- 1.9) with Z-scores less than -2.0 were assigned to a placebo (n = 13) or treatment (n = 10) arm. After 18 months, those who received PTH showed a 13.5 +/- 3% increase in bone mass, significantly greater than the placebo group whose bone density did not change. Femoral neck bone density increased significantly by 2.9 +/- 1.5%. The distal radius site did not change. During an open label extension for an additional 12 months, there was no further increase in bone density in the lumbar spine but the femoral neck continued to show gains. Markers of bone formation and resorption increased in the PTH arm reaching a peak between 9 and 12 months of therapy and declining thereafter. Parathyroid hormone was well tolerated. These results suggest that low-dose intermittent PTH may be an efficacious therapy for men with idiopathic 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.     

25 Years of salmon calcitonin: From synthesis to therapeutic use

Conclusion Although calcitonin has an established place in the treatment of Paget's disease of bone and certain disorders of calcium homeostasis, its most exciting clinical application is in the management of postmenopausal and senile osteoporosis. This disorder affects a vast number of women and, with the increasingly aging population, imposes a heavy burden on health care systems. Although other therapies for osteoporosis and other disorders of bone turnover (e.g., bisphosphonates, fluoride) are in use, many questions remain to be answered concerning their side effects and long-term safety, whereas salmon calcitonin is of proven safety. The introduction of salmon calcitonin nasal spray is a significant therapeutic advance, and the development of other noninjectable preparations will further increase the acceptability of calcitonin to patients and physicians alike.     

Total and regional bone mineral content and fracture rate in postmenopausal osteoporosis treated with salmon calcitonin: A prospective study

Seventy-two postmenopausal osteoporotic women having more than one nontraumatic vertebral crush fracture were studied. Thirty-six of them, aged 68.8±1.2 years (18±4 YSM-years since menopause), were treated with 100 IU/day of salmon calcitonin i.m. plus 500 mg of elemental calcium for 10 days each month. The remaining 36 patients, aged 69.6±1.4 years (19±3 YSM), were given only 500 mg of elemental calcium for 10 days each month. All patients underwent clinical and analytical evaluation every 3 months. Radiological evaluation, assessment of vertebral deformities, and metacarpal radiogrammetry were done every 6 months. Densitometric measurements of total and regional bone mass were made every 12 months. At 24 months, the calcitonin group showed a 60% reduction in the number of new fractures and the group receiving only calcium had a 45% increase (P<0.001). The incidence of vertebral fractures was 0.07 per patient-year in the group treated with calcitonin and 0.45 per patient-year in the group treated with calcium (P<0.001). At 2 years, the calcitonin group showed a 12% increase in cortical bone mass on metacarpal radiogrammetry, a 16% increase in the axial skeleton on trunk densitometry, a 3.5% increase in total body bone mineral content, a 30.7% increase in pelvic bone mineral content, and a 6.2% increase in arm bone mineral content (all P<0.001). In the group treated with calcium alone there was a loss of bone mass in every region. These findings suggest that salmon calcitonin is effective in the treatment of osteoporosis and show that it acts on cortical and trabecular bone.     

Sympathetic nervous system as transmitter of mechanical loading in bone

Sympathetic innervation has been demonstrated in bone. Adrenergic stimulation is one of the transmitters of bone loss by uncoupling between decreased bone formation and increased bone resorption. OBJECTIVE: By using a non-specific antagonist of -adrenergic pathway (propranolol per os), we hypothesized that we could rescue the uncoupling induced mechanical unloading bone loss in the rat model of tail-suspension. MATERIALS AND METHODS: Twenty-two female Wistar rats, 12 week-old, have been divided into three groups: eight tail-suspended rats (SR), six tail-suspended rats treated by propranolol (SRP) and eight non-suspended rats (NSR) during 30 days. Bone mineral density (BMD, g/cm2) has been measured by DXA (Hologic QDR-4500A) at D0 and D30 of the study, in the distal femoral metaphysis (DFM), the femoral diaphysis (FD), the whole body (WB, g) and body composition. RESULTS: Between D0 and D30, in DFM a significant variation in BMD is observed between NSR and SR (% BMD change: NSR +15.6 +/- 3.1% vs SR -1.0 +/- 1.4%, P < 0.0001) and BMD rescue in SRP group (% BMD change SRP +5.3 +/- 1.5% vs SR -1.0 +/- 1.4%, P = 0.03). In FD, gain of BMD is significant in NSR compared to SR (+17.5 +/- 1.5% vs +8.2 +/- 2.8%, P = 0.007) and to SRP (+17.5 +/- 1.5% vs +10.1 +/- 2.4%, P = 0.046). Gain in SRP group is not significant compared to SR group (P = 0.6). In WB, SRP gain more BMD than NSR (+14.0 +/- 1.8% vs +5.4 +/- 0.7%, P = 0.0002) and than SR (+14.0 +/- 1.8% vs +7.8 +/- 1.4%, P = 0.0043). There is no difference between NSR and SR groups (P = 0.19). CONCLUSION: We demonstrate that -adrenergic pathway of sympathetic nervous system is a major transmitter pathway of mechanical loading in rat bone. A specific study is necessary to analyse a possible systemic effect of propranolol in rat bone. Propranolol could be used to prevent the induced mechanical unloading bone loss as weightlessness