What are the indications for osteoanabolic therapy, such as teriparatide (recombinant human parathyroid hormone) or abaloparatide, in patients with osteoporosis?

Indications for Osteoanabolic Therapy in Osteoporosis

Osteoanabolic agents (teriparatide, abaloparatide, or romosozumab) should be initiated in postmenopausal women and men with very high fracture risk osteoporosis, defined by specific clinical and densitometric criteria, and must always be followed by antiresorptive therapy to prevent rapid bone loss. 1, 2

Very High Fracture Risk Criteria (Primary Indications)

Osteoanabolic therapy is indicated when patients meet any of the following very high-risk criteria:

• Recent osteoporotic fracture (within the past 12 months), particularly vertebral or hip fractures 1, 2
• Multiple prior clinical osteoporotic fractures at any skeletal site 1, 2
• T-score ≤ -3.5 at any site (spine, hip, or femoral neck) 2
• FRAX 10-year risk ≥30% for major osteoporotic fracture OR ≥4.5% for hip fracture 2
• Fracture while on antiresorptive therapy (treatment failure) 1, 2
• High-dose glucocorticoid exposure (≥30 mg/day prednisone equivalent for >30 days OR cumulative ≥5 g/year) 2

High Fracture Risk Criteria (Alternative Indications)

For patients not meeting very high-risk criteria, osteoanabolic agents may be considered over bisphosphonates when:

• FRAX 10-year risk 10-30% for major osteoporotic fracture OR 1-4.5% for hip fracture 2
• T-score between -2.5 and -3.5 with additional risk factors (age >74 years, parental hip fracture, smoking, low body weight) 1, 2

FDA-Approved Indications by Agent

Teriparatide (PTH 1-34)

• Postmenopausal women with osteoporosis at high risk for fracture 3
• Men with primary or hypogonadal osteoporosis at high risk for fracture 3
• Men and women with glucocorticoid-induced osteoporosis (≥5 mg/day prednisone equivalent) at high risk for fracture 3
• Patients who have failed or are intolerant to other osteoporosis therapy 3

Abaloparatide (PTHrP analog)

• Postmenopausal women with osteoporosis at high risk for fracture 2, 4
• Men with very high fracture risk (based on BMD data extrapolation) 2

Romosozumab (Sclerostin inhibitor)

• Use only in patients intolerant of other agents due to increased cardiovascular risk (myocardial infarction, stroke, death) compared to alendronate 1, 2
• Postmenopausal women with very high fracture risk when teriparatide/abaloparatide are contraindicated 1

Absolute Contraindications to Osteoanabolic Therapy

Do not use osteoanabolic agents in patients with:

• Open epiphyses (pediatric/young adult patients with growth potential) 2, 3
• Paget's disease of bone 1, 2, 3
• Bone metastases or skeletal malignancies 1, 2, 3
• Prior external beam or implant radiation therapy involving the skeleton 1, 2, 3
• Hypersensitivity to the specific agent 3
• Underlying hypercalcemic disorders (for teriparatide/abaloparatide) 3

Critical Treatment Principles

Duration of Therapy

• Maximum 24 months for teriparatide or abaloparatide during a patient's lifetime 3, 4
• 12 months for romosozumab (monthly subcutaneous injections) 1, 4
• Use beyond 2 years should only be considered if patient remains at or returns to very high fracture risk 3

Mandatory Sequential Antiresorptive Therapy

This is non-negotiable: Discontinuation of osteoanabolic agents results in rapid bone loss and increased fracture risk within 12-18 months if not followed by antiresorptive therapy 1, 2

• After teriparatide or abaloparatide: Start bisphosphonate immediately upon completion 2
• After romosozumab: Must be followed by bisphosphonate or denosumab 1, 2
• If using denosumab after teriparatide/abaloparatide: Must transition to bisphosphonate when denosumab is discontinued to prevent rebound vertebral fractures 2

Efficacy Data Supporting Use

Teriparatide

• Reduces vertebral fractures by 69 per 1000 patients and any clinical fractures by 27 per 1000 patients compared to placebo (high certainty) 1
• Reduces radiographic vertebral fractures by 66 per 1000 patients compared to bisphosphonates (moderate certainty) 1
• In glucocorticoid-induced osteoporosis, increases lumbar and hip BMD and decreases vertebral fractures at 36 months compared to alendronate 2

Abaloparatide

• Real-world data show lower rates of hip and nonvertebral fractures compared to teriparatide (HR 0.83 for hip fracture, 0.88 for nonvertebral fracture) 5
• Greater BMD improvements at total hip and femoral neck compared to teriparatide 5, 4

Romosozumab

• Reduces vertebral fractures by 13 per 1000 patients, clinical vertebral fractures by 4 per 1000, and any clinical fractures by 9 per 1000 at 12-36 months (moderate certainty) 1
• When followed by alendronate, reduces hip fractures by 12 per 1000 patients compared to placebo (moderate certainty) 1

Common Pitfalls to Avoid

• Never use bisphosphonates concurrently with teriparatide or abaloparatide—this blunts the anabolic effect 6, 7
• Do not use romosozumab in patients with recent cardiovascular events (within 12 months) due to increased cardiovascular risk 1, 2
• Ensure calcium intake does not exceed 1500 mg/day (including dietary sources) during teriparatide therapy to minimize hypercalcemia risk 3, 6
• Administer initial doses under observation for potential orthostatic hypotension 3
• Monitor serum calcium at 1 month after starting teriparatide; routine monitoring beyond this is unnecessary unless symptomatic 3, 6

Special Populations

Men with Osteoporosis

The same indications and criteria apply to men as to postmenopausal women, though evidence is extrapolated from female studies with lower certainty 1, 2

Glucocorticoid-Induced Osteoporosis

Teriparatide is superior to alendronate for increasing BMD and reducing vertebral fractures in patients requiring sustained glucocorticoid therapy 2, 3

Younger Patients (<40 years)

Use with extreme caution due to theoretical osteosarcoma risk, though observational data in 200,000 patients show no increased incidence compared to general population 1, 2