Teriparatide Research & Studies

Abaloparatide and teriparatide are osteoanabolic treatments indicated for postmenopausal women and men with osteoporosis at high risk of fracture. In the Abaloparatide Comparator Trial In Vertebral Endpoints study, bone mineral density improvements were significantly greater with abaloparatide compared to teriparatide at the total hip and femoral neck. We conducted a retrospective claims study to examine the incidences of hip and nonvertebral fractures and cardiovascular events in women aged ≥50 years initiating abaloparatide or teriparatide therapy, expanding on a previous retrospective claims study.

Osteoporosis, defined by reduced bone mineral density and macro- and micro-architectural degradation, leads to increased fracture risk, particularly in aging populations. While randomized controlled trials (RCTs) demonstrate that PTH1 receptor agonists, teriparatide and abaloparatide, are effective at reducing fracture risk, real-world evidence (RWE) remains sparse. This study reviews and compares the anti-fracture efficacy of these agents, against each other and against other osteoporosis treatments using both RCTs and RWE. We systematically searched Medline, Embase, and Cochrane up to May 2024, focusing on RCTs and RWE studies reporting reduction in vertebral, non-vertebral, hip, or all fractures as primary endpoint. A network meta-analysis (NMA) was conducted, first through pairwise meta-analyses of teriparatide versus abaloparatide, then a Bayesian NMA comparing each to other treatments. Safety assessments included adverse events classified by MedDRA, with a particular attention to hypercalcemia and cardiac events. Seventeen studies (11 RCTs, 6 RWE) met inclusion criteria. Teriparatide and abaloparatide were effective in reducing vertebral and non-vertebral fractures in all pairwise meta-analyses versus placebo. Abaloparatide showed an advantage over teriparatide for non-vertebral fractures (OR: 0.87, 95% CI: 0.80-0.95) and hip fractures (OR: 0.81, 95% CI: 0.71-0.93). In the NMA model, teriparatide and abaloparatide were superior to placebo, raloxifene, and calcitonin in reducing vertebral fracture while teriparatide was further superior to denosumab and risedronate. For non-vertebral fracture, abaloparatide was better than any other treatment while teriparatide was only superior to alendronate or placebo. PTH1 analogs were better than placebo at reducing all fractures while no difference was observed for the risk of hip fracture. Both abaloparatide and teriparatide demonstrate comparable safety to other osteoporosis treatments, with no increased cardiovascular risk. This review highlights that PTH1 receptor agonists effectively reduce fracture risk, with abaloparatide offering enhanced benefits for non-vertebral and hip fractures compared to teriparatide. Both agents exhibit acceptable safety profiles, suggesting their valuable role in managing osteoporosis, particularly for high-risk patients.

Comparative evidence on the effectiveness of romosozumab and teriparatide in preventing osteoporotic fractures remains limited. This study evaluated their effectiveness in fracture prevention.

The study found that in osteoporosis patients who had not previously received bisphosphonate treatment and were in a treatment cycle of over 12 months, both teriparatide and denosumab significantly increased bone mineral density compared to bisphosphonates. Additionally, teriparatide was also shown to significantly decrease the risk of fractures.

The purpose of this study was to determine the effect of osteoporosis medications on opportunistic CT-based Hounsfield units (HU).

This study compared the effectiveness and cardiovascular safety of romosozumab and teriparatide. The main finding was that there were no significant differences between the two drugs in fracture prevention and risk of major adverse cardiac events. This suggests that romosozumab and teriparatide are comparable options for treating osteoporosis.

In the last decades, novel therapeutics with anabolic bone properties have been developed and are currently used in the management of osteoporosis particularly in patients with high-risk of fragility fractures. These drugs include PTH-Related Analogues, teriparatide and abaloparatide, and the anti-sclerostin agent romosozumab, this latter drug currently approved only in female patients. Their efficacies in preventing fragility fractures are widely demonstrated and their potential serious side effects were progressively downgraded, including risk of malignancies in teriparatide- and cardiovascular events in romosozumab-users, respectively. Further data are warranted about their efficacy in glucocorticoids-induces osteoporosis and fracture healings.

Chronic hypoparathyroidism is usually treated with calcium and active vitamin D metabolites or analogs, despite the fact that their chronic use can lead to long-term complications. The use of hormone replacement therapy with PTH peptides [teriparatide and rhPTH (1-84)] has therefore been proposed. The main purpose of this study was to investigate the efficacy of teriparatide dose at 20 µg once or twice daily, in order to maintain normocalcemia reducing standard treatment, in adult patients with chronic hypoparathyroidism not well controlled with conventional treatment.

Parathyroid hormone (PTH) is an 84-amino-acid peptide hormone that is secreted by the parathyroid gland. It has different administration modes in bone tissue through which it promotes bone formation (intermittent administration) and bone resorption (continuous administration) and has great potential for application in sbone defect repair. PTH regulates bone metabolism by binding to PTH1R. PTH plays an osteogenic role by acting directly on mesenchymal stem cells, cells with an osteoblastic lineage, osteocytes, and T cells. It also participates as an osteoclast by indirectly acting on osteoclast precursor cells and osteoclasts and directly acting on T cells. In these cells, PTH activates the Wnt signaling, cAMP/PKA, cAMP/PKC, and RANKL/RANK/OPG pathways and other signaling pathways. Although PTH(1-34), also known as teriparatide, has been used clinically, it still has some disadvantages. Developing improved PTH-related peptides is a potential solution to teriparatide's shortcomings. The action mechanism of these PTH-related peptides is not exactly the same as that of PTH. Thus, the mechanisms of PTH and PTH-related peptides in bone metabolism were reviewed in this paper.

Current osteoporosis medications reduce fractures significantly but have rare and serious adverse effects (osteonecrosis of the jaw, atypical femoral fractures) that may limit their safety for long-term use. Insights from basic bone biology and genetic disorders have led to recent advances in therapeutics for osteoporosis. New approaches now in clinical use include the antisclerostin monoclonal antibody romosozumab, as well as the parathyroid hormone-related peptide analog abaloparatide. Clinical trial data show significant antifracture benefits with recently approved romosozumab. Studies using abaloparatide build on our longstanding experience with teriparatide and the importance of consolidating the bone mineral density gains achieved from an anabolic agent by following it with an antiresorptive. Combination and sequential treatments using osteoporosis medications with different mechanisms of action have also been tested with promising results. On the horizon is the potential for cell-based therapies (e.g., mesenchymal stem cells) and drugs that target the elimination of senescent cells in the bone microenvironment.

Atypical femur fractures (AFFs) are serious adverse events associated with bisphosphonates and often show poor healing.

New anti-osteoporotic agents have been developed, potentially enriching the therapeutic armamentarium. Currently available osteoanabolic therapies are the parathyroid hormone (PTH) and PTH-related peptide (PTHrP) synthetic analogues, teriparatide and abaloparatide. Daily administration at doses of 20 and 80 μg, respectively, in contrast to continuous PTH secretion, leads to increased bone formation and reduces vertebral and non-vertebral fracture risk. Teriparatide is more effective than bisphosphonates (alendronate, risedronate) in increasing bone mineral density (BMD), improving bone architecture and reducing fracture risk. Abaloparatide leads to greater BMD gain, has greater anti-fracture efficacy regarding major osteoporotic fractures (upper arm, wrist, hip or clinical spine) compared with teriparatide (without a difference in morphometric vertebral and non-vertebral fractures), and has a lower risk of hypercalcaemia. Romosozumab, a sclerostin inhibitor, both induces bone formation and suppresses bone resorption. Administered at monthly subcutaneous doses of 210 mg, it reduces vertebral, non-vertebral and hip fracture risk compared with either placebo or alendronate. However, concerns have arisen about increased cardiovascular risk, which has suspended its approval by the FDA. Anabolic therapy should always be followed by administration of an anti-resorptive agent, such as bisphosphonates or denosumab, which preserves and may further increase BMD gain. Denosumab provides the greatest benefit for BMD when administered sequentially after its combination with teriparatide for 24 months and constitutes a reasonable option for patients at high risk of fracture. However, longitudinal data are needed to confirm the efficacy and safety of these therapeutic interventions.

We present the case of a patient who presented with worsening chest pain and tachycardia. We were able to monitor her remotely through her pacemaker. She had been started on the injectable medication teriparatide (Forteo) and since then she had an increase in her symptoms. She was found to have intermittent atrial tachycardia with 1:1 conduction and occasional atrioventricular block transiently, coinciding with her injection of teriparatide. This specific-associated arrhythmia has yet to be described.

Osteoporosis is a common skeletal disorder characterized by low bone mass, which leads to reduced bone strength and an increased risk of fractures. Anabolic agents have been shown to improve bone mass and decrease fracture risk in osteoporosis patients by directly stimulating osteoblasts to produce new bone. Currently, two anabolic agents are available in the USA: recombinantly produced teriparatide (TPTD), which is the fully active (1-34) amino active sequence of human parathyroid hormone (PTH), and abaloparatide (APTD), a synthetic analog of parathyroid hormone-related peptide (PTHrP). At present, both agents are approved only for treatment of patients with osteoporosis at high risk of fracture. Nonetheless, their anabolic properties have led to off-label application in additional settings which include spine fusion, osteonecrosis of the jaw, arthroplasty, and fracture healing. In this article, we summarize available scientific literature regarding the efficacy, effectiveness, and safety of TPTD in these off-label settings.

Antiresorptive agents for treating postmenopausal osteoporosis include selective estrogen receptor modulator (SERM), bisphosphonates and denoumab. Teriparatide is the only Food and Drug Administration-approved anabolic agent. Synergistic effects of combining teriparatide with an antiresorptive agent have been proposed and studied. This article reviews the trial designs and the outcomes of combination therapies. Results of the combination therapy for teriparatide and bisphosphonates were mixed; while small increases of bone density were observed in the combination therapy of teriparatide and estrogen/SERM and that of teriparatide and denosumab. Those clinical studies were limited by small sample sizes and lack of fracture outcomes.

Unlike most chronic diseases, osteoporosis treatments are generally limited to a single drug at a fixed dose and frequency. Nonetheless, no approved therapy is able to restore skeletal integrity in most osteoporotic patients and the long-term use of osteoporosis drugs is controversial. Thus, many patients are treated with the sequential use of two or more therapies. The DATA study showed that combined teriparatide and denosumab increased bone mineral density more than either drug alone. Discontinuing teriparatide and denosumab, however, results in rapidly declining bone mineral density. In this DATA-Switch study, we aimed to assess the changes in bone mineral density in postmenopausal osteoporotic women who transitioned between treatments.

Hypoparathyroidism and quality of life: Even in adequately substituted patients, hypoparathyroidism (HPT) is associated with impaired quality of life. It has been hypothesized that there is a correlation between reduced quality of life and lack of parathyroid hormone (PTH) in the central nervous system. Positive effects on quality of life have been reported when treating HPT with PTH. Hypoparathyroidism and comorbidities: Comorbidities associated with HPT include an increased risk of nephrolithiasis/nephrocalcinosis and neuro-psychiatric disease. Additionally, cardiovascular risk profile and an increased susceptibility for infections have been reported. Mortality rates seem not to be increased in HPT. Hypoparathyroidism and new therapeutic strategies: Recombinant PTH has not been approved for the treatment of HPT in Europe yet. However, in early 2015, the FDA approved PTH (1-84). Daily subcutaneous delivery of PTH (1-84) and PTH (1-34) (Teriparatide) has emerged as a promising therapeutic tool. However, its use should be restricted to patients insufficiently controlled with the standard treatment consisting of active vitamin d and calcium.

As the first FDA-approved anabolic agent for osteoporosis, teriparatide has proven effective for people at highest risk of fracture, despite limitations of expense, route of delivery, and length of treatment. Available data show that combination therapy with teriparatide and antiresorptive agents does not offer a therapeutic advantage. However, treatment with an antiresorptive agent after teriparatide discontinuation is essential to prevent the ensuing bone loss. Although pretreatment with bisphosphonates may somewhat attenuate the anabolic effect of teriparatide, significant gains in bone mineral density are still achieved and prior bisphosphonate use should not dissuade clinicians from using teriparatide in select patients.

Traditionally, the management of osteoporosis in men and women has included the use of antiresorptive agents in combination with calcium and vitamin D supplementation. The mechanism of action of teriparatide is unique in that it possesses anabolic properties and therefore builds bone. Since the approval of teriparatide in the United States in 2002, a great deal of interest regarding its use in osteoporosis has developed.

To review the pharmacology, toxicology, pharmacokinetics, pharmacodynamics, efficacy, safety, therapeutic controversies, administration, patient counseling, and formulary recommendations for teriparatide (rDNA origin).