Abaloparatide: Research & Studies
Scientific evidence, clinical trials, and research findings
๐TL;DR
- โข2 clinical studies cited
- โขOverall evidence level: high
- โข5 research gaps identified
Research Studies
Effect of Abaloparatide vs Placebo on New Vertebral Fractures in Postmenopausal Women With Osteoporosis: A Randomized Clinical Trial (ACTIVE)
Miller PD, Hattersley G, Riis BJ, et al. (2016) โข JAMA
The ACTIVE trial was the pivotal phase 3 study enrolling 2,463 postmenopausal women (mean age 69) randomized to abaloparatide 80 mcg, open-label teriparatide 20 mcg, or placebo daily SC for 18 months. Abaloparatide significantly reduced vertebral and nonvertebral fractures versus placebo and demonstrated superior total hip BMD gains versus teriparatide.
Key Findings
- New vertebral fractures: 0.58% abaloparatide vs 4.22% placebo (86% RRR, P<0.001)
- Nonvertebral fractures: 2.7% vs 4.7% placebo (43% risk reduction)
- Major osteoporotic fractures: 70% risk reduction vs placebo
- Total hip BMD increase: 2.90% abaloparatide vs 2.04% teriparatide (P<0.05)
- Lumbar spine BMD increase: 9.2% abaloparatide vs 10.5% teriparatide (not significantly different)
- Hypercalcemia: 3.4% abaloparatide vs 6.4% teriparatide
Limitations: Teriparatide arm was open-label (not double-blind); 18-month duration; not powered for individual fracture types; predominantly White population
Abaloparatide Followed by Alendronate in Women with Postmenopausal Osteoporosis: Results from ACTIVExtend
Bone HG, Cosman F, Miller PD, et al. (2018) โข Journal of Clinical Endocrinology & Metabolism
ACTIVExtend was the extension study in which women who completed ACTIVE received alendronate 70 mg weekly for an additional 24 months. Sequential abaloparatide-to-alendronate therapy maintained and extended fracture protection and BMD gains over the combined 43-month period.
Key Findings
- Vertebral fracture risk reduction maintained through 43 months of follow-up
- Lumbar spine BMD continued to increase during alendronate phase
- Total hip BMD maintained during alendronate consolidation phase
- Established anabolic-to-antiresorptive sequential therapy paradigm
Limitations: Open-label extension design; patients who discontinued during ACTIVE were not included; limited to alendronate as the sequential agent
Unlock full research citations
Free access to all clinical studies, citations, and evidence summaries.
150+ peptide profiles ยท 30+ comparisons ยท 18 research tools
Community Experience Data
See how community outcomes align with (or diverge from) the research findings above.
Based on 35+ community reports
View community protocolsExplore research gaps across all peptides โ | View clinical trial pipeline โ
๐Research Gaps & Future Directions
- โขHead-to-head comparison with romosozumab (another osteoanabolic with different mechanism)
- โขOptimal duration of anabolic therapy before transitioning to antiresorptive agents
- โขLong-term fracture outcomes beyond 43 months of sequential therapy
- โขComparative data in men with osteoporosis (male trial data is limited)
- โขEffects in glucocorticoid-induced osteoporosis (not formally studied)
Research Overview#
Abaloparatide has a robust clinical evidence base centered on the ACTIVE (Abaloparatide Comparator Trial In Vertebral Endpoints) phase 3 trial and its extension study ACTIVExtend. Together, these trials enrolled over 2,000 postmenopausal women with osteoporosis and provided up to 43 months of follow-up data, including the first randomized comparison of sequential osteoanabolic-to-antiresorptive therapy.
The evidence level is classified as high based on a large, well-designed phase 3 RCT with an active comparator (teriparatide), statistically significant fracture reduction endpoints, FDA approval for two indications, and long-term follow-up through the ACTIVExtend extension.
ACTIVE Trial (Phase 3 Pivotal Study)#
Study Design#
The ACTIVE trial (Miller et al., 2016; PMID 27533157) was a phase 3, randomized, double-blind (abaloparatide vs placebo), active-controlled (open-label teriparatide) trial conducted at 28 sites across 10 countries from March 2011 to October 2014. The study enrolled 2,463 postmenopausal women aged 49-86 years (mean age 69) with osteoporosis and at least 2 of the following risk factors: age over 65, history of fracture, low BMD T-score.
Participants were randomized to one of three groups:
- Abaloparatide 80 mcg SC daily (n=824)
- Teriparatide 20 mcg SC daily, open-label (n=818)
- Placebo SC daily (n=821)
Primary Endpoint#
The primary endpoint was the percentage of participants with new morphometric vertebral fractures at 18 months, comparing abaloparatide versus placebo.
Key Results#
Abaloparatide demonstrated highly significant fracture reduction:
- Vertebral fractures: 0.58% (abaloparatide) vs 4.22% (placebo), representing an 86% relative risk reduction (P<0.001)
- Nonvertebral fractures: 2.7% (abaloparatide) vs 4.7% (placebo), representing a 43% risk reduction (P=0.049)
- Major osteoporotic fractures: Approximately 70% risk reduction versus placebo
- Clinical vertebral fractures: Significant reduction versus placebo
BMD Outcomes#
BMD changes from baseline at 18 months:
| Site | Abaloparatide | Teriparatide | Placebo |
|---|---|---|---|
| Lumbar spine | +9.2% | +10.5% | +0.5% |
| Total hip | +2.9% | +2.0% | -0.4% |
| Femoral neck | +3.4% | +2.7% | -0.3% |
The total hip BMD increase with abaloparatide was statistically significantly greater than with teriparatide (P<0.05), while lumbar spine increases were numerically similar between the two active agents.
Safety#
Hypercalcemia was less frequent with abaloparatide (3.4%) than teriparatide (6.4%). The most common adverse events were injection site reactions (abaloparatide 16% vs teriparatide 7% vs placebo 7%), nausea, dizziness, headache, and palpitations.
ACTIVExtend Trial (Sequential Therapy)#
Study Design#
ACTIVExtend (Bone et al., 2018; PMID 30324337) enrolled women who completed the 18-month ACTIVE trial and transitioned them to open-label alendronate 70 mg weekly for an additional 24 months, providing 43 months total follow-up.
Key Results#
Sequential abaloparatide-to-alendronate therapy demonstrated:
- Sustained fracture protection through the antiresorptive consolidation phase
- Continued BMD accrual at the lumbar spine during alendronate treatment
- Maintenance of hip BMD gains achieved during the anabolic phase
- Superior outcomes compared to the placebo-to-alendronate control group
The ACTIVExtend results established the clinical paradigm of anabolic-to-antiresorptive sequential therapy, confirming that the bone formed during anabolic treatment is preserved and consolidated by subsequent antiresorptive therapy.
Supporting Studies#
Male Osteoporosis#
A phase 3 trial in men with osteoporosis at high fracture risk supported the December 2022 FDA approval for the male indication. Abaloparatide 80 mcg daily produced significant increases in lumbar spine and hip BMD compared to placebo over 12 months.
Cardiovascular Safety Analysis#
A dedicated cardiovascular safety analysis of the ACTIVE trial data found no increase in major adverse cardiovascular events (MACE) with abaloparatide compared to placebo or teriparatide, addressing safety concerns about heart rate effects occasionally observed with PTH1R agonists.
Evidence Quality Assessment#
| Evidence Criterion | Assessment | Details |
|---|---|---|
| Study design | Phase 3 RCT | Double-blind vs placebo, active comparator |
| Sample size | Large (n=2,463) | Powered for fracture endpoints |
| Active comparator | Teriparatide | Open-label arm |
| Fracture endpoints | Met primary and secondary | Vertebral and nonvertebral |
| Long-term data | 43 months (ACTIVExtend) | Sequential therapy paradigm |
| Regulatory status | FDA-approved (2 indications) | Postmenopausal women, men |
| BMD outcomes | Statistically significant | Superior total hip vs teriparatide |
Key Research Gaps#
-
Comparison with romosozumab: No head-to-head trial with romosozumab (anti-sclerostin antibody), which represents a different osteoanabolic mechanism. Both are indicated for high-risk osteoporosis, and comparative data would inform treatment selection.
-
Optimal anabolic treatment duration: Whether shorter or longer anabolic courses affect long-term fracture outcomes remains uncertain.
-
Sequential therapy optimization: Whether denosumab (instead of alendronate) provides superior consolidation after anabolic therapy, and the optimal timing of transition.
-
Glucocorticoid-induced osteoporosis: Abaloparatide has not been formally studied in glucocorticoid-induced osteoporosis, though teriparatide has demonstrated superiority over alendronate in this population.
-
Male osteoporosis: The evidence base in men is more limited than in postmenopausal women, particularly for fracture reduction endpoints.
Related Reading#
Frequently Asked Questions About Abaloparatide
Explore Further
Medical Disclaimer
This website is for educational and informational purposes only. The information provided is not intended to diagnose, treat, cure, or prevent any disease. Always consult with a qualified healthcare professional before using any peptide or supplement.