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Abaloparatide

Also known as Tymlos, Eladynos, BA058, abaloparatide-SC

Synthetic PTHrP(1-34) analogue, a daily 80 mcg injection that builds bone in osteoporosis.

clinically proven Hormonal & sexual approved drug

At a glance

Category
Hormonal & sexual
Status
approved drug
Made from
synthetic Chemically synthesised peptide; no biological source material 1.
Route
subcutaneous injection into the periumbilical region of the abdomen
Half-life
approximately 1 hour after subcutaneous injection, with peak concentration at a median 0.51 hours and absolute subcutaneous bioavailability of 36% 1
Onset
the bone formation marker sPINP peaks at month 1, roughly 93% above baseline in postmenopausal women and 133% above baseline in men; measurable bone density gains by 6-12 months; vertebral fracture reduction demonstrated over 18 months 1
Molecular weight
3961 daltons; molecular formula C174H300N56O49. Abaloparatide has 76% homology to human PTHrP(1-34) and 41% homology to human PTH(1-34), the sequence of teriparatide 1
Sequence
Ala-Val-Ser-Glu-His-Gln-Leu-Leu-His-Asp-Lys-Gly-Lys-Ser-Ile-Gln-Asp-Leu-Arg-Arg-Arg-Glu-Leu-Leu-Glu-Lys-Leu-Leu-Aib-Lys-Leu-His-Thr-Ala-NH2 — a synthetic 34-amino-acid peptide with a non-natural aminoisobutyric acid residue at position 29 and an amidated C-terminus

Prescription-only medicine. Approved by the FDA on 28 April 2017 under NDA 208743 as Tymlos 6, for postmenopausal women with osteoporosis at high fracture risk and, since a later supplement, to increase bone density in men with osteoporosis at high fracture risk 1. The EU marketing authorisation was issued on 12 December 2022 as Eladynos, and is narrower: postmenopausal women only, with a maximum treatment duration of 18 months 2. The current US label carries no boxed warning; the osteosarcoma finding in rats appears under Warnings and Precautions 1. Unlike teriparatide, whose US two-year lifetime limitation was removed in 2020, abaloparatide's US label still states that use for more than 2 years in a lifetime is not recommended 1.

Doping status: Not listed by WADA

Checked against the WADA 2026 Prohibited List. For a specific product and country, Global DRO is the lookup athletes are expected to use — the List names substances, not brand names.

Mechanism of action

Abaloparatide is an agonist at the PTH1 receptor, the same class B G-protein-coupled receptor that teriparatide acts on, and activation triggers the cAMP signalling pathway in target cells. Given once daily, it stimulates new bone formation on trabecular and cortical surfaces by increasing osteoblastic activity 1.

The difference from teriparatide is in the sequence it derives from. Teriparatide is the first 34 residues of parathyroid hormone. Abaloparatide is modelled on parathyroid hormone-related protein, the locally acting peptide better known as the mediator of humoral hypercalcaemia of malignancy: 76% homologous to PTHrP(1-34) and only 41% to PTH(1-34) 1. Receptor pharmacology studies attribute the behavioural difference to conformational selectivity — abaloparatide binds preferentially to the transient RG conformation of the PTH1 receptor rather than the longer-lived R0 conformation favoured by PTH(1-34), producing a shorter signalling event 4. That work is mechanistic laboratory pharmacology, not a clinical endpoint, and it should be read as a proposed explanation rather than a demonstrated cause of any clinical difference.

What the product label does document is the shape of the bone turnover response, and it is instructive. In postmenopausal women treated for 18 months, the formation marker sPINP rose to 93% above baseline at month 1 and was still 45% above baseline at month 18, while the resorption marker sCTX peaked at only 26% above baseline at month 3 and had returned to baseline by month 18 1. Formation runs far ahead of resorption, and the gap between the two curves is the 'anabolic window' that both PTH-pathway drugs exploit. In men treated for 12 months the pattern was similar but with more resorption: sPINP peaked 133% above baseline at month 1 and sCTX 46% above baseline at month 6 1.

Two pharmacological consequences follow from the receptor being shared with parathyroid hormone. First, calcium handling: abaloparatide raises serum calcium and urinary calcium excretion, so hypercalcaemia and hypercalciuria are predictable effects rather than idiosyncratic ones 1. Second, vascular tone: the drug produces a dose-dependent rise in heart rate, a mean peak of 15 beats per minute within 15 minutes of an 80 mcg dose and 20 bpm at three times that dose, resolving over about 6 hours, with no clinically meaningful effect on the QT interval 1. Palpitations were reported by 5% of treated women against 0.4% on placebo 1. This tachycardia signal is more prominent than with teriparatide and is the most distinctive thing about abaloparatide's tolerability profile.

As with every anabolic bone agent, the gains are not self-sustaining. The registration programme was designed around this: patients who completed 18 months of abaloparatide were rolled into an open-label extension on weekly alendronate, and the fracture risk reduction was maintained through 24 months of that antiresorptive 1. Sequencing an antiresorptive after the anabolic course is part of the treatment plan, not an optional addition.

What the research shows

The evidence is strong for vertebral fracture reduction in postmenopausal women, resting on a large placebo-controlled trial with a fracture endpoint and a prespecified alendronate extension. The evidence in men is weaker in kind: a 12-month trial with bone mineral density as the primary endpoint, not fractures. Head-to-head fracture data against teriparatide do not exist.

Research in humans

Study 003 (NCT01343004, the ACTIVE trial) randomised 1645 postmenopausal women aged 49 to 86 to abaloparatide 80 mcg daily or placebo for 18 months. New vertebral fractures occurred in 0.6% on abaloparatide against 4.2% on placebo — an absolute risk reduction of 3.6% and a relative risk reduction of 86% (95% CI 61 to 95, p<0.0001). Non-vertebral fractures occurred in 2.7% against 4.7%, a relative risk reduction of 43% (p=0.049) 13. In the Study 005 extension, where both groups received 6 months of alendronate, new vertebral fractures at 25 months were 0.6% in the abaloparatide-then-alendronate group against 4.4% in the placebo-then-alendronate group 1. Study 019 (NCT03512262, the ATOM trial) randomised 228 men aged 42 to 85 to abaloparatide or placebo for 12 months; lumbar spine bone mineral density rose 8.5% against 1.2% on placebo, with total hip and femoral neck gains of 2.1% and 3.0% 15. Note that the men's trial had no fracture endpoint at all.

Animal and lab research

In a two-year rat carcinogenicity study, abaloparatide produced marked dose-dependent increases in osteosarcoma and osteoblastoma in every male and female dose group, at exposures 4, 16 and 28 times the human exposure at 80 mcg. Osteosarcoma incidence was 0-2% in untreated controls and reached 87% in high-dose males and 62% in high-dose females, accompanied by marked increases in bone mass 1. The label states plainly that the relevance of the rat findings to humans is uncertain. The same caveats that eventually resolved the teriparatide osteosarcoma question apply here: rats have continuously growing bone with open growth plates and no basic multicellular unit remodelling, and near-lifetime high-dose exposure in a growing skeleton does not correspond to an 18-month course in an older adult. Abaloparatide was not genotoxic or mutagenic in a standard battery of tests 1.

Caveats. The pivotal trials were sponsor-funded. The fracture evidence covers 18 months; the label does not recommend use beyond 2 years in a lifetime because safety and efficacy have not been evaluated beyond that point 1, and the EU authorisation caps treatment at 18 months 2. The non-vertebral fracture result was statistically marginal (p=0.049). The men's indication rests on bone density, a surrogate, in 228 patients. Anti-abaloparatide antibodies developed in 41% of treated women and neutralising antibodies in 26%, without any apparent effect on bone density, fracture reduction or adverse events over the trial period, but that is a high rate for a drug of this class and the follow-up is short 1. No drug interaction studies have been performed at all 1. And the osteosarcoma question, which took two decades and large registry datasets to settle for teriparatide, remains formally open for abaloparatide: the label notes only that an increased risk has not been observed in human observational studies 1.

What it is used for

  • Postmenopausal women with osteoporosis at high risk of fracture — defined on the US label as a history of osteoporotic fracture or multiple fracture risk factors — or who have failed or cannot tolerate other osteoporosis therapy 1
  • Men with osteoporosis at high risk of fracture, to increase bone density; this indication is on the US label but not on the EU authorisation, which covers postmenopausal women only 12
  • In practice it functions as the main alternative to teriparatide when a PTH-pathway anabolic agent is indicated. A post hoc analysis of the ACTIVE trial reported higher bone mineral density response rates with abaloparatide than with placebo or with teriparatide 7, but the trial was not powered for a fracture comparison between the two active drugs and no such comparison exists

Dosing

Dose
80 mcg once daily
Frequency
once daily, subcutaneously
Route
subcutaneous injection into the periumbilical region of the abdomen
Duration
The US label states that safety and efficacy have not been evaluated beyond 2 years and that use for more than 2 years in a patient's lifetime is not recommended. The EU authorisation sets a maximum of 18 months.
  • This is the licensed regimen from the approved product information 12. There is no titration — 80 mcg daily is the only dose. It is reference material, not treatment advice.
  • The first several doses should be taken where the patient can sit or lie down, because orthostatic hypotension can occur, typically within 4 hours of the injection, with dizziness, palpitations, tachycardia or nausea 1.
  • Supplemental calcium and vitamin D are given if dietary intake is inadequate 1. In the pivotal trials patients took 500-1000 mg calcium and 400-800 IU vitamin D daily 1.
  • An antiresorptive agent follows the anabolic course. The registration programme built this in: after 18 months of abaloparatide, patients moved to weekly alendronate, and the fracture benefit was maintained through 24 months of that treatment 1. Stopping an anabolic agent without sequencing to an antiresorptive loses most of the bone gained.
  • Abaloparatide exposure rises in renal impairment — AUC increased 1.2-, 1.7- and 2.1-fold in mild, moderate and severe impairment respectively — and patients on dialysis were not studied 1.

These figures describe what the literature and published protocols report. They are not advice and not a dosing instruction.

Protocols

Tymlos — postmenopausal osteoporosis and osteoporosis in men (US label)

approved product information

Source: TYMLOS (abaloparatide) FDA prescribing information

Every day of treatment80 mcg once daily, subcutaneously into the periumbilical region
Alongsidecalcium and vitamin D supplementation if dietary intake is inadequate
Total coursenot more than 2 years in a lifetime

A single fixed dose with no titration. The first several doses are given where the patient can sit or lie down, because of orthostatic hypotension within about 4 hours. The prefilled pen holds 30 daily doses. The EU product, Eladynos, uses the same 80 mcg daily dose but caps the course at 18 months and is licensed for postmenopausal women only.

ACTIVE / ACTIVExtend sequence (abaloparatide followed by alendronate)

published trial

Source: Study 003 (NCT01343004) and Study 005 (NCT01657162), as described in the FDA prescribing information

Months 0-18abaloparatide 80 mcg once daily, or placebo, with calcium and vitamin D
Month 19no treatment for approximately 1 month
Months 20 onwardsalendronate 70 mg weekly, open-label, in both original groups

This is the trial sequence rather than a licensed schedule, and it is included because it is how the anabolic-then-antiresorptive strategy was actually tested. New vertebral fractures at 25 months were 0.6% in the abaloparatide-then-alendronate group against 4.4% in the placebo-then-alendronate group, and the benefit was maintained through 24 months of open-label alendronate.

Schedules are reproduced as their source states them. Units, IU and milligrams explains why the figures are not interchangeable between products.

Reconstitution

Vial sizes
3120 mcg/1.56 ml (2000 mcg/ml) in a single-patient-use disposable prefilled pen delivering 30 daily doses of 80 mcg in 40 microlitres
Storage
Refrigerated at 2-8 °C before first use. After first use the pen is stored at room temperature, 20-25 °C, for up to 30 days. Do not freeze and do not expose to heat.

Worked example

Not applicable. Abaloparatide is supplied as a ready-to-use sterile solution in a disposable prefilled pen with a fixed 80 mcg dose. Nothing is reconstituted, diluted or calculated, and each pen holds 30 days of treatment.

The storage rule is the opposite way round from teriparatide, which must stay refrigerated even in use. Abaloparatide is refrigerated only until the pen is started and then kept at room temperature, which removes a practical adherence problem that teriparatide has. Discard the pen 30 days after first use even if solution remains.

Safety

Side effects

  • In postmenopausal women, adverse reactions reported in at least 2% and more often than on placebo: hypercalciuria (11% versus 9%), dizziness (10% versus 6%), nausea (8% versus 3%), headache (8% versus 6%), palpitations (5% versus 0.4%), fatigue (3% versus 2%), upper abdominal pain (3% versus 2%) and vertigo (2% versus 2%) 1
  • In men: injection site erythema, dizziness, arthralgia, injection site swelling, injection site pain, contusion, nausea, diarrhoea, abdominal distension, abdominal pain and bone pain 1
  • Orthostatic hypotension, typically within 4 hours of a dose, with dizziness, palpitations, tachycardia or nausea, usually resolving on lying down 1
  • Tachycardia, including sinus tachycardia, in 2% of treated women against 1% on placebo; the heart rate rise develops within 15 minutes of injection and resolves over about 6 hours 1
  • Injection site reactions, assessed daily in the first month: redness in 58% against 28% on placebo, oedema 11% against 3%, pain 10% against 7%. Severe redness, oedema and pain occurred in 2.9%, 0.4% and 0.4% respectively 1
  • Hypercalcaemia — the drug raises serum calcium, and the label advises against use in anyone with pre-existing hypercalcaemia or an underlying hypercalcaemic disorder such as primary hyperparathyroidism 1
  • Hypercalciuria, and an unknown effect on urolithiasis; urinary calcium excretion should be measured where active urolithiasis or pre-existing hypercalciuria is suspected 1
  • Anaphylaxis, dyspnoea and urticaria have been reported after marketing 1
  • Anti-abaloparatide antibodies in 41% of treated women and neutralising antibodies in 26% over 18 months, without an apparent effect on bone density response, fracture reduction or adverse events; cross-reactivity to PTHrP occurred in 2.4% of those tested and to PTH in 0.3% 1
  • Osteosarcoma: not a boxed warning on the current label. It appears under Warnings and Precautions on the strength of a dose-dependent rat carcinogenicity finding, with the label stating that whether abaloparatide causes osteosarcoma in humans is unknown and that an increased risk has not been observed in human observational studies 1

Do not use if

  • A history of systemic hypersensitivity to abaloparatide or to any component of the formulation; reactions have included anaphylaxis, dyspnoea and urticaria 1
  • Avoid in anyone at increased baseline risk of osteosarcoma: open epiphyses, metabolic bone disease other than osteoporosis including Paget disease of bone, bone metastases or a history of skeletal malignancy, prior external beam or implant radiation therapy involving the skeleton, and hereditary disorders predisposing to osteosarcoma 1
  • Not recommended in pre-existing hypercalcaemia or in an underlying hypercalcaemic disorder such as primary hyperparathyroidism 1
  • Not indicated in females of reproductive potential; there are no human pregnancy data and animal reproduction studies have not been conducted 1
  • Not established in children, and not recommended in children with open epiphyses or hereditary predisposition to osteosarcoma 1
  • Caution with active urolithiasis or a history of hypercalciuria, where urinary calcium should be measured 1
  • Caution in renal impairment, where exposure rises with declining renal function; patients on dialysis have not been studied 1

Interactions

No specific drug-drug interaction studies have been performed with abaloparatide 1. In vitro, at therapeutic concentrations it neither inhibits nor induces cytochrome P450 enzymes, and it is not a substrate of the renal transporters OAT1, OAT3, OCT2, MATE1 or MATE2K 1, so pharmacokinetic interactions are unlikely. The interactions that matter are pharmacodynamic: calcium supplements, vitamin D and thiazide diuretics add to the hypercalcaemic effect, and any drug that lowers blood pressure may compound the orthostatic hypotension seen in the first hours after a dose. Sequential use with an antiresorptive such as alendronate or denosumab is a treatment strategy rather than an interaction. Abaloparatide is cleared by non-specific proteolysis and renal excretion of the fragments, not by hepatic metabolism 1.

Sources