What is the first‑line management for osteopenia?

First-Line Treatment for Osteopenia

For osteopenia without additional risk factors, first-line treatment consists exclusively of calcium 1,200 mg daily, vitamin D 800 IU daily, weight-bearing exercise, smoking cessation, and alcohol limitation—pharmacologic therapy is NOT indicated unless specific high-risk criteria are met. 1

Risk Stratification Determines Whether Pharmacologic Therapy Is Needed

The critical first step is determining whether your osteopenic patient requires drug therapy at all, because osteopenia diagnosis alone does not indicate treatment—fracture risk assessment determines management. 1

High-Risk Criteria That Trigger Pharmacologic Therapy

Initiate bisphosphonates if ANY of the following are present:

• Prior fragility fracture (even a single minimal-trauma fracture mandates immediate treatment regardless of FRAX score) 2, 1
• FRAX score ≥20% for major osteoporotic fracture OR ≥3% for hip fracture over 10 years 2, 1
• Severe osteopenia (T-score <-2.0) with additional risk factors such as family history of hip fracture, body weight <127 lb, or medications causing bone loss 2, 1
• Silent vertebral fractures detected on imaging (obtain spine radiographs or DXA vertebral fracture assessment in patients reporting height loss) 1

Low-Risk Osteopenia Management

If FRAX is <20% major osteoporotic fracture AND <3% hip fracture, AND no prior fragility fracture exists, defer pharmacologic therapy and repeat DXA in 2 years (or 1 year if medically indicated). 2

Universal Non-Pharmacologic Management (ALL Patients)

Every osteopenic patient must receive these interventions regardless of whether they meet criteria for drug therapy:

Calcium and Vitamin D Supplementation

• Calcium 1,200 mg daily (from diet plus supplements) 2, 1, 3
• Vitamin D 800 IU daily targeting serum 25-hydroxyvitamin D ≥20 ng/mL 2, 1, 3
• For documented vitamin D deficiency (<20 ng/mL), use high-dose repletion: 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 maintenance 1
• Critical caveat: Pharmacologic therapy is significantly less effective without adequate calcium and vitamin D supplementation 1

Lifestyle Modifications

• Weight-bearing aerobic exercise (walking, jogging) for ≥30 minutes on ≥3 days per week 2, 1
• Resistance and muscle-strengthening exercises to reduce fall risk 1
• Balance-training programs especially in older adults 1
• Smoking cessation (tobacco accelerates bone loss) 2, 1
• Limit alcohol to ≤1-2 standard drinks per day 2, 1
• Maintain healthy body weight (BMI <19 kg/m² is an independent fracture risk factor) 1
• Fall prevention strategies including home safety assessment 2

First-Line Pharmacologic Therapy (High-Risk Patients Only)

Oral Bisphosphonates Are Mandatory First-Line

Oral bisphosphonates are the mandatory first-line agents based on high-certainty evidence showing 50% reduction in hip fractures and 47-56% reduction in vertebral fractures, with the most favorable balance of efficacy, safety, and cost. 1, 4, 5

Specific regimens:

• Alendronate 70 mg once weekly (preferred) 1, 5
• Risedronate 35 mg once weekly (alternative) 1, 5
• Zoledronic acid 5 mg IV annually (for patients unable to tolerate oral formulations) 1

Critical Administration Instructions

• Take oral bisphosphonates on an empty stomach, 0.5-2 hours before food or other medications 1
• Separate from calcium supplements (calcium inactivates bisphosphonates) 1
• Remain upright for 30-60 minutes after oral bisphosphonate administration to prevent esophageal irritation 5

Evidence Supporting Bisphosphonates in Osteopenia

In patients with severe osteopenia (T-score <-2.0), risedronate reduced fragility fracture risk by 73% compared to placebo, demonstrating effectiveness comparable to osteoporosis treatment. 1

Second-Line Pharmacologic Therapy

Denosumab 60 mg subcutaneously every 6 months is indicated for patients with:

• Contraindications to bisphosphonates 1, 5
• Intolerance of bisphosphonates 1, 5
• Severe renal impairment (eGFR <35 mL/min) 1

Critical warning: Never discontinue denosumab abruptly without transitioning to bisphosphonate therapy—abrupt discontinuation is associated with multiple vertebral fractures. 1

Treatment Duration and Monitoring

• Initial bisphosphonate treatment duration is 5 years 1, 5
• Do NOT monitor bone density during the initial 5-year treatment period—bisphosphonates reduce fractures even when BMD does not increase or actually decreases 1
• After 5 years, reassess fracture risk using FRAX to determine whether to continue, pause, or switch therapy 1

Evaluation for Secondary Causes of Bone Loss

All osteopenic patients require workup for secondary causes regardless of FRAX score:

• Vitamin D deficiency 1
• Hypogonadism/estrogen deficiency 1
• Glucocorticoid exposure (≥5 mg prednisone daily for ≥3 months) 1
• Malabsorption disorders 1
• Hyperparathyroidism 1
• Hyperthyroidism 1
• Chronic alcohol or opioid misuse 1

Laboratory screening panel: serum calcium, phosphorus, 25-hydroxyvitamin D, alkaline phosphatase, and parathyroid hormone (detects secondary causes with approximately 92% sensitivity). 1

When a reversible secondary cause is identified, initiate targeted therapy for that condition before or concurrently with anti-osteoporotic pharmacotherapy. 1

Adverse Effects Monitoring

Common, Non-Serious Events

• Mild upper GI symptoms (dyspepsia, nausea) with oral bisphosphonates 1
• Influenza-like symptoms, myalgias, arthralgias, headache (especially after zoledronic acid infusion) 1
• Rash/eczema with denosumab 1

Rare but Serious Events

• Osteonecrosis of the jaw (risk increases with prolonged use) 1
• Atypical subtrochanteric femoral fractures (risk increases with prolonged use) 1

High-certainty evidence from randomized trials shows bisphosphonates cause no difference in serious adverse events compared to placebo at 2-3 years. 1

Agents Strongly Recommended AGAINST

The American College of Physicians provides strong recommendations against the following agents due to unfavorable benefit-harm balance:

• Menopausal estrogen therapy (increased stroke, venous thromboembolism, breast cancer risk) 1
• Estrogen plus progestogen therapy (higher invasive breast cancer incidence and mortality) 1
• Raloxifene (elevated thromboembolic events, pulmonary embolism, cerebrovascular death) 1

Agents Reserved for Very High-Risk Osteoporosis (NOT Osteopenia)

Teriparatide and romosozumab should be confined to patients with very high-risk osteoporosis and are not recommended as first-line options for osteopenia. 1

Common Pitfalls to Avoid

• Do not treat osteopenia based on T-score alone—always calculate FRAX and assess for additional risk factors 1
• Do not prescribe bisphosphonates with calcium simultaneously—separate administration by several hours 1
• Do not monitor BMD annually during treatment—it provides no clinical benefit and may lead to inappropriate treatment changes 1
• Do not stop denosumab without transitioning to bisphosphonate—this causes rebound vertebral fractures 1
• Do not use hormone therapy as first-line osteopenia treatment—harms outweigh benefits 1