BACKGROUND & AIMS: CONTEXT:In the Denosumab and High-Dose Teriparatide Administration (DATA-HD) study, we reported that 15 months of combined high-dose (HD) teriparatide and denosumab increased mean areal bone mineral density (aBMD) at the hip and spine more than combined denosumab and standard-dose (SD) teriparatide. OBJECTIVE:In the current analysis, we compare the individual rates of aBMD response between the treatment groups. DESIGN:Single-site, open-label, randomized controlled trial in which postmenopausal women received either teriparatide 20-μg daily (SD) or 40-μg daily (HD) given months 0 through 9, overlapped with denosumab 60 mg, given months 3 through 15 (15 months' total duration). The proportion of participants in the SD and HD groups experiencing total hip, femoral neck, and lumbar spine aBMD gains of >3%, >6%, and >9% were compared. PARTICIPANTS:Postmenopausal women with osteoporosis completing all study visits (n = 60). MAIN OUTCOME MEASURE(S):aBMD (dual x-ray absorptiometry). RESULTS:At the end of the 15-month treatment period, a higher proportion of women in the HD group had aBMD increases >3% (83% vs. 58%, P = .037) and >6% (45% vs. 19%, P = .034) at the total hip, and >3% at the femoral neck (86% vs. 63%, P = .044). At the lumbar spine, >3% response rates were similar, whereas the >6% and >9% response rates were greater in the HD group (100% vs. 79%, P = .012 and 93% vs. 59%, P = .003, respectively). CONCLUSION:Compared with the SD regimen, more women treated with the HD regimen achieved clinically meaningful and rapid gains in hip and spine aBMD. These results suggest that this approach may provide unique benefits in the treatment of postmenopausal osteoporosis.

背景与目标：

BACKGROUND & AIMS: :Many postmenopausal women treated with teriparatide for osteoporosis have previously received antiresorptive therapy. In women treated with alendronate (ALN) or raloxifene (RLX), adding versus switching to teriparatide produced different responses in areal bone mineral density (aBMD) and biochemistry; the effects of these approaches on volumetric BMD (vBMD) and bone strength are unknown. In this study, postmenopausal women with osteoporosis receiving ALN 70 mg/week (n = 91) or RLX 60 mg/day (n = 77) for ≥18 months were randomly assigned to add or switch to teriparatide 20 µg/day. Quantitative computed tomography scans were performed at baseline, 6 months, and 18 months to assess changes in vBMD; strength was estimated by nonlinear finite element analysis. A statistical plan specifying analyses was approved before assessments were completed. At the spine, median vBMD and strength increased from baseline in all groups (13.2% to 17.5%, p < 0.01); there were no significant differences between the Add and Switch groups. In the RLX stratum, hip vBMD and strength increased at 6 and 18 months in the Add group but only at 18 months in the Switch group (Strength, Month 18: 2.7% Add group, p < 0.01 and 3.4% Switch group, p < 0.05). In the ALN stratum, hip vBMD increased in the Add but not in the Switch group (0.9% versus -0.5% at 6 months and 2.2% versus 0.0% at 18 months, both p ≤ 0.004 group difference). At 18 months, hip strength increased in the Add group (2.7%, p < 0.01) but not in the Switch group (0%); however, the difference between groups was not significant (p = 0.076). Adding or switching to teriparatide conferred similar benefits on spine strength in postmenopausal women with osteoporosis pretreated with ALN or RLX. Increases in hip strength were more variable. In RLX-treated women, strength increased more quickly in the Add group; in ALN-treated women, a significant increase in strength compared with baseline was seen only in the Add group.

背景与目标： : 许多接受teriparatide治疗骨质疏松症的绝经后妇女以前接受过抗吸收疗法。在接受阿仑膦酸盐 (ALN) 或雷洛昔芬 (RLX) 治疗的女性中，添加与改用teriparatide在区域骨矿物质密度 (aBMD) 和生物化学方面产生不同的反应; 这些方法对体积BMD (vBMD) 和骨强度的影响尚不清楚。在这项研究中，接受ALN 70  mg/周 (n   =   91) 或RLX 60  mg/天 (n   =   77) ≥ 18个月的骨质疏松症绝经后妇女被随机分配添加或转换为teriparatide 20  μ g/天。在基线，6个月和18个月进行定量计算机断层扫描以评估vBMD的变化; 通过非线性有限元分析估算强度。在评估完成之前，批准了指定分析的统计计划。在脊柱，所有组的中位vBMD和强度均较基线增加 (13.2% 至17.5%，p  <  0.01); Add组和Switch组之间无显着差异。在RLX层中，Add组在6和18个月时髋部vBMD和强度增加，而Switch组在18个月时仅增加 (强度，18个月: 2.7% Add组，p  <  0.01和3.4% Switch组，p  <  0.05)。在ALN层中，Add组的hip vBMD增加，但Switch组没有增加 (6个月时0.9% 对-0.5%，18个月时2.2% 对0.0%，两者p ≤ 0.004组差异)。18个月时，Add组髋关节力量增加 (2.7%，p  <  0.01)，而Switch组没有增加 (0%); 但组间差异不显著 (p   =   0.076)。添加或改用teriparatide对经ALN或RLX预处理的骨质疏松症的绝经后妇女的脊柱强度具有类似的益处。髋部力量的增加变化更大。在接受RLX治疗的女性中，Add组的力量增加更快; 在接受ALN治疗的女性中，仅在Add组中，力量与基线相比显着增加。

BACKGROUND & AIMS: :Teriparatide has been commercially available in the United States (US) for over 3 years. This summary spans the early experience with this therapy. As of December 31, 2005, over 235 000 patients had filled a prescription for teriparatide world-wide. Data collected from July to December 2004, from 15,000 retail pharmacies in the US, indicated that the mean age of patients was 67.5 years, and more recent data collected from January through October 2005 indicated that 90% of patients were female. According to market research conducted with prescribing physicians from February through March of 2005, it is estimated that over 80% of patients receiving prescriptions for teriparatide had already experienced one or more prior fractures. Since teriparatide is administered subcutaneously, it is important that patients receive training on the use of the teriparatide injection device (i.e., the pen device). Educational programs are available for those who have been prescribed teriparatide therapy. Patients may also contact a customer care program regarding a variety of topics, including pen device use. Based on patient feedback, design changes have been implemented in the pen device to facilitate optimal use. Updates have also been made to the prescribing information to reflect the post-marketing surveillance experience. Adverse experiences reported to date have been consistent with the current product label and with cumulative teriparatide clinical trial experience. As of December 31, 2005 no reports of pathology-confirmed osteosarcoma have been received for individuals who have been treated with teriparatide, either with the commercially available drug or in clinical trials. We are unaware of any reports of osteosarcoma in association with other preparations of teriparatide, or other peptides of parathyroid hormone, either in the setting of clinical trials or from marketed drug experience.

背景与目标： : Teriparatide已在美国 (US) 商业化销售超过3年。此摘要涵盖了这种疗法的早期经验。截至2005年12月31日，全球已有235 000多名患者填写了teriparatide的处方。从7月到2004年12月，从美国15,000家零售药店收集的数据表明，患者的平均年龄为67.5岁，从1月到2005年10月收集的最新数据表明，90% 的患者是女性。根据从2月到3月2005年的处方医生进行的市场研究，据估计，接受teriparatide处方的患者中有80% 以上已经经历过一次或多次骨折。由于teriparatide是皮下给药的，因此患者接受有关使用teriparatide注射装置 (即pen装置) 的培训非常重要。接受过teriparatide治疗的人可以使用教育计划。患者还可以就各种主题 (包括笔式设备的使用) 联系客户服务计划。根据患者的反馈，已经在pen设备中实施了设计更改，以促进最佳使用。还对处方信息进行了更新，以反映上市后的监督经验。迄今为止报告的不良经验与当前产品标签和累积的teriparatide临床试验经验一致。截至2005年12月31日，尚未收到已使用市售药物或临床试验用teriparatide治疗的患者的病理证实骨肉瘤的报告。我们不知道骨肉瘤与其他teriparatide制剂或甲状旁腺激素的其他肽相关的任何报道，无论是在临床试验中还是从上市药物经验中。

BACKGROUND & AIMS: :We describe a case of successful treatment to nonunion after multiple arthrodesis operations for Charcot arthropathy with teriparatide. We describe the case of a 25-year-old woman with severe Type I diabetes mellitus that resulted in nonunion after multiple arthrodesis operations for Charcot arthropathy. The woman sustained a femoral shaft fracture for which she underwent surgery with intramedullary nail fixation. Immediately after surgery, an empiric course of teriparatide was initiated. Femoral shaft fracture healing was observed after 2 weeks, and the woman was able to walk 12 weeks after the surgery, at which point plain film and computed tomography images revealed complete union of the ankle.

背景与目标： : 我们描述了使用teriparatide进行多次关节固定术治疗Charcot关节病后成功治疗骨不连的案例。我们描述了一名25岁的女性，患有严重的I型糖尿病，在针对Charcot关节病的多次关节固定术后导致骨不连。该妇女患有股骨干骨折，并接受了髓内钉固定手术。手术后，立即开始经验性的teriparatide疗程。2周后观察到股骨干骨折愈合，该妇女在手术后12周能够行走，此时平片和计算机断层扫描图像显示脚踝完全愈合。

BACKGROUND & AIMS: :We medicated teriparatide in three patients, who had a nonunion of the femur even after the initial surgical intervention. Teriparatide was administered for 3-9 months after a diagnosis of nonunion. A successful union was obtained in all three patients without further surgical intervention, and no adverse events related to the use of teriparatide were observed. Our report showed that teriparatide could be an alternative to surgical intervention in nonunion of the femur.

背景与目标： : 我们对三名患者进行了teriparatide的药物治疗，即使在最初的手术干预后，这些患者的股骨骨不连。诊断为骨不连后，应用Teriparatide 3-9个月。在没有进一步手术干预的情况下，所有三名患者均获得了成功的联合，并且未观察到与使用teriparatide相关的不良事件。我们的报告显示，teriparatide可以替代股骨骨不连的外科手术。

BACKGROUND & AIMS: -2

背景与目标： -2

BACKGROUND & AIMS: UNLABELLED:The progression of fractured vertebral collapse is not rare after a conservative treatment of vertebral compression fracture (VCF). Teriparatide has been shown to directly stimulate bone formation and improve bone density, but there is a lack of evidence regarding its use in fracture management. Conservative treatment with short-term teriparatide is effective for decreasing the progression of fractured vertebral body collapse. INTRODUCTION:Few studies have reported on the prevention of collapsed vertebral body progression after osteoporotic VCF. Teriparatide rapidly enhances bone formation and increases bone strength. This study evaluated preventive effects of short-term teriparatide on the progression of vertebral body collapse after osteoporotic VCF. METHODS:Radiographs of 68 women with single-level osteoporotic VCF at thoracolumbar junction (T11-L2) were reviewed. Among them, 32 patients were treated conservatively with teriparatide (minimum 3 months) (group I), and 36 were treated with antiresorptive (group II). We measured kyphosis and wedge angle of the fractured vertebral body, and ratios of anterior, middle, and posterior heights of the collapsed body to posterior height of a normal upper vertebra were determined. The degree of collapse progression was compared between two groups. RESULTS:The progression of fractured vertebral body collapse was shown in both groups, but the degree of progression was significantly lower in group I than in group II. At the last follow-up, mean increments of kyphosis and wedge angle were significantly lower in group I (4.0° ± 4.2° and 3.6° ± 3.6°) than in group II (6.8° ± 4.1° and 5.8° ± 3.5°) (p = 0.032 and p = 0.037). Decrement percentages of anterior and middle border height were significantly lower in group I (9.6 ± 10.3 and 7.4 ± 7.5 %) than in group II (18.1 ± 9.7 and 13.8 ± 12.2 %) (p = 0.001 and p = 0.025), but not in posterior height (p = 0.086). CONCLUSIONS:In female patients with single-level osteoporotic VCF at the thoracolumbar junction, short-term teriparatide treatment did not prevent but did decrease the progression of fractured vertebral body collapse.

背景与目标：

BACKGROUND & AIMS: CONTEXT:Teriparatide and denosumab are effective treatments for osteoporosis and typically reserved as second-line options after patients have used bisphosphonates. However, limited head-to-head comparative effectiveness data exist between teriparatide and denosumab. OBJECTIVE:We compared changes in bone mineral density (BMD) between groups treated with teriparatide or denosumab after using bisphosphonates, focusing on the change in BMD while on either drug over 2 years. DESIGN:Observational cohort study using electronic medical records from two academic medical centers in the United States. PARTICIPANTS:The study population included osteoporotic patients >45 years who received bisphosphonates >1 year before switching to teriparatide or denosumab. OUTCOME MEASURES:Annualized BMD change from baseline at the lumbar spine, total hip, and femoral neck. RESULTS:Patients treated with teriparatide (n = 110) were compared with those treated with denosumab (n = 105); the mean (SD) age was 70 (10) years and median duration (interquartile range) of bisphosphonate use was 7.0 (5.6 to 9.7) years. Compared with denosumab users, teriparatide users had higher annualized BMD change at the spine by 1.3% (95% CI 0.02, 2.7%) but lower at the total hip by -2.2% (95% CI -2.9 to -1.5%) and the femoral neck by -1.1% (95% CI -2.1 to -0.1%). Those who switched to teriparatide had a transient loss of hip BMD for the first year, with no overall increase in the total hip BMD over 2 years. CONCLUSIONS:Among patients who use long-term bisphosphonates, the decision of switching to teriparatide should be made with caution, especially for patients at high risk of hip fracture.

背景与目标：

BACKGROUND & AIMS: CONTEXT:In postmenopausal osteoporotic women, denosumab fully inhibits teriparatide-induced bone resorption at approved doses. This property of denosumab is distinct from that of alendronate and likely contributes to the efficacy of combination denosumab and teriparatide therapy. Whether denosumab fully inhibits bone resorption when challenged by a higher dose of teriparatide is unknown. OBJECTIVE:We aimed to define the comparative ability of denosumab and alendronate to block the acute proresorptive effects of high-dose teriparatide. DESIGN, SETTING, AND PARTICIPANTS:In this randomized controlled trial, bone resorption (serum C-telopeptide [CTX]) was measured in 25 postmenopausal women prior to and 4 hours after a single 40-μg sc teriparatide injection. Subjects then received either a single injection of denosumab 60 mg or oral alendronate 70 mg weekly for 8 weeks. After 8 weeks, serum CTX was again measured before and 4 hours after a teriparatide a 40-μg injection. OUTCOMES:The primary outcome was the between-group difference in the teriparatide-induced change in CTX from baseline to week 8. RESULTS:At baseline, 40 μg of teriparatide induced similar 4-hour increases in mean CTX in both groups (alendronate 47% ± 14%, denosumab 46% ± 16%). After 8 weeks, teriparatide was still able to stimulate bone resorption in women treated with alendronate (mean CTX increase of 43% ± 29%) but not in women treated with denosumab (-7% ± 11%; P < .001 for between group comparison). CONCLUSIONS:Denosumab, but not alendronate, fully inhibits the ability of high-dose teriparatide to increase bone resorption acutely. These results suggest that combining denosumab with a more potent anabolic stimulus may result in greater separation between bone resorption and formation and hence greater increases in bone mass.

背景与目标：

BACKGROUND & AIMS: STUDY DESIGN:A multicenter case-control study. OBJECTIVE:The aim of this study was to investigate the independent predictors of osseous union after posterior lumbar interbody fusion (PLIF). SUMMARY OF BACKGROUND DATA:PLIF is usually performed to treat lumbar degenerative diseases in elderly patients. Some patients exhibit intervertebral pseudoarthrosis. METHODS:We analyzed 66 elderly patients with osteoporosis who underwent PLIF from 2011 to 2014 (all women, mean age 71 years, follow-up period ≥6 months). Patients were randomly allocated to receive either treatment with weekly teriparatide, starting at 1 week postoperatively, or no teriparatide. Preoperative lumbar spine radiographs were obtained, and the amount of anterior slippage was measured. Osseous union was assessed by computed tomography at 6 months postoperatively. RESULTS:Thirty-three patients (50%) showed complete osseous union, while 33 did not. Teriparatide was administered in 20 (61%) patients of the union group and in 9 (27%) patients of the nonunion group (P < 0.01). The preoperative anterior slippage of the cranial vertebra next to fusion segment < 2 mm was observed in 16 (49%) and 4 (12%) patients in the union and nonunion groups, respectively (P < 0.01). Multivariate regression analysis showed that teriparatide administration (odds ratio, 4.75; 95% confidence interval: 1.51-14.90; P < 0.01) and preoperative anterior slippage of the cranial vertebra next to fusion segment < 2 mm (odds ratio, 5.90; 95% confidence interval: 1.53-22.70; P < 0.01) were independently associated with osseous union within 6 months after PLIF. At 6 months postoperatively, the mean femoral neck bone mineral density significantly increased by 1.1% in the union group and decreased by 1.3% in the nonunion group (P < 0.05). CONCLUSION:Weekly teriparatide administration and preoperative anterior slippage of the cranial vertebra next to fusion segment < 2 mm were independent predictors of osseous union within 6 months after PLIF. Our findings suggest that biological and mechanical factors may influence the improvement of spinal fusion. LEVEL OF EVIDENCE:4.

背景与目标：

BACKGROUND & AIMS: :The therapy of osteoporosis is mostly based upon the use of drugs which inhibit bone resorption. Among these, the bisphosphonate family is the best known and mostly used by clinicians. Both second and third generation bisphosphonates, like alendronate and risedronate, are now available as weekly tablets which have facilitated the patient compliance to treatment together with a decreased occurrence of gastrointestinal side effects. These compounds are used efficiently to treat postmenopausal osteoporosis and osteoporosis of men as well. Their use did provide good evidence of increased bone mineral density (BMD) and a reduction in fracture rates. The use of intravenous bisphosphonates such as Zoledronate, Ibandronate and Pamidronate remains in most of the cases limited to special indications such as intolerance to the oral formulations and treatment of patients with bone metastases. The selective estrogen modulators (SERM's) family is limited to a single product on the market as of now, Raloxifene, which does inhibit bone resorption and is well documented by postmenopausal women to increase BMD and reduce vertebral fractures. In addition, a large range of positive nonosseous effects have been documented such as the reduction of the incidence of breast cancer. Other substances do have a strong anabolic effect such as Teriparatide, a recombinant human formulation of PTH 1-34. This compound has demonstrated good efficacy in postmenopausal women, increasing vertebral and hip BMD and reducing the incidence of fractures at both sites. The exact role of Teriparatide in the clinical setting is still open but its overall impact in the therapy of osteoporosis could be major due to its major efficiency over shorter periods of time. Strontium ranelate, a new divalent Strontium salt taken orally, acts both as an anti-catabolic and anabolic agent. The first results provided with strontium ranelate are very promising due to its major effect on the increase in BMD both at the vertebral and hip sites and its ability to reduce the incidence of fractures at both locations. Additional data are awaited to confirm these initial positive results.

背景与目标： : 骨质疏松症的治疗主要基于使用抑制骨吸收的药物。其中，双膦酸盐家族是最著名的，并且大多数被临床医生使用。第二代和第三代双膦酸盐，如阿仑膦酸盐和利塞膦酸盐，现在都可以作为每周片剂获得，这有助于患者对治疗的依从性以及减少胃肠道副作用的发生。这些化合物可有效地用于治疗绝经后骨质疏松症和男性骨质疏松症。它们的使用确实为骨矿物质密度 (BMD) 增加和骨折率降低提供了良好的证据。在大多数情况下，静脉内使用双膦酸盐 (如唑来膦酸盐，伊班膦酸盐和帕米膦酸盐) 仍然仅限于特殊适应症，例如对口服制剂的不耐受和骨转移患者的治疗。到目前为止，选择性雌激素调节剂 (SERM's) 家族仅限于市场上的单一产品雷洛昔芬 (Raloxifene)，它确实抑制骨吸收，并且绝经后妇女已充分证明可以增加BMD并减少椎骨骨折。此外，已经记录了许多积极的非骨效应，例如降低了乳腺癌的发病率。其他物质确实具有很强的合成代谢作用，例如Teriparatide，PTH 1-34的重组人制剂。该化合物已在绝经后妇女中显示出良好的疗效，可增加椎骨和髋骨BMD并减少两个部位的骨折发生率。Teriparatide在临床环境中的确切作用仍然是开放的，但由于其在较短时间内的主要效率，其在骨质疏松症治疗中的总体影响可能是主要的。雷奈酸锶是一种新的口服二价锶盐，同时充当抗分解代谢和合成代谢剂。雷奈酸锶提供的第一个结果非常有希望，因为它对椎骨和髋关节部位的BMD增加有重要影响，并且能够减少两个部位的骨折发生率。等待其他数据来确认这些初步的积极结果。

BACKGROUND & AIMS: OBJECTIVE:The aim of this study was to evaluate the effect of teriparatide therapy on mandibular fracture healing in rats with medication-related osteonecrosis of the jaw (MRONJ). MATERIALS AND METHODS:To induce MRONJ, a total of 120 rats received intravenous zoledronate 0.06 mg/kg once a week for 6 weeks and their right mandibular first molar was extracted. Eighty of 94 rats with MRONJ were randomly selected and underwent unilateral mandibular osteotomy to replicate a fracture. After surgery, the rats were randomly assigned to T (teriparatide-treated) and C (control) groups. Group T (n = 40) received subcutaneous injection of 2 μg/kg/day teriparatide and group C (n = 40) received the same volume of normal saline until sacrifice. Four and 8 weeks after surgery, 20 rats in each group were sacrificed. Fracture healing was scored using a histological grading system (1 to 10). RESULTS:In group C, at 4 weeks and 8 weeks post-fracture, fibrous and cartilaginous tissues and scant bone formation at the fracture site and lacunae without osteocyte in adjacent mandibular bone were seen. In group T, substantial amounts of new trabecular bone rimmed by osteoblasts and some areas of remodeled mature bone were seen. After 8 weeks, extensive replacement of trabecular bone with mature bone occurred. Except between C4 and C8 groups, the healing score was significantly different between all subgroups. CONCLUSION:Teriparatide therapy successfully improved mandibular fracture healing in rats with MRONJ. However, this study was limited by the use of an animal model whose anatomy, physiology, and drug metabolism might be different from humans. CLINICAL RELEVANCE:The present study showed that teriparatide therapy may be used adjunctive to surgery in the treatment of mandibular fractures in MRONJ patients.

背景与目标：

BACKGROUND & AIMS: INTRODUCTION:Teriparatide effects are mediated via the preferential stimulation of osteoblastic activity over osteoclastic activity. Amino-terminal propeptide of type I procollagen (PINP) is an indicator of osteoblastic activity. OBJECTIVE:Develop an algorithm using PINP as an aid in the management of patients with postmenopausal osteoporosis treated with teriparatide. RESEARCH DESIGN AND METHODS:For inclusion in this post-hoc analysis, trials had to be investigations of teriparatide 20 microg/day in postmenopausal women with osteoporosis having measurements of PINP at 3 months and bone mineral density (BMD) at 12 months. Signal-to-noise ratio was calculated for a series of markers of bone turnover in the Fracture Prevention Trial. An algorithm was developed to monitor patients treated with teriparatide using PINP. RESULTS:Three trials met inclusion criteria and included the Fracture Prevention, Forteo-Alendronate Comparator and Anabolic After Antiresorptive trials. PINP had the highest signal-to-noise ratio of all bone-turnover markers. Positive PINP responses defined as increases > 10 microg/L were observed in 77-79% of teriparatide- and in 6% of placebo-treated patients after 3 months of study drug. Mean lumbar spine BMD increases after 12 months of teriparatide in patients having PINP changes > 10 microg/L ranged from 8.3% to 9.5% and in patients with PINP changes < or = 10 microg/L ranged from 5.9% to 7.6%. In the algorithm, PINP is measured at baseline and after 1-3 months of therapy. Patients with PINP increases > 10 microg/L are given a positive message. Patients with PINP increases < or = 10 microg/L are assessed for adherence, teriparatide administration and storage techniques, and for the presence of medical conditions that might limit their therapeutic response, and these issues are addressed as appropriate. Patients without these issues and with PINP increases < or = 10 microg/L should be given a neutral message because BMD may significantly increase with continued therapy. CONCLUSIONS:The PINP algorithm provides information regarding the anabolic response to teriparatide therapy and has the potential to identify patients requiring help with issues of adherence, injection technique, teriparatide storage, and medical problems limiting therapeutic responsiveness to teriparatide treatment. Data assessing the relationship of changes in PINP to fracture risk reduction are not available. We recommend physicians audit the use of the algorithm in practice so that improvements can be made.

背景与目标：

BACKGROUND & AIMS: UNLABELLED:Most post-vertebroplasty new-onset adjacent vertebral compression fractures (VCFs) occur within 2-3 months, and antiresorptive agents do not significantly reduce the risk of their occurrence. In opposite mechanism, teriparatide directly stimulates bone formation and improves bone strength and quality faster. The therapeutic effect of teriparatide is better than that of vertebroplasty combined with an antiresorptive treatment and is a potentially useful therapy for new-onset adjacent VCFs after vertebroplasty. INTRODUCTION:Following vertebroplasty, patients are at increased risk of new-onset adjacent-level VCFs. The therapeutic effect of antiresorptive agents is too slow, and they are associated with the risk of new VCFs. Teriparatide markedly increases bone formation and strength and reduces the incidence of new-onset VCFs. This prospective cohort study compared the therapeutic effects of teriparatide with those of combined vertebroplasty and an anti-resorber for treating new-onset adjacent VCFs after vertebroplasty. METHODS:Fifty patients with adjacent VCFs were randomly assigned to two groups: teriparatide only (group A) and additional vertebroplasty combined with an antiresorptive agent (group B). Relevant clinical data of the two groups were prospectively compared. RESULTS:The 22 patients in group A were at higher risk of new VCFs than those in group B (22 patients); they were older and had more pre-existing fractures (p < 0.05). Patients treated with teriparatide had a significantly lower incidence of new-onset VCFs (odds ratio = 0.21; 95% confidence interval, 0.02-2.10). Teriparatide-mediated VCF reduction was 78.57%, which was markedly better than that of group B. The teriparatide group had a significant decrease in the visual analog scale and an increase in the Japanese Orthopedic Association low back pain score after 6 months of treatment (p < 0.05). The increase in lumbar spine BMD was marked in the teriparatide group (21.70% vs. 6.87%) after an 18-month treatment. CONCLUSIONS:Treatment of post-vertebroplasty adjacent VCFs with teriparatide (no new vertebroplasty) was more effective than that of repeated vertebroplasties combined with an anti-resorber.

背景与目标：

BACKGROUND & AIMS: :This randomized prospective study aimed to evaluate the clinical outcome of denosumab treatment alone and in combination with teriparatide in treatment-naive postmenopausal Japanese female patients with osteoporosis. Thirty patients were randomly assigned to two groups: (1) denosumab group (denosumab alone, n=13); and (2) combination group (denosumab+teriparatide, n=17). Serum bone-specific alkaline phosphatase (BAP), serum tartrate-resistant acid phosphatase (TRACP)-5b, urinary cross-linked N-terminal telopeptides of type I collagen (NTX), and bone mineral density (BMD) of L1-4 lumbar vertebrae (L-BMD) and bilateral total hips (H-BMD) were determined at the first visit and at various time points up to 24 months post-treatment to determine percentage changes. Serum TRACP-5b and urinary NTX were equally suppressed in both groups and maintained at low levels, with slight increases at 12, 18 and 24 months. BAP was significantly decreased in both groups from 4 to 24 months, with significant differences between the groups at 4, 8 and 15 months (P<0.05). L-BMD was significantly increased at most time points in both groups, with a significant difference between the combination group and denosumab group at 24 months (17.2% increase versus 9.6% increase; P<0.05). There was no significant difference in H-BMD between the two groups, although the levels tended to be higher in the combination group than in the denosumab group (9.5% increase versus 5.6% increase). These findings suggest that denosumab+teriparatide combination therapy may represent an important treatment for primary osteoporotic patients at high risk of vertebral fracture.

背景与目标： : 这项随机前瞻性研究旨在评估denosumab单独治疗以及与特立帕肽联合治疗未经治疗的绝经后日本女性骨质疏松症患者的临床结果。30例患者被随机分为两组 :( 1) 地诺单抗组 (单独地诺单抗，n = 13); (2) 联合组 (地诺单抗 + 特立帕肽，n = 17)。血清骨特异性碱性磷酸酶 (BAP)，血清抗酒石酸酸性磷酸酶 (TRACP)-5b，尿交联的I型胶原N末端肽 (NTX)，在首次就诊时以及治疗后长达24个月的不同时间点确定L1-4腰椎 (l-bmd) 和双侧全髋 (h-bmd) 的骨矿物质密度 (BMD)，以确定百分比变化。两组的血清TRACP-5b和尿NTX均被抑制，并维持在低水平，在12、18和24个月时略有增加。两组的BAP在4至24个月期间均显着降低，在4、8和15个月时组之间有显着差异 (P<0.05)。在两组的大多数时间点，l-bmd均显着增加，在24个月时，联合组和地诺单抗组之间有显着差异 (17.2% 增加比9.6% 增加; P<0.05)。两组之间的h-bmd没有显着差异，尽管联合组的水平往往高于denosumab组 (9.5% 增加与5.6% 增加)。这些发现表明，denosumab + teriparatide联合治疗可能是对椎体骨折高风险的原发性骨质疏松患者的重要治疗。