Initial Management of Osteopenia
Risk Stratification Determines Whether Treatment Is Needed
The diagnosis of osteopenia alone does NOT indicate treatment—you must calculate fracture risk using the WHO FRAX tool and initiate pharmacologic therapy only if FRAX shows ≥20% risk of major osteoporotic fracture OR ≥3% risk of hip fracture. 1
High-Risk Criteria That Mandate Immediate Bisphosphonate Therapy
- Any history of fragility fracture (minimal trauma fracture) triggers immediate pharmacologic therapy, even with osteopenia, because this represents high fracture risk independent of FRAX calculations 1
- FRAX ≥20% for major osteoporotic fracture OR ≥3% for hip fracture over 10 years 1
- Severe osteopenia (T-score <-2.0) combined with additional risk factors such as family history of hip fracture, body weight <127 lb (58 kg), or current use of medications causing bone loss 1
- Chronic glucocorticoid use (≥7.5 mg prednisone daily for ≥3 months) 2, 3
Low-Risk Patients (No Pharmacologic Treatment)
- FRAX <20% for major osteoporotic fracture AND <3% for hip fracture, with no prior fragility fracture: manage with calcium, vitamin D, and lifestyle modifications only; repeat DXA in 2 years 1
Universal Non-Pharmacologic Management (ALL Osteopenia Patients)
Essential Supplementation
- Calcium 1,200 mg daily (from diet plus supplements) 2, 1
- Vitamin D 800 IU daily, targeting serum 25-hydroxyvitamin D ≥20 ng/mL 2, 1
- For documented vitamin D deficiency (<20 ng/mL), prescribe 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 for maintenance 1
Mandatory Lifestyle Modifications
- Weight-bearing aerobic exercise (walking, jogging) for at least 30 minutes on ≥3 days per week 1
- Resistance and muscle-strengthening exercises to reduce fall risk 1
- Balance-training programs to further diminish fall likelihood, especially in older adults 1
- Smoking cessation—tobacco accelerates bone loss and increases fracture risk 2, 1
- Limit alcohol to ≤1-2 standard drinks per day 2, 1
- Maintain healthy body weight within recommended range 2, 1
First-Line Pharmacologic Treatment (High-Risk Patients Only)
Oral bisphosphonates are the mandatory first-line therapy based on high-certainty evidence showing 50% reduction in hip fractures and 47-56% reduction in vertebral fractures over 3 years, with the most favorable balance of efficacy, safety, and cost. 1
Specific Bisphosphonate Regimens
- Alendronate 70 mg once weekly (preferred) 1
- Risedronate 35 mg once weekly (alternative) 1
- 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
Evidence Supporting Treatment in Severe Osteopenia
- In patients with severe osteopenia (T-score <-2.0), risedronate reduced fragility fracture risk by 73% compared to placebo, achieving effectiveness comparable to osteoporosis treatment 1
Second-Line Pharmacologic Treatment
Denosumab 60 mg subcutaneously every 6 months is indicated for patients with contraindications to or intolerance of bisphosphonates, and for those with severe renal impairment (eGFR <35 mL/min). 1
Critical Safety Warning for Denosumab
- Never discontinue denosumab abruptly without transitioning to bisphosphonate therapy—abrupt discontinuation is associated with multiple vertebral fractures in some patients 1
Treatment Duration and Monitoring
- Initial bisphosphonate therapy duration is 5 years 1
- 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 if continued therapy is warranted 1
Evaluate and Treat Secondary Causes (ALL Patients)
All patients with osteopenia require workup for secondary causes of bone loss, regardless of FRAX score. 1
Key Secondary Causes to Screen
- Vitamin D deficiency (most common reversible cause) 1
- Hypogonadism/estrogen deficiency or premature menopause (age <45 years) 1
- Glucocorticoid exposure (≥5 mg prednisone daily for ≥3 months) 2, 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—this panel detects secondary causes with approximately 92% sensitivity 1
Adverse Effects Monitoring
Common, Non-Serious Events
- Mild upper GI symptoms, influenza-like symptoms, myalgias, arthralgias, and headaches (especially after zoledronic acid infusion) 1
- Rash/eczema with denosumab 1
Rare but Serious Events
- Osteonecrosis of the jaw 1
- Atypical subtrochanteric femoral fractures 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 strongly recommends against using the following agents for osteopenia treatment due to unfavorable benefit-harm balance: 1
- Menopausal estrogen therapy—increased risk of stroke, venous thromboembolism, and breast cancer 1
- Estrogen plus progestogen therapy—higher incidence of invasive breast cancer and breast-cancer mortality 1
- Raloxifene—elevated risk of thromboembolic events, pulmonary embolism, cerebrovascular death, and hot flashes 1
- Teriparatide and romosozumab—reserved for very high-risk osteoporosis (not osteopenia) and should not be used as first-line therapy 1
Special Consideration: Height Loss
- In osteopenic patients who report height loss, obtain thoracic/lumbar spine radiographs or perform DXA with vertebral fracture assessment to detect silent vertebral fractures—the presence of such fractures mandates pharmacologic therapy irrespective of FRAX score 1