Abaloparatide is a synthetic 34-amino-acid peptide based on parathyroid hormone-related peptide (PTHrP), sold as Tymlos.[1] The FDA approved it in 2017 for postmenopausal women with osteoporosis at high fracture risk and in 2022 for men.[2] In the ACTIVE trial, new spine fractures occurred in 0.6% on abaloparatide versus 4.2% on placebo over 18 months.[1]
What is abaloparatide?
Abaloparatide is a bone-building (anabolic) drug. It activates the PTH1 receptor, the same receptor teriparatide uses, which stimulates bone-forming cells on both spongy and outer (cortical) bone.[1] It shares 76% of its sequence with natural PTHrP(1-34) and 41% with PTH(1-34).[1] Most other osteoporosis drugs, like alendronate, slow bone breakdown instead.
The label approves it for:[1]
- Postmenopausal women with osteoporosis at high fracture risk, or who could not use other treatments
- Men with osteoporosis at high fracture risk, to increase bone density
It appears in our healing peptides category because it builds bone, but unlike most peptides there, it is an approved drug backed by large trials.
What the research shows
- ACTIVE (2,463 women, 18 months): new spine fractures fell from 4.2% on placebo to 0.6%, an 86% relative reduction. Non-spine fractures were 2.7% versus 4.7%.[1][3]
- ACTIVExtend: women who switched to alendronate for 24 months kept the benefit. Over 43 months, new spine fractures occurred in 0.9% after abaloparatide versus 5.6% after placebo; there were no hip fractures in the abaloparatide group versus five in the placebo group.[4]
- ATOM (228 men, 12 months): spine bone density rose 8.5% versus 1.2% on placebo, with gains at the hip too. This trial measured density, not fractures.[5][1]
International research
In Japan, the ACTIVE-J trial of postmenopausal women and men found spine bone density rose 12.5% more than placebo over 78 weeks, with no new spine fractures on abaloparatide versus 3 people with new fractures on placebo.[6]
Abaloparatide dosage
| Tymlos label | |
|---|---|
| Dose | 80 mcg injected under the skin once daily[1] |
| Pen | 30 daily doses per pen[1] |
| Storage | Refrigerate before first use; then up to 30 days at room temperature[1] |
| First doses | Take where you can sit or lie down in case of dizziness[1] |
| Duration | Not studied beyond 2 years; over 2 years in a lifetime not recommended[1] |
The label advises calcium and vitamin D if dietary intake is low.[1] Tymlos comes ready to use in a prefilled pen, so no mixing is needed.
Abaloparatide side effects
Women in ACTIVE (Tymlos label):[1]
| Side effect | Abaloparatide | Placebo |
|---|---|---|
| High urine calcium | 11% | 9% |
| Dizziness | 10% | 6% |
| Nausea | 8% | 3% |
| Headache | 8% | 6% |
| Palpitations | 5% | 0.4% |
-
Men (ATOM): injection-site redness (13% vs 5%), dizziness (9% vs 1%) and joint pain (7% vs 1%) were most common.[1]
-
Fast heart rate: heart rate rises within 15 minutes of a dose, by 15 beats per minute on average, and settles in about 6 hours.[1]
-
Dizziness on standing: may occur within 4 hours of a dose, with palpitations or nausea.[1]
-
High blood calcium: 3% versus 0.1% on placebo, measured 4 hours after injection.[1]
-
Stopping: 10% stopped due to side effects versus 6% on placebo.[1]
-
Antibodies: 41% of women on Tymlos for 18 months developed antibodies to it, but they did not appear to affect safety or bone density response.[1]
Who should not use abaloparatide
- People with a history of severe allergy to abaloparatide or its ingredients.[1]
- People with high blood calcium or a disorder that raises it, such as primary hyperparathyroidism.[1]
- People at higher baseline risk of bone cancer: open growth plates, Paget’s disease, bone metastases or prior skeletal radiation.[1]
- Women who could become pregnant or are breastfeeding; it is not indicated for them.[1]
No dose change is needed for kidney impairment, although drug levels roughly doubled in severe impairment.[1]
What happens after stopping abaloparatide?
Because treatment is limited to about 2 years, abaloparatide is usually followed by a drug that slows bone breakdown. In ACTIVExtend, women who switched to alendronate after 18 months kept and further increased their bone density gains, and during the alendronate period their risk of new spine fractures was 87% lower than in women who had taken placebo first.[4] In ACTIVE-J, a marker of new bone formation rose about 140% within 6 weeks, showing how fast the drug starts working on bone.[6]
Osteosarcoma warning
Rats given abaloparatide for nearly their whole lives developed osteosarcoma at rates similar to rats given teriparatide at comparable exposures.[8] Tymlos launched with a boxed warning, which the FDA removed in December 2021;[2] Radius said the change followed a review of long-term postmarketing data on Tymlos and the PTH drug class.[9] The label still says it is unknown whether abaloparatide causes osteosarcoma in humans and advises avoiding it in people with higher baseline risk, such as Paget’s disease or prior skeletal radiation.[1]
Abaloparatide vs teriparatide
ACTIVE included a teriparatide 20 mcg group, but it was open-label and the trial was designed to compare abaloparatide with placebo, not with teriparatide.[3] Within that limit:
- High blood calcium was less common with abaloparatide (3.4% vs 6.4%).[3]
- Both drugs reduced new spine fractures versus placebo.[3]
- A 2023 meta-analysis of manufacturer-sponsored trials found slightly larger hip and femoral neck density gains with abaloparatide, but too little fracture data to show one prevents more fractures.[7]
Abaloparatide is not approved for fracture or tendon healing. A 2021 review of 55 studies noted that animal studies reported improved fracture healing.[10] In a small phase 2 placebo-controlled trial of 48 adults (average age 82) with pelvic fractures, abaloparatide did not improve healing on CT scans, pain or mobility at 3 months.[12] For the healing evidence on its sister drug, see teriparatide.
Is abaloparatide legal?
Yes, by prescription in the US. Products sold online as “research” abaloparatide are not FDA-approved Tymlos.[1]
