Abaloparatide (Tymlos) - PTHrP Analog for Osteoporosis — Bone & Mineral
FDA-approved PTH-related peptide analog for severe osteoporosis with superior BMD gains and lower hypercalcemia risk vs teriparatide.
Overview
Abaloparatide (Tymlos) is a synthetic analog of PTH-related peptide (PTHrP) approved by the FDA in April 2017 for postmenopausal women with osteoporosis at high fracture risk, and in December 2022 for men. ACTIVE Phase 3 trial (n=2,463) showed 86% reduction in vertebral fractures and 43% reduction in non-vertebral fractures. Head-to-head comparison with teriparatide demonstrated superior BMD gains at lumbar spine, total hip, and femoral neck, with lower hypercalcemia risk (3.4% vs 6.4%, p=0.006). Preferentially activates the RG conformational state of PTH1R receptor, providing anabolic effects with better safety profile. Maximum treatment duration: 24 months (2-year lifetime limit). Real-world data suggests 22% hip fracture risk reduction vs teriparatide.
Indications
- Severe osteoporosis in postmenopausal women at high fracture risk
- Men with osteoporosis at high fracture risk (FDA approved Dec 2022)
- Prior osteoporotic fractures or very low BMD (T-score ≤-2.5)
- Failed or intolerant to bisphosphonates
- Glucocorticoid-induced osteoporosis (off-label)
Mechanism of Action
Low bone mass, prior fractures, or inadequate response to bisphosphonates
Dosing
| Compound | Dose | Frequency | Notes |
|---|---|---|---|
| Abaloparatide 80 mcg pre-filled pen | 80 mcg SC daily | Once daily | Inject into periumbilical region (abdomen); maximum 24 months lifetime use |
Evidence Grade
GRADE A
Safety & Contraindications
- ⚠️ PRESCRIPTION MEDICATION - Physician supervision required
- LIFETIME LIMIT: 24 months maximum cumulative use (2-year limit)
- LOWER hypercalcemia risk than teriparatide: 3.4% vs 6.4% (p=0.006)
- Transient heart rate increase and small postdose BP decrease (no increased MACE)
- Dizziness, nausea, headache, palpitations: More common in first 6 months
- Slightly higher discontinuation rate vs teriparatide in first 6 months (nausea 1.6%, dizziness 1.2%)
- Contraindications: Same as teriparatide (Paget's, skeletal malignancy, prior radiation, hyperparathyroidism, severe renal impairment)
- NOT for children/adolescents (open growth plates)
- Must refrigerate; lower cost than teriparatide (~$1,768/month vs ~$3,359/month)