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Continuing Education Activity

Abaloparatide is a medication used in the management and treatment of osteoporosis. It is in the parathyroid hormone-related protein analog class of medications. Most cases of osteoporosis occur in post-menopausal women. This activity highlights the indications, contraindications, activity, adverse effects, monitoring, and other key elements of abaloparatide therapy in the clinical setting as it relates to the essential information needed by an interprofessional care team managing patients with post-menopausal osteoporosis and its related conditions.


  • Describe the mechanism of action of abaloparatide.
  • Identify the indications for abaloparatide therapy.
  • Identify the most common adverse effect associated with abaloparatide therapy.
  • Explain the importance of monitoring patients on abaloparatide therapy, including serum calcium levels.



Osteoporosis is defined as low bone mineral density caused by altered bone microstructure, leading to increased fracture risk. Bone mineral density is commonly measured utilizing a dual-energy x-ray absorptiometry (DEXA or DXA) scan to assess bone mineral density.[1]

A DEXA scan reports the t-score, measured in standard deviations, and reflects the difference between the patient's measured bone mineral density and the mean value of bone mineral density.

  • A t-score between -1 and +1 reflects healthy bone.
  • A t-score between -1.0 and -2.5 reflects the diagnosis of osteopenia.
  • A t-score below -2.5 reflects a diagnosis of osteoporosis.
  • The lower the bone density is, the greater the fracture risk.

Abaloparatide is a synthetic peptide analog of human parathyroid hormone-related protein (PTHrP). In 2017, the FDA approved its use in postmenopausal women with osteoporosis at high risk for fracture.[2] Patients who are intolerant or have failed to respond to traditional osteoporosis therapy are often prescribed abaloparatide.[3][4]

In the abaloparatide Comparator Trial In Vertebral Endpoints (ACTIVE), subcutaneous abaloparatide reduced the risk of new vertebral and nonvertebral fractures, along with clinical and major osteoporotic fractures, significantly, compared to placebo.[5] In the ACTIVE trial, 86% relative risk reduction (RRR) in new vertebral fractures and 43% RRR in nonvertebral fractures were observed.[5] The use of abaloparatide is not recommended for more than two years during a patient's lifetime.

Traditional therapy for osteoporosis includes bisphosphonates and teriparatide. Studies have compared the efficacy of traditional therapy to abaloparatide. In a phase II double-blind randomized control trial, the safety and efficacy of abaloparatide were assessed by comparison to teriparatide and placebo. Among these treatment groups, abaloparatide was superior in increasing total bone mineral density.[6] 

A comparative study comparing two sequential therapies (2 years of initial teriparatide followed by alendronate therapy and two years of abaloparatide followed by alendronate therapy) demonstrated that abaloparatide followed by alendronate has a greater treatment efficacy.[7] Abaloparatide can be combined with or administered before antiresorptive therapies such as bisphosphonates to maximize effects.[6]

Abaloparatide This drug has an off-label use for symptomatic pseudarthrosis patients with metabolic syndromes.[6] Abaloparatide can also be used to treat epididymitis and orchitis.[8] It prevents bone loss that results from ovariectomy, orchiectomy, and long-term use of glucocorticoids, in addition to improving fracture healing.[9] Abaloparatide is approved by the FDA to treat osteoporosis in postmenopausal women at high risk for fracture.

FDA Approved Use

  • Osteoporosis in postmenopausal women at high risk for fracture

Abaloparatide is not recommended in pediatric patients with open epiphyses or genetic predispositions to bone malignancies.[20] The effects of abaloparatide on pregnancy, breastfeeding mothers, breastfed infants, milk production, and the pediatric population are unknown.

Mechanism of Action

Abaloparatide, a human parathyroid hormone-related protein (PTHrP), is a selective parathyroid hormone type 1 receptor (PTH1R) agonist.[10] It has anabolic activity on PTH1R on osteoblasts to stimulate the Gs-protein-mediated cAMP pathway, which activates phospholipase C (PLC) and phosphokinase A (PKA) to increase osteoblast activity.[11]

Abaloparatide shifts the balance of bone remodeling to favor bone formation by osteoblasts with a minimal increase in osteoclast bone resorption.[11][12] It increases the formation of bone at periosteal, trabecular, and endocortical surfaces.[11] Recent studies suggest that parathyroid hormone or PTHrP analogs can differentiate between R0 and RG conformations of PTHR1.[12][13] 

Binding to the R0 conformation of PTHR1 induces a longer-lasting signaling response that gradually increases cAMP.[12][13] This leads to an increased risk of hypercalcemia due to increased osteoclast activity, as seen with teriparatide. 

Abaloparatide binding capacity to the two high-affinity PTHR1 conformations was assessed using radioligand competition methods. Abaloparatide exhibited greater selectivity for the RG conformation, with weak binding to R0.[14] The anabolic effects of abaloparatide can be explained by its greater affinity for RG, which leads to a rapid and swift increase in cAMP signaling while maintaining low osteoclast resorption.[14] 

This explains why patients taking abaloparatide are less likely to develop hypercalcemia than those taking teriparatide. In a study determining the efficacy and safety of abaloparatide in increasing bone mineral density (BMD) in Japanese patients with osteoporosis at high fracture risk, significant increases in serum markers of bone formation [procollagen type 1 N-terminal propeptide (P1NP)] and bone resorption [C-terminal cross-linking telopeptide of type 1 collagen (CTX)] were observed following treatment with subcutaneous abaloparatide (80 µg once daily) compared to placebo.[15]

Abaloparatide has off-label effects by activating Gq and β-arrestin-1 mechanisms in target cells such as the testis and epididymis to alleviate symptoms of epididymitis and orchitis.[8]


Abaloparatide is administered through subcutaneous injection. The recommended dose for subcutaneous injections is 80 mcg once daily into the periumbilical region of the abdomen. It is supplied as a single-patient-use prefilled pen intended to deliver 30 doses. Subcutaneous administration of abaloparatide should be supplemented with calcium and vitamin D if the patient's dietary intake is inadequate. The patient should be in an environment where they can sit or lie down for the first few doses of abaloparatide administration, as this drug can cause orthostatic hypotension within four hours of injection.[16]

As some patients prefer not to use injectables, it can lower their medication adherence; transdermal patches may become a viable alternative. The transdermal patch is a novel mode of administration currently in clinical trials and under evaluation.[17] The patch is a microneedle system that administers abaloparatide at variable doses of 50 mcg, 100 mcg, and 150 mcg daily for up to 6 months.[18] It is applied to the thigh for five minutes and delivers abaloparatide intradermally.[17] 

In a randomized, open-label, active-controlled study of 500 patients with postmenopausal osteoporosis with a high risk for fractures, the efficacy and safety of the transdermal patch were compared to the subcutaneous injection of abaloparatide. The subcutaneous injection of abaloparatide resulted in 3.7% and 3.4% increases in total bone density in the total hip and femoral neck, respectively.

The transdermal patch showed increases of 2.0% and 1.9% for total hip and femoral neck bone density, respectively. While transdermal patches prove to be safer and more tolerable, with fewer subjects withdrawing, interrupting, or discontinuing the patch compared to subcutaneous injection, it is unknown whether transdermal administration reduces vertebral fractures.[18] 

The efficacy of the transdermal patch was compared to a placebo control group, with results indicating a reduction in nonvertebral fractures, increased bone mineral density of the hip, spine, and femoral neck, and reduced incidence of hypercalcemia. Based on clinical studies, 80 mcg of abaloparatide is recommended for administration once daily via injection into the periumbilical region.[18] Abaloparatide should not be used for more than two years in a patient's lifetime because of the unknown relevance of rodent osteosarcoma findings to humans.


The absolute bioavailability after 80 mcg of abaloparatide in healthy women is 36%. The mean half-life of abaloparatide is 1.7 hours.[16] After nonspecific proteolytic degradation, abaloparatide peptide fragments are primarily eliminated through renal excretion.[19] In women with mild, moderate, or severe renal impairment, no abaloparatide dose adjustment is necessary.[19] However, close monitoring for adverse reactions is required in women with severe impairment.

Adverse Effects

Abaloparatide is well tolerated and has mild adverse effects.[2] Patients taking abaloparatide experience nausea, dizziness, headache, palpitations, and hypercalciuria.[20] Abaloparatide has a black box warning of increased risk of osteosarcoma.[21]

In a two-year animal study, abaloparatide administration showed increased events of osteosarcoma and osteoblastoma.[1] A comprehensive pathology study of rats undergoing prolonged PTH analog treatment exhibited increased rates of osteosarcoma, osteosarcoma-related mortality, and metastatic potential. It is still unknown if this occurs in humans.[21] Abaloaratide has a US Boxed Warning suggesting a risk of osteosarcoma.

Adverse Effects

  • Hypercalcemia (11%)
  • Dizziness (10%)
  • Nausea (8%)
  • Headache (8%)
  • Palpitations (5%)
  • Fatigue (3%)
  • Upper abdominal pain (3%)
  • Vertigo (2%)

These adverse effects were reported from a randomized, double-blind, placebo-controlled trial among postmenopausal women with osteoporosis receiving 80 mcg of abaloparatide daily for 18 months.[2]


Abaloparatide does not have any absolute contraindications. Patients with severe renal impairment should use abaloparatide cautiously, as the drug is eliminated through the kidneys.[11] Dose adjustments for patients with mild to moderate renal impairment are unnecessary.[22] 

Abaloparatide use is not indicated in reproductive females. It is not recommended in patients with open epiphyses or genetic predispositions to osteosarcoma. Abaloparatide use is also not recommended in patients with Paget disease, idiopathic increased alkaline phosphatase levels, open epiphyseal plates, or bone malignancies. It is unknown whether any risks exist with abaloparatide in pregnancy, breastfeeding mothers, or breastfed infants or if there is any impact on milk production.


Abaloparatide use increases the risk of osteosarcoma and osteosarcoma-related mortality.[21] Compared to teriparatide, another parathyroid hormone analog, abaloparatide, has a reduced incidence of hypercalcemia. Patients with preexisting conditions of severe renal impairment, hypercalcemia, or primary hyperparathyroidism should be closely monitored for hypercalciuria or active urolithiasis while taking abaloparatide.

The injection site should be monitored for reactions, and administration should be stopped if a reaction does occur. Blood pressure should also be monitored after injection to evaluate the patient for orthostatic hypotension.[23][15]


Symptoms of abaloparatide toxicity include headache, nausea, asthenia, and vertigo. No specific antidote for abaloparatide toxicity currently exists. If an overdose is suspected, abaloparatide should be discontinued by closely monitoring calcium and phosphorus levels. Supportive measures should be implemented. 

Enhancing Healthcare Team Outcomes

Osteoporosis is a chronic disease that decreases bone mineral density and, thus, increases the risk of fractures. Managing osteoporosis requires an empathetic interdisciplinary team of rheumatologists, endocrinologists, orthopedic surgeons, nutritionists, nurses, nuclear medicine technicians, and physical therapists to diagnose, treat and rehabilitate patients.

Abaloparatide is a human parathyroid hormone-related protein analog that is FDA-approved in postmenopausal women with osteoporosis at a high fracture risk to reduce vertebral and nonvertebral fractures. Patients should be educated on postmenopausal osteoporosis, self-treatment with abaloparatide, and possible adverse effects. In addition to abaloparatide treatment, nutritionist intervention can be beneficial in ensuring the patient's adequate calcium and vitamin D intake.[24] 

Individuals who experience fractures or bone breakage should be treated by orthopedic surgeons and physical therapists for rehabilitation and to improve their quality of life. Rheumatologists and endocrinologists should maintain regular follow-ups to monitor calcium and phosphorus levels and assess for hypercalcemia or other adverse effects. Abaloparatide is associated with an increased risk of osteosarcoma. Thus, individuals taking abaloparatide may require a nuclear medicine technician to monitor them for the development of malignancies or possible metastasis. All individuals on the interprofessional team should be continuously updated on the patient's status and osteoporosis management guidelines.

Abaloparatide treatment is self-administered in an environment where the patient can sit or stand if orthostatic hypotension occurs. Patients should be educated on proper administration methods. They can be given the first dose in a healthcare setting for educational purposes and monitored for orthostatic hypotension or injection site reaction. Individuals should be cautious and watch for these adverse effects when self-administering abaloparatide injections. Patients not taking adequate amounts of calcium or vitamin D should be advised to take vitamin D and calcium supplements. The patient should be informed that abaloparatide cannot be accepted for more than two years.

Dose adjustments may be necessary for patients with preexisting severe renal impairment. Patients with mild to moderate renal impairment do not require dose adjustments. A rheumatologist or endocrinologist should closely monitor individuals with hypercalcemia or primary hyperparathyroidism for hypercalciuria or active urolithiasis.

Abaloparatide use is indicated in postmenopausal women and not in reproductive females. The effects of abaloparatide on pregnancy, breastfeeding mothers, breastfed infants, milk production, and the pediatric population are unknown. Abaloparatide is not recommended in pediatric patients with open epiphyses or genetic predispositions to bone malignancies.[24] Patient education, improved physician-patient communication, and ease of medication administration all play a significant role in successful treatment initiation, management, and overall patient outcomes.

Article Details

Article Author

Miis Akel

Article Editor:

Mayur Parmar


1/17/2023 3:58:40 PM



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