Calculating Creatinine Clearance for Bisphosphonate Safety
Use the Cockcroft-Gault equation to calculate creatinine clearance before initiating bisphosphonate therapy, as this is the formula referenced in bisphosphonate prescribing information and contraindications (CrCl <30-35 mL/min). 1, 2
The Cockcroft-Gault Formula
The calculation requires four variables:
- Serum creatinine (mg/dL)
- Age (years)
- Weight (kg) - actual body weight
- Gender (male or female)
Formula:
- For men: CrCl = [(140 - age) × weight in kg] / (72 × serum creatinine in mg/dL)
- For women: CrCl = [(140 - age) × weight in kg × 0.85] / (72 × serum creatinine in mg/dL)
Why Cockcroft-Gault Matters for Bisphosphonates
All bisphosphonates carry labeled warnings or contraindications for use when CrCl <30-35 mL/min, making accurate calculation essential before prescribing. 2
Oral bisphosphonates (alendronate, risedronate, ibandronate) are contraindicated when CrCl <35 mL/min. 2
Intravenous bisphosphonates (zoledronic acid) are contraindicated when CrCl <35 mL/min, though transient postinfusion increases in serum creatinine can occur even with normal renal function. 2, 3
Critical Clinical Considerations
The Cockcroft-Gault equation may dramatically underestimate kidney function in older adults compared to CKD-EPI, potentially inappropriately excluding patients from bisphosphonate therapy who could safely receive it. 3
In patients aged 75 and older with CrCl >35 mL/min calculated by Cockcroft-Gault, the risk of acute kidney injury after zoledronic acid was only 1.4%, and no AKI occurred in the small subset with CrCl <35 mL/min. 3
Measure serum creatinine before initiating bisphosphonate therapy to calculate baseline CrCl and ensure the patient meets safety criteria. 1
Alternative Treatments When CrCl <30-35 mL/min
If bisphosphonates are contraindicated due to renal impairment:
Denosumab is the preferred alternative as it does not require renal dose adjustment and is not contraindicated in severe renal impairment, though calcium levels require strict monitoring. 4
Raloxifene may be considered for postmenopausal women when other options are not appropriate. 5
Teriparatide can be used if bisphosphonates and denosumab are not appropriate. 5
Monitoring During Bisphosphonate Therapy
Renal function should be monitored periodically during treatment, particularly in elderly patients or those with baseline renal impairment. 2, 4
Clinical trial data show that bisphosphonates do not cause long-term renal function deterioration when used according to prescribing information, even in elderly frail patients with mild-moderate renal impairment. 2