绝经后骨质疏松症的发生机制与治疗

许多因素都可以影响骨代谢,雌激素与绝经后骨质疏松症的关系更为重要.目前性激素替代疗法 (HRT)仍是绝经后骨质疏松症的主要治疗方法,但应全面、深刻地认识 HRT的受益与风险.     

鹿瓜多肽注射液治疗类风湿性关节炎继发骨质疏松症的疗效分析

目的 探究鹿瓜多肽注射液治疗类风湿性关节炎继发骨质疏松症的临床疗效.方法 将70例类风湿性关节炎继发骨质疏松症患者随机分为治疗组和对照组,各35例,分别给予中药鹿瓜多肽注射液治疗和常规西药治疗,比较两组临床治疗效果.结果 治疗组患者血清IL-18水平和症状消失时间均低(短)于对照组,治疗总有效率(94.3％)高于对照组(80.0％),比较差异显著(P＜0.05).结论 鹿瓜多肽注射液治疗类风湿性关节炎继发骨质疏松症疗效显著,安全性较高,推荐临床应用.     

唑来膦酸注射液治疗骨质疏松症的研究进展

双膦酸盐是目前各国指南认可的治疗骨质疏松症的一线药物,唑来膦酸注射液(密固达)作为新一代的双膦酸盐制剂而备受关注.文中综述了密固达治疗骨质疏松症的作用机制、研究现状、临床应用、不良反应及依从性,为其治疗骨质疏松症的临床应用提供依据.     

乐力联合维生素D3治疗原发性骨质疏松症的临床观察

目的:探讨乐力联合维生素D3治疗原发性骨质疏松症的临床效果.方法:349例骨质疏松症患者用不同的钙剂(钙尔奇和乐力)联合维生素D3治疗18个月.结果:钙尔奇组40%患者症状改善,但骨量无明显变化,而乐力组58%患者症状缓解,且骨量上升.结论:长期服用乐力钙剂,同时配合户外活动(阳光照射)是预防骨质疏松症的有效方法.     

唑来膦酸与阿仑膦酸钠治疗Ⅰ型骨质疏松症的对比

目的:探讨唑来膦酸与阿仑膦酸钠治疗Ⅰ型骨质疏松症的疗效差异.方法:Ⅰ型骨质疏松症患者112例分为两组,分别给予唑来膦酸治疗(观察组56例)及阿仑膦酸治疗(对照组56例),对比两组治疗效果差异.结果:观察组的治疗有效率高于对照组,P<0.05;观察组治疗后的腰椎Oswestry功能指数评分(ODI指数)、视觉模拟疼痛评分(VAS)明显低于对照组,P<0.05;治疗后两组的腰椎及髋部骨密度值(BMD)无明显差异,P>0.05.结论:唑来膦酸与阿仑膦酸钠治疗Ⅰ型骨质疏松症均有一定的效果,唑来膦酸在改善症状、提高髋关节功能方面优于阿仑膦酸钠.     

活性维生素D代谢物治疗骨质疏松的进展

1,25(OH)2 D3是活性维生素D代谢物中最具活性的药物.骨质疏松症及由此而导致的骨折与骨组织内的1,25(OH)2 D3水平下降密切相关.活性维生素D代谢物通过增加胃肠道钙吸收,反馈性抑制PTH的释放而减少骨丢失,以提高骨质量来治疗骨质疏松症.它对绝经后骨质疏松症、老年性骨质疏松、糖皮质激素性骨质疏松均具有预防和治疗作用.     

脾肾双补十四味建中汤治疗原发性骨质疏松症临床观察

目的观察古方十四味建中汤对原发性骨质疏松症骨密度的影响.方法将68例患者分成脾肾双补组(34例)和补肾组(34例),分别采用十四味建中汤和六味地黄汤治疗,连续治疗2个月,观察治疗前后骨密度和临床症状改善情况.结果脾肾双补组运用古方十四味建中汤治疗后在提高骨密度和改善临床症状方面均显著高于补肾六味地黄汤组(P＜0.05).结论脾肾两虚是原发性骨质疏松症发病的主要病理机制,运用脾肾双补治疗本病优于单纯补肾治疗.     

治疗骨质疏松症药物的合理选择

骨质疏松症是世界范围内不断增长的健康问题 ,很多人由骨质疏松症而骨折。骨质疏松症可分为原发性和继发性两类。原发性骨质疏松包括绝经期后骨质疏松 (Ⅰ型 )和老年人骨质疏松 (Ⅱ型 ) ,是中老年人常见多发病 ,是一种退行性病变。绝经后雌激素减少 ,老年人钙吸收功能下降 ,钙代谢障碍是其主要原因。近年来治疗骨质疏松症药物受到社会各界的广泛关注 ,怎样合理选择有效、安全、经济的骨质疏松症治疗药物 ,是目前研究的热门话题。本文就合理选择治疗骨质疏松药物作一分析。1　雌激素类1 1　雌、孕激素复合制剂 :主要为倍美力、替勃龙、妇复春…     

补益脾肾方治疗老年骨质疏松症(脾肾不足型)的临床效果观察

目的 观察补益脾肾方治疗老年骨质疏松症(脾肾不足型)的临床效果.方法 将82例老年骨质疏松症患者随机分成治疗组、阳性药组,治疗组采用补益脾肾方联合钙剂治疗,阳性药组仅采用钙剂治疗.比较两组治疗前后的骨密度、血生化指标(血清钙、磷、碱性磷酸酶)及临床疗效.结果 治疗后,治疗组的骨密度显著提高(P＜0.01),阳性药组治疗前后的骨密度比较,差异无统计学意义(P＞0.05);两组治疗前后的血生化指标比较,差异无统计学意义(P＞0.05);治疗组的总有效率为87.8％,明显高于阳性药组的26.8％ (P＜0.01).结论 补益脾肾方联合钙剂治疗老年骨质疏松症(脾肾不足型)的效果满意.     

骨化三醇联合阿仑膦酸钠治疗偏瘫后继发

目的 观察骨化三醇联合阿仑膦酸钠治疗偏瘫后继发废用性骨质疏松症的临床疗效.方法 采用骨化三醇联合阿仑膦酸钠对47例偏瘫后继发废用性骨质疏松症患者进行治疗,观察治疗前后患者骨密度(BMD)、疼痛指数及Barthel指数的变化情况.结果 经治疗后,所有患者BMD、疼痛指数及Barthel指数均较治疗前明显好转,差异具有统计学意义(P<0.05).结论 骨化三醇联合阿仑膦酸钠治疗偏瘫后继发废用性骨质疏松症疗效肯定.     

Denosumab: a review of its use in the treatment of postmenopausal osteoporosis

Denosumab (Prolia?) is a human recombinant monoclonal antibody that is approved for the treatment of postmenopausal osteoporosis in women at high or increased risk of fracture in the US, the EU and several other countries. Denosumab has a novel mechanism of action; it binds to receptor activator of nuclear factor κB ligand and inhibits bone resorption by inhibiting osteoclast formation, function and survival. In postmenopausal women with osteoporosis, denosumab reduced the risk of vertebral, nonvertebral and hip fractures compared with placebo over 3 years in the large, phase III FREEDOM study. In postmenopausal women with low bone mineral density (BMD) or osteoporosis, treatment with denosumab increased BMD and decreased markers of bone turnover more than alendronate in those who were essentially treatment-naive in the 1-year DECIDE study and also in the 1-year STAND study, in which women were switched from alendronate to denosumab or continued alendronate treatment. Denosumab was generally well tolerated in clinical trials, although long-term effects of very low bone turnover remain to be established. Denosumab is administered once every 6 months via subcutaneous injection, which may be a preferred method of administration and may improve adherence to treatment compared with other osteoporosis treatments. Denosumab is a valuable new option for the treatment of postmenopausal osteoporosis in women at increased or high risk of fractures, and may be useful as a first-line treatment in women at increased risk of fractures who are unable to take other osteoporosis treatments.     

Clinical use of denosumab for the treatment for postmenopausal osteoporosis

Abstract

Denosumab is a fully human monoclonal antibody with high affinity and specificity for human receptor activator of nuclear factor kappa B ligand (RANKL), the principal regulator of osteoclastic bone resorption. By binding to RANKL, denosumab prevents it from binding to its receptor on the cell surface of pre-osteoclasts and mature osteoclasts, thereby reducing the formation, activity, and survival of osteoclasts and inhibiting osteoclastic bone resorption. In a large, randomized, placebo-controlled clinical trial in postmenopausal women with osteoporosis, denosumab 60?mg administered subcutaneously every 6 months reduced levels of bone turnover markers, increased bone mineral density, and reduced the risk of vertebral fractures, hip fractures, and non-vertebral fractures. There was no significant difference between denosumab and placebo in the overall risk of adverse events or serious adverse events. Denosumab was associated with a significant increase in the risk of eczema and cellulitis, and a significant decrease in the risk of falling and concussions. Denosumab recently received regulatory approval for the treatment of postmenopausal women with osteoporosis at high risk for fracture, with no dose adjustment in patients with renal impairment. Denosumab is a new therapeutic option to reduce fracture risk in women with postmenopausal osteoporosis, especially for those with impaired renal function or with intolerance or poor response to oral therapy.     

Clinical use of denosumab for the treatment for postmenopausal osteoporosis

Denosumab is a fully human monoclonal antibody with high affinity and specificity for human receptor activator of nuclear factor kappa B ligand (RANKL), the principal regulator of osteoclastic bone resorption. By binding to RANKL, denosumab prevents it from binding to its receptor on the cell surface of pre-osteoclasts and mature osteoclasts, thereby reducing the formation, activity, and survival of osteoclasts and inhibiting osteoclastic bone resorption. In a large, randomized, placebo-controlled clinical trial in postmenopausal women with osteoporosis, denosumab 60 mg administered subcutaneously every 6 months reduced levels of bone turnover markers, increased bone mineral density, and reduced the risk of vertebral fractures, hip fractures, and non-vertebral fractures. There was no significant difference between denosumab and placebo in the overall risk of adverse events or serious adverse events. Denosumab was associated with a significant increase in the risk of eczema and cellulitis, and a significant decrease in the risk of falling and concussions. Denosumab recently received regulatory approval for the treatment of postmenopausal women with osteoporosis at high risk for fracture, with no dose adjustment in patients with renal impairment. Denosumab is a new therapeutic option to reduce fracture risk in women with postmenopausal osteoporosis, especially for those with impaired renal function or with intolerance or poor response to oral therapy.     

Denosumab: an update

Denosumab is a fully human monoclonal antibody that inhibits the formation, function and survival of osteoclasts, preventing the interaction of tumor necrosis factor ligand superfamily member 11 (receptor activator of nuclear factor kappa-B ligand, RANKL) with the tumor necrosis factor receptor superfamily member 11A (osteoclast differentiation factor receptor, ODFR, receptor activator of NF-KB, RANK). This results in a reduction in bone resorption and an increase in bone mineral density. In clinical studies, denosumab has been shown to decrease the risk for vertebral, hip and nonvertebral fractures in women with postmenopausal osteoporosis and the risk for new vertebral fractures in men with nonmetastatic prostate cancer receiving androgen deprivation therapy, with a rate of side effects similar to placebo. A number of clinical trials with denosumab are ongoing to demonstrate its value for other indications and to further characterize its effects on immunomodulation. Denosumab is a new alternative for the prevention and treatment of postmenopausal osteoporosis and a promising agent for the treatment of other bone diseases associated with bone loss.     

Denosumab for postmenopausal osteoporosis?

Osteoporosis is the most common clinical disorder of bone metabolism, and is characterised by low bone mass and deterioration of the microarchitecture of bone tissue that results in increased bone fragility and susceptibility to bone fracture. In the UK, it is estimated that osteoporosis affects over 3 million people and leads to 230,000 fractures per year. It occurs most commonly in postmenopausal women and prevalence increases markedly with age, from 2% in women at 50 years to more than 25% at 80 years of age. Denosumab (Prolia - Amgen) is a monoclonal antibody that decreases bone resorption. It has been licensed in the EU for the treatment of osteoporosis in postmenopausal women at increased risk of fractures, and also for the treatment of bone loss associated with hormone ablation in men with prostate cancer at increased risk of fractures. Here, we review the role of denosumab in the management of postmenopausal osteoporosis.     

狄诺塞麦靶向干扰RANK配体通路治疗类风湿关节炎的研究进展

类风湿关节炎（rheumatoid arthritis,RA）是一种系统性自身免疫病,以关节损害和病理性骨量丢失为特征。近年来研究表明,核因子κB受体激活蛋白（receptor activator of nuclear factor κB,RANK）配体（RANK ligand,RANKL）-RANK通路在RA骨损害中起关键作用。人源化单克隆抗体狄诺塞麦（Denosumab,DMab）可特异性结合RANKL,阻断RANKL-RANK通路,起到骨保护作用。DMab作为一种新的治疗手段,对RA患者的局部骨侵蚀和全身性骨质疏松治疗具有明确的理论基础。此文对近5年国内外使用DMab治疗RA的研究进展做一综述。     

Cost effectiveness of denosumab compared with oral bisphosphonates in the treatment of post-menopausal osteoporotic women in Belgium

Background: Denosumab has recently been shown to be well tolerated, to increase bone mineral density (BMD) and to significantly reduce the risk of hip, vertebral and non-vertebral fractures in the FREEDOM (Fracture REduction Evaluation of Denosumab in Osteoporosis every 6 Months) trial. It is becoming increasingly important to evaluate not only the therapeutic value of a new drug but also the cost effectiveness compared with the most relevant treatment alternatives. Objective: The objective of this study was to estimate the cost effectiveness of denosumab compared with oral bisphosphonates (branded and generic drugs) in the treatment of post-menopausal osteoporotic women in Belgium. Methods: Cost effectiveness of 3 years of treatment with denosumab was compared with branded risedronate and branded and generic alendronate using an updated version of a previously validated Markov microsimulation model. The model was populated with relevant cost, adherence and epidemiological data for Belgium from a payer perspective and the results were presented as costs per QALY gained (&U20AC;, year 2009 values). Analyses were performed in populations (aged ≥60 years) in which osteoporosis medications are currently reimbursed in many European countries, i.e. those with BMD T-score of -2.5 or less or prevalent vertebral fracture. Patients receiving denosumab were assumed to have a 46% lower risk of discontinuation than those receiving oral bisphosphonates, and the effect of denosumab after treatment cessation was assumed to decline linearly to zero over a maximum of 1 year. Results: Denosumab was cost effective compared with all other therapies, assuming a willingness to pay of &U20AC;40?000 per QALY gained. In particular, denosumab was found to be cost effective compared with branded alendronate and risedronate at a threshold value of &U20AC;30?000 per QALY and denosumab was dominant (i.e. lower cost and greater effectiveness) compared with risedronate from the age of 70 years in women with a T-score of -2.5 or less and no prior fractures. The cost effectiveness of denosumab compared with generic alendronate was estimated at &U20AC;38?514, &U20AC;22?220 and &U20AC;27?862 per QALY for women aged 60, 70 and 80 years, respectively, with T-scores of -2.5 or less. The equivalent values were &U20AC;37?167, &U20AC;19?718 and &U20AC;19?638 per QALY for women with prevalent vertebral fractures. Conclusion: This study suggests, on the basis of currently available data, that denosumab is a cost-effective strategy compared with oral bisphosphonates (including generic alendronate) for the treatment of post-menopausal osteoporotic women, aged ≥60 years in Belgium. Denosumab therefore appears to have the potential to become a first-line treatment for post-menopausal women with osteoporosis. However, further studies would be required to evaluate the long-term safety and adherence of denosumab in real-world clinical practice as well as head-to-head effectiveness compared with oral bisphosphonates.     

Denosumab: in the prevention of skeletal-related events in patients with bone metastases from solid tumours

Denosumab, a fully human monoclonal antibody, binds to the receptor activator of nuclear factor-κB ligand (RANKL) and thereby inhibits RANKL-mediated bone resorption. In various individual countries, subcutaneous denosumab is indicated for the prevention of skeletal-related events in patients with bone metastases from solid tumours (featured indication), and/or for the treatment of postmenopausal osteoporosis and/or of cancer treatment-induced bone loss in prostate or breast cancer patients. In three, pivotal, double-blind, multinational trials in adult patients with cancer-related bone metastases (total n?>?5700), including trials in patients with advanced breast or prostate cancer, subcutaneous denosumab (120 mg every 4 weeks) was shown to be noninferior to intravenous zoledronic acid (4 mg every 4 weeks), as determined by the median time to first on-study skeletal-related event (primary endpoint) at the time of the primary analysis (≈34 or 41 months). Denosumab treatment was superior to zoledronic acid in terms of the primary endpoint in two trials in patients with breast cancer or prostate cancer, based on secondary superiority analyses. In a third trial in patients with solid tumours excluding breast or prostate cancer, superiority of denosumab treatment versus zoledronic acid treatment was not demonstrated. The tolerability profile of denosumab was manageable in patients with bone metastases from solid tumours. Osteonecrosis of the jaw occurred in 1.8% and 1.3% of patients in the denosumab and zoledronic acid groups during the primary treatment phase; the incidence after approximately 4 additional months of denosumab treatment was 2.2%.     

Denosumab. The first inhibitor of RANK-ligand for treatment of osteoporosis

Denosumab is a fully human monoclonal antibody, that specifically binds with high affinity to RANK-ligand (RANKL) and prevents interaction of RANKL with its receptor, called RANK (Receptor activator of nuclear factor kappa B). Blocking this signalling pathway (RANKL/RANK pathway) inhibits osteoclast differentiation and activation, and reduces bone resorption. Application of denosumab (60 mg s. c., every six months) results in increased bone mineral density, as showed in several clinical trials. Incidence of new vertebral fractures in postmenopausal women with osteoporosis was reduced significantly by semi-annual application of denosumab versus placebo. Patients suffering from malignant diseases could also benefit from treatment with denosumab in future.     

The clinical use of denosumab for the management of low bone mineral density in postmenopausal women

Osteoporosis is a leading cause of debility and declining quality of life in postmenopausal women worldwide. Treatment of osteoporosis has been ubiquitous throughout the developed world since the mid-1990s, most notably with the introduction of bisphosphonates in 1995. Nonetheless, the incidence of hip fractures increased by 25% between 1990 and 2000, despite advances in osteoporosis therapy. Studies indicate that bone density increases over the first 3 years of bisphosphonate therapy and then plateaus or perhaps even declines, placing these patients at greater risk of fracture. Since hip fractures are associated with increased morbidity, mortality, and increased cost of health care, improvements in treating osteoporosis are critical. Denosumab is a novel monoclonal antibody targeted against the receptor activator of nuclear factor-κB ligand (RANKL) that inhibits osteoclast activity. Initial data suggest that denosumab increases bone mineral density for greater than 3 years. Of greater importance, denosumab has been shown to decrease vertebral fractures by 68%, nonvertebral fractures by 19%, and hip fractures by 42% for at least 36 months. Data also indicate that the safety profile of denosumab is equivalent to other drugs used in osteoporosis management, but potential risks of immunosuppression and cancer have been hypothesized.