What is the recommended evaluation and treatment approach for patients at risk of osteoporosis?

Evaluation and Treatment Approach for Patients at Risk of Osteoporosis

For patients at risk of osteoporosis, initial evaluation should include bone mineral density (BMD) testing with dual-energy x-ray absorptiometry (DXA), assessment of clinical risk factors, and appropriate laboratory testing, followed by risk stratification and treatment with lifestyle modifications and pharmacologic therapy based on fracture risk. 1

Initial Risk Assessment and Screening

Who to Screen

• Adults ≥65 years (women) or ≥70 years (men)
• Postmenopausal women <65 years with additional risk factors
• Adults on glucocorticoid therapy ≥2.5 mg/day for >3 months
• Patients with cancer on treatments that cause bone loss (aromatase inhibitors, antiandrogens, GnRH agonists)
• Adults with history of fragility fracture
• Adults with conditions associated with bone loss

Clinical Risk Factor Assessment

• Age (advanced age increases risk)
• Prior fracture history (including asymptomatic vertebral fractures)
• Family history of hip fracture
• Low body weight/significant weight loss
• Smoking status
• Alcohol consumption (>2 drinks daily)
• Glucocorticoid use
• Secondary causes of osteoporosis:
  • Hypogonadism
  • Rheumatoid arthritis
  • Hyperparathyroidism
  • Malabsorption
  • Chronic liver disease
  • Inflammatory bowel disease

Diagnostic Testing

Primary Diagnostic Tools

• DXA scan of lumbar spine and hip - gold standard for BMD measurement 1

  • Provides T-scores for diagnosis (T-score ≤-2.5 indicates osteoporosis)
  • Should be performed as soon as possible within 6 months of initiating glucocorticoid therapy in at-risk patients

• Vertebral Fracture Assessment (VFA) or spinal x-rays - to identify asymptomatic vertebral fractures 1

  • Particularly important for patients on glucocorticoids

• FRAX® calculation (for patients ≥40 years) 1

  • Incorporates clinical risk factors with BMD to calculate 10-year fracture probability
  • Apply glucocorticoid adjustment if prednisone dose >7.5 mg daily
  • Note: FRAX may underestimate risk with very high glucocorticoid doses (≥30 mg/day)

Follow-up Testing

• Repeat BMD every 1-2 years for high-risk patients or those on medications causing bone loss
• Annual testing may be appropriate for very high-risk patients until BMD stabilizes
• Testing should generally not be conducted more frequently than annually 1

Treatment Approach

Non-Pharmacologic Interventions (for all patients)

1. Calcium and vitamin D supplementation

   • Calcium: 1,000-1,200 mg/day (dietary + supplements)
   • Vitamin D: 800-1,000 IU/day (target serum 25(OH)D levels ≥30-50 ng/mL) 1

2. Exercise regimen

   • Combination of weight-bearing, resistance/strengthening, balance, and flexibility exercises
   • Tailor to individual patient abilities 1

3. Lifestyle modifications

   • Smoking cessation
   • Limit alcohol to ≤2 drinks daily
   • Fall prevention strategies 1

Pharmacologic Treatment Based on Risk Stratification

Very High Fracture Risk

• First-line: Anabolic agents (PTH/PTHrP analogs - teriparatide) 1, 2
  • Conditionally recommended over antiresorptive agents
  • Indicated for those with history of osteoporotic fracture or multiple risk factors 2
  • Note: Requires sequential therapy with antiresorptive agent after discontinuation to prevent bone loss

High Fracture Risk

• First-line: Oral bisphosphonates (strongly recommended) 1, 3

  • Risedronate, alendronate, or other oral bisphosphonates
  • Take in upright position with plain water
  • Remain upright for 30 minutes after administration

• Alternative options (conditionally recommended):

  • Denosumab 1, 4
  • PTH/PTHrP analogs 1, 2
  • IV bisphosphonates (if oral not tolerated)

Moderate Fracture Risk

• Oral or IV bisphosphonates, denosumab, or PTH/PTHrP (all conditionally recommended) 1
  • Selection based on patient factors, comorbidities, and preferences

Low Fracture Risk

• Non-pharmacologic interventions only
• Monitor with periodic reassessment

Special Considerations

Glucocorticoid-Induced Osteoporosis

• More aggressive intervention thresholds
• Treatment recommended for moderate, high, and very high fracture risk patients
• Initial assessment within 6 months of starting glucocorticoids 1

Cancer Treatment-Related Bone Loss

• Consider DXA screening for all patients on bone-depleting cancer therapies
• Treatment decisions should account for the additional fracture risk from cancer therapies 1

Treatment Duration and Monitoring

• Optimal duration not definitively established
• Consider drug holiday after 3-5 years for bisphosphonates in lower-risk patients
• Reassess fracture risk if therapy is discontinued 3
• Sequential therapy required after discontinuation of denosumab or anabolic agents to prevent rebound bone loss 1

Pitfalls and Caveats

• FRAX is not validated for patients <40 years old
• FRAX underestimates risk with very high glucocorticoid doses
• Denosumab discontinuation can lead to rebound bone loss and increased vertebral fracture risk if not followed by another antiresorptive agent
• BMD alone may not capture all fracture risk - clinical risk factors and prior fractures are important
• Calcium supplements should be taken at different times than iron supplements or certain medications to avoid absorption issues

By following this structured approach to evaluation and treatment, clinicians can effectively identify and manage patients at risk for osteoporotic fractures, thereby reducing morbidity and mortality associated with this common condition.