What are the recommended pharmacologic and lifestyle treatments for osteoporosis in adults?

Treatment for Osteoporosis

Start with oral bisphosphonates (alendronate, risedronate, or zoledronate) as first-line therapy for all adults with osteoporosis, combined with calcium 1000-1200 mg daily, vitamin D 600-800 IU daily, and lifestyle modifications. 1, 2

Risk Stratification and Treatment Initiation

Who Needs Treatment

• Postmenopausal women and men ≥50 years with T-score ≤-2.5 at hip, femoral neck, or lumbar spine 3
• Any patient with a history of fragility fracture (from standing height or less), regardless of bone density 3
• Patients with osteopenia (T-score -1.0 to -2.5) if FRAX shows 10-year major osteoporotic fracture risk ≥20% OR hip fracture risk ≥3% 3
• Women ≥65 years and men ≥70 years should undergo screening with DEXA 3

Risk Categories Matter for Drug Selection

• High/Very High Risk: History of vertebral or hip fracture, multiple fractures, T-score ≤-2.5 with additional risk factors 1
• Very High Risk Specifically: Recent vertebral fractures, hip fracture with T-score ≤-2.5, or imminent fracture risk 1, 4

Pharmacologic Treatment Algorithm

First-Line: Oral Bisphosphonates

Use oral bisphosphonates (alendronate, risedronate, zoledronate) for initial treatment in all adults ≥40 years with high or very high fracture risk. 1, 2

• These reduce vertebral fractures by 140 per 1000 treated patients and hip fractures by 6 per 1000 person-years 1, 4
• Generic formulations are preferred due to cost-effectiveness and equivalent efficacy 1
• Duration: Treat for 5 years, then reassess 1, 5

Second-Line: Denosumab

If bisphosphonates are contraindicated or cause adverse effects, use denosumab (RANK ligand inhibitor). 1

• Particularly useful for patients with renal impairment where bisphosphonates are contraindicated 6
• Requires subcutaneous injection every 6 months 6

Anabolic Agents for Very High Risk

For very high-risk patients, consider starting with anabolic agents (teriparatide, abaloparatide, or romosozumab) before antiresorptives. 1, 2, 4

• Teriparatide or abaloparatide: Use for 18-24 months maximum, then transition to bisphosphonate or denosumab 1, 7, 4
• Romosozumab: Can be used for very high-risk postmenopausal women 1
• Critical caveat: Always follow anabolic therapy with an antiresorptive agent to prevent rebound bone loss and multiple vertebral fractures 1, 5

Treatment Selection for Glucocorticoid-Induced Osteoporosis

For patients on chronic glucocorticoids (≥2.5 mg/day prednisone for >3 months), adjust FRAX scores upward (multiply major osteoporotic fracture risk by 1.15 and hip fracture risk by 1.2) 1, 2

• Use oral bisphosphonates as first-line 1
• For very high risk, use teriparatide/PTH analogs over antiresorptives 1
• Maintain vitamin D levels ≥30-50 ng/mL (higher than general population) 1, 3

Essential Non-Pharmacologic Interventions (For Everyone)

Calcium and Vitamin D

• Calcium: 1000-1200 mg/day (preferably from diet rather than supplements) 1, 2, 3, 8
• Vitamin D: 600-800 IU/day to maintain serum 25(OH)D ≥20-30 ng/mL 1, 2, 3
• Higher vitamin D doses (up to 800 IU daily) present minimal toxicity risk 9

Lifestyle Modifications

• Weight-bearing and resistance training exercises (squats, push-ups, heel raises) 1, 2, 3, 4
• Smoking cessation 1, 2, 3
• Limit alcohol to ≤2 servings per day 1, 2, 3
• Fall prevention strategies and balance exercises (standing on one foot, tai chi) 1, 4
• Maintain healthy body weight 2, 3, 6

Treatment Duration and Monitoring

When to Stop Bisphosphonates

After 5 years of continuous bisphosphonate therapy, reassess fracture risk and consider a drug holiday unless: 1, 5

• History of vertebral fracture during treatment
• T-score remains ≤-2.5
• Ongoing very high fracture risk factors

Rationale: Extending beyond 5 years reduces vertebral fractures but increases long-term harms (osteonecrosis of jaw, atypical femoral fractures) without reducing hip or other non-vertebral fractures 1, 5

Monitoring Schedule

• BMD testing every 1-2 years during active treatment for high-risk patients 2, 5
• BMD testing every 2-3 years after completing treatment 5
• Vertebral fracture assessment (VFA) or spinal X-rays at baseline and periodically 2

Critical Pitfalls to Avoid

Rebound Bone Loss

Never discontinue anabolic agents (teriparatide, abaloparatide, romosozumab) without immediately starting an antiresorptive agent (bisphosphonate or denosumab) to prevent serious rebound bone loss and multiple vertebral fractures 1, 5

Polypharmacy in Older Adults

For patients ≥65 years with multiple comorbidities, assess fall risk and drug interactions before selecting treatment, as these patients face higher adverse event risk 1, 5

Combination Therapy

Do not use two different osteoporosis medications simultaneously (very low quality evidence, not recommended) 1

Excessive Calcium

Avoid calcium intake >2000 mg/day due to potential cardiovascular risks, urolithiasis, and paradoxically increased fracture risk 8

Special Populations

Men with Primary Osteoporosis

Use the same treatment algorithm as postmenopausal women: bisphosphonates first-line, denosumab second-line 1

Younger Adults (<40 Years)

For adults <40 years with Z-score <-3 or bone loss ≥10%/year on glucocorticoids, consider oral bisphosphonates 1

Women of Childbearing Potential

Use oral bisphosphonates only if effective contraception is in place and pregnancy is not planned during treatment period 1