Biochemical response to combination of disodium etidronate with calcitonin in Paget's disease

The biochemical responses to salmon calcitonin (SCT: 100 MRC units thrice weekly) and disodium etidronate (EHDP: 400 mg daily) alone and in combination for 6 months were compared in 72 patients with symptomatic Paget's disease of bone unresponsive to simple analgesic agents. SCT produced a 53% reduction in alkaline phosphatase (AP) and a 38% reduction in 24 h urinary hydroxyproline excretion (HYPRO). The response to EHDP was not significantly different--56% reduction in AP and 48% reduction in HYPRO. Their use in combination produced a significantly greater reduction of 71% in AP (P less than 0.002) and 69% reduction in HYPRO (P less than 0.0001). In those that remained symptomatic with increased disease activity treatment for longer than 6 months had a unpredictable effect and normal bone turnover was rarely achieved. Once therapy was withdrawn AP and HYPRO increased rapidly in those given SCT alone, returning to initial levels within 6 months. More sustained control of disease activity was achieved in those given EHDP either alone or with SCT but the combination retained the advantage obtained during treatment. Combinations of SCT + EHDP may find a place in the treatment of very active Paget's disease.     

Intranasal salmon calcitonin treatment of Paget's disease of bone. Results in nine patients

To ascertain whether salmon calcitonin, usually given parenterally, could control active Paget's disease when given by nasal insufflation, intranasal salmon calcitonin (INSC) was given to nine men with Paget's disease whose serum alkaline phosphatase (SAP) levels were elevated twofold or more. Treatment with 100, 200, and 400 IU/day for three to nine months was well tolerated. SAP fell 31%-51% in three patients and more than 20% in two others. Three of four men who had previously received salmon calcitonin (SC) by injection had no response of SAP but had a rise in antibodies to SC. INSC is mildly effective and more convenient than parenteral SC, but dose response and efficacy relative to parenteral SC have not been established, thereby raising questions of cost-effectiveness.     

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.     

Comparison of the acute effect of the intranasal and intramuscular administration of salmon calcitonin in Paget's disease

Summary On 7 patients with mild-to-moderately active Paget's disease, 200 IU of salmon calcitonin (SCT) nasal spray (NS), induced a significant decrease of the total urinary hydroxyproline excretion (THP) during the 8–16 hour and the 0–24 hour (P<0.05) periods after treatment as compared to control day. However, the administration of 100 IU of SCT intramuscularly (i.m.) caused a significantly greater effect than 200 IU-NS during the second 8 hour period after its administration (P<0.01) and on the over-all 24 hour effect (P<0.05). On 3 patients with severe Paget's disease, SCT-NS was essentially ineffective whereas the injection of SCT induced a marked diminution of the THP excretion.     

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.     

The effect of rectal and nasal administration of salmon calcitonin in normal subjects

Summary In order to ascertain the blood levels and the biologic responses obtained after administration of two noninjectable forms of salmon calcitonin (SCT) (i.e., a nasal spray and a suppository), two doses of 200 IU each were administered at 3 hour intervals nasally to 8 normal subjects, and rectally to 9 normal subjects. Five untreated subjects served as controls. All were given a standardized diet for 2 days before the test. Plasma salmoncalcitonin, ionized calcium, phosphate, sodium, proteins, creatinine, and alkaline phosphatase were measured repeatedly after the administration of the drug. Modifications in fractionated urinary calcium, phosphate, sodium, and creatinine excretions (and hydroxyproline for the 8 subjects treated by the nasal spray) were compared with the values measured on the previous day. Plasma concentrations of SCT were found to increase sharply with both routes of administration, the peaks being high and short after rectal administration, low but more sustained after nasal application. Despite these differences, almost similar biologic effects could be demonstrated: transient hypocalcemia, increased calciuria, phosphaturia, and natriuria. Urinary hydroxyproline excretion decreased. Plasma sodium did not increase, whereas it did in the controls. In conclusion, nasal sprays and suppositories of SCT appear to exert the known biologic effects of SCT, and might be favored for long-term treatment in diseases representing indications for calcitonin therapy.     

Acute effects of nasal salmon calcitonin on calcium and bone metabolism

Summary Effects of a single dose of 200 IU of nasal salmon calcitonin (SCT) on calcium metabolism and biochemical markers of bone turnover were investigated in 12 healthy male volunteers in a randomized, placebo-controlled, crossover design. The nasal spray was given in the morning, and subsequently blood and urine samples were collected for 26 hours. There was a significant decrease in serum ionized calcium with a nadir 4 hours after administration of nasal SCT accompanied by a significant increase in serum parathyroid hormone (P = 0.01) and serum calcitriol (P = 0.04). Nasal SCT did not reduce urinary hydroxyproline/creatinine. Urinary deoxypyridinoline/creatinine was lowered significantly 2 hours after administration of nasal SCT and throughout the first 24 hours, but remained unchanged for the last 2 hours. On a 24-hour basis, urinary deoxypyridinoline/creatinine decreased from 14.1 (3.5) nmol/mmol to 11.7 (3.2) nmol/mmol after nasal SCT (P = 0.04). Nasal SCT did not change the serum levels of alkaline phosphatase, osteocalcin, and the carboxyterminal propeptide of type 1 procollagen. The results indicate that nasal SCT given as a single dose provokes a modest decrease in bone resorption lasting several hours, but leaves bone formation unaffected.     

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.     

Clinical efficacy of salmon calcitonin in Paget's disease of bone

Clinical interest in salmon calcitonin began in 1972 when this peptide was shown to be effective in the treatment of Paget's disease. Salmon calcitonin is more potent than porcine calcitonin, with human calcitonin intermediate in potency. Salmon calcitonin is a highly effective therapeutic agent in the treatment of Paget's disease. During chronic treatment with salmon calcitonin, alkaline phosphatase activity and urinary hydroxyproline excretion decrease on an average of 50% in patients with Paget's disease. Patients may experience a variety of clinical benefits during chronic treatment, including relief of bone pain, a reversal of neurological deficits, stabilization or improvement of hearing loss, and improvement of vascularity of bone. Radiologic healing of osteolytic lesions is particularly striking with calcitonin treatment. Paget's disease patients prefer treatment with salmon calcitonin administered by means of a nasal spray. Salmon calcitonin has an excellent safety profile and produces mild side effects in a small percentage of patients. The most common side effects associated with salmon calcitonin administration are nausea and facial flushing. It is unusual to observe severe side effects. In about 20% of patients, production of antibodies may neutralize the effects of the exogenously administered calcitonin; these patients respond to human calcitonin. At this time salmon calcitonin should still be considered a valuable therapeutic agent in the treatment of Paget's disease, particularly in patients with osteolytic lesions.     

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。     

Comparison of the acute biological action of injectable salmon calcitonin and an injectable and oral calcitonin analogue

Summary In most countries, calcitonin is available in the form of injections, and less frequently as an intranasal spray. An oral route of administration should improve compliance. In a preliminary feasibility study, we have compared the acute biological action of injectable salmon calcitonin (50 IU), with the injectable calcitonin analogue ASC 710 (0.2 mg) and oral ASC 710 (20 mg) in 6 patients suffering from active Paget's disease of bone. The intensity and duration of the biological response were not significantly different in the 3 modes of therapy. In conclusion, the oral calcitonin analogue ASC 710 possesses an antiresorbing activity in Paget's disease comparable to that of an injection of salmon calcitonin which demonstrates that it can cross the intestinal barrier.     

New modes of administration of salmon calcitonin in Paget's disease. Nasal spray and suppository

In volunteers the activity of various doses of a nasal spray and of a suppository of salmon calcitonin was compared to a placebo and to the parenteral route of administration. Both new modes of administration were found to be active on the kidney (and the suppository was found to affect bone turnover as well). The parenteral route proved more effective, but the nasal and/or rectal routes were devoid of systemic side effects and had minimal local intolerance. The nasal spray was used at 200 units daily in 15 patients with Paget's disease, and at 400 units daily in another nine patients, both trials lasting one year. The two regimens proved active on the parameters of bone turnover and the higher dose was more effective than the lower one. Similarly, a 300 unit suppository was given to another 12 patients. This trial is still being completed at this time. At the third month of therapy, the parameters of bone turnover were significantly depressed. Both new modes of therapy were able to improve the focal bone balance of the osteolytic lesions monitored on sequential roentgenograms. Systemic side effects were absent and local side effects were minimal. Only one patient interrupted the nasal spray therapy, and no one interrupted the suppository therapy.     

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.     

Prevention of osteoporosis with nasal salmon calcitonin: Effect of anti-salmon calcitonin antibody formation

The amino acid sequence of salmon calcitonin (SCT) differs considerably from that of the human hormone and specific antibodies (Ab) develop in a significant proportion of patients after parenteral or nasal administration of SCT. Controversy remains regarding the functional importance of these Ab. We report on the development of specific anti-SCT Ab in a population of postmenopausal women receiving nasal SCT for prevention of postmenopausal bone loss, and compare the effects of nasal SCT in women with or without Ab. Thirty-nine per cent of women developed Ab after 6 months of treatment with SCT, 52% after 12 months, and 61% after 18 and 24 months. After 24 months the AB titre was 3.47–17.7×10^–9 M/l (mean ±SD: 13.3±3.1×10^–9 M/l). No significant differences appeared between the changes in lumbar bone mineral density (BMD) measured in the whole population (n=44) (mean±SD: + 1.06±3.9%), the patients without Ab (n=17) (+0.05±3.7%) or in those with Ab (n=27) (+1.7±4.6%). During the same period, a control population randomly assigned to a 500 mg/day calcium intake showed a significant loss of lumbar BMD (–4.57±4.9%) (p<0.01). In conclusion, in healthy postmenopausal women nasal SCT seems to maintain the same preventive effect against bone loss whether or not Ab are present.     

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.     

74例老年骨质疏松患者应用鲑鱼降钙素联合阿仑膦酸钠治疗的疗效观察

目的　评估联合应用鲑鱼降钙素与阿仑膦酸钠治疗缓解老年性骨质疏松症患者骨关节疼痛及血清骨钙素(BGP)、降钙素(CT)及骨密度(BMD)水平的变化。方法 联合应用鲑鱼降钙素和阿仑膦酸钠治疗本院收治的74例老年性骨质疏松症患者,给予鲑鱼降钙素50IU肌肉注射,隔日1次,连续使用15次后改为口服阿仑膦酸钠1粒/周,共经6个月治疗,采用数字模拟评分法(VAS)比较治疗前、后全身骨关节疼痛程度,治疗前、后骨钙素、降钙素及第2～第4腰椎(L2-4 )、股骨颈、Ward区骨密度水平的变化,并进行统计学分析。结果 鲑鱼降钙素联合阿仑膦酸钠治疗老年性骨质疏松症患者6个月后,对缓解骨关节疼痛症状疗效良好,治疗前与治疗后比较差异显著(P<0.01);治疗前后骨密度、血清骨钙素和降钙素水平均有显著差异（P<0.05）。结论 鲑鱼降钙素联合阿仑膦酸钠治疗老年性骨质疏松症使血清降钙素的水平明显升高,骨钙素水平明显降低,能显著减轻患者骨关节疼痛,改善症状,并增加骨密度,对老年性骨质疏松症有明显的疗效。     

Future horizons for calcitonin: A U.S. perspective

Injectable salmon calcitonin has been in use in the United States for more than a decade for the treatment of patients with postmenopausal osteoporosis, Paget's disease, and hypercalcemia, Sandoz Pharmaceuticals Corp. is currently in the process of developing a nasal formulation of salmon calcitonin. Studies are in progress to compare the efficacy of this nasal formulation with that of the injectable hormone in preventing bone loss and restoring bone, as well as in reducing pain associated with bone diseases. The rationale for development of a nasal formulation is to attempt to reduce the incidence of systemic side effects, inconvenience, and resulting noncompliance associated with the injectable product. In studies to date, the nasal form of calcitonin has been well tolerated by most subjects and was not notably associated with nasal irritation. The tolerability seen within the context of clinical trials suggests that a nasal formulation might be well accepted, even among asymptomatic osteoporotic patients. Asymptomatic patients with secondary osteoporosis due to steroid administration or solid organ transplantation may also be studied as possible candidates for the prophylactic use of this drug. Additional future research includes the development of an oral calcitonin agent.     

Severe hypocalcemia following bisphosphonate treatment in a patient with Paget's disease of bone

Bisphosphonate therapy is a common and effective treatment for Paget's disease of bone, osteoporosis, hypercalcemia of malignancy and cancer metastatic to bone. Clinically significant hypocalcemia has not been reported in patients with Paget's disease of bone and normal parathyroid function treated with an aminobisphosphonate. We treated a 52-year-old woman with polyostotic Paget's disease of bone (serum alkaline phosphatase level-1971 IU/L [normal 31-110 IU/L]), who had not previously received bisphosphonates, with daily oral 30 mg risedronate, oral 1000 mg elemental calcium and oral 400 IU cholecalciferol. After 10 days of treatment, she developed severe hypocalcemia (5.4 mg/dL [normal 8.7-10.2 mg/dL]), requiring hospitalization and support with 5 days of intravenous calcium gluconate. On the day risedronate treatment began, her PTH was low normal at 14 pg/mL (normal 12-72 pg/mL), consistent with a relatively suppressed PTH axis due to high bone turnover. Her vitamin D level was within normal limits (serum 25(OH)D 19 ng/mL [normal 8-38 ng/mL]), although possibly not optimally repleted. We hypothesize that this case represents an example of hungry bone syndrome in a patient with extensive Paget's disease of bone who received risedronate, causing acute suppression of bone resorption while elevated bone formation rates continued. In the year following her recovery, the patient was successfully treated with slowly titrated anti-resorptive therapy (subcutaneous calcitonin followed by titrated doses of risedronate), and is now clinically well. Physicians should be aware of the potential for hypocalcemia when patients with polyostotic Paget's disease and markedly elevated indicators of bone remodeling are initiated on powerful anti-resorptive therapy.     

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 intranasal salmon calcitonin therapy on bone mineral density in idiopathic male osteoporosis without vertebral fractures--an open label study

The aim of this study was to examine the effect of intranasal salmon calcitonin therapy on bone mineral density (BMD) in idiopathic male osteoporosis without vertebral fractures. We conducted a randomized, open label, controlled trial in 71 male patients (mean age 59 +/- 6 years) suffering from idiopathic osteoporosis (femoral neck T-score < -2.5) without vertebral deformity. Patients in the control group (n = 31) received 400 IU Vitamin D + 1000 mg elemental calcium daily while the treatment group (n = 40) received 400 IU Vitamin D, 1000 mg elemental calcium plus 200 IU calcitonin nasal spray daily during alternate months. The study period was 18 months. Compared to controls, nasal calcitonin was associated with significant increases in bone mineral density at the lumbar spine (+3.5 +/- (-4.3%) vs. +0.83 +/- 6.4%, P = 0.04) and the femoral neck (+3.2 +/- 3.9% vs. +0.68 +/- 5.7%, P = 0.004). No significant difference was observed at the radius between the treatment groups (+1.4 +/- 8.8% vs. +1.4 +/- 10.9%, P = 0.98). Treatment was well tolerated with no premature discontinuations or significant side effects compared to the control group. We conclude that 200 IU salmon calcitonin nasal spray used daily, intermittently proved to be an effective and safe therapy in male idiopathic osteoporosis.