What is the recommended workup and treatment for patients at high risk of osteoporosis?

Osteoporosis Workup and Treatment for High-Risk Patients

The recommended workup for patients at high risk of osteoporosis includes bone mineral density (BMD) testing via dual-energy x-ray absorptiometry (DXA), vertebral fracture assessment (VFA), FRAX risk calculation, and laboratory testing for secondary causes, followed by appropriate pharmacologic and non-pharmacologic interventions based on fracture risk stratification.

Initial Assessment and Risk Stratification

Clinical Risk Assessment

• Obtain detailed history focusing on:
  • Previous fragility fractures
  • Family history of hip fracture
  • Glucocorticoid use (≥2.5 mg/day for >3 months)
  • Smoking status and alcohol consumption
  • Low body weight or significant weight loss
  • Secondary causes: hypogonadism, malabsorption, chronic liver/kidney disease, inflammatory conditions
  • Fall history and risk factors

Diagnostic Testing

1. BMD Testing:

   • DXA scan of lumbar spine, total hip, and femoral neck 1
   • Include VFA or spinal x-rays to detect asymptomatic vertebral fractures 1
   • For patients ≥40 years: Calculate FRAX score (10-year fracture risk)
   • For patients <40 years: Z-scores ≤-2.0 indicate low bone mass for age

2. Laboratory Testing for Secondary Causes:

   • Basic tests for all patients:

     • 25-hydroxyvitamin D level
     • Serum calcium and phosphorus
     • Renal function (eGFR)
     • Complete blood count
     • Liver function tests
     • Alkaline phosphatase
     • Thyroid stimulating hormone
     • Parathyroid hormone (if calcium abnormal)
     • 24-hour urinary calcium

   • Additional tests based on clinical suspicion:

     • Serum protein electrophoresis (if myeloma suspected)
     • Testosterone (in men)
     • Celiac disease antibodies (if malabsorption suspected)
     • 24-hour urinary free cortisol (if Cushing's suspected)

Treatment Approach

Non-Pharmacologic Interventions

1. Calcium and Vitamin D:

   • Calcium: 1000-1200 mg daily (diet + supplements if needed) 1
   • Vitamin D: 800-1000 IU daily 1
   • For vitamin D deficiency: Consider higher replacement doses (e.g., 50,000 IU weekly for 8-12 weeks) 1

2. Exercise:

   • Weight-bearing exercises at least 3 days/week for 30 minutes 1
   • Combination of balance training, flexibility exercises, and resistance training 1
   • Tailor exercise program to individual abilities 1

3. Fall Prevention:

   • Home safety assessment and modification
   • Balance training
   • Vision and hearing assessment
   • Review medications that may increase fall risk
   • Consider hip protectors for high fall risk 1

4. Lifestyle Modifications:

   • Smoking cessation 1
   • Limit alcohol consumption 1

Pharmacologic Treatment

Indications for Treatment:

• T-score ≤-2.5 at hip, femoral neck, or spine 1
• History of fragility fracture 1
• FRAX 10-year risk ≥20% for major osteoporotic fracture or ≥3% for hip fracture 1
• Patients on long-term glucocorticoids (≥2.5 mg/day for >3 months) 1

Treatment Selection:

1. For Very High-Risk Patients:

   • Anabolic agents (teriparatide, abaloparatide) are preferred first-line 1
   • Very high risk defined as:
     • Recent vertebral fractures
     • Multiple fractures
     • Hip fracture with T-score ≤-2.5
   • Teriparatide dosing: 20 mcg subcutaneously once daily 2
   • Maximum treatment duration: 2 years 2
   • Must be followed by antiresorptive therapy to prevent bone loss 1

2. For High-Risk Patients:

   • Denosumab or bisphosphonates are recommended 1
   • Denosumab dosing: 60 mg subcutaneously every 6 months 3
   • Oral bisphosphonates (alendronate, risedronate) are cost-effective options
   • IV bisphosphonates for those who cannot tolerate oral formulations

3. For Moderate-Risk Patients:

   • Oral or IV bisphosphonates are first-line options 1
   • Consider denosumab if bisphosphonates are contraindicated

Special Populations:

1. Glucocorticoid-Induced Osteoporosis:

   • Start treatment at higher BMD thresholds than for primary osteoporosis 1
   • Consider treatment for all patients on prednisone ≥5 mg/day for >3 months 2

2. Cancer Patients:

   • More frequent monitoring (every 1-2 years) 1
   • Avoid estrogen therapy in hormone-responsive cancers 1

Monitoring

• BMD testing every 2 years for patients on medications causing bone loss 1
• More frequent testing if clinically indicated, but generally not more than annually 1
• Reassess fracture risk and treatment response

Common Pitfalls to Avoid

1. Failing to recognize secondary causes of osteoporosis
2. Not treating patients with previous fragility fractures
3. Overlooking vitamin D deficiency
4. Not providing sequential therapy after anabolic agents or denosumab
5. Inadequate calcium and vitamin D supplementation during pharmacologic therapy
6. Neglecting fall prevention strategies
7. Not adjusting FRAX for high-dose glucocorticoid use (>7.5 mg/day)

By following this comprehensive approach to osteoporosis workup and treatment, clinicians can significantly reduce fracture risk and improve outcomes for high-risk patients.