When should bone health medications, such as bisphosphonates (e.g. alendronate) or denosumab, be considered for patients with conditions like osteoporosis or rheumatoid arthritis?

When to Consider Bone Health Medications

Bone health medications should be initiated immediately for adults ≥40 years with high or very high fracture risk (prior osteoporotic fracture, T-score ≤-2.5, or FRAX 10-year hip fracture risk ≥3% or major osteoporotic fracture risk ≥20%), with oral bisphosphonates (alendronate or risedronate) as first-line therapy. 1

Risk Stratification Framework

Adults ≥40 Years of Age

Initial assessment should include: 1

• FRAX calculation for 10-year fracture probability
• BMD measurement via DXA with vertebral fracture assessment (VFA)
• Clinical fracture history (both symptomatic and asymptomatic vertebral fractures)
• Assessment of fall risk and secondary causes of osteoporosis

Treatment thresholds by risk category: 1

• Very High Risk (treat immediately with pharmacotherapy):

  • Prior hip or vertebral fracture 1
  • Multiple fractures 2
  • Recent fracture while on osteoporosis therapy 1
  • T-score ≤-2.5 with fracture history 1

• High Risk (strongly recommend treatment):

  • T-score ≤-2.5 at spine, hip, or femoral neck without fracture 1
  • FRAX 10-year hip fracture risk ≥3% 1
  • FRAX 10-year major osteoporotic fracture risk ≥20% 1

• Moderate Risk (consider treatment with shared decision-making):

  • T-score between -1.0 and -2.5 (osteopenia) with FRAX 10-year hip fracture risk 1-3% 1
  • Age ≥65 years with osteopenia and additional risk factors 1

Adults <40 Years of Age

Treatment indications are more restrictive: 1, 3

• History of osteoporotic fracture 1, 3
• Z-score ≤-3 at hip or spine on glucocorticoid therapy ≥7.5 mg/day for ≥6 months 1, 3
• Rapid bone loss ≥10%/year at hip or spine during glucocorticoid treatment 1, 3

Glucocorticoid-Induced Osteoporosis (GIOP)

Initiate treatment as soon as possible (within 6 months) for patients on prednisone ≥2.5 mg/day for >3 months: 1

• All adults with medium, high, or very high fracture risk should receive osteoporosis therapy 1
• For prednisone >7.5 mg/day, adjust FRAX upward by 15% for major fracture risk and 20% for hip fracture risk 1
• Very high-dose glucocorticoids (≥30 mg/day prednisone, cumulative >5 gm/year): treat with oral bisphosphonate regardless of BMD 1

Risk stratification in GIOP patients ≥40 years: 1

• Use FRAX with glucocorticoid adjustment
• Perform BMD with VFA or spine x-rays
• Consider additional risk factors not captured by FRAX (falls, frailty, number/timing of fractures) 1

Rheumatoid Arthritis Considerations

Patients with rheumatoid arthritis have elevated fracture risk independent of glucocorticoid use: 1

• RA itself is a clinical risk factor for fracture in FRAX calculations 1
• Many RA patients require long-term glucocorticoids, triggering GIOP treatment thresholds 1
• Apply standard GIOP guidelines if on prednisone ≥2.5 mg/day for >3 months 1

First-Line Medication Selection

Oral bisphosphonates (alendronate or risedronate) are strongly recommended as first-line therapy for most patients: 1

• Women with known osteoporosis: alendronate, risedronate, zoledronic acid, or denosumab reduce hip and vertebral fractures 1
• Men with osteoporosis: bisphosphonates reduce vertebral fractures (weaker evidence than for women) 1
• GIOP patients at high/very high risk: oral bisphosphonates strongly recommended over no treatment 1

Alternative agents when bisphosphonates are inappropriate: 1

• Very high fracture risk: anabolic agents (teriparatide, abaloparatide, romosozumab) conditionally recommended over antiresorptives, followed by bisphosphonate or denosumab 1, 2
• High fracture risk in adults ≥40: denosumab or anabolic agents conditionally recommended over bisphosphonates 1
• Moderate fracture risk: oral/IV bisphosphonates, denosumab, or anabolic agents all conditionally recommended 1

For adults <40 years, treatment hierarchy is: 3

1. Oral bisphosphonates (first-line) 3
2. IV bisphosphonates (if oral not tolerated) 3
3. Teriparatide (if bisphosphonates contraindicated) 3
4. Denosumab (only as last option) 3

Critical Caveats

Denosumab-specific warnings: 1, 4

• Requires sequential therapy after discontinuation to prevent rebound bone loss and vertebral fractures 1
• Discontinuation causes rapid reversal of BMD gains and increased fracture risk 4
• Should be avoided in young adults unless all other options exhausted 3
• Not recommended in transplant patients on multiple immunosuppressants due to infection risk 1

Renal impairment considerations: 5

• Bisphosphonates not recommended if creatinine clearance <35 mL/min 5
• Denosumab preferred in moderate-to-severe renal impairment 4

Treatment duration: 1

• Initial treatment course of 5 years for bisphosphonates 1
• Reassess fracture risk after 5 years; continue if moderate-to-high risk persists 1
• Do not perform routine BMD monitoring during the initial 5-year treatment period 1

All patients should receive: 1, 2

• Calcium 1000-1200 mg/day 1, 2
• Vitamin D 600-800 IU/day 1, 2
• Weight-bearing and muscle resistance exercises 2
• Smoking cessation and alcohol limitation 1