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approvedBone & Joint

Abaloparatide

Also known as: Tymlos, BA058, PTHrP Analog, ITM-058

Abaloparatide (Tymlos) is a synthetic 34-amino acid peptide analog of parathyroid hormone-related protein (PTHrP) approved by the FDA in 2017 for the treatment of postmenopausal osteoporosis in women at high fracture risk. As the second anabolic bone-building agent after teriparatide, abaloparatide was engineered for preferential activation of the RG conformation of the PTH1 receptor, producing a more transient signaling profile that maximizes osteoblast-mediated bone formation while minimizing bone resorption and hypercalcemia. The landmark ACTIVE trial demonstrated a 86% reduction in new vertebral fractures and a 43% reduction in non-vertebral fractures versus placebo.

3 cited references·5 researched benefits

Quick Answer

Abaloparatide (Tymlos) is a synthetic PTHrP analog approved in 2017 for postmenopausal osteoporosis at high fracture risk. It stimulates new bone formation through selective PTH1 receptor activation with less hypercalcemia than teriparatide. The ACTIVE trial showed 86% reduction in vertebral fractures and 43% reduction in non-vertebral fractures. Given as a daily subcutaneous injection for up to 2 years, it is now also available as a transdermal patch.

Key Facts

Mechanism
Abaloparatide binds to the PTH1 receptor (PTH1R) but preferentially stabilizes the RG (G-protein-dependent) receptor conformation rather than the R0 (G-protein-independent) conformation favored by PTH. This results in a more transient cAMP signaling response that potently stimulates osteoblast differentiation and bone formation while producing less sustained calcium-mobilizing activity. Like teriparatide, intermittent (once-daily) administration creates an anabolic window where bone formation outpaces resorption, increasing trabecular and cortical bone mass. Abaloparatide also suppresses sclerostin and increases Wnt pathway signaling, promoting osteoblast precursor proliferation and mature osteoblast activity. The distinct receptor pharmacology translates clinically to equivalent or superior bone-building efficacy with approximately half the incidence of hypercalcemia compared to teriparatide.
Research Status
approved
Half-Life
~1 hour (subcutaneous)
Molecular Formula
C₁₇₁H₂₈₁N₅₃O₅₃S₂
Primary Use
Bone & Joint
Table of Contents

Benefits

  • Reduces new vertebral fractures by 86% versus placebo in the ACTIVE trial — the largest reduction seen in any osteoporosis anabolic trialstrong
  • Reduces non-vertebral fractures by 43% and demonstrates significant major osteoporotic fracture risk reductionstrong
  • Increases lumbar spine BMD by 9-11% and total hip BMD by 3-4% over 18 months of treatmentstrong
  • Lower incidence of hypercalcemia compared to teriparatide (3.4% vs 6.4%) due to more transient receptor activationstrong
  • Transdermal patch formulation (abaloparatide-sTD) under development provides needle-free delivery with comparable bone-building efficacymoderate

Dosage Protocols

RouteDosage RangeFrequencyNotes
Subcutaneous injection (Tymlos pen)80 mcgOnce dailyFDA-approved dose. Inject in the periumbilical region of the abdomen. Maximum treatment duration is 2 years. Must be refrigerated prior to first use; stable at room temperature for up to 30 days after first use.
Transdermal microneedle patch (investigational)300 mcgOnce daily for 5 minutesAbaloparatide-sTD patch delivers drug via coated microneedles applied to the thigh. Phase 3 trial showed non-inferior BMD increases. Not yet commercially available in all markets.

Medical disclaimer

Dosage information is provided for educational reference only. Always follow your prescriber's instructions and consult a qualified healthcare provider before starting any peptide protocol.

Side Effects

  • Hypercalcemia — occurs in ~3.4% of patients but generally mild and transient; lower rate than teriparatidecommon
  • Dizziness — reported in 10% of patients, attributed to transient hypotension; patients should administer injection while seated initiallycommon
  • Nausea — occurs in 8% of patients, usually mild and most frequent during the first month of treatmentcommon
  • Injection site reactions — redness, swelling, and pain at the subcutaneous injection site in 6-10% of patientscommon
  • Palpitations and tachycardia — heart rate increases of 2-3 bpm reported; monitor in patients with cardiac historyrare
  • Osteosarcoma risk (black box warning) — carries same class warning as teriparatide based on PTH1R agonist mechanism; treatment limited to 2 yearsserious

Frequently Asked Questions

How does abaloparatide compare to teriparatide?
Both are anabolic bone agents given as daily injections for up to 2 years. The ACTIVE trial directly compared abaloparatide to open-label teriparatide and showed comparable vertebral fracture reduction but numerically greater non-vertebral fracture reduction with abaloparatide (2.7% vs 4.7%). Abaloparatide produces less hypercalcemia (3.4% vs 6.4%) and causes fewer nausea events. However, teriparatide has 20+ years of post-marketing data, more extensive clinical trial evidence, and available biosimilars at lower cost. Choice between them often depends on individual risk factors, insurance coverage, and tolerability.
Why does abaloparatide cause less hypercalcemia than teriparatide?
The difference relates to receptor pharmacology. Abaloparatide preferentially activates the RG conformation of the PTH1 receptor, which produces a brief, transient cAMP signal that effectively stimulates osteoblast bone formation. Teriparatide also activates the R0 receptor conformation, producing more sustained signaling that includes greater calcium mobilization from bone and kidneys. The result is that abaloparatide achieves comparable bone-building effects with less disruption of calcium homeostasis, making it potentially preferable for patients prone to hypercalcemia.
What should follow abaloparatide treatment?
Like teriparatide, the bone gains from abaloparatide are lost without follow-up anti-resorptive therapy. The ACTIVExtend trial demonstrated that transitioning from 18 months of abaloparatide to 24 months of alendronate maintained and further increased BMD while providing sustained fracture risk reduction — total fracture reductions of 84% for vertebral and 39% for non-vertebral fractures over 43 months. Guidelines recommend starting a bisphosphonate or denosumab immediately upon completing the anabolic treatment course.
Is abaloparatide approved for men or premenopausal women?
The FDA approval is currently limited to postmenopausal women at high fracture risk. However, clinical trials investigating abaloparatide for male osteoporosis have shown significant BMD increases at the spine and hip comparable to results in women. An FDA approval for osteoporosis in men at high fracture risk has been submitted. It is not approved or studied for premenopausal women, and carries a contraindication in patients with open epiphyses (children and adolescents) due to the theoretical osteosarcoma risk.

References

  1. 1
    Abaloparatide for the treatment of postmenopausal osteoporosis: the ACTIVE randomized clinical trial(2017)PubMed ↗
  2. 2
    Abaloparatide followed by alendronate for fracture risk reduction: ACTIVExtend study results(2018)PubMed ↗
  3. 3
    Comparative effectiveness of abaloparatide and teriparatide in fracture prevention(2019)PubMed ↗

Latest Research

Last updated: 2026-02-19