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

Key Diagnostic Criteria

• Osteoporosis is defined as a T-score ≤-2.5 at the femoral neck, total hip, or lumbar spine 1, 3
• Use the FRAX tool to calculate 10-year fracture risk, incorporating BMD and clinical risk factors beyond bone density alone 1, 2
• Obtain 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, use a female reference database for densitometric diagnosis 2

High-Risk Factors Requiring Assessment

• Prior fragility fracture (most important predictor) 2, 3
• Age >50 years, low body weight, parental history of hip fracture 2
• Glucocorticoid use ≥2.5 mg/day prednisone for >3 months 1, 2
• Cancer treatments causing hypogonadism (aromatase inhibitors, GnRH agonists, androgen deprivation therapy) 1, 2
• Current smoking, excessive alcohol consumption, increased fall risk 2

Non-Pharmacologic Management (Universal 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

Essential Lifestyle Modifications

• Implement a multi-component exercise program at least 3 times weekly for ≥30 minutes, including: 1, 2
  • Weight-bearing exercises
  • Resistance/progressive strengthening exercises (e.g., squats, push-ups) 3
  • Balance training (e.g., heel raises, standing on one foot) to reduce fall risk by 23% 1, 3
  • 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

Pharmacologic Treatment Algorithm

Treatment Thresholds (When to Start Medication)

Initiate pharmacologic therapy if ANY of the following criteria are met: 1, 2

• T-score ≤-2.5 at femoral neck, total hip, or lumbar spine
• Prior fragility fracture (vertebral or hip)
• FRAX 10-year probability ≥20% for major osteoporotic fracture OR ≥3% for hip fracture
• Chronic glucocorticoid therapy ≥2.5 mg/day prednisone for ≥3 months with high/very high fracture risk 1

First-Line Therapy: Oral Bisphosphonates

Oral bisphosphonates (alendronate or risedronate) are strongly recommended as first-line monotherapy for most patients due to safety, efficacy, and cost-effectiveness. 1, 2, 3

Alendronate Administration (Critical for Efficacy)

• Take with plain water (6-8 ounces) first thing upon arising, at least 30 minutes before any food, beverage, or other medication 5
• Do not lie down for at least 30 minutes after taking and until after first food of the day 5
• Do not take at bedtime or with orange juice/coffee, as this markedly reduces absorption 5
• Swallow whole; do not chew or suck on tablet to prevent oropharyngeal ulceration 5
• If a weekly dose is missed, take one dose the morning after remembering, then return to original schedule 5

Expected Outcomes with Bisphosphonates

• Reduce vertebral fractures by 52 per 1,000 person-years 3
• Reduce hip fractures by 6 per 1,000 person-years 3
• Continue for at least 3-5 years if fracture risk remains elevated 4

Alternative Therapies for Specific Situations

IV bisphosphonates (zoledronate) or denosumab are recommended for patients who cannot tolerate oral bisphosphonates or are at very high fracture risk. 1, 2

Denosumab Considerations

• Administered subcutaneously every 6 months 2
• Significantly improves BMD at multiple sites 2
• CRITICAL WARNING: Never discontinue denosumab without immediately transitioning to antiresorptive therapy—rebound bone loss and vertebral fractures can occur 1, 6
• Increased risk of serious infections, jaw osteonecrosis, and unusual thigh bone fractures 6
• Requires dental screening before initiation 4, 6

Very High-Risk Patients: Anabolic-First Strategy

For very high-risk patients, start with anabolic agents (teriparatide, abaloparatide, or romosozumab) FIRST, followed by antiresorptive therapy to maintain gains. 1, 3

Very High-Risk Criteria

• Recent vertebral fracture 1
• Hip fracture with T-score ≤-2.5 1
• Multiple fractures 1
• Glucocorticoid-induced osteoporosis at very high risk 1

Critical Sequencing Rule

Never start antiresorptives before anabolics in very high-risk patients who will eventually need both—the bone anabolic effect is blunted if anabolics are used after prolonged antiresorptive therapy. 1

Never use two different osteoporosis medications concurrently—this is conditionally recommended against due to lack of fracture reduction data, blunted anabolic effects, and increased costs/adverse effects. 1

Special Populations

Glucocorticoid-Induced Osteoporosis

• For adults ≥40 years taking prednisone ≥2.5 mg/day for >3 months with high/very high fracture risk, strongly recommend osteoporosis therapy in addition to calcium and vitamin D 1
• Very high-risk patients: conditionally recommend teriparatide over bisphosphonates 1
• High-risk patients: strongly recommend oral bisphosphonates as first-line 1
• Adjust FRAX risk by multiplying by 1.15 for major osteoporotic fracture and 1.2 for hip fracture if prednisone dose >7.5 mg/day 4

Cancer Survivors

• Cancer treatments causing hypogonadism (aromatase inhibitors, GnRH agonists, androgen deprivation) accelerate bone loss 1, 2
• Consider earlier intervention with bisphosphonates or denosumab at osteoporosis-indicated dosages 4, 2
• Perform dental screening before bone-modifying agents to reduce osteonecrosis risk 4

Men with Osteoporosis

• Assess serum total testosterone as part of pre-treatment evaluation 4, 2
• Consider appropriate hormone replacement if low testosterone levels 2
• Multi-component exercise demonstrates significant BMD benefits in middle-aged and older men 1, 2
• Monitor adherence closely—up to 64% of men are non-adherent to bisphosphonates by 12 months 1, 2

Monitoring Strategy

Repeat DXA every 2 years to assess treatment response, but not more frequently than annually. 1, 2

• Biochemical markers of bone turnover can assess adherence to anti-resorptive therapy at baseline and 3 months 2
• Recalculate FRAX score at each DXA scan to reassess treatment need 4
• Monitor medication adherence regularly, as poor adherence significantly reduces treatment effectiveness 2
• When T-scores improve, consider discontinuation of bone-modifying agents with periodic DXA follow-up 4

Critical Pitfalls to Avoid

Ensure adequate calcium and vitamin D before starting any osteoporosis medication—deficiency must be corrected first. 1

• Never combine two osteoporosis medications simultaneously without compelling individual circumstances 1
• Never discontinue denosumab, romosozumab, or teriparatide without immediately transitioning to antiresorptive therapy 1
• Instruct patients on proper bisphosphonate administration—failure to follow instructions increases esophageal complication risk 5
• Stop bisphosphonates immediately if symptoms of esophageal disease develop (difficulty swallowing, retrosternal pain, new/worsening heartburn) 5
• Avoid excessive calcium supplementation, which may increase cardiovascular risk 4
• Educate patients about osteoporosis to reduce stigma, particularly in men who may view it as a "female condition" 2

Comprehensive Care Model

Implement fracture liaison services (comprehensive inpatient/outpatient management after fracture) to increase medication initiation and adherence from 17% to 38%, potentially reducing subsequent fracture rates. 3