What is the treatment for osteoporosis?

Treatment of Osteoporosis

Oral bisphosphonates (alendronate, risedronate) are the first-line pharmacologic treatment for osteoporosis due to their proven efficacy in reducing fracture risk, favorable safety profile, and low cost. 1

First-Line Pharmacologic Treatment Options

Bisphosphonates

• Alendronate: 70 mg weekly (treatment) or 35 mg weekly (prevention) 1
• Risedronate: 35 mg weekly, 75 mg on two consecutive days monthly, or 150 mg monthly 1
• Zoledronic acid: 5 mg IV annually (treatment) or every two years (prevention) 1

Bisphosphonates work by inhibiting osteoclast activity, reducing bone resorption without directly inhibiting bone formation 2. High-quality evidence shows that alendronate, risedronate, and zoledronic acid reduce vertebral, nonvertebral, and hip fractures in postmenopausal women with osteoporosis 3.

Second-Line Options

• Denosumab: 60 mg subcutaneous injection every six months
  • Particularly useful for patients with renal impairment 1
  • Reduces radiographic vertebral, nonvertebral, and hip fractures 3

Treatment Algorithm Based on Fracture Risk

For High-Risk Patients (T-score ≤-2.5 OR FRAX 10-year risk ≥20% for major osteoporotic fracture or ≥3% for hip fracture)

1. Oral bisphosphonates (alendronate or risedronate) 1
2. If oral bisphosphonates are contraindicated: IV zoledronic acid or denosumab 1

For Very High-Risk Patients (Prior fracture, T-score ≤-3.5, OR FRAX 10-year risk ≥30% for major osteoporotic fracture or ≥4.5% for hip fracture)

1. Consider anabolic agents (teriparatide, romosozumab) followed by an antiresorptive agent 1
   • Teriparatide: 20 mcg SC daily 1, 4
   • Note: After discontinuation of anabolic agents, patients should be offered an antiresorptive agent to preserve gains and prevent rebound fractures 3

Treatment Duration and Monitoring

• Initial treatment duration is typically 5 years 3, 1
• Consider stopping bisphosphonate treatment after 5 years unless there is a strong indication for continuation 3
  • Extended treatment beyond 5 years reduces risk for new vertebral fractures but not other fractures 3
  • Longer treatment increases risk of long-term harms 3
• Bone density measurements (DXA) should be performed every 1-3 years 1
  • More frequent evaluations (annually) in patients on glucocorticoids or with previous fractures 1
  • The ACP recommends against bone density monitoring during the 5-year pharmacologic treatment period 3

Supplementation and Lifestyle Modifications

• Calcium: 1000-1200 mg/day 1
• Vitamin D: 800 IU/day 1
• Weight-bearing and resistance-training exercise 1, 5
• Fall prevention strategies 1, 6
• Smoking cessation and limiting alcohol intake 1, 7

Important Side Effects and Precautions

Bisphosphonates

• Mild upper GI symptoms (remain upright for 30 minutes after taking oral bisphosphonates) 1
• Rare but serious: osteonecrosis of the jaw and atypical femoral fractures 1

Denosumab

• Hypocalcemia, infections, skin reactions 1
• Discontinuation requires transition to another antiresorptive agent to prevent rapid bone loss 1

Teriparatide

• Orthostatic hypotension (patients should sit or lie down if they feel lightheaded) 4
• Limited to 2 years of treatment due to concerns about osteosarcoma in animal studies 4

Clinical Pearls

• Generic medications should be prescribed when possible to reduce cost 3
• Patients initially treated with an anabolic agent should transition to an antiresorptive agent after discontinuation 3
• Consider individual risk factors, comorbidities, and concomitant medications when selecting treatment 3
• Treatment adherence is critical for efficacy; 30-50% of patients do not take their medication correctly 7

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