Abaloparatide
PTHrP Analog | Anabolic Bone-Building Agent
Abaloparatide is an FDA-approved anabolic bone-building agent and synthetic analog of parathyroid hormone-related protein (PTHrP). It selectively activates the PTH1 receptor to stimulate new bone formation while minimizing bone resorption. In the phase III ACTIVE trial, abaloparatide showed superior BMD increases at the hip compared to teriparatide, with substantial fracture risk reduction. It was approved in the US in 2017 and EU in 2022 for postmenopausal women and men with osteoporosis at high fracture risk.
Mechanism of Action
Abaloparatide works through selective activation of the parathyroid hormone 1 receptor (PTH1R), a G protein-coupled receptor expressed on osteoblasts and osteocytes. It preferentially binds to the RG (relaxed, G-protein-coupled) conformational state of PTH1R, which elicits a transient downstream cyclic AMP signaling response favoring anabolic bone formation over resorption. This selective binding pattern produces more bone-building activity with less hypercalcemic effect compared to native PTH. The result is increased cortical and trabecular bone volume, density, and improved microarchitecture.
Key Benefits
- FDA-approved for osteoporosis treatment
- Actively builds new bone (anabolic mechanism)
- Superior hip BMD gains vs teriparatide in trials
- Reduces vertebral fracture risk significantly
- Reduces nonvertebral fracture risk
- Lower hypercalcemia risk than teriparatide
- Works through selective PTH1R activation
- Benefits seen within 6 months
C174H299N56O49 - 41% homology to PTH(1-34), 76% homology to PTHrP(1-34) Complex or non-standard sequence format
Osteoporosis (FDA-Approved)
- Postmenopausal Osteoporosis
FDA-approved for postmenopausal women with osteoporosis at high risk for fracture or who have failed other therapies.
- Male Osteoporosis
FDA-approved for men with osteoporosis at high risk for fracture or intolerant to other treatments.
Bone Health Research
- Fracture Prevention
Phase III trials demonstrated substantial reduction in vertebral and nonvertebral fractures.
- Sequential Therapy
ACTIVExtend trial showed benefits of abaloparatide followed by alendronate for maintained bone protection.
Abaloparatide is administered as a once-daily subcutaneous injection in the periumbilical (around the navel) region of the abdomen. It comes in pre-filled pen devices (Tymlos). Cumulative lifetime use is limited to 2 years due to theoretical osteosarcoma risk observed in rodent studies. A transdermal patch formulation is also in development.
| Goal | Dose | Frequency | Route |
|---|---|---|---|
| Osteoporosis treatment | 80 mcg | Once daily | SubQ (periumbilical abdomen) |
Reconstitution Instructions
- Pre-filled pen device (Tymlos)
- Pen needles
- Alcohol swabs
- 1 Store pen refrigerated at 2-8°C (do not freeze)
- 2 Allow to reach room temperature before injection
- 3 Attach new needle for each injection
- 4 Inject subcutaneously in periumbilical region
- 5 Rotate injection sites
- 6 Discard pen after 30 days even if medication remains
ACTIVExtend trial showed sequential abaloparatide then alendronate maintained and extended bone benefits.
Adequate calcium (500-1000mg) and vitamin D (400-800 IU) supplementation recommended during therapy.
Do not use concurrently; both are PTH receptor agonists. Choose one or use sequentially.
Different mechanisms; no known interactions.
Different mechanisms; no known interactions.
Bone formation markers increase; initial BMD changes begin
Significant BMD increases at spine, hip, and femur
Continued bone density improvements; fracture risk reduction
Maximum benefits in ACTIVE trial; substantial fracture reduction
Transition to maintenance therapy (e.g., bisphosphonates) recommended
Common Side Effects
- Hypercalciuria (high calcium in urine)
- Dizziness
- Nausea
- Headache
- Palpitations
- Fatigue
- Upper abdominal pain
- Vertigo
- Injection site reactions
Stop Signs - Discontinue if:
- Signs of hypercalcemia (confusion, fatigue, excessive thirst)
- Persistent bone pain
- Severe dizziness or fainting
- Allergic reactions
Contraindications
- Paget's disease of bone
- Prior external beam or implant radiation therapy to skeleton
- Bone metastases or history of skeletal malignancies
- Metabolic bone diseases other than osteoporosis
- Pre-existing hypercalcemia
- Pregnancy or nursing
- Cumulative use exceeding 2 years lifetime
Good Signs
- Clear, colorless solution
- Pharmaceutical grade (Tymlos/Eladynos)
- Proper cold chain maintained
- Intact pen device
- Within expiration date
Warning Signs
- Research-grade products lack FDA oversight
- Temperature excursions may affect potency
Bad Signs
- Cloudy or discolored solution
- Particulates visible
- Exposed to freezing or high temperatures
- Damaged pen device
- Effect of Abaloparatide vs Placebo on New Vertebral Fractures in Postmenopausal Women With Osteoporosis (ACTIVE Trial)Miller PD, Hattersley G, Riis BJ, et al.JAMA (2016)
Abaloparatide showed substantial reduction in vertebral fractures and greater BMD increases at spine, hip, and femur compared to placebo and teriparatide.
- ACTIVExtend Trial: Abaloparatide Followed by AlendronateCosman F, Miller PD, Williams GC, et al.Mayo Clinic Proceedings (2017)
18 months abaloparatide followed by alendronate significantly reduced vertebral and nonvertebral fractures.
- Phase 2 Dose-finding Study of BA058 in Postmenopausal WomenLeder BZ, O'Dea LS, Zanchetta JR, et al.Journal of Clinical Endocrinology and Metabolism (2015)
Significant BMD increases at 40 and 80 mcg doses; abaloparatide showed superior anabolic effects on hips vs teriparatide.
- Profile of Abaloparatide and Its Potential in Postmenopausal OsteoporosisTella SH, Kommalapati A, Correa RCureus (2017)
Abaloparatide preferentially binds RG conformational state of PTH1R, producing more anabolic bone effects.
Disclaimer
This information is for educational and research purposes only. Consult a healthcare professional before use.