When should bisphosphonates (bone density conservation medication) be initiated in patients?

When to Start Bisphosphonates

Bisphosphonates should be initiated in patients with documented osteoporosis (T-score ≤-2.5), history of fragility fractures, or high fracture risk, while patients with monoclonal gammopathy of undetermined significance or smoldering myeloma without lytic bone disease should not receive bisphosphonates. 1

Indications for Bisphosphonate Therapy

Established Osteoporosis

• Patients with T-score ≤-2.5 at the hip, spine, or forearm 1
• Patients with a history of fragility fracture, regardless of BMD 1
• Patients with osteopenia (T-score between -1.0 and -2.5) AND 10-year fracture risk ≥20% for major osteoporotic fracture or ≥3% for hip fracture based on FRAX calculation 2

Multiple Myeloma

• All patients receiving primary myeloma therapy (category 1 recommendation) 1
• Multiple myeloma patients with osteopenia but no radiographic evidence of lytic bone disease 1
• Patients with pain due to osteolytic disease 1

NOT Recommended For

• Patients with solitary plasmacytoma or smoldering/indolent myeloma without documented lytic bone disease 1
• Patients with monoclonal gammopathy of undetermined significance (MGUS) 1

Pre-Treatment Considerations

Required Before Starting Therapy

• Comprehensive dental examination and appropriate preventive dentistry 1, 3, 4
• Correction of vitamin D deficiency prior to initiation (goal 25(OH)D level >32 ng/mL) 1
• Assessment of renal function (bisphosphonates not recommended for patients with creatinine clearance <35 mL/min) 4
• Baseline bone mineral density testing 1

Risk Assessment

• Evaluate for secondary causes of osteoporosis
• Consider FRAX calculation for patients ≥40 years old 2
• Assess fall risk factors

Bisphosphonate Selection Algorithm

1. For patients with normal renal function:

   • Oral alendronate 70mg weekly or risedronate 35mg weekly
   • IV zoledronic acid 5mg annually if concerns about absorption or adherence exist

2. For patients with renal impairment (GFR 35-60 mL/min):

   • Consider dose adjustment or extended infusion time for IV bisphosphonates
   • Monitor renal function more frequently

3. For patients with severe renal impairment (GFR <35 mL/min):

   • Avoid bisphosphonates
   • Consider denosumab as an alternative 2

4. For multiple myeloma patients:

   • IV pamidronate or zoledronic acid (zoledronic acid preferred for hypercalcemia) 1

Duration of Therapy

• Initial therapy for 3-5 years 5, 6
• After 3-5 years, reassess fracture risk:
  • Low-risk patients: Consider drug holiday if BMD is stable and no fractures have occurred 5
  • High-risk patients: Continue for up to 10 years, then consider a shorter drug holiday (1-2 years) 5
  • For multiple myeloma: Continue monthly for 2 years, then consider stopping in patients with responsive or stable disease 1
• Resume therapy if bone density decreases significantly, fracture occurs, or high-risk status returns 1, 5

Monitoring During Treatment

• BMD testing every 1-2 years to assess treatment response 1, 2
• Serum creatinine and calcium monitoring 1
• Urinalysis for proteinuria every 3-6 months for patients on IV bisphosphonates 1
• If unexplained albuminuria (≥500 mg/24 hours) occurs, discontinue until resolved 1

Important Precautions

• Osteonecrosis of the jaw: Risk increases with duration of exposure; avoid invasive dental procedures when possible 3, 4
• Atypical femur fractures: Evaluate patients with thigh or groin pain; consider drug holiday after 5-10 years 3, 4
• Musculoskeletal pain: Can be severe; discontinue if significant symptoms develop 3, 4
• Esophageal irritation: Take oral bisphosphonates with a full glass of water and remain upright for at least 30 minutes 1

By following these guidelines, clinicians can appropriately initiate bisphosphonate therapy to reduce fracture risk while minimizing potential adverse effects, ultimately improving morbidity, mortality, and quality of life outcomes for patients.