Best Injectable Medications for Osteoporosis
For patients with osteoporosis requiring injectable treatment, denosumab is recommended as the first-line injectable option, with teriparatide reserved for those at very high fracture risk or who have failed other treatments. 1, 2
First-Line Injectable Therapy: Denosumab
Denosumab (Prolia) is a RANK ligand inhibitor administered as a subcutaneous injection every 6 months. It offers several advantages:
- Efficacy: Significantly increases bone mineral density (BMD) at the lumbar spine (5.80%), femoral neck (2.07%), and total hip (2.28%) 1
- Fracture reduction: Reduces the risk of vertebral, nonvertebral, and hip fractures 3
- Convenience: Twice-yearly subcutaneous injections improve adherence compared to oral medications 2
- Renal safety: Can be used in patients with renal impairment, unlike some bisphosphonates 2
Indications for Denosumab
- Second-line treatment after bisphosphonates (when oral bisphosphonates are contraindicated) 1
- Patients with contraindications to oral bisphosphonates 2
- Patients with creatinine clearance <35 mL/min 2
Administration
- 60 mg subcutaneous injection every 6 months 3
- Requires adequate calcium and vitamin D supplementation (calcium 1,000-1,200 mg/day and vitamin D 800-1,000 IU/day) 2
Cautions
- Risk of multiple vertebral fractures after discontinuation (requires transition to another antiresorptive) 3
- Increased risk of urinary infections and eczema 4
Second-Line Injectable Therapy: Teriparatide
Teriparatide is a recombinant parathyroid hormone (PTH) analog administered as a daily subcutaneous injection:
- Mechanism: Anabolic agent that stimulates bone formation rather than reducing resorption 5
- Indications: Reserved for patients at very high fracture risk (prior fracture, T-score ≤-3.5, FRAX ≥30% for major osteoporotic fracture) 1, 2
- Administration: 20 mcg subcutaneous injection daily for up to 24 months 5
- Efficacy: Superior to bisphosphonates in preventing vertebral and clinical fractures in patients with severe osteoporosis 6
Specific Indications for Teriparatide
- Postmenopausal women with osteoporosis at high risk for fracture 5
- Men with primary or hypogonadal osteoporosis at high risk for fracture 5
- Men and women with glucocorticoid-induced osteoporosis 5
- Patients who have failed or are intolerant to other osteoporosis therapies 5
Limitations and Precautions
- Limited to 2 years of treatment due to theoretical risk of osteosarcoma 5
- Should not be used in patients with Paget's disease, prior radiation therapy, bone cancer history, or hypercalcemia 5
- Requires daily injections, which may affect adherence 5
- May cause orthostatic hypotension, particularly after initial doses 5
Treatment Algorithm for Injectable Osteoporosis Medications
Assess fracture risk:
- Measure BMD (T-score ≤ -2.5 indicates osteoporosis)
- Evaluate fracture history
- Calculate FRAX score
First attempt oral bisphosphonates unless contraindicated 1, 2
Choose injectable therapy based on risk profile:
- Moderate-high risk: Denosumab (60 mg SQ every 6 months)
- Very high risk: Consider teriparatide (20 mcg SQ daily)
- Very high risk defined as: prior fracture, T-score ≤-3.5, FRAX ≥30% for major osteoporotic fracture 2
Monitor treatment:
- Reassess BMD after 2 years
- Monitor calcium and vitamin D levels
- Assess for adverse effects
Important Clinical Considerations
Sequential therapy: For severe osteoporosis, consider starting with an anabolic agent (teriparatide) followed by an antiresorptive (denosumab or bisphosphonate) for better long-term fracture prevention 6
Calcium and vitamin D: All injectable therapies should be accompanied by adequate calcium (1,000-1,200 mg/day) and vitamin D (800-1,000 IU/day) supplementation 2
Duration of therapy: While denosumab can be continued long-term with appropriate monitoring, teriparatide is limited to 2 years of use 5, 3
Discontinuation effects: Denosumab discontinuation can lead to rapid bone loss and increased vertebral fracture risk, requiring transition to another antiresorptive agent 3