abaloparatide and Osteoporosis--Postmenopausal

Osteoporosis poses a challenge to public health, causing fragility fractures, especially in postmenopausal women. Abaloparatide (ABL) is an effective anabolic agent to improve bone formation and resorption among postmenopausal women with osteoporosis. Our meta-analysis aims to assess the effectiveness and safety of ABL versus teriparatide (TPTD) in improving bone mineral density (BMD).. We searched Medline, Embase, Web of Science, Cochrane databases and Clinicaltrial.gov until September 2, 2022. We included data from randomized controlled trials (RCTs) and post hoc analyses of RCTs. Outcomes included BMD change from baseline and risks of adverse events. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) tool was used to evaluate the quality of outcomes.. Four studies including 16 subgroups were included in this study. In particular, RCTs with head-to-head comparisons of ABL and TPTD were used in the meta-analysis, and all were from manufacturer-sponsored trials. All parameters in 24 weeks except lumbar spine (versus TPTD) showed significant advantages in the ABL group. Only the results of two subgroups in ABL versus TPTD demonstrated High GRADE quality (femoral neck: weighted mean difference (WMD) = 1.58 [0.52, 2.63]; Total hip: WMD = 1.46 [0.59, 2.32]). However, our fracture data were insufficient. Besides, we found no evident difference in serious adverse events or deaths in either group and the incidence of hypercalcemia in the ABL group lessened by 51% compared with the TPTD group. Nevertheless, compared with placebo, ABL demonstrated higher risks of nausea and palpitations.. ABL demonstrated a beneficial effect on BMD compared to both placebo and TPTD for postmenopausal women with osteoporosis. ABL also had insignificantly lowered adverse event risk than TPTD. ABL is an alternative for patients with postmenopausal osteoporosis.

Topics: Bone Density; Bone Density Conservation Agents; Female; Fractures, Bone; Humans; Lumbar Vertebrae; Osteoporosis; Osteoporosis, Postmenopausal; Teriparatide

Chronic kidney disease (CKD) is an independent risk factor for osteoporosis and is more prevalent among people with CKD than among people who do not have CKD. Although several drugs have been used to effectively treat osteoporosis in the general population, it is unclear whether they are also effective and safe for people with CKD, who have altered systemic mineral and bone metabolism.. To assess the efficacy and safety of pharmacological interventions for osteoporosis in patients with CKD stages 3-5, and those undergoing dialysis (5D).. We searched the Cochrane Kidney and Transplant Register of Studies up to 25 January 2021 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.. Randomised controlled trials comparing any anti-osteoporotic drugs with a placebo, no treatment or usual care in patients with osteoporosis and CKD stages 3 to 5D were included.. Two review authors independently selected studies, assessed their quality using the risk of bias tool, and extracted data. The main outcomes were the incidence of fracture at any sites; mean change in the bone mineral density (BMD; measured using dual-energy radiographic absorptiometry (DXA)) of the femoral neck, total hip, lumbar spine, and distal radius; death from all causes; incidence of adverse events; and quality of life (QoL). Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) for continuous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.. Seven studies involving 9164 randomised participants with osteoporosis and CKD stages 3 to 5D met the inclusion criteria; all participants were postmenopausal women. Five studies included patients with CKD stages 3-4, and two studies included patients with CKD stages 5 or 5D. Five pharmacological interventions were identified (abaloparatide, alendronate, denosumab, raloxifene, and teriparatide). All studies were judged to be at an overall high risk of bias. Among patients with CKD stages 3-4, anti-osteoporotic drugs may reduce the risk of vertebral fracture (RR 0.52, 95% CI 0.39 to 0.69; low certainty evidence). Anti-osteoporotic drugs probably makes little or no difference to the risk of clinical fracture (RR 0.91, 95% CI 0.79 to 1.05; moderate certainty evidence) and adverse events (RR 0.99, 95% CI 0.98 to 1.00; moderate certainty evidence). We were unable to incorporate studies into the meta-analyses for BMD at the femoral neck, lumbar spine and total hip as they only reported the percentage change in the BMD in the intervention group. Among patients with severe CKD stages 5 or 5D, it is uncertain whether anti-osteoporotic drug reduces the risk of clinical fracture (RR 0.33, 95% CI 0.01 to 7.87; very low certainty evidence). It is uncertain whether anti-osteoporotic drug improves the BMD at the femoral neck because the certainty of this evidence is very low (MD 0.01, 95% CI 0.00 to 0.02). Anti-osteoporotic drug may slightly improve the BMD at the lumbar spine (MD 0.03, 95% CI 0.03 to 0.04, low certainty evidence). No adverse events were reported in the included studies. It is uncertain whether anti-osteoporotic drug reduces the risk of death (RR 1.00, 95% CI 0.22 to 4.56; very low certainty evidence).. Among patients with CKD stages 3-4, anti-osteoporotic drugs may reduce the risk of vertebral fracture in low certainty evidence. Anti-osteoporotic drugs make little or no difference to the risk of clinical fracture and adverse events in moderate certainty evidence. Among patients with CKD stages 5 and 5D, it is uncertain whether anti-osteoporotic drug reduces the risk of clinical fracture and death because the certainty of this evidence is very low. Anti-osteoporotic drug may slightly improve the BMD at the lumbar spine in low certainty evidence. It is uncertain whether anti-osteoporotic drug improves the BMD at the femoral neck because the certainty of this evidence is very low. Larger studies including men, paediatric patients or individuals with unstable CKD-mineral and bone disorder are required to assess the effect of each anti-osteoporotic drug at each stage of CKD.

Topics: Antibodies, Monoclonal; Bias; Bone Density; Bone Density Conservation Agents; Denosumab; Female; Femur Neck; Fractures, Spontaneous; Hip; Humans; Indoles; Lumbar Vertebrae; Osteoporosis, Postmenopausal; Parathyroid Hormone-Related Protein; Raloxifene Hydrochloride; Randomized Controlled Trials as Topic; Renal Dialysis; Renal Insufficiency, Chronic; Spinal Fractures; Teriparatide; Thiophenes; Watchful Waiting

Fractures due to osteoporosis represent a serious burden on patients and healthcare systems. The objective of this review is to provide an overview of the anabolic agent abaloparatide (ABL) for the treatment of postmenopausal women with osteoporosis at high risk for fracture.. A literature review was conducted using PubMed to identify articles focused on ABL published prior to February 10, 2020, using the search term "abaloparatide".. ABL, a synthetic analog of human parathyroid hormone-related protein, increased bone mineral density (BMD), improved bone microarchitecture, and increased bone strength in preclinical and clinical studies. The pivotal phase 3 trial ACTIVE and its extension (ACTIVExtend) demonstrated the efficacy of initial treatment with ABL for 18 months followed by sequential treatment with alendronate (ALN) for an additional 24 months to reduce the risk of vertebral, nonvertebral, clinical, and major osteoporotic fractures and to increase BMD in postmenopausal women with osteoporosis. Discontinuations from ACTIVE were slightly more common in ABL-treated patients due to dizziness, palpitations, nausea, and headache.. ABL is an effective and well-tolerated treatment for women with postmenopausal osteoporosis at high risk for fracture. Its therapeutic effects are sustained with subsequent ALN therapy.

Topics: Alendronate; Animals; Bone Density; Bone Density Conservation Agents; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Female; Humans; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Parathyroid Hormone-Related Protein; Postmenopause; Risk Factors

Musculoskeletal disorders represent an elevated socioeconomic burden for developed aging societies. Osteoporosis (OP) has been treated with antiresorptive therapies or with teriparatide that was until recently the only anabolic therapy. However, approval of osteoporosis treatment in postmenopausal women with abaloparatide, which is an analog of parathyroid hormone-related peptide (PTHrP), has created a new alternative for OP management. The success of this new treatment is related to differential mechanisms of activation of PTH receptor type 1 (PTH1R) by abaloparatide and PTH. Here, we address the distinguishing mechanisms of PTH1R activation; the effects of PTH1R stimulation in osteoblast, osteocytes, and chondrocytes; the differences between PTH and abaloparatide actions on PTH1R; potential safety concerns; and future perspectives about abaloparatide use in other musculoskeletal disorders.

Topics: Chondrocytes; Female; Humans; Middle Aged; Osteoblasts; Osteocytes; Osteoporosis; Osteoporosis, Postmenopausal; Parathyroid Hormone-Related Protein; Receptor, Parathyroid Hormone, Type 1; Teriparatide

To systematically evaluate the effects of bone anabolic therapies (BATs) - specifically, drug therapy with teriparatide, abaloparatide or romosozumab - on fractures, bone mineral density (BMD), and bone metabolites in postmenopausal osteoporosis.. Six computerized engines were searched through to November 2018. We selected randomized controlled trials (RCTs) evaluating the effect of BATs on postmenopausal osteoporosis and with at least 6 months of follow-up. Controls were placebo, no treatment, or bisphosphonates. Primary outcomes were vertebral and non-vertebral fractures. Secondary outcomes were: BMD determined by dual energy X-ray absorptiometry at total hip, lumbar spine, and femoral neck; N-terminal propeptide of type I procollagen (PINP); C-terminal telopeptide of type I collagen (CTX); and severe adverse events (SAE). We followed the PRISMA guidelines for reporting, and used version 2 of the Cochrane risk-of-bias tool. Frequentist network meta-analyses were performed per outcome. Effects for dichotomous and continuous outcomes were expressed as relative risks and mean differences and their 95% confidence intervals. We used p-scores to rank best treatments per outcome.. Sixteen RCTs (n = 18,940) were evaluated. Mean ages ranged between 61 and 74 years, and follow-up times between 6 and 30 months. Four RCTs (n = 971) excluded patients with previous fractures. In contrast to placebo/no treatment, all BATs significantly reduced the risk of vertebral fractures, but no intervention significantly reduced the risk of non-vertebral fractures; abaloparatide ranked better than other interventions for both fracture types (p-scores: 0.95, and 0.89, respectively). All BATs significantly increased BMD at all locations in comparison with placebo/no treatment; romosozumab consistently ranked better than other interventions at all BMD locations (p-scores >0.86). Teriparatide ranked better than other interventions for increasing PINP. No differences in SAE were observed among treatments.. Abaloparatide, romosozumab, and teriparatide are the best treatments, respectively, to reduce vertebral/non-vertebral fractures, increase BMD, and increase bone formation.

Topics: Antibodies, Monoclonal; Bone Density; Bone Density Conservation Agents; Collagen Type I; Female; Humans; Network Meta-Analysis; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Parathyroid Hormone-Related Protein; Peptide Fragments; Peptides; Procollagen; Randomized Controlled Trials as Topic; Teriparatide

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.. A MEDLINE search was conducted for full text English-language articles, using the terms abaloparatide, parathyroid hormone, and osteoporosis. Published articles pertinent to the short- and long-term efficacy and safety of abaloparatide among postmenopausal women with osteoporosis were reviewed and summarized. Based on randomized, placebo-controlled and active-comparator studies, abaloparatide can reduce the risk of new vertebral and nonvertebral fractures in postmenopausal women with osteoporosis. Abaloparatide can also significantly increase bone mineral density (BMD) at the total hip, femoral neck, and lumbar spine. Patients receiving abaloparatide experience faster and more robust changes in BMD compared to those receiving teriparatide. Overall, abaloparatide is well tolerated with a mild adverse effect profile, including dizziness, headache, nausea, and palpitations. Additionally, there is a lower incidence of hypercalcemia with abaloparatide than with teriparatide. At this time, the differences demonstrated between abaloparatide and teriparatide would not be considered clinically significant. Larger and more robust studies are needed to determine future clinical significance of abaloparatide compared with other agents for use in the postmenopausal osteoporotic population.. Abaloparatide is an effective anabolic agent to improve bone formation and resorption amongst postmenopausal women with osteoporosis. Based on its clinical evidence, abaloparatide can result in greater BMD increases and less hypercalcemia compared with the only current marketed anabolic agent, teriparatide. Adverse events associated with abaloparatide are generally mild in nature and include nausea, dizziness, headache, and palpitations.

Topics: Bone Density; Bone Density Conservation Agents; Female; Fractures, Bone; Humans; Osteoporosis; Osteoporosis, Postmenopausal; Parathyroid Hormone-Related Protein

Osteoporosis is a skeletal disorder characterized by loss of bone mass and strength affecting up to 30-50% of postmenopausal women worldwide. Current therapeutic options include antiresorptives such as aminobisphosphonates or denosumab and osteoanabolic compounds such as teriparatide. Areas covered: In this review, the authors summarize the clinical development, safety and efficacy profile of abaloparatide, a new osteoanabolic agent recently marketed in the US for the treatment of postmenopausal osteoporosis in women who are at high risk for fracture or who fail antiresorptive therapy. Expert opinion: Abaloparatide is a 1-34 PTH related peptide-like molecule that has been modified in order to potentiate the osteoanabolic effect. In its pivotal phase 3 trial in postmenopausal women with osteoporosis, subcutaneous abaloparatide 80 mcg/day reduced the risk of vertebral, nonvertebral, major osteoporotic, and clinical fractures compared with placebo and reduced the risk of major osteoporotic fractures compared with teriparatide. These results, together with a reduced prevalence of hypercalcemia and a lower cost of the marketed compound, point toward improved cost effectiveness with abaloparatide versus teriparatide. However, some concerns have been raised due to a somewhat higher occurrence of adverse effects (particularly with palpitations and increased heart rate) or the resultant discontinuation due to these adverse effects when compared to teriparatide.

Topics: Bone Density Conservation Agents; Female; Half-Life; Humans; Hypercalcemia; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Parathyroid Hormone-Related Protein; Treatment Outcome

This network meta-analysis assessed the efficacy of abaloparatide versus other treatment options to reduce the risk of fractures in women with postmenopausal osteoporosis. The analysis indicates that abaloparatide reduces the risk of fractures in women with postmenopausal osteoporosis versus placebo and compared with other treatment options.. This network meta-analysis (NMA) assessed the relative efficacy of abaloparatide versus other treatments to reduce the risk of fractures in women with postmenopausal osteoporosis (PMO).. PubMed®, Embase®, and the Cochrane Central Register of Controlled Trials were searched for randomized controlled trials published before December 20, 2017, that included women with PMO who were eligible to receive interventions for primary or secondary fracture prevention. The NMA was conducted by fracture site (vertebral [VF], nonvertebral [NVF], and wrist), with the relative risk (RR) of fracture versus placebo the main clinical endpoint. The NMA used fixed-effects and random-effects approaches.. A total of 4978 articles were screened, of which 22 were included in the analysis. Compared with other treatments, abaloparatide demonstrated the greatest treatment effect relative to placebo in the VF network (RR = 0.13; 95% credible interval [CrI] 0.04-0.34), the NVF network (RR = 0.50; 95% CrI 0.28-0.85), and the wrist fracture network (RR = 0.39; CrI 0.15-0.90). Treatment ranking showed that abaloparatide had the highest estimated probability of preventing fractures in each of the networks (79% for VF, 70% for NVF, and 53% for wrist fracture) compared with other treatments. Individual networks demonstrated a good level of agreement with direct trial evidence and direct pair-wise comparisons.. This NMA indicates that abaloparatide reduces the RR of VF, NVF, and wrist fracture in women with PMO with or without prior fracture versus placebo, compared with other treatment options. Limitations include that adverse events and drug costs were not considered, and that generalizability is limited to the trial populations and endpoints included in the NMA.

Topics: Bone Density Conservation Agents; Female; Hip Fractures; Humans; Network Meta-Analysis; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Parathyroid Hormone-Related Protein; Randomized Controlled Trials as Topic; Risk Reduction Behavior; Spinal Fractures; Wrist Injuries

Globally, a great number of elderly suffer from osteoporosis, especially postmenopausal women. Osteoporosis results in low bone mineral density (BMD) and high risk of fragility fracture. However, there is no defined strategy to select the most suitable anti-osteoporotic drugs for osteoporosis patients. Therefore, this study aims to select the most effective anti-osteoporotic drug for postmenopausal women with osteoporosis.. Literature search was conducted in PubMed, EMBASE, and the Cochrane Library. Raw data from the related randomized clinical trials were extracted. A pairwise and network meta-analysis model was utilized to assess the efficacy of ten drugs on the percentage change of BMD in the lumbar spine and total hip from baseline to one year of treatment. Risks of vertebral fracture and non-vertebral fracture were evaluated as well. We reported the effect size with a weighted mean difference (WMD) for continuous outcomes and odds ratio (OR) for dichotomous outcomes. All the drugs were ranked based on the surface under the cumulative ranking curve (SUCRA) value. Furthermore, the heterogeneity, consistency and publication bias of enrolled literature were assessed.. With regard to lumbar spine BMD, the ten selected drugs all showed significant efficacy compared with placebo. In regard to total hip BMD and vertebral fracture, with the exception of calcitonin, the remaining nine drugs all showed significant efficacy compared with placebo. Six drugs - abaloparatide, alendronate, risedronate, strontium ranelate, teriparatide, and zoledronate - were significantly more effective compared with placebo for the treatment of non-vertebral fractures. As the SUCRA values indicated, abaloparatide performed the best on improving lumbar spine BMD, vertebral fracture and non-vertebral fracture, while denosumab was the best choice to improve total hip BMD.. To sum up, abaloparatide, denosumab, and teriparatide showed the best efficacy for the treatment of postmenopausal osteoporosis, especially abaloparatide.

Topics: Bone Density; Bone Density Conservation Agents; Denosumab; Female; Fractures, Bone; Humans; Incidence; Lumbar Vertebrae; Network Meta-Analysis; Osteoporosis, Postmenopausal; Parathyroid Hormone-Related Protein; Treatment Outcome

To review the efficacy, safety, and economics of abaloparatide in the treatment of postmenopausal osteoporosis.. PubMed (1966 to October 2017), Clinicaltrials.gov (October 2017), and Scopus (1970 to October 2017) were searched using abaloparatide, Tymlos, BA058, PTHrP 1-34 analog, and parathyroid hormone-related peptide 1-34 analog.. Human studies published in peer-reviewed publications in English were the primary sources for efficacy, safety, and economic data.. In the 2 randomized, published clinical studies of 24 weeks and 18 months duration, bone mineral density changes were higher for abaloparatide (lumbar spine, 6.7%-11.2%; femoral head, 3.1%-3.2%; total hip, 2.6%-4.2%) compared with placebo (lumbar spine, 0.6%-1.6%; femoral head, -0.4% to 0.8%; total hip, -0.1% to 0.4%; P < 0.05) and compared with teriparatide in the 24-week study (total hip 2.6% vs +0.5%, P < 0.05). New vertebral and nonvertebral fractures occurred in 0.6% and 2.7% of patients on abaloparatide compared with 4.2% and 4.7% on placebo in the 18-month study ( P < 0.05). Abaloparatide appears to have a somewhat higher risk for adverse effects, discontinuation as a result of adverse effects, and serious or severe adverse effects than teriparatide, but teriparatide has a higher risk for hypercalcemia. Pharmacoeconomic modeling appears to favor abaloparatide if differences in efficacy and cost are maintained.. Abaloparatide, which has less effect on osteoclasts, is an alternative to teriparatide in patients with postmenopausal osteoporosis who are at high risk for fractures or who have failed antiresorptive therapy based on initial clinical studies and economic modeling.

Topics: Animals; Bone Density Conservation Agents; Female; Humans; Osteoporosis, Postmenopausal; Parathyroid Hormone-Related Protein; Teriparatide; Treatment Outcome

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.

Topics: Bone and Bones; Bone Density Conservation Agents; Clinical Trials as Topic; Female; Humans; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Parathyroid Hormone-Related Protein

The purpose is to review the efficacy and optimal use of parathyroid hormone and parathyroid hormone-related protein analogs in osteoporosis treatment.. The parathyroid hormone analog teriparatide, a potent stimulator of bone remodeling, increases hip and spine bone mineral density and reduces the risk of vertebral and non-vertebral fractures in postmenopausal osteoporotic women. The parathyroid hormone-related protein analog, abaloparatide, also reduces fracture incidence but has pharmacological effects that differ from teriparatide, particularly in cortical bone. These analogs provide maximal benefit when their use is followed by a potent antiresorptive medication. Moreover, studies have shown that the combination of teriparatide and the RANK-ligand inhibitor, denosumab, increase bone density and estimated strength more than monotherapy and more than any currently available regimen. Parathyroid hormone and parathyroid hormone-related protein analogs, whether as monotherapy, in combination with antiresorptive agents or in sequence with antiresorptive agents, will likely play an expanding role in osteoporosis management.

Topics: Bone Density; Bone Density Conservation Agents; Denosumab; Drug Therapy, Combination; Humans; Osteoporosis; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Parathyroid Hormone; Parathyroid Hormone-Related Protein; Spinal Fractures; Teriparatide

Anabolic therapies, recommended for patients at very high fracture risk, are administered subcutaneously (SC). The objective of this study was to evaluate the efficacy and safety of the abaloparatide microstructured transdermal system (abaloparatide-sMTS) as an alternative to the SC formulation. This phase 3, noninferiority study (NCT04064411) randomly assigned postmenopausal women with osteoporosis (N = 511) 1:1 to open-label abaloparatide administered daily via abaloparatide-sMTS or SC injection for 12 months. The primary comparison between treatment groups was the percentage change in lumbar spine bone mineral density (BMD) at 12 months, with a noninferiority margin of 2.0%. Secondary endpoints included percentage change in total hip and femoral neck BMD, bone turnover markers, dermatologic safety, and new clinical fracture incidence. At 12 months, percentage increase from baseline in lumbar spine BMD was 7.14% (SE: 0.46%) for abaloparatide-sMTS and 10.86% (SE: 0.48%) for abaloparatide-SC (treatment difference: -3.72% [95% confidence interval: -5.01%, -2.43%]). Percentage change in total hip BMD was 1.97% for abaloparatide-sMTS and 3.70% for abaloparatide-SC. Median changes from baseline at 12 months in serum procollagen type I N-terminal propeptide (s-PINP) were 52.6% for abaloparatide-sMTS and 74.5% for abaloparatide-SC. Administration site reactions were the most frequently reported adverse events (abaloparatide-sMTS, 94.4%; abaloparatide-SC, 70.5%). Incidence of serious adverse events was similar between groups. Mild or moderate skin reactions occurred with abaloparatide-sMTS with no identifiable risk factors for sensitization reactions. Few new clinical fractures occurred in either group. Noninferiority of abaloparatide-sMTS to abaloparatide-SC for percentage change in spine BMD at 12 months was not demonstrated; however, clinically meaningful increases from baseline in lumbar spine and total hip BMD were observed in both treatment groups. © 2023 Radius Health, Inc and The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Topics: Bone Density; Bone Density Conservation Agents; Female; Humans; Lumbar Vertebrae; Minerals; Osteoporosis; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Postmenopause

This study aimed to determine the efficacy of abaloparatide in increasing bone mineral density (BMD) and its safety in postmenopausal Japanese women with osteoporosis.. Randomized, double-blind, placebo-controlled, dose-finding study of abaloparatide in postmenopausal Japanese women at high fracture risk. The primary endpoint was the change in lumbar spine (LS) BMD from baseline at the last visit after daily subcutaneous injections of placebo or 40 or 80 µg abaloparatide. Other endpoints included time-course changes in LS BMD at 12, 24, and 48 weeks, in total hip (TH) and femoral neck (FN) BMDs, and in bone turnover markers.. Increases in LS BMD with 40 and 80 µg abaloparatide were significantly higher than that with placebo (6.6% and 11.5%, respectively), with significant between-group differences for the abaloparatide groups (4.9%). TH BMD increased by 0.4%, 1.6%, and 2.9% and FN BMD increased by 0.6%, 1.5%, and 2.4% in the placebo and 40 and 80 µg abaloparatide groups, respectively. Serum PINP rapidly increased by 67.3% and 140.7% and serum CTX slowly increased by 16.4% and 34.5% in the 40 and 80 µg abaloparatide groups, respectively. Although more adverse events were observed in the abaloparatide groups, they were mild to moderate and not dose dependent.. In postmenopausal Japanese women with osteoporosis at high fracture risk, abaloparatide for 48 weeks dose-dependently increased LS, TH, and FN BMDs, supporting further investigation with 80 μg abaloparatide for the treatment of osteoporosis in this population.. JapicCTI-132381.

Topics: Bone Density; Bone Density Conservation Agents; Double-Blind Method; Female; Humans; Lumbar Vertebrae; Osteoporosis; Osteoporosis, Postmenopausal; Postmenopause

Abaloparatide reduced fracture risk in postmenopausal women with osteoporosis in the Abaloparatide Comparator Trial In Vertebral Endpoints (ACTIVE). Its effect in Japanese patients remains unexamined.. This work aimed to determine the efficacy and safety of abaloparatide in increasing bone mineral density (BMD) in Japanese patients with osteoporosis at high fracture risk.. This was a randomized, double-blind, placebo-controlled study conducted in Japan. Postmenopausal women and men with osteoporosis with high fracture risk were given daily subcutaneous 80 µg abaloparatide or placebo for 78 weeks (18 months). The primary end point was percentage change in lumbar spine (LS) BMD from baseline at the last visit. Secondary end points included time-course changes in LS, total hip (TH), and femoral neck (FN) BMDs and bone turnover markers, and cumulative number of fractures.. Abaloparatide increased LS, TH, and FN BMDs (mean [95% CI]) by 12.5% (10.3%-14.8%; P < .001), 4.3% (3.3%-5.3%), and 4.3% (2.9%-5.6%), respectively, vs placebo. Serum procollagen type I N-terminal propeptide increased rapidly to ~ 140% above baseline at 6 weeks and gradually decreased but was approximately 25% higher than baseline at 78 weeks. Serum carboxy-terminal cross-linking telopeptide of type I collagen gradually increased to 50% above baseline at 24 weeks and decreased gradually to the placebo-group level from 60 weeks. Four vertebrae of 3 participants in the placebo group, but none in the abaloparatide group, developed new vertebral fractures. The safety profile was similar to that in the ACTIVE study.. In Japanese patients with postmenopausal and male osteoporosis with high fracture risk, abaloparatide for 78 weeks robustly increased LS, TH, and FN BMDs, suggesting a similar efficacy in Japanese patients vs the ACTIVE study population.

Topics: Bone Density; Bone Density Conservation Agents; Collagen Type I; Double-Blind Method; Female; Humans; Japan; Lumbar Vertebrae; Male; Osteoporosis; Osteoporosis, Postmenopausal; Parathyroid Hormone-Related Protein

Abaloparatide, an anabolic osteoporosis treatment administered by subcutaneous (SC) injection, increases bone mineral density (BMD) and reduces fracture risk in postmenopausal women with osteoporosis. The abaloparatide-solid Microstructured Transdermal System [abaloparatide-sMTS (Kindeva, St Paul, MN, USA)], which delivers abaloparatide intradermally, is in development to provide an alternative method for abaloparatide delivery. The objective of this study was to evaluate the ability of subjects to self-administer abaloparatide-sMTS, based on pharmacokinetic and pharmacodynamic markers.. In this single-arm, open-label, Phase 1b study, 22 healthy postmenopausal women aged 50-85 years with low BMD were trained to self-administer abaloparatide-sMTS 300 μg once daily to the thigh for 5 min for 29 days. The primary endpoint was systemic exposure to abaloparatide. Secondary endpoints included percent change from baseline in serum procollagen type I N-terminal propeptide (s-PINP), patient experience, and safety.. Subjects successfully self-administered abaloparatide-sMTS, which provided a consistent pharmacokinetic profile over 29 days and produced s-PINP increases from baseline similar to that observed in the pivotal trial with abaloparatide-SC. Observed patient experience along with the clinical data support continued clinical development of abaloparatide-sMTS.. NCT04366726, Date of registration 04/29/2020, retrospectively registered.. Osteoporosis is a serious health condition that causes more than 2 million fractures in the USA annually. Treatment options for osteoporosis include drugs that prevent bone resorption and anabolic agents that build new bone. Bone anabolic agents, such as abaloparatide, have been shown to increase bone mineral density and reduce the risk of fracture in postmenopausal women with osteoporosis. Currently, all bone anabolic agents are delivered by subcutaneous injection. However, some patients do not like injectable treatments, which can negatively impact patients’ adherence to prescribed medication. In this study, we describe a novel mode of administration, the abaloparatide-solid Microstructured Transdermal System (abaloparatide-sMTS), which is applied to the thigh for 5 min and delivers abaloparatide intradermally. The study showed that this new method delivered abaloparatide into the blood as effectively as subcutaneous injections and demonstrated signs of activity in the body. Study participants were satisfied with abaloparatide-sMTS and found it easy to use. The most common side effects were skin related, including redness, pain, and swelling, which resolved shortly after dosing.

Topics: Aged; Aged, 80 and over; Bone Density; Bone Density Conservation Agents; Female; Humans; Injections, Subcutaneous; Lumbar Vertebrae; Middle Aged; Osteoporosis, Postmenopausal; Parathyroid Hormone-Related Protein; Peptide Fragments; Procollagen

The ACTIVE study demonstrated the antifracture efficacy of abaloparatide in postmenopausal women with osteoporosis. ACTIVExtend demonstrated sustained fracture risk reduction with alendronate in abaloparatide-treated participants from ACTIVE. A direct comparison of the efficacy of abaloparatide and antiresorptive therapies has not been performed.. The objective of this analysis is to compare the antifracture efficacy of abaloparatide in ACTIVE with that of alendronate in ACTIVExtend.. In this post hoc analysis, the rate of new vertebral fractures for women in ACTIVExtend (N = 1139) was calculated based on baseline and endpoint radiographs for placebo or abaloparatide in ACTIVE and alendronate in ACTIVExtend. Vertebral fracture rates between abaloparatide and alendronate were compared in a Poisson regression model. Fracture rates for nonvertebral and clinical fractures were compared based on a Poisson model during 18 months of abaloparatide or placebo treatment in ACTIVE and 18 months of alendronate treatment in ACTIVExtend.. The vertebral fracture rate was lower during abaloparatide treatment in ACTIVE (0.47 fractures/100 patient-years) than alendronate treatment in ACTIVExtend (1.66 fractures/100 patient-years) (relative risk reduction 71%; P = .027). Although the comparisons did not meet statistical significance, after switching from placebo (ACTIVE) to alendronate (ACTIVExtend), the rate of new vertebral fractures decreased from 2.49 to 1.66 fractures per 100 patient-years, and after switching from abaloparatide to alendronate from 0.47 to 0.19 fractures per 100 patient-years. The rates of nonvertebral fractures and clinical fractures were not significantly different.. Initial treatment with abaloparatide may result in greater vertebral fracture reduction compared with alendronate in postmenopausal women with osteoporosis.

Topics: Aged; Alendronate; Bone Density; Bone Density Conservation Agents; Drug Therapy, Combination; Female; Femur Neck; Humans; Lumbar Vertebrae; Middle Aged; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Parathyroid Hormone-Related Protein; Placebos; Radiography; Risk Factors; Spinal Fractures; Treatment Outcome

Current treatment guidelines recommend treatment for postmenopausal women with a T score <2.5 regardless of age. This subgroup analysis evaluated the efficacy and safety of abaloparatide in younger postmenopausal women considered to be at high risk for fracture.. Subgroup analysis of women in the Abaloparatide Comparator Trial in Vertebral Endpoints (ACTIVE) trial who were <65 years old and met modified utilization management criteria (baseline T score ≤-2.5 [any site] and ≥1 prevalent vertebral and/or ≥1 prior clinical fracture within 5 years of randomization).. A total of 296 women (age range, 49-64 years) were included. Significant increases in bone mineral density from baseline were observed for abaloparatide versus placebo at all 3 sites at 6 months (p < 0.01 for total hip and femoral neck; p < 0.0001 for lumbar spine), 12 months (p < 0.0001 at all 3 sites), and 18 months (p < 0.0001 at all 3 sites). Fracture rates were numerically lower for abaloparatide versus placebo, consistent with the overall trial results, although the differences were not statistically significant. The number needed to treat to prevent 1 additional vertebral fracture after 18 months of treatment versus placebo was 18 for abaloparatide and 21 for teriparatide. The number needed to treat had nonsignificant trends toward lower values with abaloparatide versus teriparatide for nonvertebral fractures (23 vs 40) and clinical fractures (16 vs 73) and similar for major osteoporotic fractures (24 vs 27). The safety profile was consistent with the overall ACTIVE population.. Findings of this subgroup (post hoc) analysis are consistent with the overall ACTIVE population. Abaloparatide appears to be effective and well tolerated in this subgroup of younger postmenopausal women. ClinicalTrials.gov identifier: NCT01343004.

Topics: Bone Density; Bone Density Conservation Agents; Double-Blind Method; Female; Humans; Incidence; Middle Aged; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Parathyroid Hormone-Related Protein; Postmenopause; Risk

Early PINP changes correlate with 18-month lumbar spine BMD changes and the correlation was greater with abaloparatide versus teriparatide. The uncoupling index was similar between the two agents.. We evaluated the relationship between early PINP changes and subsequent changes in spine BMD following abaloparatide and teriparatide treatments. We also explored the use of an "uncoupling index" (UI), the balance between bone formation and bone resorption, which we hypothesised would be similar in response to these treatment groups.. Blood samples were taken for measurement of bone turnover markers (BTMs) s-PINP and s-CTX at baseline, 1, 3, 6, 12, and 18 months from 189 abaloparatide patients and 227 teriparatide patients randomly selected from all participants who completed the study. BMD was measured by DXA at baseline, 6, 12, and 18 months. Correlations were calculated between log ratio of BTMs from baseline to 3 months and percent change from baseline in BMD at 18 months. A UI was calculated using log transformation and subtraction of the standard deviate for s-CTX from the standard deviate for s-PINP for each patient.. Early BTM changes were associated with subsequent BMD changes for both treatments. Pearson correlations for the log ratio of PINP over baseline at 3 months and BMD percent change from baseline at 18 months were larger (P < 0.0001) with abaloparatide (r = 0.561) than teriparatide (r = 0.198). The mean UI at 1 month was greater for abaloparatide versus teriparatide (1.743 and 1.493, respectively; P = 0.03) but was similar at 3 months or later time points.. Early s-PINP changes correlate with percentage change in lumbar spine BMD 18 months after treatment with both abaloparatide and teriparatide, though the correlation with abaloparatide was greater. The UI was similar between abaloparatide and teriparatide suggesting that the balance between formation and resorption markers was similar.

Topics: Aged; Biomarkers; Bone Density; Bone Density Conservation Agents; Bone Remodeling; Collagen Type I; Double-Blind Method; Female; Humans; Lumbar Vertebrae; Middle Aged; Osteoporosis, Postmenopausal; Parathyroid Hormone-Related Protein; Peptide Fragments; Peptides; Procollagen; Teriparatide

We evaluated the efficacy of abaloparatide in women who were at increased risk for fracture, based on CHMP recommended risk thresholds, at the Abaloparatide Comparator Trial In Vertebral Endpoints (ACTIVE) study baseline. Among patients at high risk based on FRAX probabilities, 18 months of abaloparatide significantly decreased risk for all fracture endpoints compared with placebo.. Abaloparatide, a novel anabolic agent for the treatment of postmenopausal osteoporosis, significantly reduced the risk of vertebral and nonvertebral fractures in the ACTIVE study compared with placebo. In this post hoc analysis, we evaluated abaloparatide's efficacy in a subset of women in the study at an increased risk of fracture at baseline, based on the Committee for Medicinal Products for Human Use (CHMP) recommended risk thresholds for inclusion in clinical trials.. Women with a baseline 10-year risk of major osteoporotic fracture ≥ 10% or hip fracture ≥ 5%, assessed using the FRAX® tool (including femoral neck bone mineral density), were included in the analysis. The proportion with one or more events of new morphometric vertebral fractures was calculated. Event rates for nonvertebral, major osteoporotic, and all clinical fractures were estimated using Kaplan-Meier analysis.. Following 18 months of treatment, abaloparatide significantly reduced incident vertebral fractures compared with placebo (relative risk reduction = 91%; 0.5% versus 5.6%; p < 0.001). Abaloparatide treatment was also associated with significantly fewer nonvertebral, major osteoporotic, and clinical fractures compared with placebo: 2.7% versus 5.8%, p = 0.036; 1.3% versus 6.0%, p < 0.001; and 3.5% versus 8.2%, p = 0.006, respectively. The effect of abaloparatide on major osteoporotic fractures (78% reduction) was significantly greater than that seen with teriparatide (23% reduction, p = 0.007).. In a subset of postmenopausal women at increased risk of fracture as judged by CHMP guidance, abaloparatide significantly decreased the risk of all fracture endpoints compared with placebo.

Topics: Aged; Bone Density; Bone Density Conservation Agents; Female; Hip Fractures; Humans; Middle Aged; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Parathyroid Hormone-Related Protein; Postmenopause; Risk Factors; Spinal Fractures; Treatment Outcome

Wrist fractures are common, contribute significantly to morbidity in women with postmenopausal osteoporosis, and occur predominantly at the ultradistal radius, a site rich in trabecular bone. This exploratory analysis of the phase 3 ACTIVE study evaluated effects of abaloparatide versus placebo and teriparatide on forearm bone mineral density (BMD) and risk of wrist fracture.. Forearm BMD was measured by dual energy X-ray absorptiometry in a subset of 982 women from ACTIVE, evenly distributed across the three treatment groups. Wrist fractures were ascertained in the total cohort (N = 2463).. After 18 months, ultradistal radius BMD changes from baseline were 2.25 percentage points greater for abaloparatide compared with placebo (95% confidence interval (CI) 1.38, 3.12, p < 0.001) and 1.54 percentage points greater for abaloparatide compared with teriparatide (95% CI 0.64, 2.45, p < 0.001). At 18 months, 1/3 radius BMD losses (versus baseline) were similar for abaloparatide compared with placebo (-0.42; 95% CI -1.03, 0.20; p = 0.19) but losses with teriparatide exceeded those of placebo (-1.66%; 95% CI -2.27, -1.06; p < 0.001). The decline with abaloparatide was less than that seen with teriparatide (group difference 1.22%; 95% CI 0.57, 1.87; p < 0.001). The radius BMD findings, at both ultradistal and 1/3 sites, are consistent with the numerically lower incidence of wrist fractures observed in women treated with abaloparatide compared with teriparatide (HR = 0.43; 95% CI 0.18, 1.03; p = 0.052) and placebo (HR = 0.49, 95% CI 0.20, 1.19, p = 0.11).. Compared with teriparatide, abaloparatide increased BMD at the ultradistal radius (primarily trabecular bone) and decreased BMD to a lesser extent at the 1/3 radius (primarily cortical bone), likely contributing to the numerically lower wrist fracture incidence observed with abaloparatide.

Topics: Absorptiometry, Photon; Aged; Aged, 80 and over; Bone Density; Bone Density Conservation Agents; Double-Blind Method; Female; Humans; Kaplan-Meier Estimate; Middle Aged; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Parathyroid Hormone-Related Protein; Radius; Radius Fractures; Wrist Injuries

In a phase 2 trial of 222 postmenopausal women with osteoporosis aged 55 to 85 years randomized to one of three different doses of abaloparatide-SC, subcutaneous teriparatide, or placebo for 24 weeks, abaloparatide-SC resulted in improvements in skeletal microarchitecture as measured by the trabecular bone score.. Subcutaneous abaloparatide (abaloparatide-SC) increases total hip and lumbar spine bone mineral density and reduces vertebral and non-vertebral fractures. In this study, we analyzed the extent to which abaloparatide-SC improves skeletal microarchitecture, assessed indirectly by trabecular bone score (TBS).. This is a post hoc analysis of a phase 2 trial of 222 postmenopausal women with osteoporosis aged 55 to 85 years randomized to abaloparatide-SC (20, 40, or 80 μg), subcutaneous teriparatide (20 μg), or placebo for 24 weeks. TBS was measured from lumbar spine dual X-ray absorptiometry (DXA) images in 138 women for whom the DXA device was TBS software compatible. Assessments were made at baseline, 12 and 24 weeks. Between-group differences were assessed by generalized estimating equations adjusted for relevant baseline characteristics, and a pre-determined least significant change analysis was performed.. After 24 weeks, TBS increased significantly by 2.27, 3.14, and 4.21% versus baseline in participants on 20, 40, and 80 μg abaloparatide-SC daily, respectively, and by 2.21% in those on teriparatide (p < 0.05 for each). The TBS in the placebo group declined by 1.08%. The TBS increase in each treatment group was significantly higher than placebo at 24 weeks (p < 0.0001 for each) after adjustment for age, BMI, and baseline TBS. A dose-response was observed at 24 weeks across the three doses of abaloparatide-SC and placebo (p = 0.02). The increase in TBS in the abaloparatide-SC 80 μg group was significantly greater than TPTD (p < 0.03).. These results are consistent with an effect of abaloparatide-SC to improve lumbar spine skeletal microarchitecture, as assessed by TBS.

Topics: Absorptiometry, Photon; Aged; Aged, 80 and over; Bone Density; Bone Density Conservation Agents; Cancellous Bone; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Injections, Subcutaneous; Lumbar Vertebrae; Middle Aged; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Parathyroid Hormone-Related Protein; Teriparatide

The recently published results of the sequential treatment of postmenopausal osteoporotic women with subcutaneous abaloparatide (80 µg/day) (ABL) for 18 months followed by 6 months of oral alendronate (70 mg/week) (ALN) support the administration of an anti-resorptive agent after completion of a treatment course with an osteoanabolic agent. The ABL/ALN sequence resulted in greater bone mineral density gains at all skeletal sites and in a reduction of vertebral, non-vertebral, major and clinical fractures compared to what is observed after 18 months of placebo followed by 6 months of ALN. Whereas questions remained unanswered about the ideal anti-resorptive agent to be used after ABL, the optimal duration of the administration of the anti-resorptive drug or the potential interest of re-initiating a course of ABL after a limited administration of ALN, these results support the use of the ABL/ALN sequence in the management of postmenopausal osteoporosis.

Topics: Alendronate; Biomarkers; Bone Density; Bone Density Conservation Agents; Drug Administration Schedule; Drug Therapy, Combination; Female; Fractures, Bone; Humans; Injections, Subcutaneous; Osteoporosis, Postmenopausal; Parathyroid Hormone-Related Protein; Peptide Fragments; Placebo Effect; Procollagen

Geographic heterogeneity has been observed in fracture risk and efficacy of therapeutic intervention in postmenopausal osteoporosis. The objectives of these analyses were to assess across geographic and ethnic subgroups the heterogeneity of fracture incidence and baseline risk, and consistency of effect of abaloparatide-SC vs placebo on fracture risk reduction in the 18-month, phase 3, multinational, ACTIVE randomized controlled trial. Prespecified exploratory analyses of geographic subgroups (North America, South America, Europe, Asia) and post hoc analyses of ethnic subgroups (Hispanic or Latino, other) of postmenopausal women with osteoporosis enrolled in the abaloparatide-SC and placebo cohorts (n = 1645) were performed. Country-specific FRAX models were used to calculate 10-year absolute fracture risks. Relative risk reductions for vertebral fractures and hazard ratios for non-vertebral, clinical, and major osteoporotic fractures were calculated. Forest plots were constructed to assess treatment-by-subgroup interactions for each geographic region and ethnicity. Baseline prevalence of vertebral fractures was similar across geographies; baseline prevalence of non-vertebral fractures was more variable. Ten-year major osteoporosis fracture and hip fracture risks were variable across and within regions. The effects of abaloparatide-SC on reducing the risk of vertebral, non-vertebral, clinical, and major osteoporotic fractures were similar across regions, and for Hispanic or Latino vs other ethnicities. A limitation was the limited power to detect interactions with few events. In conclusion, despite geographic variability in fracture incidence and risk at baseline, no differences were detected in the effects of abaloparatide-SC in reducing vertebral, non-vertebral, clinical, and major osteoporotic fracture risk across assessed geographic regions and ethnicities.

Topics: Aged; Aged, 80 and over; Bone Density Conservation Agents; Female; Humans; Incidence; Middle Aged; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Parathyroid Hormone-Related Protein; Postmenopause; Spinal Fractures; Treatment Outcome

Advanced age is an important risk factor for fracture. The Abaloparatide Comparator Trial In Vertebral Endpoints (ACTIVE) trial showed that subcutaneous abaloparatide increased bone mineral density (BMD) and reduced the risk of vertebral and nonvertebral fractures in postmenopausal women with osteoporosis. This study describes the effects of abaloparatide in the subgroup of women aged 80 or more years in ACTIVE.. Post hoc analyses of BMD and fracture incidence in this subgroup of women who received abaloparatide or placebo in the 18-month, phase 3, double-blind, randomized controlled ACTIVE trial.. The mean ages of the women ≥80 years were 81.9 and 81.7 years in the placebo (n = 43) and abaloparatide (n = 51) groups, respectively. The increases in BMD from baseline to 18 months with abaloparatide treatment were 3.9% at the total hip (P < 0.001), 3.6% at the femoral neck (P < 0.01), and 12.1% at the lumbar spine (P < 0.001), and were similar to those observed in the overall population. Abaloparatide therapy was associated with numerical, but not statistically significant, reductions in the risk of vertebral and nonvertebral fractures in this subpopulation, compared with placebo. The proportion of participants reporting adverse events was similar between treatment groups and between the older subgroup and the overall population.. Abaloparatide was effective in increasing BMD in the very elderly subgroup of ACTIVE, with a safety profile similar to that of the overall study population.

Topics: Aged, 80 and over; Bone Density; Bone Density Conservation Agents; Double-Blind Method; Female; Femur Neck; Humans; Incidence; Lumbar Vertebrae; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Parathyroid Hormone-Related Protein; Pelvic Bones; Postmenopause; Risk Factors; Spinal Fractures; Treatment Outcome

In women with postmenopausal osteoporosis, we investigated the effects of 24 months of treatment with alendronate (ALN) following 18 months of treatment with abaloparatide (ABL) or placebo (PBO).. Women who completed ABL or PBO treatment in ACTIVE were eligible to receive up to 24 months of ALN. We evaluated the incidence of vertebral and nonvertebral fractures and changes in bone mineral density (BMD) during the entire 43-month period from ACTIVE baseline to the end of ACTIVExtend and for the 24-month extension only.. Five hundred fifty-eight women from ACTIVE's ABL group and 581 from its PBO group (92% of ABL and PBO completers) were enrolled. During the full 43-month treatment period, 0.9% of evaluable women in the ABL/ALN group experienced a new radiographic vertebral fracture vs 5.6% of women in the PBO/ALN group, an 84% relative risk reduction (RRR, P < 0.001). Kaplan-Meier incidence rates for other reported fracture types were significantly lower for ABL/ALN vs PBO/ALN (all P < 0.05). Gains in BMD achieved during ACTIVE were further increased during ACTIVExtend. For ACTIVExtend only, RRR for vertebral fractures was 87% with ABL/ALN vs PBO/ALN (P = 0.001). Adverse events were similar between groups. A supplemental analysis for regulatory authorities found no hip fractures in the ABL/ALN group vs five in the PBO/ALN group.. Eighteen months of ABL followed by 24 months of ALN reduced the risk of vertebral, nonvertebral, clinical, and major osteoporotic fractures and increased BMD. Sequential ABL followed by ALN appears to be an effective treatment option for postmenopausal women at risk for osteoporosis-related fractures.

Topics: Aged; Aged, 80 and over; Alendronate; Bone Density; Bone Density Conservation Agents; Drug Administration Schedule; Drug Substitution; Female; Femur Neck; Humans; Maintenance Chemotherapy; Middle Aged; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Parathyroid Hormone-Related Protein; Placebos; Spinal Fractures

Abaloparatide (ABL) is a 34-amino acid peptide designed to be a selective activator of the parathyroid hormone receptor type 1 signaling pathway. In the Abaloparatide Comparator Trial In Vertebral Endpoints (ACTIVE), subcutaneous ABL reduced the risk of new vertebral, nonvertebral, clinical, and major osteoporotic fracture compared with placebo and of major osteoporotic fracture compared with teriparatide. To further evaluate the effectiveness of ABL, we calculated the number needed to treat (NNT) to prevent one fracture using ACTIVE data. To estimate the potential effectiveness of ABL in populations at higher fracture risk than in ACTIVE, we calculated NNT for vertebral fracture using reference populations from historical placebo-controlled trials, assuming an 86% relative risk reduction in vertebral fracture with ABL treatment as observed in ACTIVE. NNT was calculated as the reciprocal of the absolute risk reduction in ACTIVE. The projected NNT for ABL in other populations was calculated based on incidence rate (IR) for vertebral fractures in the placebo arms of the FREEDOM (placebo IR 7.2%), FIT-1 (placebo IR 15.0%), and FIT-2 (placebo IR 3.8%) trials. NNT for ABL in ACTIVE was 28 for vertebral, 55 for nonvertebral, 37 for clinical, and 34 for major osteoporotic fracture. NNT for these fracture types for teriparatide in ACTIVE were 30, 92, 59, and 75, respectively. Using placebo IRs from FREEDOM, FIT-1, and FIT-2, projected NNTs for vertebral fracture with ABL were 17, 8, and 31. These data are useful for further evaluating ABL for the treatment of osteoporosis in postmenopausal women.

Topics: Aged; Aged, 80 and over; Bone Density Conservation Agents; Female; Humans; Middle Aged; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Parathyroid Hormone-Related Protein; Research Design; Teriparatide

Daily subcutaneous (SC) injections of the investigational drug abaloparatide-SC (80 mcg) for 18 months significantly decrease the risk of vertebral and nonvertebral fracture compared with placebo in postmenopausal women. We examined the efficacy of abaloparatide-SC as a function of baseline fracture risk, assessed using the FRAX tool. Baseline clinical risk factors (age, body mass index [BMI], prior fracture, glucocorticoid use, rheumatoid arthritis, and smoking) were entered into country-specific FRAX models to calculate the 10-year probability of major osteoporotic fractures, with or without femoral neck bone mineral density (BMD). The interaction between probability of a major osteoporotic fracture and treatment efficacy was examined by a Poisson regression. A total of 821 women randomized to placebo and 824 women to abaloparatide-SC, mean age 69 years in both groups, were followed for up to 2 years. At baseline, the 10-year probability of major osteoporotic fractures (with BMD) ranged from 2.3% to 57.5% (mean 13.2%). Treatment with abaloparatide-SC was associated with a 69% (95% confidence interval [CI] 38-85%) decrease in major osteoporotic fracture (MOF) and a 43% (95% CI 9-64%) decrease in any clinical fracture compared with placebo. For all outcomes, hazard ratios tended to decrease (ie, greater efficacy) with increasing fracture probability. Whereas the interaction approached significance for the outcome of any fracture (p = 0.11), there was no statistically significant interaction for any of the fracture outcomes. Similar results were noted when FRAX probability was computed without BMD. Efficacy of abaloparatide-SC to decrease the risk of major osteoporotic fracture or any clinical fracture in postmenopausal women with low BMD and/or prior fracture appears independent of baseline fracture probability. © 2017 American Society for Bone and Mineral Research.

Topics: Age Factors; Aged; Aged, 80 and over; Body Mass Index; Bone Density; Double-Blind Method; Female; Femoral Neck Fractures; Femur Neck; Humans; Middle Aged; Osteoporosis, Postmenopausal; Parathyroid Hormone-Related Protein; Risk Factors

To assess the efficacy and safety of 18 months of subcutaneous abaloparatide (ABL-SC) or placebo (PBO) followed by 6 months of alendronate (ALN) (preplanned interim analysis).. ACTIVExtend, an extension of ACTIVE, enrolled patients who completed 18 months of ABL-SC or PBO in ACTIVE to receive up to 24 additional months of open-label ALN; there was 1 month between the studies to re-consent patients.. Of 1243 eligible ACTIVE patients, 1139 (92%) were enrolled in ACTIVExtend beginning November 20, 2012. These results are from a prespecified 6-month interim analysis (cutoff date, June 2, 2015); the study is ongoing. Findings indicated percentages of patients with new morphometric vertebral fractures: PBO/ALN, 4.4% vs ABL-SC/ALN, 0.55%; relative risk reduction, 87% (relative risk, 0.13; 95% CI, 0.04-0.41; P<.001). Kaplan-Meier estimated rates of nonvertebral fractures were PBO/ALN, 5.6% vs ABL-SC/ALN, 2.7%; risk reduction, 52% (hazard ratio [HR], 0.48; 95% CI, 0.26-0.89; log-rank P=.02). There was also a 58% risk reduction of major osteoporotic fractures (HR, 0.42; 95% CI, 0.21-0.85; log-rank P=.01) and a 45% risk reduction of clinical fractures (HR, 0.55; 95% CI, 0.33-0.92; log-rank P=.02) in the ABL-SC/ALN group vs the PBO/ALN group. At 25 months, bone mineral density percentage change from ACTIVE baseline for ABL-SC/ALN vs PBO/ALN was as follows: lumbar spine, 12.8%; total hip, 5.5%; femoral neck, 4.5% vs 3.5%, 1.4%, 0.5%, respectively (group differences at all sites P<.001).. Use of ABL-SC for 18 months followed by ALN for 6 months improved bone mineral density and reduced fracture risk throughout the skeleton and may be an effective treatment option for postmenopausal women with osteoporosis.. clinicaltrials.gov Identifier: NCT01657162.

Topics: Aged; Aged, 80 and over; Alendronate; Bone Density; Bone Density Conservation Agents; Female; Humans; Injections, Subcutaneous; Kaplan-Meier Estimate; Middle Aged; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Parathyroid Hormone-Related Protein; Proportional Hazards Models; Spinal Fractures

Additional therapies are needed for prevention of osteoporotic fractures. Abaloparatide is a selective activator of the parathyroid hormone type 1 receptor.. To determine the efficacy and safety of abaloparatide, 80 μg, vs placebo for prevention of new vertebral fracture in postmenopausal women at risk of osteoporotic fracture.. The Abaloparatide Comparator Trial In Vertebral Endpoints (ACTIVE) was a phase 3, double-blind, RCT (March 2011-October 2014) at 28 sites in 10 countries. Postmenopausal women with bone mineral density (BMD) T score ≤-2.5 and >-5.0 at the lumbar spine or femoral neck and radiological evidence ≥2 mild or ≥1 moderate lumbar or thoracic vertebral fracture or history of low-trauma nonvertebral fracture within the past 5 years were eligible. Postmenopausal women (>65 y) with fracture criteria and a T score ≤-2.0 and >-5.0 or without fracture criteria and a T score ≤-3.0 and >-5.0 could enroll.. Blinded, daily subcutaneous injections of placebo (n = 821); abaloparatide, 80 μg (n = 824); or open-label teriparatide, 20 μg (n = 818) for 18 months.. Primary end point was percentage of participants with new vertebral fracture in the abaloparatide vs placebo groups. Sample size was set to detect a 4% difference (57% risk reduction) between treatment groups. Secondary end points included change in BMD at total hip, femoral neck, and lumbar spine in abaloparatide-treated vs placebo participants and time to first incident nonvertebral fracture. Hypercalcemia was a prespecified safety end point in abaloparatide-treated vs teriparatide participants.. Among 2463 women (mean age, 69 years [range, 49-86]), 1901 completed the study. New morphometric vertebral fractures occurred less frequently in the active treatment groups vs placebo. The Kaplan-Meier estimated event rate for nonvertebral fracture was lower with abaloparatide vs placebo. BMD increases were greater with abaloparatide than placebo (all P < .001). Incidence of hypercalcemia was lower with abaloparatide (3.4%) vs teriparatide (6.4%) (risk difference [RD], −2.96 [95%CI, −5.12 to −0.87]; P = .006). [table: see text].. Among postmenopausal women with osteoporosis, the use of subcutaneous abaloparatide, compared with placebo, reduced the risk of new vertebral and nonvertebral fractures over 18 months. Further research is needed to understand the clinical importance of RD, the risks and benefits of abaloparatide treatment, and the efficacy of abaloparatide vs other osteoporosis treatments.. clinicaltrials.gov Identifier: NCT01343004.

Topics: Aged; Aged, 80 and over; Bone Density; Bone Density Conservation Agents; Double-Blind Method; Female; Femur Neck; Humans; Hypercalcemia; Injections, Subcutaneous; Lumbar Vertebrae; Middle Aged; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Parathyroid Hormone-Related Protein; Pelvic Bones; Placebos; Postmenopause; Radiography; Spinal Fractures; Teriparatide; Thoracic Vertebrae

Abaloparatide is a novel synthetic peptide analog of parathyroid hormone-related protein (PTHrP) that is currently being developed as a potential anabolic agent in the treatment of postmenopausal osteoporosis.. This study sought to assess the effects of abaloparatide on bone mineral density (BMD) at the lumbar spine, total hip, and femoral neck in postmenopausal women with osteoporosis.. Multi-center, multi-national, double-blind placebo controlled trial in which postmenopausal women were randomly assigned to receive 24 weeks of treatment with daily sc injections of placebo, abaloparatide, 20, 40, or 80 μg, or teriparatide, 20 μg. A 24-week extension was also performed in a subset of subjects.. Postmenopausal women with osteoporosis (n = 222).. BMD by dual-x-ray absorptiometry and biochemical markers of bone turnover.. At 24 weeks, lumbar spine BMD increased by 2.9, 5.2, and 6.7% in the abaloparatide, 20-, 40-, and 80-μg groups, respectively, and 5.5% in the teriparatide group. The increases in the 40- and 80-μg abaloparatide groups and the teriparatide group were significantly greater than placebo (1.6%). Femoral neck BMD increased by 2.7, 2.2, and 3.1% in abaloparatide, 20-, 40-, and 80-μg groups, respectively, and 1.1% in the teriparatide group. The increase in femoral neck BMD with abaloparatide, 80 μg was significantly greater than placebo (0.8%). Total hip BMD increased by 1.4, 2.0, and 2.6% in the abaloparatide, 20-, 40-, and 80-μg groups, respectively. The total hip increases in the 40- and 80-μg abaloparatide groups were greater than both placebo (0.4%) and teriparatide (0.5%).. Compared with placebo, 24 weeks of daily sc abaloparatide increases BMD of the lumbar spine, femoral neck, and total hip in a dose-dependent fashion. Moreover, the abaloparatide-induced BMD increases at the total hip are greater than with the marketed dose of teriparatide. These results support the further investigation of abaloparatide as an anabolic therapy in postmenopausal osteoporosis.

Topics: Aged; Aged, 80 and over; Bone Density; Bone Density Conservation Agents; Double-Blind Method; Female; Femur Neck; Humans; Lumbar Vertebrae; Middle Aged; Osteoporosis, Postmenopausal; Parathyroid Hormone-Related Protein; Radiography; Teriparatide; Treatment Outcome

Abaloparatide (ABL) significantly increases bone mineral density in men with osteoporosis similar to what was reported in postmenopausal women with osteoporosis. The cost effectiveness of sequential treatment with ABL followed by alendronate (ALN) in men at high fracture risk was compared to relevant alternative treatments.. A Markov-based microsimulation model based on a lifetime US healthcare decision maker perspective was developed to evaluate the cost (expressed in US$2021) per quality-adjusted life-years (QALYs) gained of sequential ABL/ALN. Comparators were sequential treatment unbranded teriparatide (TPTD)/ALN, generic ALN monotherapy, and no treatment. Discount rates of 3% were used. Consistent with practice guidelines, patients received 18 months of ABL or TPTD followed by ALN for 5 years, or 5 years of ALN monotherapy. Analyses were conducted in high-risk men aged over 50 years defined as having a bone mineral density T-score ≤-2.5 and a recent fracture. Time-specific risk of subsequent fracture after a recent fracture, incremental costs up to 5 years following fractures, real-world medication adherence, and mostly US men-specific data were included in the model. One-way and probabilistic sensitivity analyses were conducted to assess the robustness of results.. Over the full age range, sequential ABL/ALN led to more QALYs for lower costs than sequential unbranded TPTD/ALN, while no treatment was dominated (more QALYs, lower costs) by ALN monotherapy. The costs per QALY gained of sequential ABL/ALN were lower than the US threshold of US$150,000 versus generic ALN monotherapy. The probabilities that sequential ABL/ALN was cost effective compared to ALN monotherapy were estimated at 51% in men aged 50 years and between 88 and 90% in those aged ≥ 60 years.. Sequential therapy using ABL/ALN may be cost effective compared with generic ALN monotherapy in US men aged ≥ 50 years at high fracture risk, especially in those aged ≥ 60 years. Unbranded TPTD/ALN and no treatment were dominated interventions (less QALY, more costs) compared with ABL/ALN or ALN monotherapy.

Topics: Alendronate; Bone Density Conservation Agents; Cost-Benefit Analysis; Female; Humans; Male; Middle Aged; Osteoporosis; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Quality-Adjusted Life Years; Teriparatide; United States

Real-world evidence on the comparative effectiveness and safety of abaloparatide versus teriparatide in women with osteoporosis may help inform treatment decisions. Following 18 months of treatment, abaloparatide was comparable to teriparatide for prevention of nonvertebral fractures, resulted in a 22% risk reduction for hip fractures, and demonstrated similar cardiovascular safety. Osteoporotic fracture risk can be reduced with anabolic or antiresorptive medications. In addition to efficacy and safety data from controlled clinical trials, real-world evidence on comparative effectiveness and safety may help inform treatment decisions.. The real-world effectiveness of abaloparatide versus teriparatide on nonvertebral fracture (NVF) incidence and cardiovascular safety during the 19-month period after treatment initiation were evaluated (NCT04974723).. Anonymized US patient claims data from Symphony Health, Integrated Dataverse (IDV)®, May 1, 2017 to July 31, 2019, included women aged ≥ 50 years with ≥ 1 prescription of abaloparatide or teriparatide and no prior anabolic therapy. Most were enrolled in commercial and Medicare health plans. Index was the date of the initial prescription dispensed during the identification period. In 1:1 propensity score matched cohorts, time to first NVF following index date, major adverse cardiovascular events (MACE), and MACE + heart failure (HF) were compared between cohorts using a Cox proportional hazards model.. Propensity score matching yielded 11,616 patients per cohort. Overall median age (interquartile range) was 67 (61, 75) years, and 25.6% had a fracture history. Over 19 months, 335 patients on abaloparatide and 375 on teriparatide had a NVF (hazard ratio [95% confidence interval]: 0.89 [0.77, 1.03]), and 121 and 154 patients, respectively, had a hip fracture [HR (95% CI): 0.78 (0.62, 1.00)]. The MACE and MACE + HF rates were similar between cohorts.. Following 18 months of treatment, abaloparatide was comparable to teriparatide for prevention of NVF and similar cardiovascular safety was demonstrated between cohorts.

Topics: Aged; Bone Density Conservation Agents; Female; Hip Fractures; Humans; Medicare; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Parathyroid Hormone-Related Protein; Postmenopause; Teriparatide; United States

Anabolic osteoporosis drugs improve bone mineral density by increasing bone formation. The objective of this study was to evaluate the early effects of abaloparatide on indices of bone formation and to assess the effect of abaloparatide on modeling-based formation (MBF), remodeling-based formation (RBF), and overflow MBF (oMBF) in transiliac bone biopsies. In this open-label, single-arm study, 23 postmenopausal women with osteoporosis were treated with 80 μg abaloparatide daily. Subjects received double fluorochrome labels before treatment and before biopsy collection at 3 months. Change in dynamic histomorphometry indices in four bone envelopes were assessed. Median mineralizing surface per unit of bone surface (MS/BS) increased to 24.7%, 48.7%, 21.4%, and 16.3% of total surface after 3 months of abaloparatide treatment, representing 5.5-, 5.2-, 2.8-, and 12.9-fold changes, on cancellous, endocortical, intracortical, and periosteal surfaces (p < .001 versus baseline for all). Mineral apposition rate (MAR) was significantly increased only on intracortical surfaces. Bone formation rate (BFR/BS) was significantly increased on all four bone envelopes. Significant increases versus baseline were observed in MBF on cancellous, endocortical, and periosteal surfaces, for oMBF on cancellous and endocortical surfaces, and for RBF on cancellous, endocortical, and intracortical surfaces. Overall, modeling-based formation (MBF + oMBF) accounted for 37% and 23% of the increase in bone-forming surface on the endocortical and cancellous surfaces, respectively. Changes from baseline in serum biomarkers of bone turnover at either month 1 or month 3 were generally good surrogates for changes in histomorphometric endpoints. In conclusion, treatment with abaloparatide for 3 months stimulated bone formation on cancellous, endocortical, intracortical, and periosteal envelopes in transiliac bone biopsies obtained from postmenopausal women with osteoporosis. These increases reflected stimulation of both remodeling- and modeling-based bone formation, further elucidating the mechanisms by which abaloparatide improves bone mass and lowers fracture risk. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Topics: Aged; Bone Density; Female; Humans; Middle Aged; Osteogenesis; Osteoporosis; Osteoporosis, Postmenopausal; Parathyroid Hormone-Related Protein; Postmenopause

In postmenopausal osteoporotic women in ACTIVE, abaloparatide reduced fracture risk and increased areal bone mineral density (BMD) more than teriparatide at the hip and wrist. DXA-based 3D modeling showed significantly greater increases in hip cortical volumetric BMD with abaloparatide versus teriparatide. This may explain differences reported in aBMD by DXA.. In ACTIVE, abaloparatide (ABL) increased bone mineral density (BMD) shown by dual-energy X-ray absorptiometry (DXA) while reducing fracture incidence in postmenopausal osteoporotic women. Changes in DXA BMD with ABL, 80 μg, were significantly greater than with open-label teriparatide (TPTD), 20 μg, at cortical sites including total hip, femoral neck, and 1/3 distal radius. The purpose of this study was to better understand the relative effects of ABL and TPTD on cortical and cancellous compartments in the proximal femur.. Hip DXA images from a subset of randomly selected patients in the ACTIVE trial (n = 250/arm) were retrospectively analyzed using three-dimensional modeling methods (3D-SHAPER software) to evaluate changes from baseline at months 6 and 18.. Similar significant increases in trabecular volumetric BMD (vBMD, + 9%) and cortical thickness (+ 1.5%) were observed with ABL and TPTD by 3D-DXA at 18 months. In contrast, only ABL significantly increased cortical vBMD versus baseline (+ 1.3%), and changes in both cortical vBMD and cortical surface BMD were significantly greater with ABL versus TPTD. In the TPTD group, changes in cortical vBMD were inversely correlated with changes in serum CTX (carboxy-terminal telopeptide of type I collagen) and PINP (procollagen type I N-terminal propeptide), suggesting that higher bone turnover may have attenuated cortical gains.. These results suggest previously reported differences in areal BMD increases between ABL and TPTD may be due to differential effects on cortical vBMD. Further studies are warranted to investigate how these differences affect therapeutic impact on hip strength in postmenopausal women with osteoporosis.

Topics: Absorptiometry, Photon; Bone Density; Female; Humans; Osteoporosis, Postmenopausal; Parathyroid Hormone-Related Protein; Retrospective Studies; Teriparatide

Fracture risk increases with age, but few studies focus on persons ≥80 years. In the ACTIVE trial, treatment with abaloparatide for 18 months reduced osteoporotic fracture risk and increased bone mineral density. These effects were maintained with 24 months alendronate treatment in ACTIVExtend. We postulated that similar improvements in bone mineral density and safety would be demonstrated in women ≥80 years.. Post hoc analyses of bone mineral density and fracture incidence in women with osteoporosis at high risk of fracture ≥80 years from ACTIVExtend.. In total, 56 women aged ≥80 years at ACTIVE baseline entered the ACTIVExtend study; 46 of these completed the study. Mean age was 83.3 years; other baseline characteristics were similar. At the end of ACTIVE, bone mineral density increased at all sites for abaloparatide versus placebo. Bone mineral density increased in parallel in both groups during alendronate therapy (19 to 43 months) in ACTIVExtend. At month 43, mean percent change in bone mineral density from baseline was 17.2% abaloparatide/alendronate versus 8.6% placebo/alendronate (P < 0.0001) at the lumbar spine, 5.3% abaloparatide/alendronate versus 3.0% placebo/alendronate (P = 0.024) at the total hip, and 4.6% abaloparatide/alendronate versus 3.1% placebo/alendronate (P = 0.044) at the femoral neck. Fracture incidence was low and did not differ significantly between groups. Sequential treatment with abaloparatide followed by alendronate was well tolerated; the proportion of participants reporting adverse events was similar between groups.. Sequential treatment with abaloparatide followed by alendronate (43 months follow-up) in this small subgroup of ACTIVExtend participants suggests abaloparatide is well tolerated and effective in women aged ≥80 years. : Video Summary:http://links.lww.com/MENO/A618.. Video Summary:http://links.lww.com/MENO/A618.

Topics: Aged, 80 and over; Alendronate; Bone Density; Bone Density Conservation Agents; Double-Blind Method; Female; Humans; Osteoporosis; Osteoporosis, Postmenopausal; Parathyroid Hormone-Related Protein

We characterized patients initiating abaloparatide (ABL), teriparatide (TPTD), or denosumab (DMAB) in a real-world clinical setting from a large medical and pharmacy claims database. Differences were noted in sex, age, pathologic fractures, comorbidity index, and prior bisphosphonate use for patients initiating ABL and TPTD compared with those receiving DMAB.. To characterize patients initiating abaloparatide (ABL), teriparatide (TPTD), or denosumab (DMAB) treatment in a real-world clinical setting.. Patients aged ≥ 18 years initiating ABL, TPTD, or DMAB between May 1, 2017, and September 24, 2018 (without receiving the same drug in the previous 12 months), were identified using the OM1 Data Cloud, which contains medical and pharmacy claims from approximately 200 million US patients. The index date was the date of initial prescription or dispensing for ABL, TPTD, or DMAB during the study period.. During the study period, 2666 patients initiated ABL, 9210 TPTD, and 116,718 DMAB. Mean age (standard deviation) was 69.2 (10.6) years for the ABL cohort, 68.6 (11.3) for TPTD, and 72.1 (10.2) for DMAB (P < 0.001; ABL vs DMAB). Proportionally more patients initiating ABL were female (95.2% ABL, 86.9% TPTD, and 91.3% DMAB, P < 0.001 ABL vs TPTD or DMAB). Nearly twice as many patients initiating ABL (19.1%) and TPTD (18.8%) had a previous pathologic/fragility fracture vs DMAB (9.6%; P < 0.001 ABL vs DMAB). Fewer patients initiating ABL (36.3%) or TPTD (39.7%) had Charlson comorbidity index of ≥ 2 vs DMAB (48.4%; P < 0.001 ABL vs DMAB). Before initiating ABL, TPTD, or DMAB, 44.3%, 33.8%, and 33.9% of patients had prior osteoporosis treatment, respectively. Bisphosphonate use was more common before initiating ABL (19.2%) or TPTD (19.6%), than before initiating DMAB (16.6%; P < 0.001 ABL vs DMAB).. Patients initiating ABL and TPTD differed in sex, age, pathologic fractures, comorbidity index, and prior bisphosphonate use compared with those initiating DMAB.

Topics: Aged; Bone Density; Bone Density Conservation Agents; Denosumab; Female; Humans; Infant; Male; Medicare; Osteoporosis, Postmenopausal; Parathyroid Hormone-Related Protein; Teriparatide; United States

The US Food and Drug Administration has recently approved abaloparatide (ABL) for treatment of women with postmenopausal osteoporosis (PMO) at high risk of fracture. With increasing health care spending and drug prices, it is important to quantify the value of newly available treatment options for PMO.. To determine cost-effectiveness of ABL compared with teriparatide (TPTD) for treatment of women with PMO in the United States.. A discrete-event simulation (DES) model was developed to assess cost-effectiveness of ABL from the US health care perspective. The model included three 18-month treatment strategies with either placebo (PBO), TPTD, or ABL, all followed by additional 5-year treatment with alendronate (ALN). High-risk patients were defined as women with PMO ⩾65 years old with a prior vertebral fracture. Baseline clinical event rates, risk reductions, and patient characteristics were based on the Abaloparatide Comparator Trial in Vertebral Endpoints (ACTIVE) trial.. Over a 10-year period, the DES model yielded average total discounted per-patient costs of $10 212, $46 783, and $26 837 and quality-adjusted life-years (QALYs) of 6.742, 6.781, and 6.792 for PBO/ALN, TPTD/ALN, and ABL/ALN, respectively. Compared with TPTD/ALN, ABL/ALN accrued higher QALYs at lower cost and produced an incremental cost-effectiveness ratio (ICER) of $333 266/QALY relative to PBO/ALN. In high-risk women, ABL/ALN also had more QALYs and less cost over TPTD/ALN and yielded an ICER of $188 891/QALY relative to PBO/ALN. Conclusion and Relevance: ABL is a dominant treatment strategy over TPTD. In women with PMO at high risk of fracture, ABL is an alternative cost-effective treatment.

Topics: Aged; Aged, 80 and over; Alendronate; Bone Density Conservation Agents; Cost-Benefit Analysis; Drug Administration Schedule; Drug Costs; Female; Fractures, Bone; Health Care Costs; Humans; Middle Aged; Models, Economic; Osteoporosis, Postmenopausal; Parathyroid Hormone-Related Protein; Quality-Adjusted Life Years; Teriparatide; Treatment Outcome; United States

Topics: Bone Density; Bone Density Conservation Agents; Female; Humans; Injections, Subcutaneous; Osteoporosis, Postmenopausal; Parathyroid Hormone-Related Protein

The objective is to formulate clinical practice guidelines for the pharmacological management of osteoporosis in postmenopausal women.. Evidence from clinical trials and insights from clinical experience with pharmacologic therapies for osteoporosis were critically evaluated in formulating this guideline for the management of postmenopausal osteoporosis. Patient preferences, data on adherence and persistence, and risks and benefits from the patient and provider perspectives were also considered in writing committee deliberations. A consensus by the Writing Committee members was achieved for four management principles: (i) The risk of future fractures in postmenopausal women should be determined using country-specific assessment tools to guide decision-making. (ii) Patient preferences should be incorporated into treatment planning. (iii) Nutritional and lifestyle interventions and fall prevention should accompany all pharmacologic regimens to reduce fracture risk. (iv) Multiple pharmacologic therapies are capable of reducing fracture rates in postmenopausal women at risk with acceptable risk-benefit and safety profiles.

Topics: Absorptiometry, Photon; Accidental Falls; Bone Density Conservation Agents; Calcitonin; Calcium; Clinical Decision-Making; Denosumab; Diphosphonates; Estrogen Receptor Modulators; Estrogen Replacement Therapy; Female; Humans; Norpregnenes; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Parathyroid Hormone-Related Protein; Patient Preference; Raloxifene Hydrochloride; Risk Assessment; Risk Reduction Behavior; Selective Estrogen Receptor Modulators; Teriparatide; Vitamin D

Topics: Bone Density Conservation Agents; Bone Remodeling; Female; Humans; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Parathyroid Hormone-Related Protein; Postmenopause; Treatment Outcome

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.

Topics: Aged; Aged, 80 and over; Bone Density; Bone Density Conservation Agents; Drug Approval; Female; Humans; Middle Aged; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Parathyroid Hormone-Related Protein; United States; United States Food and Drug Administration

The goal of this study was to assess and compare the potential clinical and economic value of emerging bone-forming agents using the only currently available agent, teriparatide, as a reference case in patients at high, near-term (imminent, 1- to 2-year) risk of osteoporotic fractures, extending to a lifetime horizon with sequenced antiresorptive agents for maintenance treatment.. Analyses were performed by using a Markov cohort model accounting for time-specific fracture protection effects of bone-forming agents followed by antiresorptive treatment with denosumab. The alternative bone-forming agent profiles were defined by using assumptions regarding the onset and total magnitude of protection against fractures with teriparatide. The model cohort comprised 70-year-old female patients with T scores below -2.5 and a previous vertebral fracture. Outcomes included clinical fractures, direct costs, and quality-adjusted life years. The simulated treatment strategies were compared by calculating their incremental "value" (net monetary benefit).. Improvements in the onset and magnitude of fracture protection (vs the teriparatide reference case) produced a net monetary benefit of $17,000,000 per 10,000 treated patients during the (1.5-year) bone-forming agent treatment period and $80,000,000 over a lifetime horizon that included 3.5 years of maintenance treatment with denosumab.. Incorporating time-specific fracture effects in the Markov cohort model allowed for estimation of a range of cost savings, quality-adjusted life years gained, and clinical fractures avoided at different levels of fracture protection onset and magnitude. Results provide a first estimate of the potential "value" new bone-forming agents (romosozumab and abaloparatide) may confer relative to teriparatide.

Topics: Aged; Antibodies, Monoclonal; Bone Density Conservation Agents; Cost-Benefit Analysis; Denosumab; Female; Humans; Models, Theoretical; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Parathyroid Hormone-Related Protein; Postmenopause; Quality-Adjusted Life Years; Risk; Teriparatide