abaloparatide and Fractures--Bone

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

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

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

Daily subcutaneous injection of 80 μg abaloparatide increased bone mineral density in Japanese patients with osteoporosis at high fracture risk in the ACTIVE-J trial. Dual-energy X-ray absorptiometry-based hip structural analysis from ACTIVE-J data showed improved hip geometry and biomechanical properties with abaloparatide compared with placebo.. Abaloparatide (ABL) increased bone mineral density (BMD) in Japanese patients with osteoporosis at high fracture risk in the ACTIVE-J trial. To evaluate the effect of ABL on hip geometry and biomechanical properties, hip structural analysis (HSA) was performed using ACTIVE-J trial data.. Hip dual-energy X-ray absorptiometry scans from postmenopausal women and men (ABL, n = 128; placebo, n = 65) at baseline and up to week 78 were analyzed to extract bone geometric parameters at the narrow neck (NN), intertrochanteric region (IT), and proximal femoral shaft (FS). Computed tomography (CT)-based BMD and HSA indices were compared between baseline and week 78.. ABL treatment showed increased mean percent change from baseline to week 78 in cortical thickness at the NN (5.3%), IT (5.3%), and FS (2.9%); cross-sectional area at the NN (5.0%), IT (5.0%), and FS (2.6%); cross-sectional moment of inertia at the NN (7.6%), IT (5.1%), and FS (2.5%); section modulus at the NN (7.4%), IT (5.4%), and FS (2.4%); and decreased mean percent change in buckling ratio (BR) at the IT (- 5.0%). ABL treatment showed increased mean percent change in total volumetric BMD (vBMD; 2.7%) and trabecular vBMD (3.2%) at the total hip and decreased mean percent change in BR at femoral neck (- 4.1%) at week 78 vs baseline. All the changes noted here were significant vs placebo (P < 0.050 using t-test).. A 78-week treatment with ABL showed improvement in HSA parameters associated with hip geometry and biomechanical properties vs placebo.. JAPIC CTI-173575.

Topics: Absorptiometry, Photon; Bone Density; East Asian People; Female; Femur Neck; Fractures, Bone; Humans; Male; Osteoporosis

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

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

Background and purpose - Teriparatide accelerates fracture healing in animals and probably in man. Abaloparatide is a new drug with similar although not identical effects on the teriparatide receptor. Given at 4 times the teriparatide dose in a human osteoporosis trial, abaloparatide increased bone density more than teriparatide, and both reduced fracture risk. We investigated in mice whether abaloparatide stimulates fracture healing, and if it does so with the suggested dose effect relation (4:1). Patients and methods - In a validated mouse model for metaphyseal healing (burr hole with screw pull-out), 96 mice were randomly allocated to 11 groups: control (saline), teriparatide or abaloparatide, where teriparatide and abaloparatide were given at 5 different doses each. In a femoral shaft osteotomy model, 24 mice were randomly allocated to 3 groups: control (saline), teriparatide (15 µg/kg) or abaloparatide (60 µg/kg). Each treatment was given daily via subcutaneous injections. Results were evaluated by mechanical testing and microCT. Results - In the metaphyseal model, a dose-dependent increase in screw pull-out force could be seen. In a linear regression analysis (r = 0.78) each increase in ln(dose) by 1 (regardless of drug type) was associated with an increase in pull-out force by 1.50 N (SE 0.18) (p < 0.001). Changing drug from teriparatide to abaloparatide increased the force by 1.41 N (SE 0.60; p = 0.02). In the diaphyseal model, the callus density was 23% (SD 10), 38% (SD 10), and 47% (SD 2) for control, for teriparatide and abaloparatide respectively. Both drugs were significantly different from controls (p = 0.001 and p = 0.008), but not from each other. Interpretation - Both drugs improve fracture healing, but in these mouse models, the potency per µg of abaloparatide seems only 2.5 times that of teriparatide, rather than the 4:1 relation chosen in the clinical abaloparatide-teriparatide comparison trial.

Topics: Animals; Bone Density Conservation Agents; Bone Screws; Bones of Lower Extremity; Fracture Healing; Fractures, Bone; Male; Mice, Inbred C57BL; Models, Animal; Parathyroid Hormone-Related Protein; Teriparatide