Risedronate: a new oral bisphosphonate

BACKGROUND: Bisphosphonates have been effective in the treatment of osteoporosis and Paget's disease of bone. Risedronate, the newest oral bisphosphonate, is approved by the US Food and Drug Administration for the prevention and treatment of postmenopausal osteoporosis and glucocorticoid-induced osteoporosis and the treatment of Paget's disease of bone. OBJECTIVE: This article reviews current studies of risedronate in osteoporosis and Paget's disease of bone and, to the extent possible, compares risedronate with other bisphosphonates and other therapies. Information on the pharmacokinetics and adverse effects of risedronate, and the drug's use in other disorders, is also reviewed. METHODS: Clinical studies and review articles concerning the use of risedronate published in the English-language literature from 1966 through October 2000 were identified through searches of MEDLINE, PREMEDLINE, and International Pharmaceutical Abstracts using the search terms risedronate and NE 58095. Recent clinical studies, review articles, and consensus statements regarding the use of other bisphosphonates were identified through searches of the same databases for this period using the search terms bisphosphonates, alendronate, osteoporosis, and Paget's disease of bone. RESULTS: The use of risedronate therapy in patients with postmenopausal osteoporosis has been shown to increase bone mineral density (BMD) and decrease the incidence of fractures compared with placebo. In glucocorticoid-induced osteoporosis, risedronate has been shown to increase BMD without having a consistently significant effect on the risk of fractures. Although there are no direct comparisons between bisphosphonates in glucocorticoid-induced osteoporosis, risedronate appears to be less effective than alendronate and more effective than etidronate in terms of effects on BMD and/or fracture risk. In Paget's disease of bone, risedronate has been reported to be more effective than etidronate in decreasing serum alkaline phosphatase levels and bone pain. Finally, risedronate has been associated with a lower incidence of gastric ulcers than alendronate. CONCLUSIONS: In terms of efficacy in the prevention and treatment of osteoporosis and the treatment of Paget's disease of bone, risedronate is comparable to alendronate, the other orally available bisphosphonate. It appears to have better gastrointestinal tolerability than alendronate and may be preferred for patients in whom this is a concern. However, direct comparative and pharmacoeconomic studies are necessary to determine risedronate's relative place in the therapy of osteoporosis and Paget's disease of bone.     

Osteoporosis associated with rheumatoid arthritis

Patients with rheumatoid arthritis(RA) develop both generalized and periarticular osteoporosis. Both of them are believed to be associated with increased production of inflammatory cytokines(TNF alpha, IL-1 beta, IL-6) and increased formation and activation of osteoclasts. Whether glucocorticoids work positively or negatively on generalized/periarticular osteoporosis is still controversial. RANKL has been shown to be expressed on T cells and fibroblast-like cells in the synovium, thus 'RANKL-RANK' pathway is likely to play an important role in periarticular osteoporosis and bone erosion as well as generalized osteoporosis. Among various therapies for generalized/periarticular osteoporosis in RA, anti-cytokine antibodies/antagonists and osteoclast inhibitors including bisphosphonates are promising.     

中国中老年人骨质疏松症患病率的Meta分析

背景：中国很多学者对不同地方做过骨质疏松症的流行病学调查,但大样本多中心的随机抽样调查仍相对缺乏,目前的文献仍不能很好地全面描述国内骨质疏松症的总体流行病学趋势。 目的：对中国中老年人骨质疏松流行病学的资料进行汇总,综合分析骨质疏松症流行状况。 方法：采用Meta分析对中国2000至2013年发表的有关中老年人骨质疏松流行病学的文献进行归纳和统计学分析。提取资料中40岁以上人群骨质疏松症的患病率,并以10岁为一个年龄组段分别进行汇总,采用stata12.0软件进行分析。 结果与结论：共对32篇文献进行分析,提取40岁以上人群样本总量58254例,其中男26844例,女31410例。中国40岁以上人群骨质疏松症总体患病率13.2%,其中男性11.8%,女性14.2%,差异有显著性意义（P 〈0.05）。随年龄增加,男性及女性的骨质疏松症患病率均逐渐增加,男性增长则相对平缓,女性进入50岁后,患病率明显增高。从Lumbar,Neck,Troch,Ward＇s 4个检测部位来看骨质疏松症患病率在北方地区以 Lumbar 检出率最高,可能与北方地区重体力活动相对南方地区多,加速了腰椎的退变有关。南方地区以Ward＇s检出率最高,有待进一步研究。男性人群中近5年的患病率较5年前明显增加,女性人群中近5年的患病率较5年前明显减小。提示中国为骨质疏松高发地区,开展骨质疏松宣传和相关疾病的防治意义重大。     

Effects of an osteoporosis educational programme for men

AIM: This paper reports an evaluation of the effects on knowledge, health beliefs and preventive behaviours of an osteoporosis educational programme for men. BACKGROUND: Osteoporosis is an increasing global health concern, and educational programmes have been identified as a crucial strategy in its prevention. However, the effectiveness of osteoporosis educational programmes has mainly been evaluated in women. METHODS: A randomized controlled trial was carried out to identify the effects of an osteoporosis educational programme for men. The study was conducted between September 2004 to February 2005, and 128 Hong Kong Chinese men were randomly assigned to an intervention or control group, with 64 in each group. The intervention group attended an osteoporosis educational programme. All participants completed pre- and post-test self-administered questionnaires: Osteoporosis Knowledge Test, Osteoporosis Health Belief Scale and Osteoporosis Self-Efficacy Scale. RESULTS: The intervention group showed a statistically significant increase in both knowledge (P < 0.0005) and health beliefs (P = 0.007) about osteoporosis and preventive behaviours in comparison with the control group. However, the difference in self-efficacy between the two groups was not statistically significant (P = 0.154). CONCLUSIONS: An osteoporosis educational programme can increase men's knowledge levels and change their health beliefs about osteoporosis and preventive behaviours. This approach should be more widely used in nursing practice to promoting the adoption of osteoporosis prevention behaviours in men.     

Pharmacologic prevention of osteoporotic fractures

Osteoporosis is characterized by low bone mineral density and a deterioration in the microarchitecture of bone that increases its susceptibility to fracture. The World Health Organization defines osteoporosis as a bone mineral density that is 2.5 standard deviations or more below the reference mean for healthy, young white women. The prevalence of osteoporosis in black women is one half that in white and Hispanic women. In white women 50 years and older, the risk of osteoporotic fracture is nearly 40 percent over their remaining lifetime. Of the drugs that have been approved for the prevention or treatment of osteoporosis, the bisphosphonates (risedronate and alendronate) are most effective in reducing the risk of vertebral and nonvertebral fractures. Risedronate has been shown to reduce fracture risk within one year in postmenopausal women with osteoporosis and in patients with glucocorticoid-induced osteoporosis. Hormone therapy reduces fracture risk, but the benefits may not outweigh the reported risks. Teriparatide, a recombinant human parathyroid hormone, reduces the risk of new fractures and is indicated for use in patients with severe osteoporosis. Raloxifene has been shown to lower the incidence of vertebral fractures in women with osteoporosis. Salmon calcitonin is reserved for use in patients who cannot tolerate bisphosphonates or hormone therapy.     

贵阳地区成人骨密度与骨质疏松症调查

背景：中国很多地方做过骨密度的变化规律及骨质疏松症的调查,但对于地处西部的贵阳地区,尚缺乏对的骨密度变化规律和骨质疏松症全面系统的随机调查。目的：调查贵阳地区成人骨密度,为该地区骨质疏松的预防、诊断、治疗提供参考依据。方法：2008/2011用双能X射线骨密度仪对贵阳地区共1334例年龄为20～79岁的人群进行骨密度测定,测定部位包括腰椎1～4椎体、右股骨近端,以峰值骨密度减低2.0SD为诊断骨质疏松症标准,按性别、10岁一个年龄分组进行统计学分析。结果与结论：贵阳地区男、女骨密度峰值均在20～29岁年龄组,女性50岁、男性60岁以后骨密度值明显降低。20～29岁的女性人群中出现骨质疏松症发病率和骨丢失率较高的异常现象。提示对于女性小于50岁和男性小于60岁,应加强普及骨质疏松预防知识,50岁以上的女性和60岁以上的男性还应同时采取相应干预措施,以减少骨质疏松症的发生,同时该调查为贵阳地区骨质疏松症的诊治提供了参考依据。     

男性骨质疏松症

男性骨健康的维持不仅需要雄激素的作用而且与雌激素的作用关系密切。尽管临床上采用睾酮、双磷酸盐等类药物治疗骨质疏松症取得了一定的经验，但尚缺乏充足的实验依据。     

A review on the performance of osteoporosis self-assessment tool for Asians in determining osteoporosis and fracture risk

The prevalence of osteoporosis in Asian countries is growing. An effective screening method will enable patients at risk for osteoporosis to receive early diagnosis and treatment, and avoid overcrowding the limited dual-energy x-ray absorptiometry (DXA) machines available in Asian countries. Many simple osteoporosis screening algorithms have been developed but they are not validated for use in Asian populations. osteoporosis self-assessment tools for Asians (OSTA), established using a multinational Asian cohort, is the first screening algorithm that caters for the Asian populations. It considers only body weight and age in the algorithm. It shows consistently high performance and sensitivity in identifying postmenopausal women at risk for osteoporosis in many Asian countries. Its usage has been expanded for identifying osteoporosis in men, as well as determining fracture risk for both sexes. However, the performance of OSTA is influenced by age, sex, ethnicity and site of BMD measurement to define osteoporosis. Its usage is also limited in individuals without apparent risk factors. These limitations should be noted by physicians considering the use of OSTA in clinical setting. As a conclusion, OSTA is a cost-effective measure for osteoporosis screening in primary healthcare setting.     

Guidelines on the management and treatment of glucocorticoid-induced osteoporosis

The 2004 edition of guidelines on the management and treatment of glucocorticoid-induced osteoporosis of the Japanese Society for Bone and Mineral Research had been developed based on the results of a longitudinal study by subcommittee members and the results of an analysis of patients collected by the Subcommittee to Study Diagnostic Criteria for Corticosteroid-Induced Osteoporosis, together with evidence obtained overseas and in Japan at 2004. This guideline is now going to be revised. In this review, I want to introduce the history of guidelines on the management and treatment of glucocorticoid-induced osteoporosis and American College of Rheumatology 2010 recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis.     

环状RNA在骨质疏松症中的作用及机制研究进展

随着人口老龄化程度的加剧,老年人骨质疏松症患病率逐年升高,骨质疏松症已成为全世界面临的重要公共卫生问题之一。近年来临床对骨质疏松症的研究多集中于成骨细胞、破骨细胞方面,而对其机制研究甚少。环状RNA是一种新型的稳定的非编码RNA,已有不少研究证实其在骨质疏松中起着重要作用。本文以“骨质疏松症”“环状RNA”为主题词检索中国知网、万方、Pubmed、Embase等数据库,将国内外关于环状RNA对骨质疏松症的作用及机制的研究进展综述如下。     

糖尿病性骨质疏松及相关危险因素分析

目的明确2型糖尿病患者是否易患骨质疏松症.探讨糖尿病性骨质疏松发生的危险因素.方法检测糖尿病患者及正常同龄者骨密度,比较有无骨质疏松的2型糖尿病患者的有关指标.结果2型糖尿病并发骨质疏松的比例(51.9%)明显高于同龄对照组(22.6%);2型糖尿病患者的糖化血红蛋白(HbA1c)、体重指数(BMI)与骨密度存在相关关系.结论2型糖尿病患者易发生骨质疏松;血糖控制不良、体重指数偏低是2型糖尿病患者并发骨质疏松的主要危险因素.     

水疗与电刺激联合防治大鼠失用性骨质疏松

背景:电刺激和水疗均对失用性骨质疏松有治疗作用,二者联合应用未见报道。目的:观察水疗与电刺激联合作用对失用性骨质疏松模型大鼠生物力学的影响。方法:采用切断坐骨神经和股神经的方法制备SD大鼠失用性骨质疏松模型。伤口愈合后采用电刺激、水疗及二者联合干预8周,观察大鼠体质量及股骨生物力学指标的变化。结果与结论:去神经后失用性骨质疏松大鼠体质量显著增加,股骨的材料力学和结构力学指标上均出现明显异常,经电刺激和(或)水疗干预后失用性骨质疏松大鼠的体质量有所下降,股骨的材料力学和结构力学指标有所改善,尤其是电刺激和水疗联合应用,可明显改善失用性骨质疏松大鼠股骨的最大载荷、破断载荷、弹性模量和极限强度。     

胰高血糖素样肽在骨质疏松症中的研究进展

近年来,胰高血糖素样肽(GLP)在骨质疏松中的作用逐渐被发现。GLP-1除可引起胰岛素分泌增加外,还可促进骨形成、抑制骨吸收。GLP-2除可改善肠道屏障功能,促进营养物质吸收外,还对骨吸收有抑制作用,但对骨形成的影响仍不明确。本文回顾了近年来GLP-1和GLP-2对骨代谢调控作用的相关研究,并重点探讨了GLP-1和GLP-2及其相关药物对骨质疏松症的潜在治疗作用,以期探索骨质疏松的诊疗新思路。     

Glucocorticoid-induced osteoporosis.

Glucocorticoids are important drugs in the treatment of variety diseases, but long-term period use can lead to various adverse effects, including osteoporosis. Glucocorticoid-induced osteoporosis is mainly caused by inhibition of osteoblastic bone formation, which results not only in decreased bone mineral density, but reduction of bone strength by trabecular thinning in bone microstructures. The evidence suggests that daily oral glucocorticoid doses higher than 5 mg prednisolone or equivalent increase the risk of fracture within 3-6 months after the start of therapy. High-dose inhaled glucocorticoids may also increase fracture risk. The diagnostic procedures are similar to those for primary osteoporosis, but the diagnostic threshold for bone mineral density needs to be higher than that for primary osteoporosis. Treatment with vitamin D, calcitonin, sex hormone replacement, and bisphosphonates has been shown to be effective, and bisphosphonates have been demonstrated to be the most valuable drugs for glucocorticoid-induced osteoporosis. There are several lines of evidence indicating that they are effective in preventing and treating low bone mineral density and in reducing fracture risk.     

Osteoblast as a target of anti-osteoporotic treatment

Osteoblasts are mesenchymal cells that play a key role in maintaining bone homeostasis; they are responsible for the production of extracellular matrix proteins, regulation of matrix mineralization, control of bone remodeling and regulate osteoclast differentiation. Osteoblasts have an essential role in the pathogenesis of many bone diseases, particularly osteoporosis. For many decades, the main current available treatments for osteoporosis have been represented by anti-resorptive drugs, such as bisphosphonates, which act mainly by inhibiting osteoclasts maturation, proliferation and activity; nevertheless, in recent years much attention has been paid on anabolic aspects of osteoporosis treatment. Many experimental evidences support the hypothesis of direct effects of the classical anti-resorptive drugs also on osteoblasts, and recent progress in understanding bone physiology have led to the development of new pharmacological agents such as anti-sclerostin antibodies and teriparatide which directly target osteoblasts, inducing anabolic effects and promoting bone formation.     

Comprehensive osteoporosis management with easy access to bone mineral density measurements

Background The majority of people with osteoporosis are never evaluated even though effective treatments are available. The County Council of Värmland in Sweden has implemented an osteoporosis management model that has been shown to be effective in promoting awareness and providing care for osteoporosis patients. Discussions among a prevention group on osteoporosis in the county council were opened in 1997. The county of Värmland covers a large area, and the distances from the peripheral parts to the main city are approximately 300 km and cumbersome for the inhabitants. The importance of having an osteoporosis service that could reach the county inhabitants in a convenient way was therefore recognized. Methods Three thousand four hundred patients were evaluated between March 2001 and December 2003. Guidelines for patient selection for bone density testing and treatment guidelines were formulated. Promoting awareness was an important prerequisite for the model to function. This was accomplished by having the measurement devices where the patients showed up and by regular education of the primary care doctors. Results and conclusions A multidisciplinary team was established and consisted of primary care doctors, orthopaedic surgeons, internists, physiotherapists, a patient organization member, a county health care representative and nurses. Team members met every third month and agreed upon clinical guidelines for implementing the system. The presented osteoporosis management system is not a screening approach as all patients had risk factors for osteoporosis before they were suggested for bone density testing. This study shows that providing a comprehensive package of measures makes it possible to establish an effective osteoporosis management system with limited economical resources.     

Study of the association between female obesity and osteoporosis

Background and objectives: Although several studies have considered obesity as a confounder for female osteoporosis, obesity's role as risk factor or a protective factor is not clear. No conclusion has been made about the correlation between obesity and osteoporosis. In this study, we examined the association between obesity and osteoporosis in Chinese women. Material and methods: 4202 qualified women were enrolled between August 2003 and December 2005. Data on their age, height, weight, basic disease, frequency of exercise and smoking habits were obtained via a questionnaire. Body mass index (BMI) was assessed as a surrogate measurement of fat mass and to describe obesity status in this study. The women were divided into an osteoporosis group or non-osteoporosis group according to the bone mineral density (BMD) of the lumbar spine (L1-L4), which was assessed by a peripheral dual-energy x-ray absorptiometry scanner. A T test was used to determine if the difference between the two groups had statistical significance. The rank sum test was used for ordinal numeration data analysis, and the Chi-squared test was used for unordered categorical data. Multiple logistic regressions were used to analyse the association between BMI and osteoporosis. Results: The logistic regression revealed five independent factors associated with osteoporosis, age, hypertension, smoking, exercise, and BMI, and three risk factors for osteoporosis: age, smoking and BMI. Conclusion: In Southwest China, obesity increases the risk of female osteoporosis. This finding provides a theoretical basis for its prevention in developing countries. Level of evidence: Level III (retrospective study).     

Risedronate for the prevention and treatment of corticosteroid-induced osteoporosis

OBJECTIVE: To evaluate the role of risedronate in corticosteroid-induced osteoporosis. DATA SOURCES: Clinical literature was accessed through MEDLINE (1966-February 2001). Key search terms included risedronate, corticosteroid, osteoporosis, and bisphosphonate. DATA SYNTHESIS: Corticosteroid-induced osteoporosis (CIO) is clinically challenging and can lead to fractures. Risedronate, an oral bisphosphonate, has been studied for use in CIO. Trials focusing on the use of risedronate in these patients were reviewed. CONCLUSIONS: Risedronate 5 mg/d increased bone mineral density at lumbar, femoral neck, and trochanter skeletal sites in patients recently initiated on or receiving long-term corticosteroid therapy. Further investigation is needed to determine risedronate's effects on fracture prevention. The drug was well tolerated.