临床科研方法学-文献评价

文献：Fracture Prevention with Zoledronate in Older Women with Osteopenia来自杂志：《The new england journal of medicine》1. 研究背景及研究目的研究背景原文：Prevention of fractures with bisphosphonates has been shown most clearly in patients with osteoporosis, which is defined either by a bone-density T score of less than−2.5or by the presence of prevalent vertebral fractures; whether bisphosphonates are efficacious in patients with osteopenia alone is uncertain. However, treating only patients who have osteoporosis has only a limited capacity to decrease total numbers of fractures, since fractures tend to occur in the much larger group of women whose bone mineral density is in the osteopenic range.2If interventions are to achieve a substantial decrease in the total numbers of fractures, therapies shown to be effective in women with osteopenia are needed.Zoledronate (also known as zoledronic acid) has characteristics that make it attractive for use in women who have osteopenia. It is administered by intravenous injection at intervals of1year or longer, it is preferred over oral bisphosphonates by a majority of patients,7and it has had a satisfactory safety profile.8,9The current trial assesses the effects of zoledronate on fracture in postmenopausal women with hip bone mineral density that is characterized as osteopenia.研究背景简洁清晰介绍了双膦酸盐预防骨质疏松性骨折的效果明显，但在骨质减少的患者中，双膦酸盐是否有效尚不确定。

另外治疗骨质疏松减少骨折总数的能力有限，因为骨折发生在骨质减少范围内的更多妇女群体中，这部分群体的T值小于-2.5，但往往含有其他的骨折风险因素。

现有的研究尚不能充分证明双膦酸盐能够减少骨质疏松骨折发生率。

2. 设计方案：是否恰当？设计方案原文：We conducted a6-year, double-blind trial involving2000women with osteopenia (defined by a T score of−1.0to−2.5at either the total hip or the femoral neck on either side) who were65years of age or older. Participants were randomly assigned to receive four infusions of either zoledronate at a dose of5mg (zoledronate group) or normal saline (placebo group) at18-month intervals. A dietary calcium intake of1g per day was advised, but calcium supplements were not provided. Participants who were not already taking vitamin D supplements received cholecalciferol before thetrial began (a single dose of2.5mg) and during the trial (1.25mg per month). The primary end point was the time to first occurrence of a nonvertebral or vertebral fragility fracture.恰当。

进行的是一项随机、双盲、安慰剂对照试验。

文章对研究方案详细介绍，并具体描述了实施过程。

3. 随机、盲法是如何实施？随机、盲法具体实施原文：Consecutive eligible participants were assigned to one of the two trial groups on the basis of a randomization list with variable block size that was prepared by the trial statistician. Infusion bottles were labeled by staff members who had no contact with trial participants. All the trial personnel were unaware of the initial trial-group assignments.4. 受试对象的选择及代表性受试者选择的原文：Eligible participants were ambulatory postmenopausal women65years of age or older, with a T score of−1.0to−2.5at either the total hip or the femoral neck on either side; both hips were assessed in all patients. A T score of less than−2.5at one hip site (total hip or femoral neck on either side) did not preclude participation in the trial, as long as another hip site met the criteria, so patients at the interface of osteopenia and osteoporosis were included. The presence of spinal osteoporosis was not an exclusion criterion as long as the T score was above−3.0. Other exclusion criteria were an estimated glomerular filtration rate of less than30ml per minute per1.73 m2of body-surface area, major systemic disease, cancer in the previous2 years, metabolic bone disease, or regular use of bone-active drugs in the previous year (including bisphosphonates, estrogen, antiestrogens, and prednisone at a dose of2.5mg or greater per day or equivalent).文章详细描述了纳入排除标准，受试者均来自新西兰奥克兰地区使用选民登记册招募的2000名妇女。

5. 施加因素：标准化、稳定性、合理性施加因素原文：A total of2000women were recruited with the use of electoral registers from the Auckland region of New Zealand and were randomly assigned, in a 1:1ratio, to receive four infusions of either zoledronate at a dose of5mg (zoledronate group) or normal saline(placebo group), packaged in identical containers, at18-month intervals.Women who were not already taking vitamin D supplements were given a single oral dose of cholecalciferol(2.5mg[100,000IU]) at least1weekbefore their first infusion and subsequently received cholecalciferol at a dose of1.25mg per month for the duration of the trial. A dietary calcium intake of1g per day was advised, but calcium supplements were not supplied.安慰剂（生理盐水）与唑来膦酸均采用相同的容器包装；两组均每18个月输注4次。