What are the treatment options for osteoporosis?

Treatment Options for Osteoporosis

Bisphosphonates are the recommended first-line pharmacologic treatment for osteoporosis to reduce fracture risk in both men and women. 1

First-Line Treatment Options

Oral Bisphosphonates

• Alendronate (70mg once weekly) or Risedronate
  • Mechanism: Inhibit osteoclast activity without interfering with recruitment or attachment 2
  • Benefits: Reduce risk of vertebral, nonvertebral, and hip fractures 1, 3
  • Administration: Take in fasting state with water at least 30 minutes before food 4
  • Duration: Consider stopping after 5 years unless strong indication for continuation 1
  • Common side effects: Mild upper GI symptoms 3

Intravenous Bisphosphonate

• Zoledronic acid (5mg IV once yearly)
  • Particularly effective for patients with severe osteoporosis and high fracture risk 3
  • Requires:
    • Checking vitamin D levels before administration
    • Ensuring adequate renal function (GFR >35 mL/min)
    • Premedication with acetaminophen to reduce acute phase reaction 3

Second-Line Treatment Options

Denosumab

• Mechanism: RANK ligand inhibitor 1, 3
• Dosing: 60mg subcutaneous injection every 6 months 3
• Advantages:
  • No renal clearance concerns
  • Higher BMD gains than bisphosphonates 3
  • Effective for patients with contraindications to bisphosphonates 1
• Important safety concerns:
  • Risk of rebound bone loss after discontinuation
  • Requires transition to another antiresorptive agent if discontinued
  • Rare risks of osteonecrosis of jaw and atypical femur fractures 3, 5

Anabolic Agents

Teriparatide

• Mechanism: Stimulates new bone formation 3
• Indications:
  • Postmenopausal women with osteoporosis at high fracture risk
  • Men with primary or hypogonadal osteoporosis at high risk
  • Osteoporosis associated with sustained glucocorticoid therapy 6
• Dosing: 20mcg subcutaneous injection daily for up to 24 months 3
• Important note: Must transition to an antiresorptive agent after completion to preserve gains and prevent rebound fractures 1, 7

Treatment Algorithm Based on Patient Characteristics

1. For newly diagnosed osteoporosis:

   • Start with oral bisphosphonate (alendronate or risedronate) 1, 3
   • If unable to tolerate oral medication or severe osteoporosis: Consider zoledronic acid 3

2. For patients with contraindications to bisphosphonates or who experience adverse effects:

   • Use denosumab as second-line treatment 1

3. For patients at very high fracture risk (history of osteoporotic fracture, multiple risk factors):

   • Consider teriparatide for up to 24 months 3, 6
   • Follow with antiresorptive agent to maintain gains 1, 7

4. For men with primary osteoporosis:

   • Use bisphosphonates as first-line therapy 1
   • Use denosumab as second-line if contraindications to bisphosphonates 1

5. For glucocorticoid-induced osteoporosis:

   • Bisphosphonates are effective 8
   • Teriparatide is indicated for those at high fracture risk 6

Important Adjunctive Measures

• Ensure adequate calcium (1000-1200mg daily) and vitamin D (800-1000 IU daily) intake 3
• Recommend weight-bearing exercise and resistance training 3
• Implement fall prevention strategies 3
• Limit alcohol consumption and encourage smoking cessation 3

Monitoring and Duration of Therapy

• The American College of Physicians recommends treating osteoporotic women with pharmacologic therapy for 5 years 1
• Consider stopping bisphosphonate treatment after 5 years unless strong indication for continuation exists 1
• For patients initially treated with anabolic agents, transition to antiresorptive therapy is essential to preserve gains 1, 7

Pitfalls and Caveats

1. Bisphosphonate discontinuation: Consider individual fracture risk factors when deciding on a drug holiday 1

2. Denosumab discontinuation: Must transition to another antiresorptive agent to prevent rebound bone loss and multiple vertebral fractures 3, 5

3. Anabolic therapy: Limited to 24 months for teriparatide; must follow with antiresorptive therapy 3, 7

4. Long-term bisphosphonate use: Associated with rare but serious risks of osteonecrosis of jaw and atypical femoral fractures 3, 9

5. Combination therapy: While combining antiresorptive and anabolic agents may increase BMD compared to monotherapy, more information is needed regarding effects on fracture risk 10