What are the first line treatment options for osteoporosis?

First-Line Treatment Options for Osteoporosis

Oral bisphosphonates are the first-line treatment for osteoporosis due to their proven efficacy in reducing fractures, favorable safety profile, and low cost. 1

Treatment Algorithm for Osteoporosis

First-Line Treatment:

• Bisphosphonates (alendronate, risedronate, zoledronate)
  • Most effective for reducing vertebral fractures
  • Should be used for initial pharmacologic treatment in both men and women with primary osteoporosis 2
  • Available in oral and intravenous formulations
  • Generic formulations are preferred when available to reduce cost 2
  • Treatment duration typically 3-5 years, after which a reassessment should be made 2

Second-Line Treatment:

• Denosumab (RANK ligand inhibitor)
  • Recommended for patients who have contraindications to or experience adverse effects from bisphosphonates 2
  • Requires continuous treatment without interruption to prevent rapid bone loss 1
  • If discontinued, transition to another antiresorptive agent is necessary 1

For Very High-Risk Patients:

• Anabolic agents (teriparatide, romosozumab) followed by an antiresorptive
  • Reserved for patients with very high fracture risk (prior vertebral fractures, T-score ≤ -3.5, or recent hip fracture) 1
  • Patients initially treated with anabolic agents should be offered an antiresorptive agent after discontinuation to preserve gains and prevent rebound fractures 2

Adjunctive Measures for All Patients

• Calcium and vitamin D supplementation

  • Recommended intake: 1000-1200 mg calcium and 600-800 IU vitamin D daily 1
  • Should be part of fracture prevention in all adults with low bone mass or osteoporosis 2

• Lifestyle modifications

  • Regular weight-bearing and resistance exercise
  • Fall prevention strategies
  • Smoking cessation
  • Limiting alcohol consumption 1

Patient Selection Based on Fracture Risk

Risk Category	Characteristics	Recommended Treatment
High Risk	T-score ≤ -2.5 but > -3.5 OR FRAX 10-year risk of major osteoporotic fracture ≥ 20%	Oral bisphosphonates
Very High Risk	Prior osteoporotic fracture OR T-score ≤ -3.5 OR FRAX 10-year risk ≥ 30%	Consider anabolic agents followed by antiresorptives

Important Considerations

• Duration of therapy: Consider stopping bisphosphonate treatment after 5 years unless there is a strong indication for continuation, as longer treatment may increase risk of long-term harms while only reducing vertebral fractures 2

• Monitoring: Bone density measurements should be performed every 1-3 years to assess treatment response 1

• Special populations: Treatment selection should be individualized for older adults (>65 years) with increased fall risk or polypharmacy 2

• Common pitfalls to avoid:

  1. Failing to assess baseline fracture risk before initiating treatment
  2. Not providing adequate calcium and vitamin D supplementation
  3. Discontinuing denosumab without transitioning to another antiresorptive agent
  4. Neglecting to consider drug holidays after 3-5 years of bisphosphonate therapy
  5. Not addressing modifiable risk factors such as fall prevention

The evidence consistently supports bisphosphonates as first-line therapy for osteoporosis, with denosumab as a strong second-line option. Anabolic agents should be reserved for those at highest risk of fracture. All pharmacologic treatments should be accompanied by adequate calcium and vitamin D intake along with appropriate lifestyle modifications.