What are the typical treatment options for osteoporosis?

Osteoporosis Treatment

Bisphosphonates (oral alendronate or risedronate, or intravenous zoledronic acid) are the first-line pharmacologic treatment for osteoporosis in both postmenopausal women and men, with strong evidence for reducing hip, vertebral, and nonvertebral fractures. 1

First-Line Treatment: Bisphosphonates

• Oral bisphosphonates or intravenous zoledronic acid should be prescribed as initial therapy for postmenopausal women and men with osteoporosis, with high-certainty evidence for fracture reduction. 1
• Generic formulations must be prescribed whenever possible due to significantly lower cost with equivalent efficacy. 1
• Alendronate reduces vertebral fractures by 47-56% and hip fractures significantly in postmenopausal women with existing vertebral fractures. 2
• Treatment duration should be 5 years initially, then reassess fracture risk to determine whether to continue or take a drug holiday. 1
• After 5 years of bisphosphonate therapy, consider stopping unless the patient has strong indication for continuation (such as new fractures, very low T-score, or high ongoing fracture risk). 3

Bisphosphonate Administration Critical Points

• Alendronate must be taken on an empty stomach with a full glass of water, and patients must remain upright for at least 30 minutes to reduce risk of esophageal adverse events. 4
• Weekly dosing (alendronate 70 mg once weekly) is as effective as daily dosing (10 mg/day) and may improve adherence. 2
• Upper GI adverse events (abdominal pain, nausea, dyspepsia, acid regurgitation) are the most common side effects, though large trials show no statistically significant difference from placebo. 2

Second-Line Treatment: Denosumab

• Denosumab 60 mg subcutaneously every 6 months is recommended as second-line therapy for patients with contraindications to bisphosphonates or who experience adverse effects from bisphosphonates. 1
• This recommendation has moderate-certainty evidence for women and low-certainty evidence for men. 1
• Critical warning: Denosumab discontinuation causes rebound bone loss and multiple vertebral fractures—patients must transition to bisphosphonate therapy after stopping denosumab. 1
• Never discontinue denosumab without immediately starting antiresorptive therapy. 5

Very High-Risk Patients: Anabolic Agents First

For patients at very high risk for fracture, anabolic agents (teriparatide, abaloparatide, or romosozumab) should be initiated before bisphosphonates, followed by mandatory transition to bisphosphonates or denosumab. 1

Defining Very High Risk

Very high risk includes patients with: 1, 6

• Age >74 years
• Recent fracture within 12 months
• Multiple prior osteoporotic fractures
• T-score ≤-3.0
• Fractures despite ongoing bisphosphonate therapy
• High FRAX scores (≥20% for major osteoporotic fracture or ≥3% for hip fracture)

Anabolic Agent Selection and Protocol

• Teriparatide is the preferred anabolic agent, reducing vertebral fractures by 69 per 1000 patients and any clinical fractures by 27 per 1000 patients. 1, 6
• Teriparatide is administered as 20 mcg daily subcutaneous injection for 18-24 months. 6
• Expected outcomes include 10% increase in spine BMD and 3% increase in hip BMD. 6
• Romosozumab is conditionally recommended for very high-risk postmenopausal women, limited to 12 monthly doses due to waning anabolic effect. 1
• Mandatory transition: After completing anabolic therapy, patients must immediately transition to bisphosphonates or denosumab to maintain bone gains and prevent rebound fractures. 1, 6, 5

Anabolic Agent Contraindications

Before prescribing teriparatide, verify absence of: 6

• Paget's disease of bone
• Prior skeletal radiation therapy
• Bone metastases or history of skeletal malignancies
• Active malignancies prone to bone metastases

Monitoring During Anabolic Therapy

• Monitor serum calcium and urinary calcium at 1 month after initiation and then as clinically indicated to prevent hypercalcemia. 6
• Common adverse effects include hypercalcemia, gastrointestinal symptoms, headache, and hypercalciuria. 5
• Teriparatide may increase risk for serious adverse events and withdrawals due to adverse events. 5

Essential Adjunctive Measures for ALL Patients

All patients with osteoporosis require the following non-pharmacologic interventions: 1

• Calcium 1000-1200 mg daily
• Vitamin D 800-1000 IU daily (target serum 25(OH)D ≥20 ng/mL, ideally 30-50 ng/mL)
• Weight-bearing and muscle resistance exercises (squats, push-ups)
• Balance exercises and fall prevention counseling (heel raises, standing on one foot)
• Smoking cessation
• Alcohol reduction

Treatment Algorithm

1. Confirm diagnosis: T-score ≤-2.5, T-score between -1.0 and -2.5 with high FRAX risk, or low-trauma fracture. 1

2. Assess fracture risk category:

   • Standard risk: Start oral bisphosphonate (alendronate or risedronate) or IV zoledronic acid. 1
   • Very high risk (see criteria above): Start anabolic agent (teriparatide preferred), then mandatory transition to bisphosphonate or denosumab. 1, 6

3. If bisphosphonates fail or are not tolerated: Switch to denosumab 60 mg subcutaneously every 6 months. 1

4. Duration and reassessment:

   • Treat for 5 years, then reassess fracture risk. 1
   • If low ongoing risk, consider drug holiday (for bisphosphonates only, never for denosumab). 3
   • If high ongoing risk, continue treatment. 3

5. Ensure all patients receive calcium, vitamin D, exercise, and fall prevention counseling throughout treatment. 1

Common Pitfalls to Avoid

• Never use anabolic agents as first-line therapy in patients who are not at very high fracture risk—bisphosphonates are first-line for standard-risk patients. 1, 5
• Never discontinue anabolic therapy without immediately starting antiresorptive therapy—this causes rapid bone density loss and rebound vertebral fractures. 1, 5
• Never discontinue denosumab without transitioning to bisphosphonates—rebound fractures are a serious risk. 1
• Do not monitor bone density during the initial 5-year treatment period—reassess fracture risk at 5 years instead. 1
• Do not prescribe brand-name medications when generic bisphosphonates are available and equally effective. 1