Abaloparatide Research & Studies

The goal of treatment for women at high risk of fracture who have a T-score ≤-2.5 is to mitigate fracture risk by achieving T-scores at least above -2.5. In the ACTIVE trial, 2463 women with osteoporosis aged 49-86 yr were treated for 18 mo with abaloparatide (80 μg), teriparatide (20 μg), or placebo. In ACTIVExtend, eligible women from the abaloparatide and placebo groups received weekly treatment with 70 mg of alendronate for 2 additional years. This post hoc analysis of ACTIVE and ACTIVExtend included women with baseline TH or LS T-scores ≤-2.5. Logistic regression was used to predict the probability of achieving a T-score >-2.5 at the TH or LS during 18 mo of treatment with abaloparatide or teriparatide and during 3.5 yr with the sequence of abaloparatide/alendronate compared to placebo/alendronate. At baseline, 23% and 74% of women enrolled in ACTIVE had T-scores ≤-2.5 at the TH and LS, respectively. Over 18 mo of treatment, more than 50% of women were likely to achieve TH T-scores >-2.5, with baseline TH T-scores as low as -2.7 for both abaloparatide and teriparatide. More than 50% of women were predicted to achieve an LS T-score >-2.5 with a baseline LS T-score as low as -3.3 for abaloparatide or -3.2 on teriparatide. Over 3.5 yr of sequential treatment with abaloparatide/alendronate, >50% of women with baseline TH T-scores ≥-2.9 and LS T-scores ≥-3.5 were predicted to achieve T-scores >-2.5, respectively. A patient's BMD at baseline and the probability of achieving target T-scores with treatment should be considered when determining that treatment should be initiated in patients at high or very high risk of fracture.

Breast cancer cells frequently spread to the bone, causing osteoclast-mediated bone destruction and pathological fractures. Bone anabolic agents, such as abaloparatide, are used clinically to increase bone formation in osteoporotic patients, but their effectiveness against tumor-induced bone destruction is poorly understood. In this study, we present the first evaluation of abaloparatide in preclinical models of breast cancer cells disseminated to the bone marrow and demonstrate that intermittent abaloparatide dramatically increases trabecular bone volume in mice inoculated with triple negative breast cancer cells. Abaloparatide also increases BMD in a model of estrogen receptor positive breast cancer, despite elevated baseline bone volume due to estradiol supplementation. Importantly, abaloparatide does not increase tumor burden or incidence in bone or soft tissue sites in either model. These results suggest that abaloparatide may be effectively used to increase bone mass without stimulating growth of cancer cells in the bone marrow and may be beneficial for cancer patients with low bone mass.

Insufficient alveolar bone thickness increases the risk of periodontal dehiscence and fenestration, especially in orthodontic tooth movement. Abaloparatide (ABL), a synthetic analog of human PTHrP (1-34) and a clinical medication for treating osteoporosis, has recently demonstrated its potential in enhancing craniofacial bone formation. Herein, we show that intraoral submucosal injection of ABL, when combined with mechanical force, promotes in situ alveolar bone thickening. The newly formed bone is primarily located outside the original compact bone, implying its origin from the periosteum. RNA sequencing of the alveolar bone tissue revealed that the focal adhesion (FA) pathway potentially mediates this bioprocess. Local injection of ABL alone enhances cell proliferation, collagen synthesis, and phosphorylation of focal adhesion kinase (FAK) in the alveolar periosteum; when ABL is combined with mechanical force, the FAK expression is upregulated, in line with the accomplishment of the ossification. In vitro, ABL enhances proliferation, migration, and FAK phosphorylation in periosteal stem cells. Furthermore, the pro-osteogenic effects of ABL on alveolar bone are entirely blocked when FAK activity is inhibited by a specific inhibitor. In summary, abaloparatide combined with mechanical force promotes alveolar bone formation via FAK-mediated periosteal osteogenesis. Thus, we have introduced a promising therapeutic approach for drug-induced in situ alveolar bone augmentation, which may prevent or repair the detrimental periodontal dehiscence, holding significant potential in dentistry.

The aging of the population increases the incidence of postmenopausal osteoporosis, which threatens the health of elderly women. Abaloparatide is a synthetic peptide analogue of the human parathyroid hormone-related protein that has recently been approved for the treatment of postmenopausal osteoporosis. Its efficacy and safety have not been systematically evaluated. Therefore, studies on the efficacy and safety of abaloparatide could be of assistance in the clinical medication of postmenopausal osteoporosis. The aim of this study was to evaluate the clinical efficacy and safety of abaloparatide in postmenopausal osteoporosis.

Prospective randomized placebo controlled animal trial.

Osteoporosis is a debilitating disease characterized by reduced bone mineral density and an increased risk of fractures. This review aims to provide a comprehensive overview of, and map current knowledge, obtained from preclinical and clinical studies of the osteoanabolic agent abaloparatide. PubMed and Embase were meticulously searched from inception to May 4, 2021.178 titles and abstracts were screened, and 57 full-text articles were assessed for inclusion. A total of 55 articles were included; 5 (9%) in vitro studies, 21 (38%) in vivo studies, and 29 (53%) clinical studies. Preclinical in vitro studies have demonstrated receptor conformation preferability, structural insights into the receptor-agonist complex, and proliferative effects of abaloparatide on osteoblasts. Preclinical studies have shown abaloparatide to be similarly effective to teriparatide using comparable doses in both ambulating mice and rats challenged by disuse. Other animal studies have reported that abaloparatide effectively mitigates or prevents bone loss from ovariectomy, orchiectomy, and glucocorticoids and improves fracture healing. The pivotal clinical study ACTIVE demonstrated 18 months of treatment with abaloparatide substantially increase bone mineral density and reduce fracture risk in post-menopausal women compared with placebo. The extension study ACTIVExtend highlighted that subsequent treatment with alendronate sustained the bone gained by abaloparatide treatment and the reduced fracture risk for up to two years. Post-hoc sub-group analyses have also supported the efficacy and safety of abaloparatide treatment independent of various baseline risk factors. In conclusion, mounting evidence from preclinical and clinical studies has uniformly reported that abaloparatide increases bone mineral density and reduces fracture risk.

Osteoporosis is a common and debilitating condition characterized by diminished bone mass and architecture leading to bone fragility. Antiresorptive medicines like bisphosphonates (and less commonly denosumab) are the typical first-line agents for the medical treatment of osteoporosis. However, newer anabolic agents have been shown to improve bone mass and architecture, as well as reduce fracture risk, to a greater degree than traditional antiresorptive therapies. Teriparatide (human recombinant parathyroid hormone (PTH) 1-34, Forteo, Ely Lilly, Indianapolis, IN), which was the first in class to be approved in the United States, is the most widely used anabolic osteoporosis medicine and has shown significant benefit over traditional antiresorptive therapies. However, abaloparatide (synthetic parathyroid-related peptide (PTHrP), Tymlos, Radius Health, Waltham, MA), the second drug in this family, has recently become available for use. In this narrative review, we review the mechanism, effects, and benefits of abaloparatide compared to alternative treatments as well as discuss the current literature in regard to its effect on osteoporosis-related complications in the spine.

The efficacy and safety of abaloparatide, a parathyroid hormone-related protein analog for the treatment of osteoporosis in postmenopausal women at high fracture risk, is reviewed.

To review the efficacy, safety, and economics of abaloparatide in the treatment of postmenopausal osteoporosis.

Abaloparatide is a synthetic 34-amino acid peptide analogue of the 1-34 portion of the human parathyroid hormone-related protein (PTHrP). It has been approved in the U.S. for the treatment of postmenopausal women with osteoporosis at a high risk for fracture. Abaloparatide is an anabolic agent and it seems to have a potent anabolic activity with reduced effects on bone resorption. It reduces the risk of vertebral and nonvertebral fractures, major osteoporotic fractures and clinical fractures, with a significant improvement in bone mineral density at femoral neck, total hip and lumbar spine. In this article we summarize the development of the abaloparatide molecule and preclinical and clinical studies published so far. Results from clinical trials indicate that abaloparatide may become an important option for the anabolic treatment of postmenopausal osteoporosis.

Abaloparatide (previously known as BA058) is a synthetic 34-amino acid peptide and novel selective activator of parathyroid hormone receptor 1 (PTHR1) currently under development as a new anabolic agent in the management of osteoporosis. This paper reviews the profile and potential of abaloparatide in the treatment of postmenopausal osteoporosis. This paper is based on clinical trials and a PubMed search. Search terms used were "abaloparatide", "BA058", and "PTHrP". This review outlines the effects of this anabolic PTHR1 activator, which increases bone mineral density in patients at high risk for osteoporosis. The potential adverse effects of abaloparatide are also summarized. Abaloparatide has 41% homology to parathyroid hormone (PTH) (1-34) and 76% homology to parathyroid hormone-related protein (PTHrP) (1-34). The molecule was meticulously selected to retain stability and potent bone anabolic activity, and it has a limited effect on bone resorption (hence, a low calcium-mobilizing potential). Abaloparatide has shown promising results in a reduction of new onset vertebral (approximately 86% reduction) and nonvertebral fractures (approximately 43% reduction). In clinical trials to date, abaloparatide appears to have a good safety and tolerability profile with a significantly lower degree of hypercalcemia compared to that of teriparatide. Based on the clinical trials, the optimum dose of abaloparatide is 80 mcg subcutaneous once daily.

Abaloparatide (Tymlos™) is a synthetic peptide analogue of human parathyroid hormone-related protein that was developed by Radius Health as an osteoanabolic agent for the treatment of postmenopausal osteoporosis. Abaloparatide acts through selective activation of the parathyroid hormone type 1 receptor signalling pathway. In April 2017, subcutaneous abaloparatide received its first global approval, in the USA, for the treatment of postmenopausal women with osteoporosis at high risk for fracture, defined as a history of osteoporotic fracture, multiple risk factors for fracture, or patients who have failed or are intolerant to other available osteoporosis therapy. A Marketing Authorization Application for subcutaneous abaloparatide for the treatment of postmenopausal women with osteoporosis was accepted by the European Medicines Agency and is currently under review. Radius is also developing a transdermal formulation of abaloparatide, with administration via a microneedle patch. This article summarizes the milestones in the development of abaloparatide leading to this first approval for the treatment of women with postmenopausal osteoporosis.

Additional therapies are needed for prevention of osteoporotic fractures. Abaloparatide is a selective activator of the parathyroid hormone type 1 receptor.