Who should not receive bisphosphonates (BIS) for osteoporosis?

Contraindications for Bisphosphonate Therapy in Osteoporosis

Bisphosphonates should not be prescribed to patients with esophageal emptying disorders, inability to sit upright, creatinine clearance less than 30 mL/min, uncorrected vitamin D deficiency, or those requiring dental procedures. 1

Absolute Contraindications

• Renal impairment: Intravenous bisphosphonates are generally not recommended in patients with creatinine clearance less than 30 mL/min due to risk of increased serum creatinine and potential acute renal failure 1
• Esophageal disorders: Patients with esophageal emptying disorders or those who cannot sit upright for at least 30 minutes should avoid oral bisphosphonates due to high risk of pill esophagitis 1
• Uncorrected hypocalcemia or vitamin D deficiency: Vitamin D deficiency should be corrected before initiating bisphosphonate therapy, especially intravenous formulations, as hypocalcemia has been reported in patients with unrecognized vitamin D deficiency 1, 2

Relative Contraindications and Special Considerations

Dental Health Concerns

• Planned dental procedures: Patients requiring invasive dental procedures should delay starting bisphosphonate therapy if possible 1
• Poor oral hygiene: Patients with poor oral hygiene are at increased risk for osteonecrosis of the jaw (ONJ) 1
• Recent dental extraction: Dental extractions are a risk factor for ONJ in patients on bisphosphonate therapy 1

Renal Considerations

• Moderate renal impairment: For patients with creatinine clearance between 30-60 mL/min, dose adjustments may be required for zoledronic acid 1
• Chronic kidney disease progression: Recent evidence shows a modest 15% increased risk of CKD progression with bisphosphonate use in patients with moderate to severe CKD 3
• Dialysis-dependent patients: Extreme caution is warranted as these patients have high risk of mineral and bone disorders that complicate treatment 4

Patient Populations

• Asymptomatic myeloma or monoclonal gammopathy of undetermined significance (MGUS): Bisphosphonates are not recommended unless osteopenia/osteoporosis is present 1
• Solitary plasmacytoma: Starting bisphosphonates is not recommended 1
• Pregnant women or women planning pregnancy: Bisphosphonates should be avoided due to potential fetal harm 1

Alternative Treatments for Contraindicated Patients

• For patients with renal impairment: Consider oral bisphosphonates which appear to have better renal safety in patients with lower creatinine clearance than IV formulations 1, 5
• For patients who cannot tolerate oral formulations: Consider intravenous bisphosphonates if renal function permits 1
• For patients with severe renal impairment: Consider denosumab with careful monitoring of calcium levels or raloxifene as alternative treatments 1, 5
  • Caution: Denosumab has been associated with severe hypocalcemia in dialysis-dependent patients 4

Monitoring Recommendations

• Before initiating therapy:

  • Assess renal function with creatinine clearance 1
  • Check vitamin D status and correct deficiency 1
  • Perform dental examination and complete necessary dental procedures 1
  • Optimize calcium intake 1

• During therapy:

  • Monitor renal function and serum calcium regularly 1
  • For patients with CKD, monitor parathyroid hormone (PTH) levels 5
  • Ensure adequate calcium and vitamin D supplementation 1

Important Precautions

• Osteonecrosis of the jaw risk: Though rare with osteoporosis dosing (<1/10,000-1/100,000), patients should be advised against unnecessary invasive oral surgery while on bisphosphonate therapy 1
• Atypical femur fractures: Long-term use of bisphosphonates has been associated with atypical femur fractures 6
• Acute phase reactions: Influenza-like symptoms can occur with both IV and oral bisphosphonates but are typically transitory and self-limiting 6

By carefully screening patients for these contraindications and taking appropriate precautions, the safety profile of bisphosphonates can be optimized while effectively treating osteoporosis.