What are the recommended treatment options for an adult with osteoporosis, such as a post‑menopausal woman or older man?

Treatment Options for Osteoporosis

Bisphosphonates are the mandatory first-line pharmacologic treatment for osteoporosis in both postmenopausal women and men, reducing hip fractures by 50% and vertebral fractures by 47-56% over 3 years, with the most favorable balance of efficacy, safety, and cost. 1, 2

First-Line Pharmacologic Treatment: Bisphosphonates

Specific bisphosphonate regimens include:

• Alendronate 70 mg orally once weekly 1, 2
• Risedronate 35 mg orally once weekly 1, 2
• Zoledronic acid 5 mg intravenously annually (for patients unable to tolerate oral formulations) 1, 2

The 2023 American College of Physicians guideline provides high-certainty evidence that bisphosphonates offer superior cost-effectiveness compared to all alternatives, particularly when generic formulations are prescribed. 2 Randomized controlled trials demonstrate no difference in serious adverse events compared to placebo at 3+ years. 1, 2

Essential Concurrent Supplementation

All patients receiving osteoporosis treatment must take:

• Calcium 1,200 mg daily 1, 3, 2
• Vitamin D 800 IU daily 1, 3, 2
• Target serum 25-hydroxyvitamin D ≥20 ng/mL 3, 2

Pharmacologic therapy is significantly less effective without adequate calcium and vitamin D supplementation. 3, 2 For documented vitamin D deficiency (<20 ng/mL), prescribe high-dose repletion with vitamin D₂ 50,000 IU weekly for 8-12 weeks followed by monthly dosing, or vitamin D₃ 2,000 IU daily for 12 weeks then 1,000-2,000 IU daily for maintenance. 3

Treatment Duration and Monitoring Strategy

Initial bisphosphonate treatment duration is 5 years. 1, 2 After 5 years, reassess fracture risk to determine whether continued therapy is warranted. 1, 2 Patients at low risk for fracture should be considered for drug discontinuation after 3-5 years. 1

Do not monitor bone mineral density during the initial 5-year treatment period—bisphosphonates reduce fractures even when bone density does not increase or actually decreases. 3, 4 The American College of Physicians found no clinical benefit to routine BMD monitoring during active treatment. 3

Second-Line Treatment: Denosumab

For patients with contraindications to or intolerance of bisphosphonates, prescribe denosumab 60 mg subcutaneously every 6 months. 1, 2, 5 This is a conditional recommendation based on low-certainty evidence in males and moderate-certainty evidence in postmenopausal women. 1

Critical safety warning: Never discontinue denosumab abruptly without transitioning to bisphosphonate therapy—abrupt discontinuation is associated with multiple vertebral fractures in some patients. 1, 2 Patients treated with any anabolic agent should also be offered an antiresorptive agent after discontinuation to preserve gains and prevent serious risk for rebound and multiple vertebral fractures. 1

Anabolic Agents for Very High-Risk Patients

Reserve anabolic medications (teriparatide, abaloparatide, romosozumab) for very high-risk individuals only:

• Recent vertebral fractures 6
• Hip fracture with T-score ≤-2.5 6
• History of osteoporotic fracture or multiple risk factors for fracture 1
• Patients who have failed or are intolerant to other available osteoporosis therapy 1

After completing anabolic therapy, transition to an antiresorptive agent (bisphosphonate or denosumab) to preserve bone gains. 1 Romosozumab use should be limited to 12 monthly doses because the anabolic effect wanes after 12 doses. 1 Avoid romosozumab in patients with high cardiovascular risk—FDA safety warnings recommend avoiding use in patients with documented coronary heart disease or at increased risk for major cardiovascular events. 1

Mandatory Lifestyle Modifications

All patients require:

• Weight-bearing aerobic exercise (walking, jogging) for ≥30 minutes on ≥3 days per week 3, 2
• Resistance and muscle-strengthening exercises to reduce fall risk 3, 2
• Balance-training programs especially in older adults 3
• Smoking cessation—tobacco accelerates bone loss and fracture incidence 3, 2
• Limit alcohol to ≤1-2 standard drinks per day 3, 2
• Maintain healthy body weight within recommended range 3, 2
• Fall prevention strategies 1, 2

Evaluation for Secondary Causes

Perform comprehensive workup for secondary contributors to bone loss in every osteoporotic patient: 3

• Vitamin D deficiency 3
• Hypogonadism/estrogen deficiency 3
• Glucocorticoid exposure 3
• Malabsorption syndromes 3
• Hyperparathyroidism 3
• Hyperthyroidism 3
• Chronic alcohol or opioid misuse 3

Laboratory screening should include: serum calcium, phosphorus, 25-hydroxyvitamin D, alkaline phosphatase, and parathyroid hormone—this panel detects secondary causes with approximately 92% sensitivity. 3 When a reversible secondary cause is identified, initiate targeted therapy for that condition before or concurrently with anti-osteoporotic pharmacotherapy. 3

Special Population: Males with Primary Osteoporosis

Bisphosphonates are first-line treatment for males with primary osteoporosis (conditional recommendation; low-certainty evidence). 1 There is no evidence suggesting differences in treatment benefits and harms by sex. 1 Denosumab is second-line for males with contraindications to or adverse effects from bisphosphonates (conditional recommendation; low-certainty evidence). 1

Agents to Avoid

The American College of Physicians strongly recommends against using menopausal estrogen therapy, estrogen plus progestogen therapy, or raloxifene for osteoporosis treatment due to unfavorable benefit-harm balance. 1, 3 Estrogen therapy carries higher risk for venous thromboembolism and fatal stroke in women with documented coronary heart disease or at increased risk for major coronary events. 1

Safety Profile and Adverse Effects

High-certainty evidence from randomized controlled trials shows bisphosphonates cause no difference in serious adverse events compared to placebo at 2-3 years. 1, 2, 4 Common mild adverse effects include upper GI symptoms, influenza-like symptoms, myalgias, arthralgias, and headaches. 1

Rare but serious adverse effects include:

• Osteonecrosis of the jaw 1, 2, 4
• Atypical subtrochanteric and diaphyseal femoral fractures 1, 2, 4

Risk of severe adverse effects increases with prolonged bisphosphonate use, which is why treatment duration is limited and reassessment is required after 5 years. 3, 4

Cost Considerations

Prescribe generic bisphosphonates whenever possible rather than expensive brand-name medications or newer agents—they are significantly more cost-effective while maintaining equivalent efficacy. 2 Bisphosphonates offer the most favorable balance of efficacy, safety, patient preferences, and cost compared to all other drug classes. 2

Special Considerations for High-Risk Patients

Older postmenopausal women at increased risk for falls and other adverse events due to polypharmacy or drug interactions need individualized treatment selection based on comorbidities and concomitant medications associated with higher risk for falls/fractures. 1 However, this does not change the first-line recommendation for bisphosphonates—it simply requires more careful monitoring and fall prevention strategies. 1