Use of Teriparatide to improve fracture healing: What is the evidence?

Teriparatide is a recombinant form of the biologically active component of Parathyroid hormone. It has been shown to increase bone mass and prevent fractures in osteoporotic bone. It is licensed by the Food and Drug Administration for the treatment of Osteoporosis. Over the last decade, a growing body of evidence has accumulated suggesting a role for Teriparatide in the management of fractures. Studies in both normal and delayed healing models have shown improvement in callus volume and mineralisation, bone mineral content, rate of successful union and strength at fracture sites. However most of these results have been derived from animal studies. The majority of this research on humans has comprised low level evidence, with few randomised controlled trials, many case reports and case series. Nevertheless, the results from these studies seem to support research from animal models. This has led to a growing number of clinicians using Teriparatide “off license” to treat fractures and non-unions in their patients. This review presents a critical appraisal of the current evidence supporting the use of Teriparatide for fracture healing, delayed unions and non unions and in the setting of osteoporotic fractures, the studies producing this evidence and their transferability to human beings.     

Romosozumab versus Teriparatide for the Treatment of Postmenopausal Osteoporosis: A Systematic Review and Meta‐analysis through a Grade Analysis of Evidence

ObjectiveTo provide a systematic review about the efficacy and safety of romosozumab and teriparatide for the treatment of postmenopausal osteoporosis.MethodRandomized controlled trials (RCTs) were searched from electronic databases, including PubMed (1996 to June 2019), Embase (1980 to June 2019), Cochrane Library (CENTRAL, June 2019), Web of Science (1998 to June 2019), and others. The primary outcomes included the following: the percentage change in bone mineral density of lumbar spine and total hip from baseline at month 6 and month 12 in each group. The secondary outcomes included the following: the percentage change in bone mineral density of femoral neck from baseline at month 6 and month 12 in each group and the incidence of adverse events at month 12 in each group.ResultsFour studies containing 1304 patients met our selection criteria. The result of our analysis indicated that romosozumab showed better effects in improving BMD of lumbar spine (month 6: MD = 3.54, 95% CI [3.13, 3.94], P<0.001; month 12: MD = 4.93, 95% CI [4.21, 5.64], P<0.001), total hip (month 6: MD = 2.27, 95% CI [0.62, 3.91], P = 0.007; month 12: MD = 3.17, 95% CI [2.68, 3.65], P<0.001), and femoral neck (month 6: MD = 2.30, 95% CI [0.51, 4.08], P = 0.01; month 12: MD = 3.04, 95% CI [2.29, 3.78], P<0.001). Also, the injection‐site reaction was less (month 12: RR = 2.84, 95% CI [1.22, 6.59], P = 0.02), but there were no significant difference in the incidence of serious adverse events (month 12: RR = 0.78, 95% CI [0.46, 1.33], P = 0.37) and death (month 12: RR = 0.61, 95% CI [0.08, 4.62], P = 0.63).ConclusionBased on the available studies, our current results demonstrate that romosozumab was better than teriparatide both in terms of efficacy and side effects.     

Present and future scope of recombinant parathyroid hormone therapy in orthopaedics

Parathyroid Hormone (PTH) has a significant role in calcium metabolism. Its intermittent administration has an anabolic effect on bone mineralization. Teriparatide (PTH 1-34), a recombinant form of parathyroid hormone, is useful in the treatment of osteoporosis, fracture healing, non-union, stress fracture, augmentation of implant fixation with bone, and chondroprotection in osteoarthritis. The present review article will elaborate on the potential approved uses of recombinant PTH in orthopedics and its evolving role in the management of fracture osteosynthesis and other common challenging bone pathologies.     

芪骨胶囊联合重组特立帕肽治疗骨质疏松症的临床研究

目的 观察芪骨胶囊联合注射用重组特立帕肽治疗骨质疏松症的临床疗效。方法 选取2020年1月—2021年3月南阳医学高等专科学校第一附属医院收治的111例骨质疏松症患者，根据治疗方案的不同将所有患者分为对照组（54例）和治疗组（57例）。对照组患者大腿或腹部皮下注射注射用重组特立帕肽，20μg/次，1次/d。治疗组患者在对照组的基础上口服芪骨胶囊，3粒/次，3次/d。28d为1个疗程，共治疗6个疗程。观察两组的临床疗效，比较两组的不同部位骨密度、骨吸收和骨形成指标。结果 治疗后，治疗组的总有效率为94.74%，高于对照组患者的总有效率77.78%，组间比较差异显著（P<0.05）。治疗后，两组腰椎L_2～4、股骨颈、桡骨远端1/3处的骨密度均较治疗前升高（P<0.05），且治疗后治疗组的腰椎L_2～4、股骨颈、桡骨远端1/3处的骨密度高于对照组（P<0.05）。治疗后，两组血清Ⅰ型原胶原C-端前肽（PICP）、骨特异性碱性磷酸酶（BALP）、骨钙素（BGP）水平均较治疗前升高（P<0.05），且治疗后，治疗组的血清PICP、BALP、BGP水平高于对照组（P<0.05）。治疗后，两组血清抗酒石酸酸性磷酸酶（TRACP）、Ⅰ型胶原C-末端肽交联（S-CTX）水平均较治疗前下降（P<0.05），且治疗后治疗组的血清TRACP、S-CTX水平低于对照组（P<0.05）。结论 芪骨胶囊联合注射用重组特立帕肽治疗骨质疏松症具有较好的临床疗效，可有效改善机体骨密度，调节血清PICP、BALP、BGP、TRACP、S-CTX水平。     

Recombinant PTH: A Study of the Outcome of Teriparatide Therapy for 138 Patients with Osteoporosis

Introduction

Osteoporosis results in significant morbidity and mortality for a large number of patients within Northern Ireland. Recombinant PTH (Teriparatide) is one of a growing number of treatment options for the disease.

Methods

A retrospective analysis was carried out for all patients who had been commenced on Teriparatide since it was first used in the Belfast Health and Social Care Trust (BHSCT) in 2007. Patient demographics, clinical history and prior treatment were recorded prior to an eighteen month treatment protocol. Outcome measures including bone densitometry, bone turnover markers and health status were assessed on commencement and completion.

Results

138 patients have commenced teriparatide therapy since 2007 (9 male, 129 female). At the time of analysis 60 patients had completed treatment, 53 patients were receiving ongoing treatment and 25 patients did not complete the 18 month course. On completion vertebral bone mineral density (BMD) had increased by 8.3% while femoral neck BMD had increased by 3.5%. Bone turnover markers demonstrated a significant increase of bone formation and resorption at 4 months, with a smaller increase at 18 months. Health outcome measures (EuroQoL-5 and patient visual analogue scale) indicated improvement in the quality of life of patients of those who completed the treatment course.

Conclusions

Experience in the BHSCT with teriparatide since 2007 demonstrates improvement in BMD comparable to published data, changes in bone turnover markers consistent with increased bone remodeling and better health outcomes for patients.     

Reduction in the risk of developing back pain persists at least 30 months after discontinuation of teriparatide treatment: a meta-analysis

Introduction Teriparatide [rhPTH (1–34)] reduces fracture risk, and in a published meta-analysis of clinical trials, teriparatide-treated patients had reduced incidence of back pain relative to placebo or to antiresorptive drugs. The aim of this study was to evaluate back pain in teriparatide-treated versus comparator-treated patients during an interval including controlled clinical trials plus 30 months of additional follow-up.Methods A meta-analysis of four completed randomized, double-blinded trials of teriparatide [rhPTH (1–34)] versus comparator was performed. A multivariate Cox proportional hazards model was used to assess the heterogeneity of results and to estimate the relative risk of back pain.Results Patients in the pooled teriparatide group had reduced risk for any back pain [relative risk, 0.73 (95% CI, 0.61–0.87)], moderate or severe back pain [0.72 (0.58–0.89)], and severe back pain [0.39 (0.25–0.61)] compared with pooled controls, from initiation of the study drug through the end of follow-up. Sensitivity analysis showed that the results were robust to the removal of each individual trial from the meta-analysis. Separate meta-analyses comparing teriparatide versus placebo or antiresorptive drugs gave similar results.Conclusions Teriparatide-treated patients had a reduced incidence of back pain versus those receiving a comparator during an observation encompassing clinical trials plus 30 months of posttreatment observation. Presented at the annual meeting of the European League Against Rheumatism, Vienna, Austria, June 8–11, 2005, and the Sixth European Congress on Clinical and Economic Aspects of Osteoporosis and Osteoarthritis, Vienna, Austria, March 15–18, 2006.     

Rationale, objectives and design of the Direct Analysis of Nonvertebral Fracture in the Community Experience (DANCE) Study

The experience in randomized placebo-controlled clinical trials may differ from that in community practice. The pivotal teriparatide [rhPTH(1–34)] studies were initiated when few therapeutic options for osteoporosis were available. The Direct Analysis of Non-Vertebral Fractures in Community Experience (DANCE) study is a prospective observational trial designed to examine the occurrence of nonvertebral fragility fractures in a large, diverse patient population treated with teriparatide. The occurrence of clinical vertebral fractures and back pain will also be examined, as will bone mineral density, bone mineral content, bone area, safety and tolerability. Subjects will be followed through a course of teriparatide therapy for up to 24 months and for an additional 24 months after cessation of treatment. Therefore, subjects may participate in this study for up to 48 months. DANCE will provide data on the effectiveness and tolerability of teriparatide therapy in clinical practice that will complement the results of published controlled clinical trials.Reprint requests to R.B. Wagman     

The importance of bisphosphonate therapy in maintaining bone mass in men after therapy with teriparatide [human parathyroid hormone(1–34)]

Teriparatide, the active fragment of human parathyroid hormone (hPTH 1–34), is an anabolic agent for the treatment of osteoporosis. Important questions remain regarding management strategy beyond the recommended 18- to 24-month course of teriparatide treatment. We followed 21 men for up to 2 years after discontinuing teriparatide. Twelve men (57%) chose treatment with bisphosphonate immediately after teriparatide withdrawal, while 9 (43%) opted for no pharmacologic agent. At the end of 1 year lumbar spine bone density increased an additional 5.1±1.0% in the bisphosphonate group, while it declined by 3.7±1.7% in those on no medication (P<0.002). In six men who delayed initiation of bisphosphonate until 1 year after teriparatide withdrawal, their subsequent gains in the second year, 2.6±1.7%, still placed them below the peak gains they achieved on teriparatide. In contrast, the 12 men who began bisphosphonates immediately and continued treatment for the entire 2-year post-PTH period had continued gains at the lumbar spine, 8.9±1.5% above their post-PTH values (P=0.002). For the 4-year period, including 2 years of teriparatide and 2 years of bisphosphonate, the total gains at the lumbar spine were 23.6±2.9%. Men, who received bisphosphonate in only the 2nd year post-teriparatide, had cumulative gains of 11.1±3.4%. Three men who did not receive any bisphosphonate at any time during the post-PTH period had cumulative gains of only 5.5±3.7%. These findings suggest that the use of bisphosphonates following teriparatide is an important component of any strategy utilizing this anabolic drug for osteoporosis in men. The immediate use of bisphosphonates after teriparatide withdrawal may help to optimize gains in bone density at the lumbar spine.     

Evaluation of teriparatide effect on healing of autografted mandibular defects in rats

Objective

To evaluate the effects of short-term teriparatide administration on healing of autologous bone graft in mandibular critical-size defects.