What are the recommended management options for osteoporosis?

Osteoporosis Management

Diagnosis and Risk Assessment

All women ≥65 years and postmenopausal women <65 years with risk factors should undergo bone mineral density (BMD) testing with dual-energy x-ray absorptiometry (DXA) of the spine, hip, and femoral neck. 1, 2

• Use the FRAX tool to calculate 10-year fracture risk, incorporating BMD and clinical risk factors (age, prior fractures, parental hip fracture history, glucocorticoid use, smoking, alcohol consumption) 1, 2, 3
• Order lateral spine X-rays to identify existing vertebral fractures, which increase future vertebral fracture risk 5-fold and hip fracture risk 2-fold 4
• For men with osteoporosis, assess serum total testosterone as part of pre-treatment evaluation 4, 2
• Repeat DXA every 2 years to monitor treatment response, but not more frequently than annually 1, 2

High-Risk Factors Requiring Intervention

• T-score ≤-2.5 at femoral neck, total hip, or lumbar spine 1, 2
• History of fragility fracture (vertebral or hip) 2, 3
• FRAX 10-year probability ≥20% for major osteoporotic fracture or ≥3% for hip fracture 1, 2, 3
• Chronic glucocorticoid use ≥2.5 mg/day prednisone for >3 months 1
• Cancer treatment-related bone loss (aromatase inhibitors, GnRH agonists, androgen deprivation therapy) 1, 2

Non-Pharmacological Management (Required for ALL Patients)

Every patient with osteoporosis must receive calcium 1,000-1,200 mg/day and vitamin D 800-1,000 IU/day, targeting serum 25(OH)D levels ≥30 ng/mL. 1, 2, 3

• Implement a multi-component exercise program at least 3 times weekly for ≥30 minutes, including: 1, 2
  • Weight-bearing exercises
  • Resistance/progressive strengthening exercises
  • Balance training (reduces fall risk by 23%) 1, 4
  • Flexibility/stretching exercises
• Mandatory smoking cessation 1
• Limit alcohol to ≤2 servings per day 1
• Ensure adequate protein intake at levels higher than the recommended daily allowance 4, 2

Pharmacological Treatment Algorithm

First-Line Therapy: Oral Bisphosphonates

For most patients meeting treatment thresholds, initiate oral bisphosphonates (alendronate or risedronate) as first-line therapy due to proven efficacy, safety profile, and cost-effectiveness. 1, 2, 3

• Alendronate inhibits osteoclast activity without interfering with bone formation, reducing bone resorption markers by 50-70% within 1-3 months 5
• Bisphosphonates reduce vertebral fractures by 52 per 1,000 person-years and hip fractures by 6 per 1,000 person-years 3
• Continue treatment for at least 3-5 years if fracture risk remains elevated 4
• Monitor adherence closely, as up to 64% of patients are non-adherent by 12 months 1, 2

Second-Line Therapy: IV Bisphosphonates or Denosumab

For patients who cannot tolerate oral bisphosphonates or are at very high fracture risk, use IV zoledronate or denosumab 60 mg subcutaneously every 6 months. 1, 2

• Denosumab significantly improves BMD at multiple sites and is administered via 6-monthly subcutaneous injections 2
• Critical warning: After stopping denosumab, there is increased risk of multiple vertebral fractures—never discontinue without transitioning to another antiresorptive agent 6
• Before initiating denosumab, perform dental screening to reduce risk of osteonecrosis of the jaw 4, 6
• Denosumab may cause serious infections (skin, abdomen, bladder, endocarditis) and severe jaw bone problems 6

Anabolic Agents for Very High-Risk Patients

For very high-risk patients (recent vertebral fractures, hip fracture with T-score ≤-2.5, multiple fractures, or FRAX scores significantly above treatment thresholds), initiate anabolic agents (teriparatide, abaloparatide, or romosozumab) followed by an antiresorptive agent. 1, 3, 7

• Teriparatide increases lumbar and hip BMD and decreases vertebral fractures compared to alendronate in glucocorticoid-induced osteoporosis 1
• Anabolic agents stimulate new bone formation, repairing architectural defects and improving bone density 3, 8
• Critical pitfall: Do not use anabolic agents after prolonged antiresorptive therapy—the bone anabolic effect is blunted 1
• Always transition to an antiresorptive agent after completing anabolic therapy to maintain gains 1, 3

Special Population Considerations

Glucocorticoid-Induced Osteoporosis

For adults ≥40 years taking prednisone ≥2.5 mg/day for >3 months with high or very high fracture risk, initiate osteoporosis therapy in addition to calcium and vitamin D. 1

• Oral bisphosphonates are first-line for high/very high risk patients 1
• For very high risk, consider teriparatide over bisphosphonates 1
• Adjust FRAX scores by multiplying by 1.15 for major osteoporotic fracture risk and 1.2 for hip fracture risk if prednisone dose >7.5 mg/day 4

Cancer Survivors

Cancer survivors have baseline osteoporosis risk plus treatment-related bone loss from hypogonadism (chemotherapy, aromatase inhibitors, GnRH agonists, androgen deprivation therapy)—consider earlier intervention with bisphosphonates or denosumab at osteoporosis-indicated dosages. 1, 4, 2

Men with Osteoporosis

Use a female reference database for densitometric diagnosis of osteoporosis in men. 1, 2

• Assess and replace testosterone if levels are low 2
• Multi-component exercise approaches demonstrate significant BMD benefits in middle-aged and older men 1, 2

Monitoring and Follow-Up

• Repeat DXA every 2 years to assess treatment response 1, 2
• Measure biochemical markers of bone turnover (deoxypyridinoline, N-telopeptides) at baseline and 3 months to assess adherence to anti-resorptive therapy 2
• Monitor for asymptomatic reductions in serum calcium (approximately 2%) and phosphate (4-6%) after initiating bisphosphonates 5
• Recalculate FRAX score at each DXA scan to reassess treatment need 4

Critical Pitfalls to Avoid

• Never stop denosumab without transitioning to another antiresorptive—risk of rebound vertebral fractures 6
• Ensure adequate calcium and vitamin D before starting any osteoporosis medication 1
• Do not use anabolic agents after prolonged antiresorptive therapy 1
• Perform dental examination before initiating bisphosphonates or denosumab to reduce osteonecrosis of the jaw risk 4, 6
• Address poor adherence to oral bisphosphonates, which significantly reduces treatment effectiveness 2
• Avoid excessive calcium supplementation, which may increase cardiovascular risk 4
• Do not delay lifestyle modifications while waiting for next DXA scan—implement immediately 4