Persistence with teriparatide in patients with osteoporosis: the UK experience

Introduction The objective of this paper was to determine the persistence with teriparatide at 12 months in all patients in the UK who were prescribed the treatment since its launch.Methods Virtually all patients prescribed teriparatide in the UK receive treatment through Healthcare at Home, Basingstoke, UK. Data was obtained to assess the start date, discontinuation date and reason for discontinuation in all patients receiving teriparatide since its launch. Persistence was defined as the number of patients continuing treatment.Results A total of 1,104 patients were included in the analysis. The median duration of use in all patients was 252 days. Of the 435 patients who were at least 12 months post-initiation of treatment, persistence was 87%. Forty-two patients (3.8%) had discontinued treatment due to adverse events.Conclusions This study demonstrates that persistence with teriparatide at 12 months is very high and is probably greater than that of existing oral therapies for osteoporosis. The reasons for the high persistence rates seen with teriparatide are likely to be multi-factorial. The high persistence rates should help to optimise the effectiveness of therapy in this group of high-risk patients.     

2014 update of recommendations on the prevention and treatment of glucocorticoid-induced osteoporosis

ObjectivesTo update the recommendations on the prevention and treatment of glucocorticoid-induced osteoporosis issued in 2003 by the French National Authority for Health (HAS). This update was performed under the aegis of the Bone Section of the French Society for Rheumatology (SFR) and Osteoporosis Research and Information Group (GRIO), in collaboration with four French learned societies (primary-care, gastroenterology, internal medicine, and nephrology).MethodsA task force composed of members of the medical specialties involved in managing patients with glucocorticoid-induced osteoporosis conducted a systematic literature review according to the method developed by the HAS then used the results to develop updated recommendations.ResultsThese recommendations are intended for all physicians involved in the management of patients who are scheduled to start, or are taking, long-term glucocorticoid therapy (≥ 3 months) in any dose and for any reason. In postmenopausal women and men older than 50 years of age, treatment is warranted in the presence of any of the following risk factors for fracture: history of bone frailty fracture after 50 years of age, bone mineral density T-score ≤ −2.5 at one or more sites, age ≥ 70 years, and dosage ≥ 7.5 mg/d prednisone-equivalent for longer than 3 months. Bisphosphonates can be used in all these situations; teriparatide can be given as first-line therapy in patients at high fracture risk but is reimbursed by the French statutory health insurance system only in patients having two or more prevalent vertebral fractures. The fracture risk is lower in nonmenopausal women and in men younger than 50 years of age, in whom treatment decisions should rest on a case-by-case evaluation.ConclusionThese recommendations are intended to clarify the pharmacological management of glucocorticoid-induced osteoporosis.     

特立帕肽治疗原发性骨质疏松症的短期疗效观察

目的：观察特立帕肽（ Teriparatide ）治疗原发性骨质疏松症的短期疗效和安全性。方法采用自身前后对照临床研究,纳入2011年12月-2012年12月在解放军第309医院骨内科住院的原发性骨质疏松症患者共10名,所有患者在每天口服补充元素钙600 mg和活性维生素D 0.25μg的同时,分别接受特立帕肽治疗,疗程6个月,具体用法为每日皮下注射特立帕肽20μg。所有患者均于用药前、用药后3、6个月采用双能X线吸收法（DEXA）测定腰椎（L2-4）、股骨颈、Ward’s区和大粗隆骨密度（BMD）,用酶联免疫吸附法（ELISA）测定血清骨钙素（sOC）、骨碱性磷酸酶（sBAP）和Ⅰ型胶原交联C端肽（sCTX）水平。观察患者治疗前后骨密度和骨标志物的变化并进行对比分析,记录患者的不良事件。结果10名患者均完成全疗程治疗。治疗3个月时,腰椎（L2-4）、股骨颈、Ward’s区和大粗隆骨密度改善不明显（P＞0.05）,血清骨钙素（sOC）和骨碱性磷酸酶（sBAP）较治疗前明显升高（P＜0.05）。治疗6个月时,腰椎（L2-4）骨密度较治疗前明显增高（P＜0.05）,而股骨颈、Ward’s区和大粗隆骨密度改善不明显（P＞0.05）。血清骨钙素（sOC）和骨碱性磷酸酶（sBAP）呈持续升高趋势（P＜0.05）,Ⅰ型胶原交联C端肽（sCTX）较治疗前略升高,但差异无统计学意义（P＞0.05）。治疗期间不良事件的发生情况：头晕发生2例,恶心发生1例,上述情况均较轻微,没有给予特殊处理即自行缓解。结论特立帕肽能在3个月内改善患者的骨代谢状况（促进骨形成）,6个月内有效增加原发性骨质疏松症患者的腰椎骨密度,适用于绝经后及老年性骨质疏松症患者的治疗。     

Persistence with teriparatide in postmenopausal osteoporosis; impact of a patient education and follow-up program: the French experience

Summary  This study evaluated the 18-month persistence with teriparatide in 5413 postmenopausal osteoporotic women who were enrolled in an education and follow-up program. Analysis showed that the persistence rate was 81.5% for women who follow the program, higher than for existing oral antiresorptive treatments. Introduction  An education and follow-up program was developed after launch of teriparatide in France in September 2004, to help women to follow the treatment. The objective of this study was to evaluate the persistence with teriparatide in postmenopausal osteoporotic women following this program. Methods  Data about persistence are available for the period September 2004 to June 2007. Persistence is defined as the percentage of patients still on treatment at the end of the 18-month course, and it has been compared to the data provided by the French universal health insurance system. Results  Since the launch of teriparatide in France in September 2004, 5413 postmenopausal women (mean age 72.3 ± 14.5 years) with osteoporosis and vertebral fractures (mean 3.9 ± 2) have participated in the program. The persistence rate at 15 months was 81.5%, and our analysis suggested that a majority of patients completed the 18-month treatment course. The main reason for discontinuation was adverse events (46.7%). Data of the French Universal Health Insurance suggest that the persistence may be close to 0% for women who are not in the program. Conclusions  Postmenopausal osteoporotic women treated by teriparatide and enrolled in an education and follow-up program have a high persistence rate.     

Effect of raloxifene after recombinant teriparatide [hPTH(1–34)] treatment in postmenopausal women with osteoporosis

Summary Loss of bone mineral density occurs after discontinuation of teriparatide, if no subsequent treatment is given. Sequential raloxifene prevented rapid bone loss at lumbar spine and further increased bone mineral density (BMD) at femoral neck, whether raloxifene was started immediately or after a one-year delay following teriparatide treatment. Introduction We compared the sequential effects of raloxifene treatment with a placebo on teriparatide-induced increases in bone mineral density (BMD). A year of open-label raloxifene extended the study to assess the response with and without delay after discontinuation of teriparatide. Methods Following a year of open-label teriparatide 20 μg/day treatment, postmenopausal women with osteoporosis were randomly assigned to raloxifene 60 mg/day (n = 157) or a placebo (n = 172) for year 2, followed by a year of open-label raloxifene. BMD was measured by dual energy x-ray absorptiometry. Results The raloxifene and placebo groups showed a decrease in lumbar spine (LS) BMD in year 2 for raloxifene and placebo groups (−1.0 ± 0.3%, P = 0.004; and −4.0 ± 0.3%, P < 0.001, respectively); the decrease was less with raloxifene (P < 0.001). Open-label raloxifene treatment reversed the LS BMD decrease with a placebo, resulting in similar decreases 2 years after randomization (−2.6 ± 0.4% (raloxifene-raloxifene) and −2.7 ± 0.4% (placebo-placebo). At study end, LS and femoral neck (FN) BMD were higher than pre-teriparatide levels, with no significant differences between the raloxifene-raloxifene and placebo-raloxifene groups, respectively (LS: 6.1 ± 0.5% vs. 5.1 ± 0.5%; FN: 3.4 ± 0.6% vs. 3.0 ± 0.5%). Conclusion Sequential raloxifene prevented rapid bone loss at the LS and increased FN BMD whether raloxifene was started immediately or after a one-year delay following teriparatide treatment. Preliminary data presented previously at the International Osteoporosis Foundation World Congress on Osteoporosis, Toronto Canada June 2–6, 2006, abstract published: Adami S, Munoz-Torres M, Econs MJ, Sipos A, Xie L, Dalsky GP, McClung M, Felsenberg D, Brown JP, Brandi ML, San Martin J. Effect of raloxifene after teriparatide treatment in postmenopausal women with osteoporosis. Osteoporos Int. 2006;17(Suppl 2):S137.     

Relationship between duration of teriparatide therapy and clinical outcomes in postmenopausal women with osteoporosis

Summary  The extent to which fracture protection and safety varies with increasing time on teriparatide [rhPTH(1-34)] therapy is a clinically relevant unanswered question. In postmenopausal women with osteoporosis, increased duration of teriparatide versus placebo treatment was associated with a progressive decrease in the rates of nonvertebral fragility fractures and back pain. Introduction  The impact of duration of teriparatide [rhPTH(1-34)] therapy on patient outcomes is a relevant unanswered question. Methods  Postmenopausal women with osteoporosis were randomized to once-daily subcutaneous injection with placebo (N = 544), teriparatide 20 μg (TPTD20; N = 541), or teriparatide 40 μg (TPTD40; N = 552) plus calcium and vitamin D supplementation. The time to first nonvertebral fragility fracture and new or worsening back pain following treatment initiation was analyzed using Cox partial likelihood regression treating time on therapy as a linear, time-dependent covariate. Results  Compared with placebo, the relative hazard for nonvertebral fragility fractures decreased by 7.3% for each additional month of TPTD20 [hazard ratio = 0.927, 95% CI (0.876 to 0.982), p = 0.009] and by 7.6% for each additional month of TPTD40 [hazard ratio = 0.924, 95% CI (0.871 to 0.981), p = 0.009]. Clinical vertebral fractures appeared to increase over time in the placebo group and occurred primarily in the first time interval in the teriparatide treatment groups. Compared with placebo, the relative hazard of back pain was decreased by 8.3% for each additional month of TPTD20 [hazard ratio = 0.920, 95% CI (0.902 to 0.939), p < 0.001] and 8.7% for each additional month of TPTD40 [hazard ratio = 0.917, 95% CI (0.898 to 0.935), p < 0.001]. Conclusions  These findings suggest increased nonvertebral fracture protection, reduced back pain, and reduced occurrence of side effects with longer duration of teriparatide therapy. Some of these findings were presented at the 67th Annual Scientific Meeting of the American College of Rheumatology in Orlando, Florida, October 23–28, 2003 and at the 31st European Symposium on Calcified Tissues in Nice, France, June 5–9, 2004.     

双膦酸盐对骨质疏松症患者腰椎融合影响的系统评价和Meta分析

目的通过Meta分析系统评价双膦酸盐对骨质疏松症患者腰椎融合的影响。方法系统检索Pub Med、Science Direct、Google Scholar、CNKI、VIP和Wan Fang Data自建库以来到2017年1月的文献,运用Stata11.0定量分析纳入的文献。结果最终有9篇研究符合纳入标准,Meta分析结果显示:双膦酸盐组与对照组的对比中,植骨融合情况[RR=1.138,95%CI(1.064,1.217)]、终末随访骨密度T值[MD=0.038,95%CI(0.025,0.052)]、ODI指数[MD=-4.36,95%CI(-6.372,-2.348)]、骨吸收生化标志物CTX值[MD=-0.401,95%CI(-0.511,-0.291)]、VAS评分[MD=0.940,95%CI(0.548,1.332)]之间差异均有统计学意义(P0.01);终末随访术后骨形成生化标志物PINP值[MD=-4.328,95%CI(-8.954,0.298)]、不良反应情况[RR=0.725,95%CI(0.420,1.251)]之间差异无统计学意义(P=0.067和P=0.248)。结论腰椎术后应用双膦酸盐并不影响骨质疏松症患者的骨融合结果,而且通过治疗能有效抑制骨吸收代谢,改善其骨量和术后功能恢复程度,且与对照组安全性相近。     

Osteonecrosis of the jaw and bisphosphonate treatment for osteoporosis

A potential side effect associated with bisphosphonates, a class of drugs used in the treatment of osteoporosis, Paget's disease and metastatic bone disease, is osteonecrosis of the jaw (ONJ). The incidence of ONJ in the general population is unknown; this rare condition also may occur in patients not receiving bisphosphonates. Case reports have discussed ONJ development in patients with multiple myeloma or metastatic breast cancer receiving bisphosphonates as palliation for bone metastases. These patients are also receiving chemotherapeutic agents that might impair the immune system and affect angiogenesis. The incidence or prevalence of ONJ in patients taking bisphosphonates for osteoporosis seems to be very rare. No causative relationship has been unequivocally demonstrated between ONJ and bisphosphonate therapy. A majority of ONJ occurs after tooth extraction. Furthermore, the underlying risk of developing ONJ may be increased in osteoporotic patients by comorbid diseases. Treatment for ONJ is generally conservative.     

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.     

The importance of bisphosphonate therapy in maintaining bone mass in men after therapy with teriparatide [human parathyroid hormone(1–34)]

Teriparatide, the active fragment of human parathyroid hormone (hPTH 1–34), is an anabolic agent for the treatment of osteoporosis. Important questions remain regarding management strategy beyond the recommended 18- to 24-month course of teriparatide treatment. We followed 21 men for up to 2 years after discontinuing teriparatide. Twelve men (57%) chose treatment with bisphosphonate immediately after teriparatide withdrawal, while 9 (43%) opted for no pharmacologic agent. At the end of 1 year lumbar spine bone density increased an additional 5.1±1.0% in the bisphosphonate group, while it declined by 3.7±1.7% in those on no medication (P<0.002). In six men who delayed initiation of bisphosphonate until 1 year after teriparatide withdrawal, their subsequent gains in the second year, 2.6±1.7%, still placed them below the peak gains they achieved on teriparatide. In contrast, the 12 men who began bisphosphonates immediately and continued treatment for the entire 2-year post-PTH period had continued gains at the lumbar spine, 8.9±1.5% above their post-PTH values (P=0.002). For the 4-year period, including 2 years of teriparatide and 2 years of bisphosphonate, the total gains at the lumbar spine were 23.6±2.9%. Men, who received bisphosphonate in only the 2nd year post-teriparatide, had cumulative gains of 11.1±3.4%. Three men who did not receive any bisphosphonate at any time during the post-PTH period had cumulative gains of only 5.5±3.7%. These findings suggest that the use of bisphosphonates following teriparatide is an important component of any strategy utilizing this anabolic drug for osteoporosis in men. The immediate use of bisphosphonates after teriparatide withdrawal may help to optimize gains in bone density at the lumbar spine.     

Racial disparity in treatment of osteoporosis after diagnosis

Introduction Racial disparities have been identified in a number of areas in clinical medicine. Patients diagnosed with osteoporosis should be treated similarly regardless of race. However, limited data are available on the relative frequency of treatment by race after diagnosis of osteoporosis.Methods We analyzed all 739 dual-energy X-ray absorptiometry (DXA) results obtained of women 50 years old and older between 1998 and 2002 at our medical center. Our study sample was 82% Caucasian and 15% African American. Of 353 women who had low bone mineral density on first DXA, we abstracted the electronic and paper medical records to compare treatment rates by race.Results Of the women diagnosed with osteoporosis or osteopenia, 80.0% and 68.3%, respectively, were started on antiresorptive medications. Of the African American women, 61.9% diagnosed with osteoporosis were started on antiresorptive treatment compared with 83.3% of Caucasian women (p<0.05). African American women with low bone mass were less likely than Caucasian women to be smokers (p<0.05) and use alcohol (p<0.01) but were more likely to be on corticosteroids (p<0.05). No other significant differences were found among treated and nontreated groups that might explain the disparity in treatment.Conclusion A smaller proportion of African American than Caucasian women with osteoporosis received antiresorptive medications after a DXA diagnosis. This significant disparity requires further study in a larger population.     

骨质疏松并发骨折的治疗新概念

骨质疏松合并骨折是一种常见而严重的疾患，本文总结了治疗方面的近期进展和新概念。骨折后由于制动治疗导致继发性骨质疏松，在原发性骨质疏松的基础上，骨丢失愈发严重，形成恶性循环，影响愈合。因此，治疗的关键是要阻断这一恶性循环，防止或减少骨丢失。尽早进行功能练习和负重活动，常规服用治疗骨质疏松的药物，两者是同等重要的。牢靠的内固定和假体置换应该是多数骨折治疗的首选方法。在药物治疗方面，降钙素、激素替代疗法（利维爱等）、双磷酸盐（福善美等）、维生素D2、维生素D3及钙剂都是适用的。     

骨质疏松症的物理治疗研究进展

骨质疏松症是一种中老年人易患的骨骼性疾病,骨质疏松的治疗方法种类繁多,主要包括药物治疗和物理治疗。药物治疗效果确切,但存在治疗周期长,患者依从性差、费用较高及药物不良反应等问题。相比其他几种方法,物理疗法具有副作用小的优点。为了更全面阐释物理治疗方法的相关研究工作,本文主要从物理治疗的角度对脉冲电磁场(PEMFs)、高压氧、超声波、电针、体外冲击波、振动以及运动疗法对骨质疏松的治疗作用进行探讨,分析它们的作用机制、临床应用研究新进展,以指导临床更合理地选择治疗方法,找出各自的优势,扬长避短,以达到更好的治疗效果。     

Epidemiology,treatment and costs of osteoporosis in Germany—the BoneEVA Study

INTRODUCTION: In Germany, accurate data on the prevalence and treatment of osteoporosis, as well as the cost of this illness, are not available. The aim of this study is to give a valid estimation of these items for the year 2003. METHODS: Routine data from a German sickness fund covering 1.5 million beneficiaries and billing data for outpatient visits were used to obtain estimates of prevalence for osteoporosis. Claims data for patients with osteoporosis (M80, M81) or an osteoporosis-related fracture diagnosis (S22, S32, S42, S52, S72, S82) or treatment with anti-osteoporosis drugs were examined. Costs were calculated from the perspective of the German health insurance system and the German nursing care insurance system, respectively. Only direct costs of osteoporosis were considered. RESULTS: In 2003, 7.8 million Germans (6.5 million women) were affected by osteoporosis. Of them, 4.3% experienced at least one clinical fracture. Only 21.7% were treated with an anti-osteoporosis drug. The total direct costs attributable to osteoporosis amounted to euros 5.4 billion. CONCLUSION: This study confirms that osteoporosis is underdiagnosed, undertreated and imposes a considerable economic burden on the health system in Germany. Effective strategies for the prevention and management of this disease are needed.     

Glucocorticosteroid-induced spinal osteoporosis: scientific update on pathophysiology and treatment

Glucocorticosteroid-induced osteoporosis (GIOP) is the most frequent of all secondary types of osteoporosis. The understanding of the pathophysiology of glucocorticoid (GC) induced bone loss is of crucial importance for appropriate treatment and prevention of debilitating fractures that occur predominantly in the spine. GIOP results from depressed bone formation due to lower activity and higher death rate of osteoblasts on the one hand, and from increased bone resorption due to prolonged lifespan of osteoclasts on the other. In addition, calcium/phosphate metabolism may be disturbed through GC effects on gut, kidney, parathyroid glands and gonads. Therefore, therapeutic agents aim at restoring balanced bone cell activity by directly decreasing apoptosis rate of osteoblasts (e.g., cyclical parathyroid hormone) or by increasing apoptosis rate of osteoclasts (e.g., bisphosphonates). Other therapeutical efforts aim at maintaining/restoring calcium/phosphate homeostasis: improving intestinal calcium absorption (using calcium supplementation, vitamin D and derivates) and avoiding increased urinary calcium loss (using thiazides) prevent or counteract a secondary hyperparathyroidism. Bisphosphonates, particularly the aminobisphosphonates risedronate and alendronate, have been shown to protect patients on GCs from (further) bone loss and to reduce vertebral fracture risk. Calcitonin may be of interest in situations where bisphosphonates are contraindicated or not applicable and in cases where acute pain due to vertebral fracture has to be managed. The intermittent administration of 1-34-parathormone may be an appealing treatment alternative, based on its documented anabolic effects on bone resulting from the reduction of osteoblastic apoptosis. Calcium and vitamin D should be a systematic adjunctive measure to any drug treatment for GIOP. Based on currently available evidence, fluoride, androgens, estrogens (opposed or unopposed) cannot be recommended for the prevention and treatment of GIOP. However, substitution of gonadal hormones may be indicated if GC-induced hypogonadism is present and leads to clinical symptoms. Data using the SERM raloxifene to treat or prevent GIOP are lacking, as are data using the promising bone anabolic agent strontium ranelate. Kyphoplasty performed in appropriately selected osteoporotic patients with painful vertebral fractures is a promising addition to current medical treatment.     

Reduced risk of back pain following teriparatide treatment: a meta-analysis

Vertebral fractures are the most common osteoporotic fracture and may result in back pain with functional limitations and diminished quality of life. Teriparatide [rhPTH (1–34)] has been shown to increase bone mass and reduce the risk of vertebral and other osteoporotic fractures. The aim of this study was to evaluate the effects of teriparatide on the risk of back pain in patients with osteoporosis. A systematic review of the literature was performed, and five trials were identified and included in our analyses. All trials were randomized, double-blinded, and parallel with either new vertebral fracture ( n =1) or bone mineral density as the primary endpoint ( n =4). Four studies were in postmenopausal women with osteoporosis, and one was in men with idiopathic or hypogonadal osteoporosis. Two trials were placebo controlled, two trials were alendronate controlled, and one trial involved teriparatide plus hormone replacement therapy versus hormone replacement therapy alone. Reports of back pain, defined as new or worsened back pain after initiating the study drug, were obtained from adverse event databases, and the risk of back pain was analyzed using a multivariate Cox proportional hazards model. Results were not statistically heterogeneous ( P =0.60) across trials, and there were no differences between groups administered teriparatide 20 or 40 mcg/day doses ( P =0.64). The rates of back pain, moderate or severe back pain, and severe back pain per 100 patient-years were numerically lower in the teriparatide versus comparator groups in each study. Compared with the pooled comparator, patients in the pooled teriparatide group had reduced risk for any back pain [relative risk, 0.66 (95% CI, 0.55–0.80)], moderate or severe back pain [relative risk, 0.60 (95% CI, 0.48–0.75)] and severe back pain [relative risk, 0.44 (95% CI, 0.28–0.68)]. Separate meta-analyses comparing teriparatide versus placebo or antiresorptive drugs gave similar results. In conclusion, patients randomized to teriparatide had a reduced risk of new or worsening back pain compared to patients randomized to placebo, hormone replacement therapy or alendronate.     

Alendronate treatment for osteoporosis: A review of the clinical evidence

Bisphosphonates have recently gained an increasing role in the management of osteoporosis. The aminobisphosphonate, alendronate has recently been introduced as a new agent for the treatment of post-menopausal osteoporosis. This paper reviews the clinical evidence for the use of this agent and seeks to assess its place in osteoporosis management.     

双膦酸盐治疗骨质疏松症与总死亡率相关性的meta分析

目的系统评价临床随机对照试验是否能够证明双膦酸盐类药物的应用与骨质疏松症患者的死亡率降低相关。 方法依据Meta分析要求，对CBM、CNKI、MEDLINE、PubMed、Springer、Embase、万方、维普、Cochrane Library、中国科技论文统计与分析网、专利数据库等进行检索，严格评价纳入以双膦酸盐药物作为主要干预措施治疗骨质疏松症的临床随机对照实验研究文献，并收录有效的相关的数据资料，检索年限从建库至2020年5月。采用NOS文献质量评价标准对符合纳入排除标准的文献进行质量评价。采用RR值及其95%可信区间评估关联强度。根据是否存在异质性，采用固定效应模型合并效应量，并根据单因素敏感性分析法进行敏感性分析。 结果最终纳入21篇文献，受试者共42 849例，双膦酸盐组患者22 605例，死亡855例，安慰剂组20 244例，死亡880例。双膦酸盐治疗骨质疏松症与总死亡率相关性的为RR=0.949（95% CI：0.866，1.040，P=0.264）。阿仑膦酸盐治疗骨质疏松症与总死亡率相关性的为RR=0.996（95% CI：0.705，1.407，P=0.982），伊班膦酸盐为RR=0.802（95% CI：0.496，1.298，P=0.369），利塞膦酸盐为RR=0.915（95% CI：0.757，1.105，P=0.354），唑来膦酸盐为RR=0.898（95% CI：0.770，1.047，P=0.168），尚未发现双磷酸盐治疗骨质疏松症与总死亡率的关联性。 结论经meta分析发现双膦酸盐治疗骨质疏松症患者的总死亡率未见明显降低。     

骨质疏松性骨折的药物治疗策略与选择

随着老龄化社会的到来,低暴力脆性骨折的发病率逐年提高。而锁定钢板和骨水泥加强技术在临床中的应用,使得手术治疗骨质疏松性骨折已不再困难,但骨质疏松再骨折已成为另一治疗难点和热点。各种新型抗骨质疏松药物的问世,使得医务工作者在使用抗骨质疏松药物时,面临更多的选择难题。本文通过对既往临床文献的阅读和结果的总结,旨在为广大医务工作者在抗骨质疏松药物治疗骨质疏松性骨折的使用方面提供参考。     

唑来膦酸盐与骨质疏松症

目的 双膦酸盐是目前抗骨质疏松治疗最常用药物.唑来膦酸盐是每年1次静脉注射用双膦酸盐,探讨唑来膦酸盐对骨质疏松的治疗作用及安全性分析.方法 PubMed上检索应用唑来膦酸盐治疗骨质疏松及其他疾病的相关文献并进行分析.结果 HORIZON-PFT 3年研究表明唑来膦酸盐与安慰剂比较,能明显降低椎体、非椎体骨折风险,增加骨密度,降低骨转换标志物水平,增加骨小梁容量.在90 d内行髋部骨折外科治疗的患者中进行的HORIZON-RFT研究发现唑来膦酸盐与安慰剂比较能够明显降低再发骨折风险,降低全因死亡率,增加髋部及股骨颈骨密度.绝经后低骨密度妇女从阿伦膦酸钠改为唑来膦酸盐3个月内平均骨转换标志物水平先下降,后逐渐增至绝经前妇女正常范围,且可维持腰椎骨密度值12个月.另一研究表明与阿伦膦酸钠比较,唑来膦酸盐能更迅速的降低骨吸收标志物,抑制骨吸收.在安全性方面唑来膦酸盐可能的副作用包括急性一过性不良反应,如发热、肌痛、流感样症状,主要为轻到中度,常发生在静脉输注后3 d内,3～7 d左右缓解.研究表明唑来膦酸盐短期内可能引起肾功能的变化,但长期对肾功能未发现明显影响.颌骨骨质疏松性坏死可能与唑来膦酸盐相关,但发生率较低,且多发生在恶性肿瘤如多发性骨髓瘤和转移癌的患者中,尚未证实颌骨骨质疏松性坏死风险增高与用于治疗骨质疏松症批准剂量的唑来膦酸盐有关.其他少见的副作用包括房颤,无症状及一过性低钙血症,尚需要大样本长期研究证实.结论 每年1次唑来膦酸盐是治疗绝经后骨质疏松新的选择.