What are the first line treatments for osteoporosis?

First-Line Treatments for Osteoporosis

Oral bisphosphonates are the recommended first-line pharmacologic treatment for osteoporosis in both men and women due to their proven efficacy in reducing fracture risk, favorable safety profile, and low cost. 1

Non-Pharmacologic Foundation (For All Patients)

• Calcium and Vitamin D:

  • Optimize calcium intake (1,000-1,200 mg/day)
  • Optimize vitamin D intake (600-800 IU/day; serum level ≥20 ng/ml) 2, 1

• Lifestyle Modifications:

  • Regular weight-bearing and resistance training exercises
  • Balanced diet and maintaining healthy weight
  • Smoking cessation
  • Limiting alcohol consumption to 1-2 drinks/day 2, 1

Pharmacologic Treatment Algorithm

First-Line Treatment

• Oral Bisphosphonates (alendronate 70mg weekly or risedronate) 1
  • Most cost-effective option
  • Reduces risk of vertebral, nonvertebral, and hip fractures
  • Consider drug holiday after 3-5 years of treatment based on fracture risk

Second-Line Options (if oral bisphosphonates are contraindicated or not tolerated)

1. IV Bisphosphonates (zoledronic acid 5mg annually) 1

   • Particularly useful for patients with GI issues on oral bisphosphonates

2. Denosumab (60mg subcutaneously every 6 months) 1, 3

   • Important: Requires continuous treatment or transition to bisphosphonate when discontinued to prevent rebound bone loss
   • Warning: Risk of hypocalcemia, especially in patients with renal impairment

For Very High Fracture Risk Patients

• Anabolic Agents should be considered first: 1
  1. Teriparatide (for patients with severe osteoporosis or multiple fractures)
  2. Romosozumab (for postmenopausal women at very high fracture risk, limited to 12 months)
  • Must be followed by antiresorptive therapy to maintain bone gains

Special Populations

Glucocorticoid-Induced Osteoporosis

• For adults ≥40 years at moderate-to-high risk of fracture receiving glucocorticoids: 2
  • Oral bisphosphonates are first-line therapy
  • Alternative options (in order of preference):
    1. IV bisphosphonates
    2. Teriparatide
    3. Denosumab
    4. Raloxifene (for postmenopausal women only when other options aren't appropriate)

Cancer Patients with Osteoporosis

• For patients with T-scores ≤-2.5 or at increased fracture risk: 2
  • Bone-modifying agents (oral/IV bisphosphonates or denosumab) are recommended
  • Avoid hormonal therapies in patients with hormone-responsive cancers

Safety Considerations

• Bisphosphonates: Risk of osteonecrosis of jaw and atypical femoral fractures with long-term use 1
• Denosumab: Risk of hypocalcemia and rebound bone loss after discontinuation 1, 3
• Teriparatide: Higher withdrawal rates due to side effects (nausea, dizziness, headache) 1

Monitoring

• The American College of Physicians recommends against bone density monitoring during the 5-year pharmacologic treatment period 1
• Monitoring is appropriate when there is evidence of inadequate response to therapy, such as new fractures

Common Pitfalls to Avoid

1. Inadequate calcium/vitamin D supplementation: These are essential components of all osteoporosis treatment regimens
2. Failure to transition after denosumab: Stopping denosumab without transitioning to another antiresorptive agent can lead to rapid bone loss and multiple vertebral fractures
3. Inappropriate drug holidays: While appropriate for some bisphosphonate users, drug holidays are not suitable for denosumab users or those at very high fracture risk
4. Overlooking non-pharmacologic interventions: Exercise, fall prevention, and lifestyle modifications are critical components of comprehensive osteoporosis management

By following this evidence-based approach to osteoporosis treatment, clinicians can significantly reduce fracture risk and improve patient outcomes.