PTH (1-34) and pelvic fracture healing: A randomized controlled trial

技术摘要 骨盆骨折的发病率随着年龄的增长而急剧增加，从每万人5.4人和3.8人- 65岁至69岁的女性和男性为93.5岁，每万人年为44.5岁 分别为90岁及以上。3骨盆骨折伴剧烈疼痛，慢性不动 老年人丧失功能和独立性。14骨盆骨折需要大量的医疗保健 资源，根据行政索赔数据，它们是与骨质疏松症相关的最昂贵的 骨折。4未愈合的骨折，发生在三分之一的骨盆骨折患者在3个月时，16可导致 持续的疼痛和冲击移动性。随着人口老龄化，预计 尽管骨盆骨折的发病率很高，但迫切需要找到有效的治疗方法来加速愈合。 耻骨升支骨折在随机双盲安慰剂对照中最相关和最实用 研究表明，这种骨折伴有严重疼痛和老年人行动不便，与延迟有关 骨折愈合，几乎总是非手术治疗。目前对骨盆骨折的护理标准 包括疼痛管理、患者动员和预防与并存相关的并发症 条件。我们假设开发一种成功的辅助疗法来加速骨折愈合 将改善护理，并降低骨盆骨折的直接和间接成本。在建议的 试验我们将招募患有急性骨质疏松症相关骨盆骨折的65岁女性和男性，并 在一项安慰剂对照的双盲研究中，在3个月的治疗中解决3个具体目标，以确定 骨盆骨折的标准护理和特瑞帕泰20微克/天与安慰剂相比： 1.在常规X线片上发现皮质桥接的早期证据，然后是确认性病灶CT，a 减少CT扫描辐射暴露的新方法(主要结果)。 2.根据数字评定量表和减少使用的评估，导致疼痛更快地减轻 毒品(次要结果)。 3.使用较短的物理性能电池评估可更快地改善功能结果 下肢功能(次要结果)。 我们将延长这项研究9个月的开放标签TPTD，以确定是否有任何潜在的差异 在3个月的治疗期间，安慰剂组和TPTD组是明显的，并随着时间的推移而持续，即使在 在三个月的安慰剂对照干预后使用TPTD的患者。 如果TPTD能促进骨折愈合，这项研究将对骨盆患者的治疗产生影响 非手术对象的骨折，经常面临剧烈疼痛、慢性不能动弹和功能丧失 老年人。骨盆骨折加速愈合的积极发现也将鼓励对TPTD的研究 用于治疗其他骨质疏松性骨折。

Technical Abstract The incidence rate of pelvic fractures increases dramatically with age, from 5.4 and 3.8 per 10,000 person- years in women and men aged 65 to 69 years to 93.5 and 44.5 per 10,000 person-years in women and men aged 90 years and older, respectively.3 Pelvic fractures are accompanied by severe pain, chronic immobility and loss of function and independence in the elderly.14 Pelvic fractures consume substantial healthcare resources, and based on administrative claims data, they are one of the most costly osteoporosis related fractures.4 Un-healed fractures, occurring in one-third of pelvic fracture patients at 3 months,16 can cause continued pain and impact mobility. With aging of the population, and expected concomitant increase in the incidence of pelvic fractures, there is a pressing need to find effective treatments that will accelerate healing. Fracture of the pubic ramus is most relevant and practical for randomized double-blinded placebo controlled study as this fracture is accompanied by severe pain and immobility in elderly, is associated with delayed fracture healing, and is almost always treated non-operatively. The current standard of care for pelvic fractures includes pain management, patient mobilization, and the prevention of complications associated with comorbid conditions. We hypothesize that development of a successful adjunctive therapy to accelerate fracture healing would lead to improved care and reduce both direct and indirect costs from pelvic fractures. In the proposed trial we will recruit women and men >65 years of age with acute osteoporosis-related pelvic fractures and address 3 specific aims over 3 months of treatment in a placebo controlled double blind study to determine if standard care and teriparatide 20 mcg/day versus placebo for pelvic fractures: 1. Results in earlier evidence of cortical bridging on routine radiographs followed by confirmatory Focus CT, a novel method to reduce radiation exposure from CT scans (primary outcome). 2. Leads to a faster reduction in pain as assessed by both the Numeric Rating Scale and a reduction in the use of narcotics (secondary outcome). 3. Leads more rapidly to improved functional outcome using a short physical performance battery to assess lower extremity function (secondary outcome). We will extend this study with 9 months of open label TPTD to determine if any potential differences between the placebo and TPTD groups during the 3 months of treatment are evident and persist over time, even in patients who use TPTD after the three month placebo controlled intervention. If TPTD can improve fracture healing, this study will have an impact on the treatment of persons with pelvic fracture who are not surgical candidates and often face severe pain, chronic immobility, and loss of function in the elderly. A positive finding of accelerated healing of pelvic fractures would also encourage study of TPTD for treatment of other osteoporotic fractures.