How should osteopenia be treated, including calcium (1,200 mg elemental) and vitamin D (800–1,000 IU) supplementation, regular weight‑bearing exercise, and criteria for initiating bisphosphonate therapy based on age >65 years, prior fragility fracture, glucocorticoid use, or a Fracture Risk Assessment Tool (FRAX) major osteoporotic fracture probability ≥20%?

Treatment of Osteopenia

For patients with osteopenia, initiate calcium (1,000-1,200 mg elemental daily) and vitamin D (800-1,000 IU daily) supplementation combined with regular weight-bearing exercise, and reserve bisphosphonate therapy for those meeting high-risk criteria: age >65 years with additional risk factors, prior fragility fracture, chronic glucocorticoid use ≥2.5 mg/day for >3 months, or FRAX 10-year major osteoporotic fracture probability ≥20% or hip fracture risk >3%. 1, 2

Universal Non-Pharmacological Management

All patients with osteopenia require foundational interventions regardless of fracture risk:

Calcium and Vitamin D Supplementation

• Elemental calcium intake of 1,000-1,200 mg daily from combined dietary sources and supplements is essential, with calcium citrate preferred over calcium carbonate in patients taking proton pump inhibitors 1, 2
• Divide calcium doses into no more than 500-600 mg per dose for optimal absorption 1
• Vitamin D supplementation of 800-1,000 IU daily is required, as doses of 400 IU or less are ineffective for fracture prevention 1, 3
• Target serum 25(OH)D level of at least 30 ng/mL (≥50 ng/mL per some guidelines) for optimal bone health 2, 1, 3
• Check baseline 25(OH)D level before initiating treatment and monitor during therapy 1, 4

Lifestyle Modifications

• Engage in weight-bearing or resistance training exercise for at least 30 minutes, 3 days per week 1, 2
• Smoking cessation is mandatory 2, 1
• Limit alcohol intake to 1-2 servings daily maximum 2, 1
• Maintain weight in the recommended range and consume a balanced diet 2

Risk Stratification for Pharmacological Therapy

High-Risk Criteria Requiring Bisphosphonate Initiation

Bisphosphonate therapy should be initiated when patients meet any of the following criteria:

• Age >65 years with T-score ≤-2.5 at hip or spine 2
• Prior fragility fracture (vertebral, hip, or other osteoporotic fracture) 2
• Chronic glucocorticoid use ≥2.5 mg/day prednisone equivalent for >3 months with moderate-to-high fracture risk 2
• FRAX 10-year major osteoporotic fracture probability ≥20% (using glucocorticoid-adjusted calculation if applicable) 2
• FRAX 10-year hip fracture risk >3% 2
• Very high-dose glucocorticoids (≥30 mg/day prednisone for >30 days or cumulative dose ≥5 grams/year) 2

Moderate-Risk Patients (Age ≥40 Years)

For patients with FRAX 10-year major osteoporotic fracture risk 10-20% or hip fracture risk 1-3%:

• Oral bisphosphonates are conditionally recommended over calcium and vitamin D alone 2
• Consider individual patient factors including comorbidities, medication tolerance, and patient preference 2

Low-Risk Patients

For patients with FRAX <10% major osteoporotic fracture risk and no other high-risk features:

• Continue calcium, vitamin D, and lifestyle modifications without bisphosphonate therapy 2
• Monitor with yearly clinical fracture risk assessment 2
• Repeat BMD testing every 2-3 years depending on risk factors 2

Pharmacological Treatment Selection

First-Line Bisphosphonate Therapy

Oral bisphosphonates (alendronate or risedronate) are the preferred first-line agents due to established efficacy, safety profile, low cost, and extensive clinical experience 2

• Alendronate and risedronate demonstrate reduction in vertebral, non-vertebral, and hip fractures 2
• Standard treatment duration is 5 years 5
• Ensure proper administration: take with full glass of water (6-8 ounces), remain upright for at least 30 minutes, avoid food/drink during this period 5

Alternative Agents (When Oral Bisphosphonates Not Appropriate)

In order of preference when oral bisphosphonates are contraindicated or not tolerated:

1. IV bisphosphonates (zoledronic acid) for patients with oral intolerance, dementia, malabsorption, or non-compliance 2
2. Denosumab for patients with renal impairment (CrCl <60 mL/min) or when bisphosphonates are contraindicated 5
3. Teriparatide or other anabolic agents for very high-risk patients with multiple vertebral fractures, T-score ≤-3.0 with additional risk factors, or fracture despite adequate bisphosphonate treatment 2

Critical Safety Considerations

• Complete all necessary dental work before initiating bisphosphonate therapy to reduce osteonecrosis of the jaw risk 5
• Correct vitamin D deficiency prior to bisphosphonate initiation, particularly for IV therapy, as deficiency increases risk of bisphosphonate-related hypocalcemia 5
• Never discontinue denosumab without immediately starting bisphosphonate therapy within 6 months, as rebound vertebral fractures can occur 5
• Alendronate is contraindicated if creatinine clearance <35 mL/min 5

Monitoring and Reassessment

During Initial Treatment

• Do NOT perform routine BMD monitoring during the initial 5-year treatment period, as fracture reduction occurs even without BMD increases 5
• Conduct yearly clinical fracture risk assessment 2
• Monitor for new fractures, changes in risk factors, and medication adherence 5

After 5 Years of Bisphosphonate Therapy

• Reassess fracture risk rather than automatically continuing therapy 5
• Patients without high-risk features (no previous hip/vertebral fractures, hip BMD T-score >-2.5) may consider a drug holiday 5
• Patients with persistent high-risk features should continue treatment beyond 5 years 2, 5

Common Pitfalls to Avoid

• Do not rely on serum calcium levels to determine need for supplementation—documented osteopenia on DEXA is the indication, as normal serum calcium does not reflect total body calcium stores 1
• Do not prescribe calcium and vitamin D as monotherapy for established osteoporosis—these are adjunctive to, not replacements for, pharmacologic therapy in high-risk patients 1
• Avoid over-supplementation of calcium beyond 2,500 mg total daily to minimize kidney stone risk 1
• Do not use high pulse doses of vitamin D, as they are associated with increased fall risk 2
• Calculate dietary calcium intake before prescribing supplements to avoid excessive supplementation 1
• Ensure adequate calcium and vitamin D supplementation throughout bisphosphonate treatment, as inadequate supplementation reduces treatment efficacy 4, 5