A randomized trial of nasal spray salmon calcitonin in postmenopausal women with established osteoporosis: the prevent recurrence of osteoporotic fractures study. PROOF Study Group

PURPOSE: We conducted a 5-year, double-blind, randomized, placebo-controlled study to determine whether salmon calcitonin nasal spray reduced the risk of new vertebral fractures in postmenopausal women with osteoporosis.SUBJECTS AND METHODS: A total of 1,255 postmenopausal women with established osteoporosis were randomly assigned to receive salmon calcitonin nasal spray (100, 200, or 400 IU) or placebo daily. All participants received elemental calcium (1,000 mg) and vitamin D (400 IU) daily. Vertebral fractures were assessed with lateral radiographs of the spine. The primary efficacy endpoint was the risk of new vertebral fractures in the salmon calcitonin nasal spray 200-IU group compared with the placebo group.RESULTS: During 5 years, 1,108 participants had at least one follow-up radiograph. A total of 783 women completed 3 years of treatment, and 511 completed 5 years. The 200-IU dose of salmon calcitonin nasal spray significantly reduced the risk of new vertebral fractures by 33% compared with placebo [200 IU: 51 of 287, placebo: 70 of 270, relative risk (RR) = 0.67, 95% confidence interval (CI): 0.47- to 0.97, P = 0.03]. In the 817 women with one to five prevalent vertebral fractures at enrollment, the risk was reduced by 36% (RR = 0.64, 95% CI: 0.43- to 0.96, P = 0.03). The reductions in vertebral fractures in the 100-IU (RR = 0.85, 95% CI: 0.60- to 1.21) and the 400-IU (RR = 0.84, 95% CI: 0.59- to 1.18) groups were not significantly different from placebo. Lumbar spine bone mineral density increased significantly from baseline (1% to 1. 5%, P<0.01) in all active treatment groups. Bone turnover was inhibited, as shown by suppression of serum type-I collagen cross-linked telopeptide (C-telopeptide) by 12% in the 200-IU group (P <0.01) and by 14% in the 400-IU group (P<0.01) as compared with placebo.CONCLUSION: Salmon calcitonin nasal spray at a dose of 200 IU daily significantly reduces the risk of new vertebral fractures in postmenopausal women with osteoporosis.     

Aging bone and osteoporosis: strategies for preventing fractures in the elderly

As the older population increases, the incidence of osteoporotic fractures is expected to dramatically rise during the next few decades. Older patients are much more susceptible to fracture at any given bone mineral density (BMD) than are younger patients because of various factors, including the quality of aging bone, which involves more than BMD. Suppression of increased bone turnover by antiresorptive therapies, even with only small changes in BMD, can reduce fracture risk, especially in the lumbar spine. Bisphosphonate treatment can significantly reduce vertebral and nonvertebral fractures, including hip fractures, even in the very elderly. Prospective analyses show that risedronate therapy consistently and significantly reduces the risk of new morphometric vertebral fractures after 1 year in postmenopausal women. Post hoc analyses report significant reductions in the risk of 1 new clinical vertebral fracture after 6 months of risedronate therapy and after 1 year of alendronate therapy. Oral raloxifene therapy and salmon calcitonin nasal spray therapy have been shown to reduce the risk of vertebral fracture after 3 and 5 years, respectively, and post hoc data show a significant reduction in clinical vertebral fracture risk at 1 year with raloxifene use. However, neither raloxifene therapy nor calcitonin therapy reduce the risk of nonvertebral and hip fractures at currently approved doses. Bisphosphonates have been shown to be safe and efficacious with 7 years' risedronate sodium and 10 years' alendronate sodium data published, and bisphosphonates reduce bone turnover and increase BMD to a greater degree than raloxifene and calcitonin, which may partly account for their nonvertebral and hip fracture reduction effect. Therefore, bisphosphonate therapy with risedronate or alendronate should be considered in patients with low BMD at the hip and in older patients with osteoporosis and osteopenia, particularly those with an existing fracture.     

Calcitonin.

Calcitonin is FDA approved for the treatment of postmenopausal osteoporosis but not for prevention. The preferred delivery system is nasal. Nasal calcitonin is safe and well tolerated. The vertebral fracture efficacy of calcitonin is less robust than the two approved bisphosphonates (alendronate and risedronate) but is similar to raloxifene in the treatment of established osteoporosis. Calcitonin has not been demonstrated to reduce hip fracture risk, although a post-hoc pooled analysis suggests potential effectiveness of nasal calcitonin. Calcitonin produces small increments in bone mass of the spine and modestly reduces bone turnover in women with osteoporosis. Calcitonin may have analgesic benefit in patients with acute painful vertebral fractures. Treatment with calcitonin should be considered for older women with osteoporosis with painful vertebral fractures and for women who fail to respond to or cannot tolerate bisphosphonates. Calcitonin may also be indicated for women who are unable to take bisphosphonates because of impaired renal function.     

Calcitonin

Calcitonin is a 32-amino acid polypeptide secreted by the parafollicular cells of the thyroid. Effects on bone include inhibition of osteoclasts, thus preventing bone resorption, as well as increased renal calcium excretion. Salmon calcitonin is often used therapeutically because it is more potent and has a longer duration of action compared with human calcitonin. Calcitonin also possesses analgesic properties. The mechanism of its analgesic effect is unknown but is thought to involve inhibition of prostaglandins and stimulation of β-endorphins. Most of the clinical data in postmenopausal osteoporosis involves the use of salmon calciton in nasal spray. Clinical trials have demonstrated a reduction in the risk of vertebral fractures and increased bone mineral density. Studies examining nonvertebral fractures have shown mixed results, some indicating a nonsignificant risk In general, calcitonin is inferior to bisphosphonates (BPs) in reducing fracture risk. Calcitonin is effective in the treatment of osteopathic pain. It has also been used in glucocorticoid-induced osteoporosis. Parenteral calcitonin is generally associated with more frequent side effects compared with intranasal calcitonin. Injectable administration can cause flushing, tingling, nausea, and injection site and allergic reactions. Side effects with intranasal use are usually limited to local effects (nasal congestion and irritation). Recent phase I trials with a new oral dosage form show promise in terms of efficacy and tolerability for treating patients who prefer this route of administration. This review of pertinent literature on calcitonin indicates that this remains a viable, though second-or third-line, agent for osteoporotic patients who refuse or cannot tolerate other treatments (e.g., BPs, raloxifene, and estrogen).     

Prevention for the older woman. A practical guide to prevention and treatment of osteoporosis

Osteoporosis causes approximately 1.5 million low-trauma fracture per year, and at all ages the incidence of fracture is higher in women than in men. Risk factors for osteoporotic fractures in postmenopausal women include family history of bone fracture, ethnicity, and weight < 127 pounds. Densitometry is used to diagnose osteoporosis and can be performed at intervals to monitor bone density during treatment. The older woman's diet should, in general, include 1,200 to 1,500 mg of calcium and 400 to 800 IU of vitamin D. Estrogens, bisphosphonates, selective estrogen receptor modulators, calcitonin, and exogenous parathyroid hormone are pharmacologic therapy options that can preserve and increase bone mass and reduce the risk of fracture.     

Osteoporosis in men

Osteoporosis is characterized by a reduction in bone density, associated with skeletal fragility and an increased risk of fracture after minimal trauma. Although osteoporosis is generally considered to be a condition affecting post-menopausal women, it is now clear that substantial bone loss occurs with advancing age in men, such that up to 20% of symptomatic vertebral fractures and 30% of hip fractures occur in men. This chapter highlights the incidence and prevalence of osteoporotic fractures in men and reviews the associated morbidity, excess mortality and health and social service expenditure. The determinants of peak bone mass and bone loss in men are discussed, as is the pathogenesis of osteoporosis and vertebral and hip fractures. The criteria for the diagnosis of osteoporosis in men are reviewed, together with the most appropriate investigations for secondary osteoporosis. The management of osteoporosis in men is also discussed, highlighting the most appropriate treatment options.     

Background for studies on the treatment of male osteoporosis: state of the art

Male osteoporosis represents an important, although long underestimated, public health problem. Both in men and in women aging is accompanied by continuous bone loss and by an exponential increase in the incidence of osteoporotic fracture, with a female to male incidence ratio of about 2 to 3 to 1 in the elderly for hip and vertebral fractures. Morbidity after osteoporotic fractures appears to be more serious and mortality more common in men than in women. To date, no single treatment has been proved to be effective and safe in published prospective studies. The present report, based on a systematic search of the literature on male osteoporosis, summarises the state of the art on the clinical consequences of male osteoporosis and its risk factors, in relation to the present state of knowledge about female osteoporosis. This constitutes the background for the design of rational clinical development strategies for therapeutic interventions in male osteoporosis. From this review of the literature it is apparent that notwithstanding the existing sex differences in pathophysiology of osteoporosis and the difference in age-specific incidence of osteoporotic fractures, there are also important similarities between osteoporosis in women and men. The higher incidence of fracture in women than in men results from quantitative differences in risk factors rather than from different risk factors. Even though there are sex differences in bone geometry, incidence of fracture seems to be similar in men and women for a same absolute areal bone mineral density. However, the lack of data on the changes in fracture rates in men resulting from pharmacological intervention, leading to changes in bone mineral density or bone turnover, remains the main limitation for extrapolation of established treatment outcomes from women to men.     

Osteoporosis in men

Osteoporosis is defined as "a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue with a consequent increase in bone fragility and susceptibility to fracture". Approximately 40-50% of women sustain osteoporotic fractures in their lifetime; as such, it is appropriate that studies initially focused upon females. Despite an increased recognition of osteoporotic fractures in men, there continues to be neglect of this disease in males. This ongoing neglect is inappropriate as 25-33% of men in some populations will sustain osteoporotic fractures in their lifetime. Testosterone plays an important role in male skeletal health. However, recent data suggest that estrogen may in fact be the dominant hormone regulating skeletal status in both men and women. BMD measurement may be utilized for osteoporosis diagnosis and to assist with fracture risk prediction in men prior to their sustaining a fracture. Recognizing this need, the International Society for Clinical Densitometry (ISCD) recommended and recently reaffirmed use of a BMD T-score of -2.5 or below be utilized to diagnose osteoporosis in men. Androgen therapy of hypogonadal men may be considered with the caveat that data do not exist to document that this treatment reduces fracture risk. At this time, the data is inadequate to support use of androgen treatment in eugonadal men with osteoporosis. Parathyroid hormone treatment does increase BMD; existing studies have not been of adequate size or duration to document fracture reduction efficacy. Bisphosphonate therapy increases BMD, reduces vertebral fracture risk and is considered the standard of care for osteoporotic men at this point in time.     

唑来膦酸与鲑鱼降钙素治疗PKP术后骨质疏松症的疗效比较

目的比较唑来膦酸与鲑鱼降钙素治疗经皮椎体后凸成形术(PKP)术后骨质疏松症的疗效。方法选择郑州大学第二附属医院102例骨质疏松性椎体压缩骨折患者,随机分为唑来膦酸组(n=52)和鲑鱼降钙素组(n=50)。唑来膦酸组接受PKP手术和唑来膦酸治疗,鲑鱼降钙素组接受PKP手术和鲑鱼降钙素治疗。比较两组患者术前及术后椎体骨密度(BMD)T评分、视觉模拟疼痛量表(VAS)评分、Oswestry功能障碍指数问卷表(ODI)评分、椎体高度、相邻椎体再骨折的发生率及相关并发症。结果两组患者术后椎体BMD T评分均比术前增高,且在术后6、12、24个月唑来膦酸组高于鲑鱼降钙素组,差异有统计学意义(P<0.05)。两组患者术后的VAS评分、ODI评分均比术前改善,且在治疗后1、3、6个月鲑鱼降钙素组优于唑来膦酸组,差异有统计学意义(P<0.05)。两组患者术后的椎体高度均较术前有明显恢复,差异有统计学意义(P<0.05),两组之间差异无统计学意义(P>0.05)。治疗期间,两组之间相邻椎体再骨折的发生率差异无统计学意义(P>0.05),其他相关并发症差异无统计学意义(P>0.05)。结论PKP术后的骨质疏松症患者应用唑来膦酸的抗骨质疏松治疗效果更好,鲑鱼降钙素的镇痛效果更好。     

Meta-analyses of therapies for postmenopausal osteoporosis. VI. Meta-analysis of calcitonin for the treatment of postmenopausal osteoporosis

OBJECTIVE: To review the effect of calcitonin on bone density and fractures in postmenopausal women. DATA SOURCE: We searched MEDLINE and EMBASE from 1966 to 2000 and examined citations of relevant articles and the proceedings of international osteoporosis meetings. We contacted osteoporosis investigators to identify additional studies and primary authors for unpublished data. STUDY SELECTION: We included 30 studies that randomized women to calcitonin or an alternative (placebo or calcium and/or vitamin D) and measured bone density or fracture incidence for at least 1 yr. DATA EXTRACTION: For each trial, three independent reviewers assessed the methodological quality and abstracted data. DATA SYNTHESIS: Calcitonin reduced the incidence of vertebral fractures, with a pooled relative risk (RR) of 0.46 [95% confidence interval (CI) 0.25-0.87, P = 0.02, n = 1404, 4 trials]. However, the RR from the one relatively large randomized controlled trial (RCT) was 0.79 (95% CI 0.62-1.00, P = 0.05, n = 1108). For nonvertebral fractures, the pooled RR was 0.52 (95% CI 0.22-1.23, P = 0.14, n = 1481, 3 trials). Once again, the single large trial showed a less impressive effect than the smaller trials (RR 0.80, 95% CI 0.59-1.09, P = 0.16, n = 1245). For bone density of the lumbar spine, the pooled weekly dose of 250 to 2800 IU per week resulted in significant increase in the weighted mean difference (WMD) of 3.74 (2.04-5.43, P < 0.01, n = 2260, 24 trials). The combined forearm showed a similar effect, with a WMD of 3.02 (95% CI 0.98-5.07, P < 0.01, n = 468, 9 trials). At the femoral neck, the pooled weighted mean difference showed a nonsignificant trend toward benefit, WMD 3.80 (95% CI -0.32-7.91, P = 0.07, 9 trials, n = 513). Methodologically weaker studies tended to show greater effects on bone density, and the lumbar spine results suggested the possibility of publication bias. CONCLUSIONS: Calcitonin likely increases bone density in postmenopausal women predominantly at the lumbar spine and forearm for weekly doses of greater than 250 IU, although the true effect may be smaller than the pooled estimate would suggest. Calcitonin likely reduces the risk of vertebral fracture; its effect on nonvertebral fracture remains uncertain.     

Predictors of osteoporosis and vertebral fractures in patients presenting with moderate-to-severe chronic obstructive lung disease

Bone mineral density (BMD) alone does not reliably predict osteoporotic fractures. The Fracture Risk Assessment Tool (FRAX) was developed to estimate the risk of fracture in the general population. This study was designed to identify predictors of osteoporosis and vertebral fractures in patients presenting with chronic obstructive pulmonary disease (COPD). We studied 85 patients (mean age = 75 years; 92% men) with moderate to very severe COPD. Osteoporosis and vertebral fractures were diagnosed with dual energy X-ray absorptiometric scan and vertebral X-rays, respectively. Patient characteristics, including age, gender, body mass index (BMI), and results of pulmonary function tests, chest computed tomography scan, blood and urinary biomarkers of bone turnover were recorded, and a FRAX score was calculated by a computer-based algorithm. Osteoporosis, defined as a T score < -2.5, found in 20 patients (24%), was associated with female gender, BMI, dyspnea scale, long-term oxygen therapy (LTOT), vital capacity (VC), emphysema score on computed tomography, measurements of serum and urinary biomarkers of bone turnover. Vertebral fractures, diagnosed in 29 patients (35%), were strongly correlated with age, LTOT, VC, and forced expiratory volume in 1 sec, treatment with oral corticosteroid or warfarin, and weakly associated with the presence of osteoporosis. There was no correlation between FRAX score and prevalence of vertebral fractures, suggesting that neither BMD alone nor FRAX score would predict the presence of vertebral fractures in COPD patients. A disease-specific algorithm to predict osteoporotic fractures is needed to improve the management of patients suffering from COPD.     

Effects of Bazedoxifene on Bone Mineral Density and Fracture in Post-Menopausal Osteoporotic Women: a Systematic Review and Meta-Analysis

Bazedoxifene (BZA) is a selective estrogen receptor modulator that reduces the risk of fracture and improves bone mineral density in post-menopausal women with osteoporosis. The aim of the present systematic review and meta-analysis was to investigate effects of BZA on bone mineral density (BMD) and fracture in post-menopausal osteoporotic women. We searched PubMed, Cochrane Central Register of Controlled Trials, Web of Sciences, Embase, and Scopus from until November 30, 2016. All randomized controlled trials that compared the effects of BZA on BMD and the incidence of vertebral and non-vertebral fractures in post-menopausal osteoporotic women compared with a control group were eligible for inclusion. Meta-analyses were conducted to calculate relative risk (RR) with 95% confidence interval (CI) for the association of BZA and vertebral and non-vertebral fractures compared with placebo. Nine randomized clinical trials met our inclusion criteria. Studies results showed that BZA significantly improves BMD, although we were not able to pool the results. Meta-analysis showed that the pooled effect of BZD on vertebral fracture was protective and significant (RR?=?0.63; 95% CI 0.48, 0.83; P?=?0.001). But pooled results did not show any association between taking BZD and the incidence of non-vertebral fracture (RR?=?0.97; 95% CI 0.83, 1.13; P?=?0.683). Evidence suggests that bazedoxifene is generally effective and safe in preventing bone loss and vertebral fracture in post-menopausal women with osteoporosis.     

Alendronate reduces the risk of multiple symptomatic fractures: results from the fracture intervention trial

OBJECTIVES: To evaluate the effect of alendronate on the occurrence rate of multiple svmptomatic fractures and on the risk of multiple symptomatic fractures (likelihood of having more than one fracture diagnosed because of the symptoms the fractures caused over the study period) among women with osteoporosis. DESIGN: Primary analysis of data from a randomized, placebo-controlled, double-blind trial. SETTING: Eleven community-based clinical research centers. PARTICIPANTS: Subset of women enrolled in the Fracture Intervention Trial: aged 55 to 81 and having at least one morphometric vertebral fracture at baseline (n=2,027) or having no vertebral fracture but meeting prevailing World Health Organization bone mineral density criteria for osteoporosis (T-score < or =2.5 at the femoral neck)(n = 1,631). INTERVENTION: All participants reporting calcium intake of 1,000 mg/day or less received a supplement of 500 mg calcium and 250 IU cholecalciferol. Participants were randomly assigned to placebo or alendronate sodium (5 mg/day for 2 years and 10 mg/day for the remainder of the study). Average total follow-up was 4.3 years. MEASUREMENTS: Symptomatic fractures were diagnosed by personal physicians and confirmed by review of radiological data by an expert committee blinded to treatment assignments. RESULTS: Eighty-six of 1,817 women receiving placebo experienced multiple symptomatic fractures during the follow-up period, compared with 51 of 1,841 receiving alendronate. Reduction of risk for multiple symptomatic fractures combined was 42% (relative risk (RR) = 0.58, 95% confidence interval (CI) = 0.41, 0.81) and for multiple symptomatic vertebral fractures was 84% (RR = 0.16,95% Cl = 0.05, 0.42). Cumulative incidence curves showed divergence after as little as 3 months of treatment, with a statistically significant (P = .044) reduction at 6 months for multiple symptomatic vertebral fractures. When all fractures over the follow-up period were included, the occurrence rates of all symptomatic fractures and symptomatic vertebral fractures were 34% and 63% lower, respectively, with alendronate than with placebo. These reductions were sustained during the follow-up period. All reductions in risk were consistent across predefined subgroups: age (<75 vs > or =75), morphometric vertebral fracture(present vs absent), prior clinical fracture since age 45 (yes vs no), and whether the subject had fallen in the 12 months before randomization. CONCLUSIONS: These data demonstrate that treatment with alendronate reduces the risk of multiple symptomatic fractures during a treatment period averaging 4.3 years. The reductions were consistent across prespecified sub-groups. This effect is evident early in treatment and is sustained.     

Salmon calcitonin nasal spray : An effective alternative to estrogen therapy in select postmenopausal women

The efficacy and safety of estrogen replacement therapy (ERT) and salmon calcitonin in the treatment of postmenopausal osteoporosis are reviewed with special consideration given to patients for whom ERT, the primary antiresorptive therapy for osteoporosis, is not indicated, tolerable, or is refused. The various formulations of estrogen and salmon calcitonin, for which the nasal spray formulation was recently approved for use in the United States, are reviewed in depth with reference to dose ranges, side effects, and convenience. Data regarding increases in bone mineral density (BMD) produced by each agent are presented. Specifically, the range of increases in BMD induced by ERT and salmon calcitonin are comparable. Given the substantial public health consequences of postmenopausal osteoporosis and osteoporotic fractures, the primary care physician is increasingly faced with the need to educated and recruit postmenopausal patients to appropriate therapy with the optimal agent for that particular patient. In the many patients who are unable or unwilling to accept, initiate, and comply with prescribed ERT, alternative therapeutic options are necessary Based on the established safety profile of salmon calcitonin, ease of administration, an uncomplicated dosing regimen, no reported drug interactions, and the lack of uterine bleeding associated with ERT or gastrointestinal adverse effects of other agents used to treat osteoporosis, salmon calcitonin nasal spray is an appropriate alternative approach for the treatment of postmenopausal bone loss.     

Predictors of Osteoporosis and Vertebral Fractures in Patients Presenting with Moderate-to-Severe Chronic Obstructive Lung Disease

Abstract

Bone mineral density (BMD) alone does not reliably predict osteoporotic fractures. The Fracture Risk Assessment Tool (FRAX) was developed to estimate the risk of fracture in the general population. This study was designed to identify predictors of osteoporosis and vertebral fractures in patients presenting with chronic obstructive pulmonary disease (COPD). We studied 85 patients (mean age = 75 years; 92% men) with moderate to very severe COPD. Osteoporosis and vertebral fractures were diagnosed with dual energy X-ray absorptiometric scan and vertebral X-rays, respectively. Patient characteristics, including age, gender, body mass index (BMI), and results of pulmonary function tests, chest computed tomography scan, blood and urinary biomarkers of bone turnover were recorded, and a FRAX score was calculated by a computer-based algorithm. Osteoporosis, defined as a T score < –2.5, found in 20 patients (24%), was associated with female gender, BMI, dyspnea scale, long-term oxygen therapy (LTOT), vital capacity (VC), emphysema score on computed tomography, measurements of serum and urinary biomarkers of bone turnover. Vertebral fractures, diagnosed in 29 patients (35%), were strongly correlated with age, LTOT, VC, and forced expiratory volume in 1 sec, treatment with oral corticosteroid or warfarin, and weakly associated with the presence of osteoporosis. There was no correlation between FRAX score and prevalence of vertebral fractures, suggesting that neither BMD alone nor FRAX score would predict the presence of vertebral fractures in COPD patients. A disease-specific algorithm to predict osteoporotic fractures is needed to improve the management of patients suffering from COPD.     

Treatment of postmenopausal osteoporosis

The aim of treatment of postmenopausal osteoporosis is to reduce the frequency of vertebral and non-vertebral fractures (especially at the hip), which are responsible for morbidity associated with the disease. Results of large placebo controlled trials have shown that alendronate, raloxifene, risedronate, the 1-34 fragment of parathyroid hormone, and nasal calcitonin, greatly reduce the risk of vertebral fractures. Furthermore, a large reduction of non-vertebral fractures has been shown for alendronate, risedronate, and the 1-34 fragment of parathyroid hormone. Calcium and vitamin D supplementation is not sufficient to treat individuals with osteoporosis but is useful, especially in elderly women in care homes. Hormone replacement therapy remains a valuable option for the prevention of osteoporosis in early postmenopausal women. Choice of treatment depends on age, the presence or absence of prevalent fractures, especially at the spine, and the degree of bone mineral density measured at the spine and hip. Non-pharmacological interventions include adequate calcium intake and diet, selected exercise programmes, reduction of other risk factors for osteoporotic fractures, and reduction of the risk of falls in elderly individuals.     

Osteoporotic vertebral fracture in clinical practice. 669 Patients diagnosed over a 10 year period.

OBJECTIVE: Few data are available on clinically diagnosed vertebral fracture. Information about osteoporotic vertebral fracture has mainly been obtained via inferences from epidemiological studies of vertebral deformity. We evaluated the characteristics of patients with osteoporotic vertebral fracture diagnosed in a rheumatology department over a 10 year period. METHODS: Patients with back pain and vertebral fracture diagnosed between January 1990 and December 1999 were recruited from our data base. Patients with high energy trauma, malignancies, and metabolic bone diseases other than osteoporosis were excluded. These variables were analyzed: sex, age at diagnosis, type of osteoporosis (primary vs secondary), number of fractures at diagnosis (single vs multiple), and percentage of admissions and length of stay. RESULTS: Of the 669 patients, 534 (80%) were women and 135 (20%) were men. Age at diagnosis ranged from 30 to 91 yrs, mean 67.1 +/- 9.1. Secondary osteoporosis was diagnosed in 177 (26%) patients and the frequency was significantly higher in men than women (55% vs 19%; p < 0.001); the most common associations for secondary osteoporosis were oral corticosteroids, chronic obstructive airway disease, and rheumatoid arthritis. At diagnosis, half of the patients presented with multiple fractures. One hundred twenty (18%) patients were admitted; length of stay ranged from 5 to 56 days, mean 15.9 +/- 7.7. The frequency of admissions was higher in men than women (27% vs 16%; p < 0.001), higher in patients with secondary osteoporosis than in those with primary osteoporosis (33% vs 12%; p < 0.001), and higher in patients with multiple fractures than in those with single fractures (27% vs 8%; p < 0.001). CONCLUSION: Characteristics of patients recruited from a clinical setting differ significantly from those of subjects included in the epidemiological studies. In a rheumatology practice, frequency of secondary osteoporosis, mainly associated with corticosteroid treatment, is notably high. Admission is by no means a rare event.     

The concept and treatment of osteoporosis

Osteoporosis is a dynamic process, thought to be caused by an uncoupling between osteoblast and osteoclast activity. Altered pulsatile secretion of growth hormone and parathyroid hormone (PTH) have been proposed as pathogenetic factors for this unbalanced coupling. The anatomical lesions are believed to be reversible until trabecular perforations develop, if fractures already occurred the anatomical defect is permanent. It is helpful to classify osteoporosis in stages of increasing severity depending on bone density and the presence of fractures. Theoretically, if the bone density is above the fracture threshold, then the only therapeutic goal is to maintain the bone mass. If instead the mineral density is below the threshold, an active therapy is needed with drugs that can possibly increase the skeletal mass. Osteoporosis with multiple fractures cannot be reversed. The authors propose a promising pharmacologic treatment for osteoporosis, based on the combination of human PTH-(1-38) and intranasal salmon calcitonin. If started in the early stages of the osteoporotic process, this regimen may restore the initial bone mass. In more advanced stages, only a correction of the metabolic defect is possible, but the irreversible vertebral deformities are not affected. On the basis of the results, cyclic therapy with human PTH-(1-38) and salmon calcitonin represents a good treatment choice for osteoporosis.     

Calcitonin treatment for osteoporosis

It has been reported that calcitonin reduces incidence of fracture in patients with osteoporosis. Calcitonin appears to have a small effect on bone density and a modest effect on the risk of fractures. Because of the analgesic effect, calcitonin is frequently used in osteoporotic patients with back pain.