Persistence with teriparatide in patients with osteoporosis: the UK experience

Introduction The objective of this paper was to determine the persistence with teriparatide at 12 months in all patients in the UK who were prescribed the treatment since its launch.Methods Virtually all patients prescribed teriparatide in the UK receive treatment through Healthcare at Home, Basingstoke, UK. Data was obtained to assess the start date, discontinuation date and reason for discontinuation in all patients receiving teriparatide since its launch. Persistence was defined as the number of patients continuing treatment.Results A total of 1,104 patients were included in the analysis. The median duration of use in all patients was 252 days. Of the 435 patients who were at least 12 months post-initiation of treatment, persistence was 87%. Forty-two patients (3.8%) had discontinued treatment due to adverse events.Conclusions This study demonstrates that persistence with teriparatide at 12 months is very high and is probably greater than that of existing oral therapies for osteoporosis. The reasons for the high persistence rates seen with teriparatide are likely to be multi-factorial. The high persistence rates should help to optimise the effectiveness of therapy in this group of high-risk patients.     

Treatment responses with once-weekly teriparatide therapy for osteoporosis

Summary

Monitoring bone mineral density is useful to assess treatment response for osteoporosis, but it does not always reflect fracture prevention. Two types of bone mineral density thresholds were used to analyze data from a once-weekly teriparatide trial, and they appear to be useful indicators of treatment success for osteoporosis.

Introduction

This study aimed to clarify whether the criteria of treatment response could be used to evaluate treatment success with once-weekly teriparatide.

Methods

The data of subjects whose lumbar or femoral neck bone mineral density (BMD) was measured in the TOWER study were included. The least significant change (LSC) and the absolute change were used as the criteria for judgment of treatment success. The correlation between the incidence of fractures and the treatment response was also assessed.

Results

There was no significant difference in baseline characteristics between the placebo and teriparatide groups. Once-weekly teriparatide therapy for 72 weeks showed treatment success in 79.2 % of the subjects for lumbar BMD and 44.1 % for femoral neck BMD by LSC and in 50.5 and 39.6 % by absolute change, respectively. A lower incidence of vertebral fracture was observed in patients who achieved treatment success for lumbar BMD. With the LSC, some treatment success was observed in the early phase of treatment, and it increased with treatment duration.

Conclusions

It appears that the LSC could be used as a surrogate efficacy indicator at an earlier stage of treatment, and the absolute criterion of ?2.5SD was confirmed as a useful marker of long-term treatment success.

     

The impact of switching once-weekly teriparatide to denosumab in osteoporosis patients

Background

It has been reported that switching from daily (d) teriparatide (TPTD) to denosumab (DMAb) is effective for severe osteoporosis patients. However, there have been no reports about switching from weekly (w) TPTD to DMAb in patients with osteoporosis. Once-weekly 56.5-μg TPTD treatment increases bone mineral density (BMD) and reduces fracture events. The objective of the current retrospective study was to elucidate the impact of switching w-TPTD to DMAb in patients with osteoporosis.

Adrenal effects of teriparatide in the treatment of severe postmenopausal osteoporosis

Summary  

The aim of our study was to investigate the effects of teriparatide on the hypophysis–adrenal axis in postmenopausal women. Treatment with teriparatide increased plasmatic and urinary levels of cortisol after 6 and 12 months. Our paper demonstrates a possible direct secretagogue effect of teriparatide on adrenals in osteoporotic postmenopausal women.     

Complicated osteoporosis in progeroid syndrome: treatment with teriparatide

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.     

Improvement in health-related quality of life in osteoporosis patients treated with teriparatide

Background  

Individuals with osteoporosis and recent vertebral fractures suffer from pain and impaired health-related quality of life (HRQL). To determine whether patients with osteoporosis treated with teriparatide experienced improvement in HRQL and pain symptoms after several months of therapy.     

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.     

Relationship between duration of teriparatide therapy and clinical outcomes in postmenopausal women with osteoporosis

Summary  The extent to which fracture protection and safety varies with increasing time on teriparatide [rhPTH(1-34)] therapy is a clinically relevant unanswered question. In postmenopausal women with osteoporosis, increased duration of teriparatide versus placebo treatment was associated with a progressive decrease in the rates of nonvertebral fragility fractures and back pain. Introduction  The impact of duration of teriparatide [rhPTH(1-34)] therapy on patient outcomes is a relevant unanswered question. Methods  Postmenopausal women with osteoporosis were randomized to once-daily subcutaneous injection with placebo (N = 544), teriparatide 20 μg (TPTD20; N = 541), or teriparatide 40 μg (TPTD40; N = 552) plus calcium and vitamin D supplementation. The time to first nonvertebral fragility fracture and new or worsening back pain following treatment initiation was analyzed using Cox partial likelihood regression treating time on therapy as a linear, time-dependent covariate. Results  Compared with placebo, the relative hazard for nonvertebral fragility fractures decreased by 7.3% for each additional month of TPTD20 [hazard ratio = 0.927, 95% CI (0.876 to 0.982), p = 0.009] and by 7.6% for each additional month of TPTD40 [hazard ratio = 0.924, 95% CI (0.871 to 0.981), p = 0.009]. Clinical vertebral fractures appeared to increase over time in the placebo group and occurred primarily in the first time interval in the teriparatide treatment groups. Compared with placebo, the relative hazard of back pain was decreased by 8.3% for each additional month of TPTD20 [hazard ratio = 0.920, 95% CI (0.902 to 0.939), p < 0.001] and 8.7% for each additional month of TPTD40 [hazard ratio = 0.917, 95% CI (0.898 to 0.935), p < 0.001]. Conclusions  These findings suggest increased nonvertebral fracture protection, reduced back pain, and reduced occurrence of side effects with longer duration of teriparatide therapy. Some of these findings were presented at the 67th Annual Scientific Meeting of the American College of Rheumatology in Orlando, Florida, October 23–28, 2003 and at the 31st European Symposium on Calcified Tissues in Nice, France, June 5–9, 2004.     

应用特立帕肽对骨质疏松症腰椎融合手术疗效影响的研究进展

腰椎融合手术是治疗腰椎退行性疾病的主要方式之一。随着人口老龄化加剧,骨质疏松症在患有脊柱退行性疾病的患者中非常多见。腰椎融合手术的骨质疏松相关并发症包括内固定失败、假关节形成、邻近节段退变、继发椎体骨折、近端交界性后凸等。骨质疏松相关并发症严重影响腰椎融合手术的效果,而在腰椎融合术前后进行抗骨质疏松治疗可以有效地降低术后1年内发生骨质疏松相关并发症的概率。甲状旁腺激素（parathyroid hormone,PTH）是一种由甲状旁腺产生的多肽,参与维持钙和磷的稳态。特立帕肽（teriparatide）,即重组人PTH（1-34）[recombinant human PTH（1-34）,rhPTH（1-34）],是骨的合成代谢剂,其通过刺激细胞表面相应的受体,激活成骨细胞增殖和分化所必需的信号通路,促进新骨组织的形成,并抑制成骨细胞和骨细胞的凋亡。作为第一个促成骨类的药物,特立帕肽自2002年开始用于治疗骨质疏松症,提高骨质疏松患者骨密度。由于特立帕肽的骨合成代谢作用,已有研究报道在其他骨病中使用特立帕肽修复和改善骨的质量。脊柱融合术的目的是实现脊柱的实体关节融合,提高脊柱的稳定性。脊柱融合的成功取决于骨的质量和数量,骨质疏松会影响脊柱融合的效果。对骨质疏松患者可以采取有效的药物治疗策略,以提高骨密度并促进新的骨形成。研究表明,特立帕肽可以提高融合骨的体积和质量,并提高脊柱的融合率。特立帕肽改善骨质疏松症腰椎融合术后融合率已在许多动物模型和临床试验中得到证实。笔者就特立帕肽在骨质疏松症腰椎融合术动物模型和临床试验中的研究进展做一综述。     

Efficacy data on teriparatide (parathyroid hormone) in patients with postmenopausal osteoporosis

Until recently, the only therapeutic agents available for postmenopausal osteoporosis acted by inhibiting bone resorption and decreased the fracture risk by no more than 50%. Teriparatide, the recombinant 1-34 fragment of human parathyroid hormone, is a bone formation enhancer that has recently been licensed for use in established postmenopausal osteoporosis. Intermittent parathyroid hormone administration preferentially stimulates bone formation. The resultant increase in bone mass and improvement in bone architecture translate into a large decrease in the fracture risk that constitutes a major advance in the treatment of postmenopausal osteoporosis. Further work is needed to define the role for teriparatide in the therapeutic strategy for postmenopausal osteoporosis and to determine whether this agent is best used alone or in synchronous or sequential combination with bone resorption inhibitors.     

Disuse osteoporosis in patients with total hip prostheses

Summary Aseptic loosening of total hip arthroplasty is still a serious problem. Bone qualitiy might be one of the major factors influencing loosening. In a previous study, bone loss during the reparation phase was evaluated with modified computed tomography at the site of the implant. The present study documents the degree of disuse osteoporosis prior to and after surgery. Bone density of both tibiae of patients with unilateral artificial hip joints was evaluated longitudinally. Preoperatively a significant right-left difference was found, that has to be attributed to the preoperative unloading of the diseased leg. After surgery a slight but significant bone loss was found in both legs attributable to the immobilization following surgery and the reduced activity in the first 6 months. In successfully operated cases this loss is temporary. In one patient bone loss continued; after 1 year there are now clinical signs of implant loosening. Although the spectrum of physical activity in our group was wide, no correlation between activity and bone loss has been found so far.     

Disuse osteoporosis in patients with total hip prostheses

Aseptic loosening of total hip arthroplasty is still a serious problem. Bone quality might be one of the major factors influencing loosening. In a previous study, bone loss during the reparation phase was evaluated with modified computed tomography at the site of the implant. The present study documents the degree of disuse osteoporosis prior to and after surgery. Bone density of both tibiae of patients with unilateral artificial hip joints was evaluated longitudinally. Preoperatively a significant right-left difference was found, that has to be attributed to the preoperative unloading of the diseased leg. After surgery a slight but significant bone loss was found in both legs attributable to the immobilization following surgery and the reduced activity in the first 6 months. In successfully operated cases this loss is temporary. In one patient bone loss continued; after 1 year there are now clinical signs of implant loosening. Although the spectrum of physical activity in our group was wide, no correlation between activity and bone loss has been found so far.     

Histomorphometric changes by teriparatide in alendronate-pretreated women with osteoporosis

Summary

The level of increased bone formation after 24 months of treatment with teriparatide (rhPTH (1–34), TPTD) is similar in patients who were either treatment-naïve (TN) or had lower bone turnover initially due to previous alendronate (ALN) therapy.

Introduction

Bone anabolic effects of TPTD in postmenopausal women with osteoporosis may be blunted during the initial phase after switching from ALN to TPTD. To explore the long-term implications, we examined histomorphometric and biochemical markers of bone turnover of patients on TPTD therapy after long-term ALN treatment.

Methods

Paired biopsies were obtained after tetracycline double labeling at baseline and after 24 months of TPTD treatment from 29 ALN-pretreated (64.5?±?16.4 months) and 16 TN patients. Biochemical markers were measured at baseline, during the treatment, or at study end.

Results

Compared with the baseline, after 24-month TPTD, activation frequency (Ac.F.) and osteoid surface (OS) increased in both groups: 0.11–0.34 cycles per year, 3.96–9.8% in the ALN-pretreated group and 0.19–0.33 cycles per year, 6.2–11.3% (p?<?0.05) in the TN group, respectively. Biochemical and histomorphometric markers correlated positively both at baseline and endpoint. Serum amino terminal propeptide of type I procollagen (PINP) correlated with Ac.F. (r?=?0.57, p?<?0.001 and r?=?0.48, p?<?0.01) and OS (r?=?0.51, p?<?0.01 and r?=?0.56, p?<?0.01) at baseline and endpoint, respectively. Following 3 months of treatment, increases in biochemical markers like PINP predicted the increase in Ac.F. (r?=?0.52, p?<?0.01) and OS (r?=?0.54, p?<?0.01) after 24 months.

Conclusions

The increased level of formation is similar in patients who were either TN or had lower bone turnover initially due to previous ALN therapy. Elevated bone formation in postmenopausal women with osteoporosis was sustained over a 24-month period by TPTD. Biochemical markers of bone formation are a good surrogate for the assessment of TPTD effects.     

The effects of once-weekly teriparatide on hip geometry assessed by hip structural analysis in postmenopausal osteoporotic women with high fracture risk

Weekly administration of teriparatide has been shown to reduce the risk of vertebral and non-vertebral fractures in patients with osteoporosis at higher fracture risk in Japan. However, its efficacy for hip fracture has not been established. To gain insight into the effect of weekly teriparatide on the hip, hip structural analysis (HSA) based on dual-energy X-ray absorptiometry (DXA) was performed using the data of 209 postmenopausal osteoporotic women who had participated in the original randomized, multicenter, double-blind, placebo-controlled trial assessing the effects of once-weekly 56.5 μg teriparatide for 72 weeks. The DXA scans, obtained at baseline, 48 weeks and 72 weeks, were analyzed to extract bone mineral density (BMD) and cross-sectional geometrical indices at the narrowest point on the neck (NN), the intertrochanteric region (IT), and the proximal shaft. Compared with placebo after 72 weeks, the teriparatide group showed significantly higher BMD, average cortical thickness, bone cross-sectional area, and section modulus, and lower buckling ratio at both the NN and IT regions. No significant expansion of periosteal diameter was observed at these regions. There were no significant differences in BMD and HSA indices at the shaft region. The results indicate that overall structural strength in the proximal femur increased compared to placebo, suggesting that once-weekly teriparatide effectively reverses changes in hip geometry and strength with aging.     

Consistency of fracture risk reduction in Japanese and Caucasian osteoporosis patients treated with teriparatide: a meta-analysis

In the global Fracture Prevention Trial, teriparatide reduced the risk of vertebral and non-vertebral fractures and significantly increased BMD. Recently, a 12-month, phase 3, randomized, multicenter, double-blind, placebo-controlled trial with BMD as a primary endpoint was conducted to assess the effects of teriparatide in Japanese subjects at high risk of fracture. Although BMD was significantly increased in the Japanese study, the study was not statistically powered to assess the anti-fracture efficacy with teriparatide treatment. A meta-analysis was carried out testing whether teriparatide had consistent anti-fracture efficacy in Japanese patients compared to that observed in the global fracture trial. Three studies in which fracture data were available from prospectively scheduled spinal radiographs were included in the analysis. A systematic review of the literature (Medline, Embase) confirmed that no studies with teriparatide had been excluded from this analysis. There was no significant heterogeneity for vertebral and non-vertebral fractures among the studies included in the meta-analysis. Odds ratio estimates (95% CI) were 0.29 (0.20, 0.43) for vertebral fracture and 0.53 (0.32, 0.86) for non-vertebral fracture. There was also a consistent effect of teriparatide to increase BMD across all studies. Furthermore, our analysis demonstrated that teriparatide-mediated increases in spine BMD accounted for 25-32% of the reduction in vertebral fracture risk in the combined population including Caucasian and Japanese patients, which was similar to that derived from Caucasian patients. These results provide evidence for the consistency of anti-fracture efficacy with teriparatide treatment in Japanese patients compared to those observed in Caucasian patients.     

The safety and effectiveness profile of daily teriparatide in a prospective observational study in Japanese patients with osteoporosis at high risk for fracture: interim report

This postmarketing surveillance study assessed the safety and effectiveness of daily teriparatide treatment in patients with osteoporosis in a Japanese clinical setting. In this prospective, multicenter, observational study, patients with osteoporosis at high risk for fracture received subcutaneous injections of teriparatide (20 μg/day) for a maximum of 24 months. For this interim report, data from 1,671 patients were eligible for analysis at the cutoff date. The mean age was 75.3 years; 93 % of patients (1,552/1,671 patients) were women. There were 117 adverse drug reactions (ADRs) reported in 101 of 1,671 patients (6.04 %); the most common reported ADRs were nausea, dizziness, headache, and palpitations. No clinically significant safety issues were identified, although 5 serious ADRs were reported in 4/1,671 (0.24 %) patients. At 12 months, 71.9 % of patients remained on teriparatide treatment. From 1 month, there were rapid increases in the biomarkers of bone formation P1NP and, to a lesser extent, BAP. In contrast, increases in the biomarkers of bone resorption, serum NTX, urinary NTX, and TRACP5b, were smaller. After 12 months of treatment, there was an increase in bone mineral density at the lumbar spine, femoral neck, and total hip, and a decrease in the Visual Analog Scale score for back pain. The incidence of new vertebral and nonvertebral fractures was 1.21 % and 3.18 %, respectively. In conclusion, the favorable safety profile and effectiveness of teriparatide observed in this population of Japanese patients with osteoporosis were accompanied by relatively high persistence with treatment, which is a key factor in the success of osteoporosis treatment.     

骨质疏松治疗培训对脆性髋部骨折患者骨质疏松诊疗率的影响

目的观察骨质疏松的治疗培训对髋部骨折患者骨质疏松诊疗率的影响。方法回顾性分析福建医科大学附属第二医院2013年1月至2015年12月收治的651例老年脆性髋部骨折住院患者,根据是否对治疗的医师进行骨质疏松治疗培训,将651例患者分为培训组和未培训组,比较两组医师对脆性髋部骨折患者骨质疏松诊疗的情况。结果培训组220例,其中接受骨密度检查者109例(49. 5%),接受骨转换标志物检测者130例(59%),骨质疏松治疗率为80. 5%;未培训组431例,其中接受骨密度检查者142例(32. 9%),接受骨转换标志物检测者124例(28. 8%),骨质疏松治疗率为72. 6%(χ~2=16. 940、56. 277、4. 800,P均0. 05)。结论通过对骨科医师进行骨质疏松相关知识的培训,有助于改善骨质疏松患者骨转换标志物及骨密度的检测率,提高骨质疏松的治疗率。     

The effects of once-weekly teriparatide on hip structure and biomechanical properties assessed by CT

Summary

Once-weekly administration of 56.5 μg teriparatide improved cortical bone parameters and biomechanical parameters at the proximal femur by CT geometry analysis.

Introduction

The aim of this study was to evaluate the effects of weekly administration of teriparatide [human PTH (1–34)] on bone geometry, volumetric bone mineral density (vBMD), and parameters of bone strength at the proximal femur which were longitudinally investigated using computed tomography (CT).

Methods

The subjects were a subgroup of a recent, randomly assigned, double-blind study (578 subjects) comparing the anti-fracture efficacy of a once-weekly subcutaneous injection of 56.5 μg teriparatide with placebo (TOWER trial).

Results

Sixty-six ambulatory postmenopausal women with osteoporosis were enrolled at 15 study sites having multi-detector row CT, and included women injected with teriparatide (n?=?29, 74.2?±?5.1 years) or with placebo (n?=?37, 74.8?±?5.3 years). CT data were obtained at baseline and follow-up scans were performed at 48 and 72 weeks. The data were analyzed to obtain cross-sectional densitometric, geometric, and biomechanical parameters including the section modulus (SM) and buckling ratio (BR) of the femoral neck, inter-trochanter, and femoral shaft. We found that once-weekly teriparatide increased cortical thickness/cross-sectional area (CSA) and total area, and improved biomechanical properties (i.e., decreasing BR) at the femoral neck and shaft. Teriparatide did not change the cortical perimeter.

Conclusions

Our longitudinal analysis of proximal femur geometry by CT revealed that once-weekly administration of 56.5 μg teriparatide improved cortical bone parameters at the femoral neck and shaft and also improved biomechanical parameters.