What is the role of Abaloparatide (abaloparatide) in the treatment of osteoporosis?

From the Guidelines

Abaloparatide is a recommended treatment option for adults at high or very high risk of fracture, particularly in postmenopausal women, as it has been shown to increase bone mineral density and reduce fracture risk 1. The standard regimen for abaloparatide is 80 micrograms administered as a daily subcutaneous injection for up to 24 months, which is the maximum recommended duration of therapy. Key points to consider when prescribing abaloparatide include:

• Patients should also take calcium (1000-1200 mg daily) and vitamin D (800-1000 IU daily) supplements while on abaloparatide.
• The medication works by stimulating bone formation through selective activation of the PTH1 receptor, leading to increased bone mineral density and reduced fracture risk.
• Abaloparatide is particularly effective at building bone in both cortical and trabecular sites, with studies showing significant reductions in vertebral, nonvertebral, and wrist fractures.
• Common side effects include dizziness, nausea, headache, palpitations, and orthostatic hypotension.
• After completing abaloparatide therapy, patients should transition to an antiresorptive medication like a bisphosphonate to maintain the bone density gains, as recommended by the American College of Physicians 1. Some important considerations when using abaloparatide include:
• Abaloparatide is contraindicated in patients with hypercalcemia, bone metastases, history of skeletal malignancies, or high risk for osteosarcoma.
• It should not be used in patients with severe renal impairment.
• The American College of Rheumatology guideline for the prevention and treatment of glucocorticoid-induced osteoporosis conditionally recommends PTH/PTHrP agonists, such as abaloparatide, for patients at very high risk of fracture 1.

From the FDA Drug Label

The efficacy of TYMLOS for the treatment of postmenopausal osteoporosis was evaluated in Study 003 (NCT 01343004), an 18-month, randomized, multicenter, double-blind, placebo-controlled clinical trial in postmenopausal women aged 49 to 86 years (mean age of 69) who were randomized to receive TYMLOS 80 mcg (N = 824) or placebo (N = 821) given subcutaneously once daily. TYMLOS resulted in a significant reduction in the incidence of new vertebral fractures compared to placebo at 18 months (0.6% TYMLOS compared to 4.2% placebo, p <0.0001). The absolute risk reduction in new vertebral fractures was 3.6% at 18 months and the relative risk reduction was 86% for TYMLOS compared to placebo.

Abaloparatide is effective in reducing the incidence of new vertebral fractures in postmenopausal women with osteoporosis.

• The primary endpoint was the incidence of new vertebral fractures in patients treated with TYMLOS compared to placebo.
• Key findings include a significant reduction in the incidence of new vertebral fractures at 18 months, with an absolute risk reduction of 3.6% and a relative risk reduction of 86% for TYMLOS compared to placebo 2.

From the Research

Efficacy of Abaloparatide for Osteoporosis

• Abaloparatide has been shown to increase bone mineral density (BMD), improve bone microarchitecture, and increase bone strength in preclinical and clinical studies 3.
• The pivotal phase 3 trial ACTIVE and its extension (ACTIVExtend) demonstrated the efficacy of initial treatment with abaloparatide for 18 months followed by sequential treatment with alendronate for an additional 24 months to reduce the risk of vertebral, nonvertebral, clinical, and major osteoporotic fractures and to increase BMD in postmenopausal women with osteoporosis 3.
• A systematic review and meta-analysis found that abaloparatide administration significantly increased the BMD of the lumbar vertebrae, femoral neck, and hip bone in postmenopausal women compared with the control group 4.
• Abaloparatide has been shown to reduce the risk of vertebral fracture and alleviate symptoms and complications of postmenopausal osteoporosis with considerable safety 4.

Safety of Abaloparatide for Osteoporosis

• Discontinuations from the ACTIVE trial were slightly more common in abaloparatide-treated patients due to dizziness, palpitations, nausea, and headache 3.
• Post hoc analyses of ACTIVE and ACTIVExtend support the efficacy and safety of abaloparatide in relevant subpopulations, including postmenopausal women with various baseline risk factors, women ≥80 years, women with type 2 diabetes mellitus, and women with renal impairment 3.
• A study found that administration site reactions were the most frequently reported adverse events with abaloparatide, but the incidence of serious adverse events was similar between abaloparatide and placebo groups 5.
• A comparative effectiveness study found that there were no significant differences in cardiovascular safety between abaloparatide and teriparatide cohorts 6.

Comparison with Other Treatments

• Abaloparatide has been compared to teriparatide in several studies, with one study finding that abaloparatide reduced the risk of vertebral, nonvertebral, major osteoporotic, and clinical fractures compared with teriparatide 7.
• A retrospective claims study found that abaloparatide was associated with significantly lower rates of hip and nonvertebral fractures compared to teriparatide 6.
• A study found that abaloparatide had a lower cost and reduced prevalence of hypercalcemia compared to teriparatide 7.