What are the treatment options for osteopenia?

Osteopenia Treatment

For patients with osteopenia, treatment decisions should be based on fracture risk assessment using FRAX, with pharmacological therapy initiated when 10-year hip fracture risk is ≥3% or major osteoporotic fracture risk is ≥20%, while all patients regardless of risk should receive calcium, vitamin D, and lifestyle modifications. 1, 2

Risk Stratification and Assessment

Calculate fracture risk using the FRAX tool (www.sheffield.ac.uk/FRAX), which incorporates BMD T-scores and clinical risk factors including age, prior fractures, glucocorticoid use, smoking, alcohol consumption, and family history. 3, 1 This calculation determines whether pharmacological intervention is warranted beyond lifestyle measures alone.

Key clinical risk factors that increase fracture risk include:

• Glucocorticoid use (particularly >7.5 mg/day prednisone) 1
• Hypogonadism or premature menopause 3
• Low body mass index 3, 1
• History of fragility fracture 1
• Height loss or vertebral compression fractures 3
• Maternal history of hip fracture 1

Obtain DEXA scanning of the lumbar spine, total hip, and femoral neck to quantify bone mineral density when one or more risk factors are present and bone-modifying therapy is being considered. 3

Non-Pharmacological Management (Universal for All Patients)

All patients with osteopenia require these foundational interventions regardless of FRAX score:

Calcium and Vitamin D Supplementation

• Calcium: 1,000-1,500 mg daily (1,000 mg for ages 19-50; 1,200 mg for ages 51+) 3, 1, 2
• Vitamin D: 800-1,000 IU daily (600 IU for ages 19-70; 800 IU for ages 71+), targeting serum 25(OH)D levels ≥20 ng/mL 3, 1, 2

Exercise and Physical Activity

• Weight-bearing exercise for at least 30 minutes, minimum 3 days per week (walking, jogging, dancing) 3, 1
• Muscle-strengthening exercises to improve bone density 1, 4
• Balance training (tai chi, physical therapy) to reduce fall risk 1, 2

Lifestyle Modifications

• Smoking cessation (mandatory recommendation) 3, 1
• Limit alcohol to 1-2 drinks per day maximum 3, 1
• Maintain healthy body weight (low BMI is an independent risk factor) 3, 1
• Fall prevention strategies: vision/hearing assessment, medication review for sedating drugs, home safety evaluation 1

Pharmacological Treatment Thresholds

Initiate bone-modifying agents when ANY of the following criteria are met:

1. FRAX calculation shows:

   • 10-year hip fracture risk ≥3%, OR
   • 10-year major osteoporotic fracture risk ≥20% 3, 1, 2

2. T-score below -2.0 with additional risk factors (particularly in cancer survivors or those on glucocorticoids) 1

3. History of fragility fracture (indicates severe osteoporosis regardless of BMD) 1

4. Presence of vertebral compression fractures on imaging (significantly increases future fracture risk) 3, 1

First-Line Pharmacological Options

Oral bisphosphonates (alendronate) are the preferred first-line therapy due to proven efficacy, safety profile, and cost-effectiveness. 1, 2, 4 Alendronate inhibits osteoclast activity, reduces bone resorption by 50-70%, and progressively increases bone mass at remodeling sites. 5 It reduces vertebral and non-vertebral fractures, including hip fractures. 5, 6

Alternative agents when bisphosphonates are not tolerated or contraindicated:

• IV bisphosphonates (zoledronic acid) for patients unable to tolerate oral formulations 1, 2
• Denosumab (subcutaneous injection every 6 months) for high-risk patients or bisphosphonate intolerance 1, 2, 4
• Selective estrogen receptor modulators (SERMs) such as raloxifene 1, 7

Anabolic agents for very high-risk patients:

• Teriparatide (daily subcutaneous injection) may be considered as initial therapy in patients at very high fracture risk or after antiresorptive failure 1, 8, 4
• Note: Teriparatide caused osteosarcoma in rats; while not observed in humans, use is limited to 2 years and requires informed consent 8

Special Population Considerations

Cancer Survivors

Cancer treatments causing hypogonadism (GnRH agonists, aromatase inhibitors, chemotherapy-induced ovarian failure, androgen deprivation) accelerate bone loss. 3, 1 For cancer survivors with osteopenia plus additional risk factors, bisphosphonates or denosumab are preferred agents. 3, 1, 2

Perform dental screening before initiating bone-modifying agents to reduce medication-related osteonecrosis of the jaw risk. 1

Glucocorticoid Users

Adjust FRAX scores upward: multiply major osteoporotic fracture risk by 1.15 and hip fracture risk by 1.2 if prednisone dose >7.5 mg/day. 1 Reassess fracture risk every 12 months in patients on chronic glucocorticoids. 1

HIV-Infected Patients

Low BMD is common and linked to low body weight, hypogonadism, tobacco/alcohol use, and nadir CD4 count. 3 FRAX may underestimate fracture risk in this population. 3 Ensure 1,000-1,500 mg calcium and 800-1,000 IU vitamin D daily. 3

Monitoring Strategy

Repeat DEXA scanning every 2 years to assess treatment response and bone density changes. 3, 1, 2 Do not perform BMD assessment more frequently than annually. 3, 1, 2

When T-scores improve significantly on treatment, consider discontinuing bone-modifying agents and continue monitoring with periodic DEXA scans. 1

For patients NOT meeting treatment thresholds: Repeat DEXA in 2 years, or in 1 year if medically indicated (e.g., starting glucocorticoids, new cancer treatment). 3

Critical Pitfalls to Avoid

Failing to identify and treat secondary causes of osteopenia is a major error. 3, 1 Screen for vitamin D deficiency, hypogonadism, alcoholism, malabsorption, hyperthyroidism, and hyperparathyroidism with targeted history and laboratory testing. 3

Poor medication adherence is extremely common: Only 5-62% of high-risk patients (e.g., those on glucocorticoids) receive appropriate preventive therapy. 1 Address barriers to adherence at each visit.

Underestimating fracture risk in patients with vertebral compression fractures: These are often clinically silent but dramatically increase future fracture risk. 3 Consider vertebral fracture assessment via DEXA or spine radiographs in patients with height loss. 3

Not adjusting risk assessment for medication effects: Glucocorticoids, aromatase inhibitors, and androgen deprivation therapy substantially increase fracture risk beyond what standard FRAX calculations capture. 3, 1