What is the first-line treatment for patients with osteoporosis, particularly those at high risk of fractures with a history of previous fractures?

Anabolic Therapy as First-Line Treatment for Osteoporosis

Anabolic agents (teriparatide or abaloparatide) should be used as first-line treatment only in patients at very high risk of fracture, defined as those with prior osteoporotic fractures, T-score ≤-3.5, FRAX 10-year major osteoporotic fracture risk ≥30% or hip fracture risk ≥4.5%, or high-dose glucocorticoid use (≥30 mg/day for >30 days or cumulative ≥5 g/year). 1

Risk Stratification Determines Treatment Choice

The decision to use anabolic therapy first-line depends entirely on fracture risk stratification:

Very High Risk Patients (Anabolic First-Line)

• Prior osteoporotic fracture(s) - particularly recent vertebral or hip fractures 1, 2
• T-score ≤-3.5 at any site 1
• FRAX-adjusted 10-year risk: Major osteoporotic fracture ≥30% OR hip fracture ≥4.5% 1
• High-dose glucocorticoids: ≥30 mg/day for >30 days or cumulative ≥5 g/year 1

For these very high-risk patients, sequential therapy starting with a bone-forming agent followed by an anti-resorptive agent is strongly recommended over starting with anti-resorptives alone. 1

High Risk Patients (Bisphosphonates First-Line)

• T-score between -2.5 and -3.5 1
• FRAX-adjusted 10-year risk: Major osteoporotic fracture 20-30% OR hip fracture 3-4.5% 1

For high-risk patients without the very high-risk features above, oral bisphosphonates (alendronate or risedronate) remain the strongly recommended first-line treatment. 1

Choosing Between Abaloparatide and Teriparatide

When anabolic therapy is indicated for very high-risk patients:

Abaloparatide is preferred over teriparatide based on superior bone mineral density gains and fracture reduction data. 1, 3

• Abaloparatide demonstrates greater BMD increases at the total hip and femoral neck compared to teriparatide 4, 3
• Real-world data shows significantly lower rates of hip fractures (HR 0.83, P=0.027) and nonvertebral fractures (HR 0.88, P=0.003) with abaloparatide versus teriparatide over 18 months 3
• Hypercalcemia occurs less frequently with abaloparatide compared to teriparatide 4

FDA-Approved Indications

Abaloparatide is FDA-approved for:

• Postmenopausal women with osteoporosis at high risk for fracture (history of osteoporotic fracture, multiple risk factors, or failed/intolerant to other therapy) 5
• Men with osteoporosis at high risk for fracture 5

Dosing: 80 mcg subcutaneously once daily in the periumbilical abdomen 5

Critical Treatment Duration and Sequential Therapy Requirements

Anabolic therapy should not exceed 2 years during a patient's lifetime. 5, 6

Mandatory Sequential Anti-Resorptive Therapy

After completing anabolic therapy, patients MUST transition to anti-resorptive therapy (bisphosphonates or denosumab) to prevent rapid bone loss and maintain gains. 1, 6

• Discontinuation of PTH/PTHrP without sequential therapy leads to gradual loss of bone gained over 12-18 months 1
• If denosumab is used after anabolic therapy, it must be followed by bisphosphonates to prevent rebound bone loss 1

Glucocorticoid-Induced Osteoporosis Context

In glucocorticoid-induced osteoporosis specifically:

For very high-risk patients, anabolic agents (PTH/PTHrP) are conditionally recommended over anti-resorptive agents as first-line therapy. 1

This represents a shift from the 2017 guidelines, reflecting recognition that anabolic agents show BMD and vertebral fracture prevention superiority compared to anti-resorptives in very high-risk populations. 1

Essential Concurrent Management

All patients receiving anabolic therapy require:

• Supplemental calcium (1000-1200 mg daily) and vitamin D (800-1000 IU daily) if dietary intake is inadequate 5, 7
• Total daily calcium should not exceed 1500 mg to avoid hypercalcemia risk 6
• Weight-bearing and muscle resistance exercises (squats, push-ups) plus balance exercises 2

Key Safety Considerations

Contraindications and Precautions

• History of osteosarcoma or bone malignancy precludes PTH1R agonist use 4, 6
• Major cardiovascular events preclude romosozumab use 4
• Orthostatic hypotension risk: Administer first several doses where patient can sit/lie down 5

Monitoring

• Serum calcium measurement after 1 month of teriparatide treatment 6
• No routine BMD monitoring during treatment is recommended by guidelines 8

Common Pitfalls to Avoid

1. Using anabolic therapy in moderate or high-risk patients who should receive bisphosphonates first-line 1
2. Failing to transition to anti-resorptive therapy after completing anabolic treatment 1
3. Exceeding 2-year lifetime exposure to PTH/PTHrP analogs 5, 6
4. Concurrent bisphosphonate use with anabolic therapy, which should be avoided 6