How do I evaluate and treat osteoporosis, including fracture risk assessment, DXA scanning, laboratory workup, calcium and vitamin D supplementation, and appropriate pharmacologic therapy?

Osteoporosis Evaluation and Treatment

For postmenopausal women with osteoporosis (T-score ≤-2.5 or prior fragility fracture), initiate treatment with oral alendronate, risedronate, zoledronic acid, or denosumab as first-line therapy to reduce hip and vertebral fractures. 1, 2

Fracture Risk Assessment

Who to evaluate:

• All postmenopausal women aged ≥50 years should undergo fracture risk assessment 2
• All men aged ≥50 years with risk factors 3
• Postmenopausal women aged <65 years with one or more risk factors 4

Risk assessment tools:

• Use FRAX (Fracture Risk Assessment Tool) to calculate 10-year fracture probability 2, 5
• FRAX should be country-specific and can be adjusted for glucocorticoid use 6, 7
• Consider trabecular bone score (TBS) with FRAX for enhanced risk stratification 5

Treatment thresholds using FRAX:

• 10-year hip fracture risk ≥3% OR
• 10-year major osteoporotic fracture risk ≥20% 2, 3, 8

DXA Scanning

Indications for DXA:

• All women aged ≥65 years 4
• Postmenopausal women aged <65 years with risk factors (use OST, ORAI, or FRAX to identify) 4
• Men aged ≥70 years 3
• Men aged 50-69 years with risk factors 3
• Adults with fragility fractures 2
• Adults on long-term glucocorticoids (≥3 months at ≥2.5 mg/day prednisone equivalent) 6, 7

DXA technique:

• Measure lumbar spine (L1-L4), total hip, and femoral neck 2, 9
• Add 1/3 radius if hyperparathyroidism or if spine/hip cannot be measured 9, 3
• For men, use female reference database for T-score calculation 5

Diagnostic criteria:

• Osteoporosis: T-score ≤-2.5 at spine, femoral neck, total hip, or 1/3 radius 2
• Osteoporosis also diagnosed with fragility fracture regardless of BMD 2
• Low bone mass (osteopenia): T-score between -1.0 and -2.5 2

Monitoring frequency:

• Baseline DXA, then repeat every 1-2 years during treatment 2
• Do NOT monitor BMD during the first 5 years of bisphosphonate therapy for treatment decisions 1
• Screening intervals of 4-8 years for those not on treatment 4

Laboratory Workup

Essential baseline tests:

• Serum calcium, phosphate, creatinine with eGFR 3
• Alkaline phosphatase, liver function tests 3
• 25-hydroxyvitamin D [25(OH)D] 3
• Complete blood count 3
• 24-hour urinary calcium, creatinine, and sodium 3

For men specifically:

• Serum total testosterone 3, 5
• Calculate free or bioavailable testosterone if total testosterone is borderline 3

Additional tests if indicated by history/exam:

• Thyroid function tests 3
• Parathyroid hormone (PTH) 3
• Serum protein electrophoresis with free light chains 3
• Tissue transglutaminase antibodies (celiac disease) 3

Vertebral fracture assessment:

• Perform vertebral fracture assessment (VFA) using DXA or lateral spine radiographs in patients with low bone mass who might have undiagnosed vertebral fractures 3

Calcium and Vitamin D Supplementation

Calcium:

• Target intake: 1,000-1,200 mg/day 6, 7, 2, 3
• Preferably from dietary sources, supplement if dietary intake insufficient 3

Vitamin D:

• Target intake: 600-800 IU/day 6, 7, 2
• Target serum 25(OH)D level: ≥20 ng/ml (≥75 nmol/L) 6, 7
• For those with low vitamin D levels (<30 ng/ml), supplement to achieve levels ≥30 ng/ml 3

Important caveat: Calcium and vitamin D alone are insufficient for fracture prevention in established osteoporosis—pharmacologic therapy is required 1, 2

Pharmacologic Therapy

First-Line Treatment for Postmenopausal Women

High fracture risk (T-score ≤-2.5 OR prior hip/vertebral fracture):

• Oral bisphosphonates: alendronate or risedronate 1, 2, 5
• Alternative first-line: zoledronic acid (IV) or denosumab (subcutaneous) 1, 2
• These agents reduce hip, vertebral, and nonvertebral fractures 1

Very high fracture risk (recent fracture within 12 months, multiple fractures, fractures on therapy, very low T-score <-3.0, high fall risk, FRAX major fracture >30% or hip >4.5%):

• Consider anabolic agents first: abaloparatide, romosozumab, or teriparatide 2
• Alternative: denosumab or zoledronic acid 2

Moderate fracture risk:

• Oral bisphosphonates preferred 6, 7
• If oral bisphosphonates not appropriate: IV bisphosphonates > teriparatide > denosumab > raloxifene 6, 7

Treatment for Men

Men with clinically recognized osteoporosis:

• Oral bisphosphonates (alendronate or risedronate) as first-line 1, 3, 5
• Second-line: denosumab or zoledronic acid 5
• For very high fracture risk: sequential therapy starting with bone-forming agent (teriparatide) followed by antiresorptive 5

Men with prior fragility fracture:

• Treat regardless of BMD 5

Glucocorticoid-Induced Osteoporosis

For adults ≥40 years at moderate-to-high fracture risk on glucocorticoids (≥2.5 mg/day prednisone for ≥3 months):

• Oral bisphosphonates as first-line 6, 7, 6
• Adjust FRAX: multiply major fracture risk by 1.15 and hip fracture risk by 1.2 if prednisone >7.5 mg/day 7

For adults <40 years:

• Treat with oral bisphosphonates if: history of osteoporotic fracture OR Z-score <-3 at hip/spine with prednisone ≥7.5 mg/day OR ≥10%/year bone loss 7, 6

Agents NOT Recommended

Strong recommendations AGAINST:

• Menopausal estrogen therapy or estrogen plus progestogen for osteoporosis treatment (increased stroke, venous thromboembolism, breast cancer risk) 1
• Raloxifene for osteoporosis treatment (increased cardiovascular events, thromboembolic events) 1

Raloxifene may be considered only:

• For spine-specific efficacy when other agents inappropriate 2
• In postmenopausal women with glucocorticoid-induced osteoporosis when no other therapy available 6, 7

Treatment Duration and Drug Holidays

Bisphosphonate duration:

• Treat for 5 years with oral bisphosphonates or 3 years with IV zoledronic acid 1, 2
• After 5 years, consider drug holiday in patients no longer at high risk 2
• Continue therapy beyond 5 years if: very high fracture risk, T-score remains <-2.5, or prior fracture on therapy 2

During drug holiday:

• Monitor with BMD and bone turnover markers 2
• Resume therapy if: new fracture occurs, BMD declines beyond least significant change, bone turnover markers rise to pretreatment values, or patient meets initial treatment criteria 2

After anabolic therapy:

• Must follow with antiresorptive agent (bisphosphonate or denosumab) to prevent rebound bone loss and multiple vertebral fractures 10

Denosumab:

• No drug holiday recommended—stopping denosumab causes rapid bone loss and increased vertebral fracture risk 10
• Transition to bisphosphonate if discontinuing 10

Monitoring During Treatment

Bone turnover markers:

• Use to assess adherence to antiresorptive therapy 5
• Measure at baseline and 3-6 months after starting treatment 2

BMD monitoring:

• Repeat DXA every 1-2 years during treatment 2
• Do not use BMD changes during first 5 years of bisphosphonates to make treatment decisions 1

Clinical monitoring:

• Reassess yearly for fracture risk, falls, and secondary causes of bone loss 2
• Earlier reassessment for those on higher glucocorticoid doses or with history of fracture 6

Lifestyle Modifications

All patients should receive counseling on:

• Weight-bearing and resistance exercise 30-40 minutes, 3-4 times weekly 2, 3
• Smoking cessation 2, 3
• Limit alcohol to 1-2 drinks/day 6, 7, 3
• Fall prevention strategies, especially in elderly 2
• Maintain healthy body weight 6, 7

Switching Therapy

If inadequate response to oral bisphosphonate:

• Switch to injectable antiresorptive (zoledronic acid or denosumab) 2

If inadequate response to injectable antiresorptive:

• Switch to anabolic agent (abaloparatide, romosozumab, or teriparatide) 2

Referral Indications

Refer to endocrinologist or osteoporosis specialist when:

• Fragility fracture with normal BMD 2
• Recurrent fractures or continued bone loss despite therapy 2
• Unexpectedly low BMD or unusual features (young age, unexplained lab abnormalities) 2
• Complicating conditions (decreased kidney function, hyperparathyroidism, malabsorption) 2
• Consider fracture liaison service referral after fragility fracture 2