What is the recommended use of Abaloparatide (parathyroid hormone-related protein analog) for treating osteoporosis?

Abaloparatide for Treating Osteoporosis

Abaloparatide is strongly recommended for patients with very high fracture risk, particularly those with prior osteoporotic fractures, as it significantly reduces vertebral fractures by approximately 86% and nonvertebral fractures by 43% compared to placebo. 1

Indications

Abaloparatide (TYMLOS) is FDA-approved for:

• Treatment of postmenopausal women with osteoporosis at high risk for fracture or patients who have failed or are intolerant to other available osteoporosis therapy 2
• Treatment to increase bone density in men with osteoporosis at high risk for fracture or patients who have failed or are intolerant to other available osteoporosis therapy 2

Dosing and Administration

• Recommended dose: 80 mcg subcutaneously once daily 2
• Administration site: Periumbilical region of abdomen 2
• Duration: Typically administered for up to 18 months in women and 12 months in men 2, 3
• Patients should receive supplemental calcium (1000-1200 mg daily) and vitamin D (600-800 IU daily) if dietary intake is inadequate 4, 2

Efficacy

Abaloparatide demonstrates significant efficacy across multiple parameters:

• Vertebral fractures: 86% reduction compared to placebo 5
• Nonvertebral fractures: 43% reduction compared to placebo 5
• BMD increases: At 18 months, increases of 9.2% at lumbar spine, 3.4% at total hip, and 2.9% at femoral neck 5
• Men with osteoporosis: Significant BMD improvements at 12 months in lumbar spine (8.48% vs 1.17% placebo), total hip (2.14% vs 0.01% placebo), and femoral neck (2.98% vs 0.15% placebo) 3

Patient Selection Based on Fracture Risk

Very High Fracture Risk

• Prior osteoporotic fracture(s)
• BMD T-score ≤−3.5
• FRAX 10-year risk of major osteoporotic fracture ≥30% or hip ≥4.5%
• High glucocorticoid use (≥30 mg/day for >30 days or cumulative doses ≥5 g/year) 6

For these patients, abaloparatide is conditionally recommended over anti-resorptive agents (bisphosphonates or denosumab) 6

High Fracture Risk

• BMD T-score ≤−2.5 but >−3.5
• FRAX 10-year risk of major osteoporotic fracture ≥20% but <30% or hip ≥3% but <4.5% 6

For these patients, abaloparatide or denosumab is conditionally recommended over bisphosphonates 6

Moderate Fracture Risk

• FRAX 10-year risk of major osteoporotic fracture ≥10% and <20%, hip >1% and <3%
• BMD T-score between −1 and −2.4 6

For these patients, bisphosphonates, denosumab, or abaloparatide are all conditionally recommended with no preference among these agents 6

Special Populations

Men with Osteoporosis

• Based on available BMD data, abaloparatide is considered an appropriate first-line treatment for men with osteoporosis at very high risk of fracture 6, 3

Glucocorticoid-Induced Osteoporosis

• For adults ≥40 years at very high fracture risk due to glucocorticoid therapy, abaloparatide is conditionally recommended over anti-resorptive agents 6
• For adults <40 years receiving high-dose glucocorticoid therapy, abaloparatide may be used but should only be used in adults with closed growth plates 6

Important Safety Considerations

Contraindications

• Known hypersensitivity to abaloparatide 2
• Should be avoided in patients with increased risk of osteosarcoma, including:
  • Patients with open epiphyses
  • Metabolic bone diseases including Paget's disease
  • Bone metastases or history of skeletal malignancies
  • Prior external beam or implant radiation therapy involving the skeleton
  • Hereditary disorders predisposing to osteosarcoma 2

Common Adverse Effects

• In postmenopausal women: hypercalciuria, dizziness, nausea, headache, palpitations, fatigue, upper abdominal pain, and vertigo 2
• In men: injection site erythema, dizziness, arthralgia, injection site swelling, injection site pain, contusion, nausea, diarrhea, abdominal distension, abdominal pain, and bone pain 2, 3

Precautions

• Orthostatic hypotension: Administer initially where the patient can sit or lie down 2
• Hypercalcemia: Avoid use in patients with pre-existing hypercalcemia 2
• Hypercalciuria and urolithiasis: Monitor urine calcium if pre-existing hypercalciuria or active urolithiasis are suspected 2

Post-Treatment Considerations

• Sequential therapy is essential after completing abaloparatide treatment to prevent rebound bone loss 6, 4
• Transition to an anti-resorptive agent (typically a bisphosphonate) is recommended after completing abaloparatide treatment 4
• In real-world practice, approximately 50.6% of patients transition to another osteoporosis medication after completing abaloparatide treatment 7

Treatment Adherence

• In real-world settings, approximately 64.8% of patients complete abaloparatide treatment as prescribed 7
• Common reasons for discontinuation include financial barriers (31.2%) and tolerability issues (22.8%) 7
• Regular follow-up visits and access to medication support programs may improve adherence 7

Abaloparatide represents an important anabolic treatment option for patients with osteoporosis, particularly those at very high fracture risk, with demonstrated efficacy in reducing fracture risk regardless of baseline fracture probability.