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。

BACKGROUND & AIMS: -2

背景与目标： -2

BACKGROUND & AIMS: OBJECTIVE:Hypophosphatasia (HPP) is a rare inherited metabolic bone disease from deficient activity of the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP). Reportedly, teriparatide (parathyroid hormone 1-34) can benefit the adult form of HPP, including fracture healing. We studied 2 women with adult HPP given teriparatide and reviewed the reports of 6 additional patients. METHODS:A 68-year-old black woman (patient 1) described low-trauma fractures and had subnormal serum alkaline phosphatase (ALP) activity. Biochemical findings were consistent with HPP. Mutation analysis revealed a heterozygous defect in exon 10 of TNSALP (ALPL). Teriparatide was injected daily for 2 years. Four years later, she fractured her right hip. Treatment was resumed for 8 months without further fractures. A 53-year-old white woman (patient 2) reported low-trauma fractures and had subnormal serum ALP. Mutation analysis revealed a heterozygous defect in exon 8 of TNSALP. She injected teriparatide daily for 2 years. One year later, bone mineral density (BMD) declined and treatment was resumed for 3 months. When she sustained a sacral fracture, teriparatide was administered for a further 18 months. RESULTS:Patient 1's serum ALP increased while receiving teriparatide and returned to baseline after its discontinuation. BMD remained unchanged, but no fractures were sustained. Patient 2's serum ALP increased, but the improvement was not sustained. Femoral neck BMD increased significantly during the first cycle, declined significantly afterwards, and was regained during a second course of teriparatide. CONCLUSION:Teriparatide shows some benefit for adult HPP. ABBREVIATIONS:ALP = alkaline phosphatase BMD = bone mineral density BSAP = bone-specific alkaline phosphatase CTX = C-telopeptide DXA = dual-energy X-ray absorptiometry FN = femoral neck HPP = hypophosphatasia LS = lumbar spine PEA = phosphoethanolamine PLP = pyridoxal 5'-phosphate PTH = parathyroid hormone SQ = subcutaneous TNSALP = tissue-nonspecific isoenzyme of alkaline phosphatase TPTD = teriparatide.

背景与目标：

BACKGROUND & AIMS: UNLABELLED:Increases in lumbar spine BMD account for 30-41% of the vertebral fracture risk reduction with teriparatide treatment. The remaining fracture risk reduction is caused by improvements in non-BMD determinants of bone strength. INTRODUCTION:Changes in BMD account for a small percentage of the fracture risk reduction seen in patients treated with antiresorptive drugs. The relationship between changes in lumbar spine BMD and vertebral fracture risk reduction with teriparatide treatment has not been assessed. MATERIALS AND METHODS:The relationship between spine BMD and the risk of new vertebral fractures after teriparatide treatment was assessed using data from the Fracture Prevention Trial. Postmenopausal women with osteoporosis (n = 1637) were randomized to placebo or teriparatide 20 or 40 microg/day for a median of 19 months. Spine BMD was assessed at baseline and 18 months. Vertebrae whose fracture status changed during the trial were removed from the calculation of BMD. Baseline and endpoint lateral spine radiographs were assessed using a visual semiquantitative technique. RESULTS:Both the baseline and change in spine BMD were contributors to vertebral fracture risk. The mean spine BMD increase in teriparatide-treated patients was 0.09 g/cm(2) across tertiles of baseline spine BMD. Compared with placebo, teriparatide significantly reduced the risk of new vertebral fracture for all endpoint BMD values. Teriparatide-mediated increases in spine BMD accounted for 30% (in the low baseline spine BMD tertile) to 41% (in the high baseline spine BMD tertile) of the reduction in vertebral fracture risk. CONCLUSIONS:Increases in BMD account for approximately one third of the vertebral fracture risk reduction seen with teriparatide. The majority of the risk reduction, however, results from improvements in non-BMD determinants of bone strength.

背景与目标：

BACKGROUND & AIMS: :Osteoporosis Pseudoglioma (OPPG) is characterized by severe juvenile-onset osteoporosis and ocular abnormalities. It is caused by one of several inactivating mutations in LRP5, a gene importantly involved in bone formation. The objective of this study was to evaluate the efficacy of teriparatide in a young man with OPPG. The subject of this case report is a 19-year-old man with congenital blindness and low trauma fractures because of OPPG. A 2-year course of teriparatide, 20 µg/day, was initiated after a 6-year course of intravenous pamidronate infusions, the latter 3 years of which had minimal effects on bone mineral density (BMD). Measurements in serum were made of C-terminal telopeptide of type I collagen (CTX), N-terminal propeptide of type I collagen (P1NP), total and ionized calcium, phosphate, uric acid, complete blood count, and renal and liver function tests. Urinary calcium/creatinine ratio was determined. BMD was measured by DXA yearly. BMD increased by 9.7% in lumbar spine and 10.2% in right femur hip. CTX rose early, peaking in month 3, followed by an increase in P1NP, peaking in month 9. Both indices returned to baseline by month 24. The increase in CTX followed by P1NP is an unusual time course when teriparatide is used to treat osteoporosis but may be typical of low bone turnover states. There were no adverse events. In a patient with OPPG, teriparatide markedly increased BMD in the lumbar spine and femur hip.

背景与目标： : 骨质疏松假性胶质瘤 (OPPG) 的特征是严重的幼年性骨质疏松症和眼部异常。它是由LRP5的几个失活突变之一引起的，LRP5是一个重要参与骨形成的基因。这项研究的目的是评估特立帕肽对患有OPPG的年轻人的疗效。该病例报告的主题是一名19岁的男性，由于OPPG而患有先天性失明和低创伤骨折。在静脉输注帕米膦酸盐6年疗程后，开始了为期2年的特立帕肽疗程，每天20 µ g，后3年对骨矿物质密度 (BMD) 的影响很小。血清中的C末端肽I型胶原 (CTX)，N末端肽I型胶原 (P1NP)，总和离子钙，磷酸盐，尿酸，全血细胞计数以及肾和肝功能测试。测定尿钙/肌酐比值。BMD通过DXA每年测量。腰椎9.7% 增加BMD，右股骨髋关节10.2%。CTX提前上涨，在第3个月达到峰值，随后P1NP上升，在第9个月达到峰值。这两个指数在第24个月前恢复到基线。当特立帕肽用于治疗骨质疏松症时，CTX的增加继之以P1NP是一个不寻常的时间过程，但可能是低骨转换状态的典型特征。无不良事件发生。在OPPG患者中，特立帕肽显着增加了腰椎和股骨髋关节的BMD。

BACKGROUND & AIMS: :Teriparatide is an anabolic therapy for osteoporosis approved in the United States since 2002 and European Union since 2003; however, approval in Japan lagged significantly. This report describes analyses based on International Conference on Harmonisation (ICH) E-5 guidelines that support bridging between Japanese studies and the large Fracture Prevention Trial (FPT). We analyzed data from single teriparatide doses in healthy Japanese and Caucasian postmenopausal women (J-PK) and from studies of 6 months [Phase 2, dose ranging (J-Ph2)] and 12 months [Phase 3, efficacy and safety (J-Ph3)] of randomized, placebo-controlled, once-daily treatment in Japanese subjects with osteoporosis. In J-PK, apparent teriparatide area-under-the-curve (AUC) and peak concentration (C (max)) were up to 40% higher in Japanese versus Caucasian women; however, body weight-adjusted values were comparable between populations; these findings were supported by population pharmacokinetic analyses. Between the FPT and Japanese studies, baseline demographic characteristics were similar but bone mineral density (BMD) at lumbar spine (L1-L4) and body weight were lower for Japanese subjects. With teriparatide 20 μg/day, significant increases in BMD were observed compared to placebo at 12 months in both the FPT and J-Ph3 study, and percent change and actual change in BMD were comparable between studies. Dose response at 6 months was also comparable across populations. No novel safety signals were identified in Japanese subjects. These analyses show that teriparatide clinical data met ICH E-5 criteria for bridging. Findings from foreign trials such as the FPT can thus be extrapolated to Japanese subjects treated with teriparatide 20 μg/day.

背景与目标： : Teriparatide是美国2002年和欧盟2003年批准的骨质疏松症的合成代谢疗法; 但是，日本的批准显着滞后。本报告描述了基于国际协调会议 (ICH) E-5指南的分析，这些指南支持日本研究与大型骨折预防试验 (FPT) 之间的衔接。我们分析了健康的日本和白种人绝经后妇女 (j-pk) 和随机，安慰剂对照的6个月 [第2阶段，剂量范围 (J-Ph2)] 和12个月 [第3阶段，疗效和安全性 (J-Ph3)] 的研究数据，在患有骨质疏松症的日本受试者中每日一次治疗。在j-pk中，日本人与白人女性相比，明显的teriparatide曲线下面积 (AUC) 和峰值浓度 (C (max)) 高达40%; 然而，体重调整值在人群之间是可比的; 这些发现得到了人群药代动力学分析的支持。在FPT和日本研究之间，基线人口统计学特征相似，但日本受试者的腰椎 (L1-L4) 骨矿物质密度 (BMD) 和体重较低。在FPT和J-Ph3研究中，使用teriparatide 20 μ g/天，与安慰剂相比，BMD在12个月时显着增加，并且BMD的百分比变化和实际变化在研究之间是可比的。6个月时的剂量反应在不同人群中也是相当的。在日本受试者中没有发现新的安全信号。这些分析表明，teriparatide临床数据符合ICH E-5桥接标准。因此，可以将国外试验 (例如FPT) 的发现外推到用teriparatide 20 μ g/天治疗的日本受试者。

BACKGROUND & AIMS: SUMMARY:Since approval by the U.S. Food and Drug Administration (FDA) in December 2002, teriparatide (recombinant 1-34 PTH; Forteo) has been safely used by more than 430,000 patients. Prior to FDA approval, however, there was concern that teriparatide might increase the risk for patients to develop osteosarcoma, as almost 45% of the rats treated with this drug at the highest-tested dose level developed this aggressive form of bone cancer. Balancing the proven benefits of teriparatide shown by clinical trials with the theoretical risk for teriparatide-induced human osteosarcoma, the FDA mandated both a 'black-box' warning of this potential side-effect and a company-sponsored postmarketing surveillance program. As a participating institute of that surveillance program, we report upon the second person with potential teriparatide-induced osteosarcoma, in this case, complicated by a history of pelvic radiation. INTRODUCTION:Given the theoretic risk of the drug teriparatide and the known risk of radiation in inducing osteosarcoma, we raise the issue of whether teriparatide magnified the risk of radiation-induced osteosarcoma in our patient and try to determine which factor played the predominant role in the development of his disease. METHODS:We analyzed preclinical rat data, human clinical experience with teriparatide, and our patient's clinical history to assess the human risk of teriparatide and radiation exposure. RESULTS:After the first case of suspected osteosarcoma was reported in December 2005, we encountered a second possible teriparatide-induced osteosarcoma less than a year later. Review of the preclinical animal data would suggest that teriparatide is safe for human use when used as recommended by the manufacturer. Given the location of the sarcoma within the field of radiation and the limited exposure to teriparatide before diagnosis, it is unlikely that teriparatide played the predominant role in the emergence of this patient's osteosarcoma. We cannot, however, exclude the possibility that teriparatide magnified the carcinogenic effect of radiation therapy to induce the osteosarcoma. CONCLUSION:Of more than 430,000 persons who have received teriparatide for treatment of severe osteoporosis, we report the second patient to develop osteosarcoma. Although teriparatide reduces osteoporosis-related fractures in select patient populations, important contraindications, such as prior radiation exposure, should be considered before use.

背景与目标：

BACKGROUND & AIMS: :Human progeroid syndromes (PSs) include a group of genetic "premature aging" diseases that affect a variety of organ systems. Bone diseases are common sequelae of patients diagnosed with PSs. Teriparatide therapy is recommended for elderly men with low bone mineral density (BMD; T-score <-2.5) and at least 1 fragility fracture who are unable to tolerate bisphosphonates. We describe a 20-yr-old patient affected by PS and severe osteoporosis complicated with femoral fracture. The patient experienced a significant improvement in lumbar spine BMD after treatment with teriparatide.

背景与目标： : 人类早衰综合症 (PSs) 包括一组影响各种器官系统的遗传 “早衰” 疾病。骨疾病是诊断为PSs的患者常见的后遗症。对于骨矿物质密度低 (BMD; T评分 <-2.5) 且至少1例脆性骨折且不能耐受双膦酸盐的老年男性，建议使用Teriparatide治疗。我们描述了一名20岁的患者，该患者患有PS和严重的骨质疏松症并伴有股骨骨折。经teriparatide治疗后，患者的腰椎BMD显着改善。

BACKGROUND & AIMS: CONTEXT:In postmenopausal osteoporosis, combining denosumab and teriparatide increases hip and spine bone mineral density more than either monotherapy. OBJECTIVE:The objective of the study was to determine the effects of 2 years of combination therapy on bone microarchitecture and estimated strength. DESIGN:This was an open-label, randomized controlled trial. PARTICIPANTS AND METHODS:We performed high-resolution peripheral quantitative computed tomography at the distal tibia and radius in 94 postmenopausal osteoporotic women randomized to 2 years of teriparatide 20 μg sc daily, denosumab 60 mg sc every 6 months, or both. RESULTS:Total volumetric bone mineral density (vBMD) at the radius and tibia, trabecular vBMD at the radius, and cortical vBMD at the tibia all increased more in the combination group than both monotherapy groups (P < .002 for all comparisons with combination). Cortical thickness at the tibia also increased more in the combination group (8.1% ± 4.3%) than both other groups (P < .001). Cortical porosity at both the radius and tibia increased progressively over the 24-month treatment period in the teriparatide group but was stable in both other groups (P < .001 teriparatide vs both other groups). Trabecular vBMD at the tibia increased similarly in all groups, whereas radius trabecular vBMD increased more in the combination group than the other groups (P < .01 for both comparisons). Finite element analysis-estimated strength improved or was maintained by all treatments at both the radius and tibia. CONCLUSIONS:Two years of combined teriparatide and denosumab improves bone microarchitecture and estimated strength more than the individual treatments, particularly in cortical bone. These findings suggest that this regimen may be beneficial in postmenopausal osteoporosis.

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BACKGROUND & AIMS: BACKGROUND:Anabolic responsiveness to teriparatide can be blunted or delayed in patients previously treated with alendronate. The extent of this effect is different for other antiresorptives. This study evaluated the early anabolic effects of teriparatide in postmenopausal women with osteoporosis previously treated with alendronate or risedronate. METHODS:Patients treated for at least 24 months with alendronate or risedronate discontinued their bisphosphonate and received teriparatide for 12 months. The primary endpoint was a comparison of changes from baseline in N-terminal propeptide of type 1 collagen after 3 months between prior bisphosphonate groups. We also examined changes in other bone turnover markers, bone mineral density (BMD), and relationships between early changes in bone turnover markers and 12-month areal and volumetric BMD. RESULTS:In the prior risedronate group, the N-terminal propeptide of type 1 collagen increase was significantly greater after 3 months of teriparatide than in the prior alendronate group (mean +/- se, 86.0 +/- 5.6 vs. 61.2 +/- 5.3 ng/ml, respectively; P < 0.001). Findings were similar for the other bone turnover markers. The changes in areal BMD and trabecular spine volumetric BMD were also greater in the prior risedronate group (P < 0.05). Early changes in bone turnover markers correlated with changes in trabecular spine volumetric BMD at 12 months (Spearman r = 0.45). Teriparatide was well tolerated. CONCLUSION:This nonrandomized but prospective study suggests that there may be differences in anabolic responsiveness to teriparatide as a function of the type of prior bisphosphonate exposure.

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