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Abaloparatide Abaloparatide
Abaloparatide Abaloparatide

Abaloparatide is a novel, synthetic peptide analog of parathyroid hormone-related protein (PTHrP), approved by FDA for the treatment of postmenopausal osteoporosis.

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Abaloparatide is a novel, synthetic peptide analog of parathyroid hormone-related protein (PTHrP), approved by FDA for the treatment of postmenopausal osteoporosis. It is a 34-amino acid peptide and has 41% homology to parathyroid hormone (PTH) (1-34) and 76% homology to parathyroid hormone-related protein (PTHrP). It has the potential to stimulate bone formation with a limited effect on bone resorption and mineral mobilization. It has demonstrated 1600-fold-greater selectivity to the receptor conformation that drives bone formation (RG) than to the receptor conformation that induces bone resorption.

Pharmacological class: Protein-Based Therapies


  • Postmenopausal osteoporosis

Pharmachologic action

Abaloparatide acts on PTH type 1 receptor (PTH1R) and activates both G protein-mediated cAMP signalling and β-arrestin-mediated ERK-1/2 signalling pathways with similar potency. PTHrP is a critical peptide essential for promoting new bone formation, with a distinct role from parathyroid hormone, or PTH, which primarily regulates calcium homeostasis and bone resorption.


Usual Adult Dose for Rheumatoid Arthritis80 mcg once daily, administered subcutaneously into the periumbilical region of the abdomen

Calcium and vitamin D supplements should be administered if dietary intake is inadequate.


Absorption: The bioavailability of Abaloparatide is 36% in healthy women. It takes about 0.25 to 0.52 hr to reach peak concentration following subcutaneous administration with the median time of 0.51hr.

Volume of distribution (VD): VD is approximately 50L.

Protein binding: Plasma protein binding is approximately 70%.

Metabolism: It is metabolized into smaller peptide fragments by non-specific proteolytic degradation.

Route of elimination: Metabolized products are eliminated through renal excretion. Patients with severe renal impairment should be monitored with increased risk of adverse effects; however, there are no recommended dosage adjustments in patients with mild, moderate or severe renal impairment.

Half-life:  The mean (SD) half-life if 1.7 (0.7) hrs.

Clearance: Not Available.


  • No contraindications are reported for Abaloparatide. However, it is contraindicated in females of reproductive potential, but there are no human studies with Abaloparatide use in pregnant and breastfeeding women.

Drug interaction

  • Abaloparatide, at therapeutic concentrations, does not induce or inhibit cytochrome P450 enzymes, as reported by in vitro studies

Side effects

A clinical review of various clinical trials indicated no significant differences between abaloparatide and teriparatide or placebo in the frequency of treatment-emergent adverse events. There were no significant differences observed in the occurrence of serious adverse events ( 9.7%, 10%, and 11%, respectively). Adverse events leading to discontinuation were higher among patients receiving abaloparatide compared with teriparatide or placebo (9.9%, 6.8%, and 6.1%, respectively). Discontinuation of abaloparatide was secondary to nausea, headache, dizziness and palpitations, which were mild to moderate in severity. The frequency of overall hypercalcemia was lower in patients receiving abaloparatide compared with teriparatide (3.4% versus 6.4%). There was no evidence of increased cardiovascular risk with hypercalcemia in patients receiving abaloparatide.

Although abaloparatide is administered subcutaneously, there was an overall low risk of injection site reactions. Patients administered with abaloparatide had a lower rate of injection site hematoma compared with teriparatide or placebo (2.2%, 13.3%, and 11.1%, respectively). Abaloparatide was also associated with a dose-dependent increase in osteoblastoma and osteosarcoma as per the results of animal studies. It is not known whether these effects are seen in humans or not. Therefore, abaloparatide carries a boxed warning to recommend no than two years of anabolic therapy in a patient’s lifetime.


  • The patients with pre-existing hypercalcemia and those diagnosed with an underlying hypercalcemic disorder, such as primary hyperparathyroidism should not be administered with Abaloparatide.
  • The urine calcium levels should be monitored if preexisting hypercalciuria or active urolithiasis are suspected.
  • It should not be recommended in patients with increased risk for osteosarcoma.
  • The patient should lie down or sit, in case symptoms of orthostatic hypotension occurs.

Clinical evidence

A Multi-center, multi-national, double-blind placebo-controlled trial was conducted by Leder BZ et al. to evaluate the effects of Abaloparatide on bone mineral density (BMD) at the lumbar spine, femoral neck and total hip in postmenopausal women with osteoporosis. Postmenopausal women were randomised to receive 24 weeks of treatment with daily subcutaneous injections of Abaloparatide, 20, 40, or 80 μg, or teriparatide, 20 μg and placebo. The primary outcome measures are biochemical markers of bone turnover and BMD determined by dual-x-ray absorptiometry. The participants administered with Abaloparatide reported an increase in total hip BMD, femoral neck BMD and lumbar spine BMD. The increase in total hip and lumbar spine BMD was more significant in 40- and the 80-μg Abaloparatide group as compared to placebo whereas an increase in femoral neck BMD was more significant in Abaloparatide, 80 μg group. The results indicated that use of daily subcutaneous Abaloparatide over 24 weeks could increase BMD of the total hip, lumbar spine and femoral neck in a dose-dependent fashion. Also, the Abaloparatide-induced BMD increases at the total hip are more significant than with the marketed dose of teriparatide. Therefore the use of Abaloparatide should be considered as anabolic therapy in postmenopausal osteoporosis.


    1. Abaloparatide. FDA label. Reference ID: 4090621.
    2. NCBI. PubChem Database. Abaloparatide. CID- 76943386.
    3. Abaloparatide. Drug Bank. Accession number: DB05084. 
    4. Cureus. 2017 May; 9(5): e1300.
    5. Endocrinology. 2016;157(1):141-149.
    6. J Clin Endocrinol Metab. 2015 Feb;100(2):697-706.

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