When should osteopenia be treated in postmenopausal women and older adults with a high risk of fracture?

When to Treat Osteopenia

Treat osteopenia with oral bisphosphonates when any of these three high-risk criteria are met: (1) any history of fragility fracture regardless of bone density, (2) FRAX 10-year risk ≥20% for major osteoporotic fracture OR ≥3% for hip fracture, or (3) T-score approaching -2.5 with additional risk factors. 1

Risk Stratification Determines Treatment Threshold

The diagnosis of osteopenia alone (T-score between -1.0 and -2.5) does not automatically indicate treatment—fracture risk assessment is mandatory before making treatment decisions. 1

Immediate Treatment Triggers (No FRAX Calculation Needed)

• Any fragility fracture history: Patients with even one minimal trauma fracture require immediate pharmacologic therapy, even with osteopenia, because prior fracture represents high fracture risk independent of bone density measurements. 1, 2
• This applies to vertebral compression fractures, hip fractures, wrist fractures, or any fracture from standing height or less. 1

FRAX-Based Treatment Thresholds (For Patients Without Prior Fracture)

• Calculate 10-year fracture risk using the WHO FRAX tool for all osteopenic patients without prior fracture. 1
• Initiate bisphosphonates if FRAX shows:
  • ≥20% risk of major osteoporotic fracture, OR
  • ≥3% risk of hip fracture 3, 1
• Women with severe osteopenia (T-score <-2.0) who received risedronate had 73% lower fragility fracture risk compared to placebo, demonstrating that treatment effects in high-risk osteopenia are similar to osteoporosis treatment. 1, 4

Additional High-Risk Features That Lower Treatment Threshold

• Family history of hip fracture in a parent 3
• Body weight <127 lb (58 kg) 3
• Current use of medications causing bone loss (glucocorticoids, aromatase inhibitors, androgen deprivation therapy) 3
• Diseases causing bone loss (hyperparathyroidism, hyperthyroidism, malabsorption disorders, hypogonadism) 1

First-Line Pharmacologic Treatment

Oral bisphosphonates are 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. 1, 5

Specific Bisphosphonate Regimens

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

Critical Administration Instructions for Oral Bisphosphonates

• Take first thing in the morning on an empty stomach with a full glass of plain water. 5
• Remain upright (sitting or standing) for at least 30 minutes after taking the medication to prevent esophageal irritation. 5

Mandatory Supplementation

All patients receiving bisphosphonates must receive calcium 1,200 mg daily and vitamin D 800 IU daily—this is not optional, as pharmacologic therapy is significantly less effective without adequate supplementation. 1, 5

• Target serum vitamin D level ≥20 ng/mL (50 nmol/L). 3, 1
• Calculate total daily calcium intake from diet plus supplements combined (not 1,200 mg from supplements alone). 6
• Be cautious of excess calcium supplementation, which increases kidney stone risk, particularly in elderly patients. 6

Treatment Duration and Monitoring

• Initial treatment duration is 5 years with bisphosphonates. 1, 5
• Do not monitor bone density during the initial 5-year treatment period—this is a strong recommendation, as monitoring does not improve outcomes and may lead to inappropriate treatment changes. 1, 5
• After 5 years, reassess fracture risk to determine if continued therapy is warranted. 1, 5

Second-Line Therapy

Denosumab 60 mg subcutaneously every 6 months is the recommended alternative for patients with contraindications to or intolerance of bisphosphonates. 1, 7

Critical Denosumab Warning

• Never discontinue denosumab abruptly without transitioning to bisphosphonate therapy—abrupt discontinuation is associated with multiple vertebral fractures in some patients. 1

Mandatory Lifestyle Modifications

All patients with osteopenia at high fracture risk require these interventions regardless of pharmacologic treatment decisions: 1

• Weight-bearing exercise and resistance training 1, 6
• Smoking cessation 3, 1
• Limit alcohol intake to <3 units/day 1, 6
• Fall prevention strategies 1, 6
• Maintain healthy body weight 1

Therapies to Avoid in Osteopenia

• Do not use menopausal estrogen therapy, estrogen plus progestogen therapy, or raloxifene for osteopenia treatment due to unfavorable benefit-harm balance. 1, 5
• Teriparatide and romosozumab are reserved for very high-risk osteoporosis (not osteopenia) and should not be used as first-line therapy. 1
• Calcitonin is no longer recommended due to limited efficacy. 5

Common Pitfalls to Avoid

• Do not delay treatment while waiting for additional testing if a fragility fracture has already occurred—the presence of a fragility fracture is sufficient indication for immediate pharmacologic therapy. 5
• Do not treat based on osteopenia diagnosis alone—always calculate fracture risk first unless there is already a fragility fracture history. 1
• Do not use Z-scores for treatment decisions in postmenopausal women—T-scores are the appropriate metric. 5
• Do not forget to evaluate for secondary causes of bone loss (vitamin D deficiency, hyperparathyroidism, hyperthyroidism, malabsorption, glucocorticoid exposure, alcohol abuse) in all patients with osteopenia. 1

Safety Profile

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

• 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 and atypical femoral fractures, which is why treatment duration is limited and reassessment is required after 5 years. 1