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.     

p38丝裂原活化蛋白激酶信号途径在鼠破骨细胞生成和骨吸收中的作用

目的研究p38丝裂原活化蛋白激酶(p38MAPK)信号途径在甲状旁腺素相关肽(PTHrP)诱导的破骨细胞生成和骨吸收中的作用。方法取小鼠骨髓细胞,在PTHrP(45ng/ml)的刺激下,在不同试验组中分别入0.1、1.0及10μmol/L的p38MAPK抑制剂Fr167653,继续培养6d。抗酒石酸染色,进行破骨细胞计数。在小鼠颅骨部位注射PTHrP建立骨吸收和高钙血症动物模型。每日给予p38MAPK抑制剂Fr16765330mg/kg,每日2次,X线片观察骨吸收面积,组织学检查计算单位面积内破骨细胞数目,采集血样观察全血内游离钙水平。结果PTHrP刺激下,大量破骨细胞生成(118.9±28.3)个/孔;加入0.1μmol/LFr167653可以部分抑制破骨细胞的生成(79.6±28.0)个/孔,加入10μmol/LFr167653几乎全抑制了破骨细胞生成(7.4±0.4)个/孔,每日给予Fr16765330mg/kg,每日2次,可以明显抑制骨吸收,表现为X线片上骨吸收面积减少,单位面积内破骨细胞数目减少,但是并不能有效地抑制高钙血症。结论抑制p38MAPK信号途径可以抑制破骨细胞的分化和局部骨吸收。     

Impact of Weekly Teriparatide on the Bone and Mineral Metabolism in Hemodialysis Patients With Relatively Low Serum Parathyroid Hormone: A Pilot Study

Adynamic bone disease in HD patients is characterized by skeletal resistance to parathyroid hormone (PTH) or suppression of PTH release, leading to a downregulated bone turnover and bone fracture. Hence, we examined the efficacy of weekly teriparatide for HD patients with low PTH indicating adynamic bone disease without a history of parathyroidectomy. Fifteen HD patients with low PTH were recruited in this prospective observational study. Of them, 10 received teriparatide for 12 months and five nontreated patients were enrolled as control. Primary outcomes were defined as the changes in bone mineral density and bone turnover markers. Bone mineral density at the lumbar spine increased by 3.7% and 2.5% at 6 and 12 months, respectively, and bone formation markers increased, while bone resorption markers did not change in the teriparatide group. At 12 months after teriparatide administration, endogenous PTH was secreted followed by the recovery of low bone turnover. 40% of patients in the teriparatide group dropped out due to adverse events and the most common adverse event was transient hypotension. This study suggests that weekly teriparatide for HD patients with low PTH in the absence of parathyroidectomy accelerates bone formation and bone turnover, leading to increased trabecular bone mass and secretion of endogenous PTH.     

特立帕肽对老年去卵巢大鼠血管钙化的影响

目的：观察特立帕肽对老年去卵巢大鼠血管钙化的影响,并探讨其发挥作用的分子机制。方法用30只10个月龄SD大鼠,随机分为3组院假手术组、去卵巢组及特立帕肽治疗组。特立帕肽治疗组给予20μg/kg特立帕肽皮下注射,隔天1次,持续12周。术前及给药期间收集大鼠血清,给药结束后观察子宫的组织学变化。酶联免疫吸附法(ELISA)检测血中未羧化基质羧基谷氨酸蛋白(uc-MGP)的量及雌激素的变化;原子分光光度计测量血管总钙含量;Von Kossa染色观察动脉钙化;免疫组化法观察血管uc-MGP的表达;荧光实时定量PCR扩增MGP mRNA,观察其在胸主动脉的表达水平。结果血清中uc-MGP含量去卵巢组最高,特立帕肽治疗组其次,假手术组最低(P<0.05)。去卵巢组及特立帕肽治疗组雌激素水平明显下降(P<0.05)。去卵巢组血管总钙含量明显高于假手术组(P<0.01),特立帕肽治疗组明显低于去卵巢组(P<0.01)。血管未羧化MGP表达出现在血管钙化周围区域,钙化严重组表达较多。特立帕肽治疗组阳性较少表达。去卵巢组表达量最低,假手术组MGP mRNA表达量最高,特立帕肽治疗组表达量介于两者之间,差异有统计学意义(P<0.01)。结论特立帕肽对绝经后血管钙化有改善作用,可能是通过调节MGP的基因表达及活性发挥作用。     

Characteristics of patients initiating teriparatide for the treatment of osteoporosis

Summary The demographic and clinical characteristics of patients initiating teriparatide were compared with those of patients initiating bisphosphonates for the treatment of osteoporosis. In these samples of commercially insured, Medicare, and Medicaid patients, patients initiating teriparatide were older, in poorer health, and appeared to have more severe osteoporosis than patients initiating bisphosphonates. Introduction The demographic and clinical characteristics of patients initiating teriparatide are compared with those of patients initiating bisphosphonates. Methods Beneficiaries (45 years and older) with at least one claim for teriparatide or a bisphosphonate from 2003 to 2005 and continuous enrollment in the previous 12 months and subsequent 6 months were identified from commercial, Medicare, and Medicaid administrative claims databases. Patients initiating teriparatide (commercial/Medicare (N = 2,218); Medicaid (N = 824)) were compared to patients initiating bisphosphonates (commercial/Medicare (N = 97,570); Medicaid (N = 77,526)) in terms of age, provider specialty, comorbidities, prior use of osteoporosis medications, fractures, BMD screening, health status, and resource utilization. Results Teriparatide patients were older and in poorer health than bisphosphonate patients. Approximately 38% of teriparatide patients in both groups had fractured in the pre-period compared to 16% of commercial/Medicare and 15% of Medicaid bisphosphonate patients. Teriparatide patients were more likely to have used osteoporosis medications in the pre-period (79.9% versus 32.1% (commercial/Medicare); 82.2% versus 19.6% (Medicaid)). Conclusions In these samples of patients, those initiating teriparatide differed from those initiating bisphosphonates. Teriparatide patients were older, in poorer health, and appeared to have more severe osteoporosis than bisphosphonate patients. Comparisons of treatment outcomes should take these differences in patient characteristics into consideration.     

不同剂量甲状旁腺素氨基端1-34片段连续刺激对SaoS-2人成骨肉瘤细胞系的影响

目的　观察不同剂量人甲状旁腺素氨基端 1 34片段 (hPTH1 34)连续刺激对SaoS 2人成骨肉瘤细胞系功能、信号传导的影响及机制。方法　对于对数生长期的SaoS 2细胞 ,采用 5、50、50 0和 5 0 0 0 μg/L浓度hPTH1 34连续刺激 8d。于刺激前、刺激中及刺激后 ,采用“金氏”化学法和放射免疫法测定培养液中碱性磷酸酶 (ALP)和骨钙素 (BGP)浓度 ;采用竞争蛋白结合法测定环磷酸腺苷(cAMP)浓度 ;采用逆转录 (RT) PCR对c fos基因表达水平进行半定量分析。结果　 50 0 μg/LhPTH1 34刺激显著增高ALP水平 (P <0 .0 5 ,比对照组 ) ,促进成骨细胞分化。 5 0 0 0 μg/L刺激组BGP水平逐渐下降 (P值均 <0 .0 5 ,比对照组和刺激前 )。 50、50 0 μg/LhPTH1 34连续刺激组cAMP明显增高 (P值均<0 .0 5)。 5μg/L和 5 0 0 0 μg/L组cAMP无显著改变。 50、50 0 μg/L组c fos基因表达水平高于其他组。结论　hPTH1 34对成骨样细胞的影响与剂量显著相关 ,50及 50 0 μg/LhPTH1 34连续刺激显著促进成骨样细胞分化 ,增加骨骼的合成代谢。ALP、cAMP的水平及c fos基因表达对不同浓度hPTH1 34刺激的反应明显同步 ,提示hPTH1 34主要通过蛋白激酶A信号途径影响成骨细胞功能及c fos基因的表达 ,后者进一步在转录水平调节成骨细胞     

Teriparatide and the risk of nonvertebral fractures in women with postmenopausal osteoporosis

Purpose

In the Fracture Prevention Trial, the risks of any nonvertebral fracture (relative risk [RR] 0.65, P = 0.04) and any fragility nonvertebral fracture (RR 0.47, P = 0.02) were significantly reduced in the teriparatide 20 μg/day (teriparatide) versus placebo group. The purpose of this analysis was to examine the efficacy of teriparatide versus placebo on a variety of other nonvertebral fracture outcomes.

Materials and methods

The Fracture Prevention Trial was a double-blind trial of postmenopausal women with osteoporosis and vertebral fractures randomly assigned to teriparatide (N = 541) or placebo (N = 544) administered by daily self-injection for a median of 19 months and a median follow-up of 21 months. All patients received calcium and vitamin D supplementation. Reports of nonvertebral fractures were collected from patients at each visit and confirmed by review of a radiograph or written radiology report. Nonvertebral fractures were recorded for the following sites: distal radius/wrist, humerus, rib/clavicle, hip, ankle, distal foot, pelvis, or other. Pathological fractures and fractures of the face, skull, metacarpals, fingers and toes were excluded. Fractures were classified by investigators as fragility or traumatic fractures. The three endpoints considered were six nonvertebral sites (nonvert-6), a set of common nonvertebral fractures described in a Food and Drug Administration Guidance document for the treatment and prevention of postmenopausal osteoporosis (FDA), and a European Union major set (major) of nonvertebral fractures.

Results

For teriparatide versus placebo, the point estimates for the RR of nonvert-6 (RR 0.54, P = 0.06; fragility RR 0.32, P = 0.014), FDA (RR 0.60, P = 0.15; fragility RR 0.38, P = 0.05), and major (RR 0.52, P = 0.02; fragility RR 0.38, P = 0.02) nonvertebral fracture endpoints were smaller than for the all nonvertebral fracture endpoint. Lower RRs were observed when the outcomes were limited to fragility fractures, and significant reductions in traumatic nonvertebral fractures were not observed.

Conclusion

In the Fracture Prevention Trial, the risk reduction for nonvertebral fracture in patients treated with teriparatide versus placebo depended on the set of nonvertebral fractures included in the analysis; lower RRs were observed for nonvertebral fractures most likely to be of osteoporotic origin. No significant reductions in traumatic nonvertebral fractures were observed.     

Adherence and persistence in patients with severe osteoporosis treated with teriparatide

Abstract

Introduction:

Medical intervention plays a key role in the treatment of postmenopausal osteoporosis and patients’ adherence to therapy is essential for optimal clinical outcomes. While adherence in RCTs is usually around 70–90%, a previous study showed that in clinical practice only 27.8% and 46.5% of the women on oral daily vs. weekly alendronate were still on treatment after 12 months. Data on adherence to teriparatide (TPTD) treatment of severe postmenopausal osteoporosis are available from only few countries. This study assessed adherence and persistence with TPTD in Germany.     

Actual versus predicted first-year utilization patterns of teriparatide in patients with employer-sponsored health insurance*

ABSTRACT

Objective: To characterize first-year utilization patterns of teriparatide derived from a claims database analysis versus predictions from an economic model.

Research design and methods: Claims data for actual teriparatide utilization were obtained from an integrated administrative database of approximately 3.4 million beneficiaries. A control group included patients with osteoporosis but without the use of teriparatide. An economic model, which relied on first-year market share projections, predicted the utilization of teriparatide from the demographic characteristics of the plan. Predictions were compared to actual utilization for eight health plans within the database.

Main outcome measures: Demographic and clinical characteristics, number of teriparatide patients, and days of teriparatide therapy.

Results: Less than 1% of patients diagnosed with osteoporosis received teriparatide. Teriparatide-treated patients, compared to other patients with osteoporosis, were older and more likely to have experienced a previous fracture or to have received previous osteoporosis pharmacotherapy. For the combined 505?300 lives in the eight plans used for the comparative analysis, there were 134 teriparatide patients; the model predicted 131. For individual plans, the predictions varied in their accuracy. The greatest under-prediction for one plan was 17 patients (40 predicted vs. 57 actual), while the greatest over-prediction was 18 patients (34 predicted vs. 16 actual). For the other 6 plans, the predictions were within four patients of the actual number of teriparatide users. A similar pattern of differences was observed by comparing actual versus predicted days of teriparatide therapy across the eight plans.

Limitations: Some clinical details of the actual patient cohorts, such as bone mineral density results, were not available in the database. The comparisons made between the teriparatide model predictions and actual utilization were based on analyses of a single model and do not speak to the broader issue of the accuracy of predictive economic models in general.

Conclusions: Overall, first-year teriparatide utilization was relatively limited, consistent with model predictions. Predictions for individual plans varied in their accuracy.