What degree of impaired renal function is contraindicated for bisphosphonate therapy?

From the Guidelines

Bisphosphonates are contraindicated in patients with severe renal impairment, specifically when the glomerular filtration rate (GFR) is less than 30 ml/min/1.73 m2 (GFR categories G4-G5) without a strong clinical rationale. This recommendation is based on the guideline by the American Journal of Kidney Diseases 1. The contraindication exists because bisphosphonates are primarily eliminated unchanged through the kidneys. In patients with compromised renal function, these medications can accumulate in the body, potentially leading to toxic effects and further kidney damage.

Key Considerations

• Bisphosphonates may cause acute kidney injury in some patients, particularly when administered intravenously at high doses or too rapidly.
• For patients with moderate renal impairment (creatinine clearance between 35-60 mL/min), dose adjustments and careful monitoring may be necessary.
• Alternative osteoporosis treatments such as denosumab might be considered for those with severe renal impairment.
• The most recent and highest quality study 1 suggests not to prescribe bisphosphonate treatment in people with GFR < 30 ml/min/1.73 m2 without a strong clinical rationale.

Renal Function and Bisphosphonate Use

• Patients with a GFR of less than 30 ml/min/1.73 m2 should not be prescribed bisphosphonates without a strong clinical rationale.
• Patients with moderate renal impairment may require dose adjustments and careful monitoring.
• The use of bisphosphonates in patients with severe renal impairment should be avoided due to the risk of toxic effects and further kidney damage.

Alternative Treatments

• Denosumab may be considered as an alternative osteoporosis treatment for patients with severe renal impairment.
• Other treatments, such as orthopedic surgery and radiotherapy, may also be considered for patients with severe renal impairment and osteoporosis.

From the FDA Drug Label

DUE TO THE RISK OF CLINICALLY SIGNIFICANT DETERIORATION IN RENAL FUNCTION, WHICH MAY PROGRESS TO RENAL FAILURE, SINGLE DOSES OF PAMIDRONATE DISODIUM SHOULD NOT EXCEED 90 MG Patients who receive pamidronate disodium should have serum creatinine assessed prior to each treatment. Patients treated with pamidronate disodium for bone metastases should have the dose withheld if renal function has deteriorated.

The renal function that is contraindicated for bisphosphonate is not explicitly stated, but it is recommended to withhold the dose if renal function has deteriorated.

• Serum creatinine should be assessed prior to each treatment.
• The dose should be withheld if renal function has deteriorated 2.

From the Research

Renal Function Contraindicated for Bisphosphonate

• Severe renal impairment is a contraindication for the use of bisphosphonates, with a creatinine clearance of less than 30 or 35 mL/min 3, 4.
• Patients with chronic kidney disease (CKD) stages 3b to 5, based on estimated glomerular filtration rate (eGFR) measurements less than 45 mL/min/1.73 m2, should use bisphosphonates with caution 5.
• Intravenous zoledronic acid should be avoided in patients with GFR levels <35 ml/min, and patients should be well hydrated and avoid concomitant use of agents that may impair renal function 4.
• The use of bisphosphonates in patients with GFR levels <30-35 ml/min requires careful consideration, as other forms of renal bone disease may need to be excluded before diagnosing osteoporosis 4.

Bisphosphonate Use in Renal Impairment

• Oral bisphosphonates have not been shown to adversely affect the kidney in doses registered for postmenopausal osteoporosis management, even in patients with eGFR down to 15 ml/min 4.
• Intravenous bisphosphonates are generally well tolerated, but adverse effects on renal function are primarily related to infusion rate and dose 6.
• There is a lack of evidence on the safety of bisphosphonates in patients with intrinsic renal disease or an estimated glomerular filtration rate of < 30 ml/min 6.

Prescribing Guidelines

• Current prescribing guidelines for bisphosphonates in patients with renal impairment may be unnecessarily restrictive, and prospective trial data with clinically important end points in CKD patients is awaited 7.
• Bisphosphonate treatment may reduce fracture risk without increasing adverse events in patients with CKD, but more research is needed to confirm this 7.