What are the treatment options for osteoporosis?

Treatment for Osteoporosis

Oral bisphosphonates (alendronate or risedronate) are the first-line pharmacologic treatment for osteoporosis, combined with calcium (1,000-1,200 mg/day) and vitamin D (600-800 IU/day) supplementation, based on their proven efficacy in reducing fractures, favorable safety profile, and lower cost compared to other medications. 1, 2

Risk Stratification and Treatment Initiation

Treatment decisions depend on fracture risk assessment:

• High-risk patients requiring treatment include those with:

  • History of vertebral or hip fracture 1, 2
  • T-score ≤ -2.5 at hip or spine on DEXA scan 1, 3
  • 10-year FRAX risk ≥20% for major osteoporotic fracture or ≥3% for hip fracture 1
  • History of any low-trauma fracture 1

• Very high-risk patients (recent vertebral fractures, hip fracture with T-score ≤-2.5, or multiple fractures) should be considered for initial anabolic therapy (teriparatide, abaloparatide, or romosozumab) followed by transition to antiresorptive agents 2, 3

First-Line Treatment: Oral Bisphosphonates

Alendronate and risedronate are the preferred initial agents due to their balance of benefits, harms, and cost 1, 2:

• These medications reduce vertebral fractures by approximately 52 per 1,000 person-years and hip fractures by 6 per 1,000 person-years 3
• Alendronate inhibits osteoclast activity, reducing bone resorption by approximately 50-70% as measured by urinary markers, with effects evident within one month 4
• Available in daily, weekly, or monthly oral formulations, as well as IV options for patients unable to tolerate oral administration 1

Key contraindications and precautions:

• Avoid in patients with esophageal abnormalities, inability to remain upright for 30 minutes after dosing, hypocalcemia, or severe renal impairment 1, 2, 4
• Long-term use beyond 5 years increases risk of osteonecrosis of the jaw and atypical femoral fractures 1
• Reassess treatment after 5 years and consider drug holidays based on individual risk factors 1, 2

Second-Line Treatment Options

When oral bisphosphonates are contraindicated, not tolerated, or ineffective, use the following hierarchy:

1. IV bisphosphonates (zoledronic acid) - for patients with GI contraindications or adherence concerns 1, 2

2. Denosumab (subcutaneous injection every 6 months):

   • Inhibits osteoclast activity through a different mechanism than bisphosphonates 5
   • Critical warning: After discontinuation, patients must transition to an antiresorptive agent to prevent rapid bone loss and rebound vertebral fractures 1, 5
   • Increases infection risk, particularly in immunocompromised patients 5
   • Can cause severe hypocalcemia if calcium/vitamin D levels are inadequate 5

3. Raloxifene (selective estrogen receptor modulator):

   • Appropriate for younger postmenopausal women 1
   • Avoid in patients with hormone-responsive cancers 1
   • Less effective than bisphosphonates for hip fracture reduction 1

Anabolic Therapy for Very High-Risk Patients

Teriparatide (daily subcutaneous injection):

• Reserved for severe osteoporosis or patients who have sustained fractures despite other treatments 1, 6
• Stimulates new bone formation rather than just preventing bone loss 6
• FDA-approved for postmenopausal women, men with primary or hypogonadal osteoporosis, and glucocorticoid-induced osteoporosis 6
• Contraindications: Open epiphyses, Paget's disease, prior skeletal radiation, bone metastases, or hereditary disorders predisposing to osteosarcoma 2
• Must be followed by antiresorptive therapy to maintain bone gains after discontinuation 1, 2

Essential Foundational Measures for All Patients

Non-pharmacologic interventions are critical and should accompany all treatment:

• Calcium supplementation: 1,000 mg/day for ages 19-50; 1,200 mg/day for ages 51+ 1, 2
• Vitamin D supplementation: 600 IU/day for ages 19-70; 800 IU/day for ages 71+ 1, 2
• Target serum vitamin D level ≥20 ng/mL (50 nmol/L) 1
• Exercise: Regular weight-bearing, muscle-strengthening (squats, push-ups), and balance exercises (heel raises, standing on one foot) 1, 3
• Lifestyle modifications: Smoking cessation and limiting alcohol to 1-2 drinks/day 7, 1
• Fall prevention: Vision/hearing assessment, medication review, and home safety evaluation 1

Special Populations

Men with osteoporosis:

• Treatment recommendations mirror those for postmenopausal women 1, 2
• Oral bisphosphonates as first-line, denosumab as second-line 1

Glucocorticoid-induced osteoporosis:

• Oral bisphosphonates are first-line for patients ≥40 years at moderate-to-high fracture risk 7, 2
• For adults <40 years with history of osteoporotic fracture, Z-score <-2.3, or bone loss ≥10%/year, use oral bisphosphonates over calcium/vitamin D alone 7
• Preferred over IV bisphosphonates, teriparatide, or denosumab due to safety, cost, and proven efficacy 7

Cancer patients:

• Bone-modifying agents (oral bisphosphonates, IV bisphosphonates, or denosumab) are recommended for those at high fracture risk 1
• Avoid hormonal therapies in patients with hormone-responsive cancers 1

Monitoring and Duration

• Bone density monitoring: Every 1-2 years while on treatment 2; every 24 months in cancer patients with elevated fracture risk 1
• Bisphosphonate duration: Typically 3-5 years, then reassess for drug holiday based on fracture risk 1, 2
• After anabolic therapy: Transition to antiresorptive agents to maintain bone gains 1, 2
• Prescribe generic medications when possible to improve affordability and adherence 1

Critical Pitfalls to Avoid

• Never stop denosumab abruptly without transitioning to another antiresorptive agent - this causes rapid bone loss and increased vertebral fracture risk 1, 5
• Do not skip dental evaluation before starting bisphosphonates or denosumab due to osteonecrosis of jaw risk 5
• Ensure adequate calcium and vitamin D before starting any osteoporosis medication to prevent hypocalcemia 2, 5
• Do not continue bisphosphonates indefinitely without reassessing after 5 years due to atypical fracture risk 1
• Recognize that anabolic agents alone are insufficient - they must be followed by antiresorptive therapy 1, 2