Is it safe to take bisphosphonates (BIS) with chronic kidney disease (CKD)?

Bisphosphonate Use in Chronic Kidney Disease

Bisphosphonates should be used with caution in CKD, with consideration for bone biopsy prior to therapy in patients with CKD G4-G5D, and are not recommended for patients with creatinine clearance less than 35 mL/min. 1, 2

Safety Considerations by CKD Stage

CKD Stage 3 (eGFR 30-59 mL/min/1.73m²)

• Bisphosphonates can be used in patients with CKD G3a-G3b, but treatment choices should take into account the magnitude and reversibility of biochemical abnormalities and the progression of CKD 2
• Recent evidence shows a modest (15%) increased risk of CKD progression associated with bisphosphonate use in patients with moderate to severe CKD 3
• Oral bisphosphonates appear to have better renal safety in patients with lower creatinine clearance compared to intravenous formulations 2

CKD Stage 4-5 (eGFR <30 mL/min/1.73m²)

• Alendronate is not recommended for patients with creatinine clearance less than 35 mL/min according to FDA labeling 1
• For patients with CKD G4-G5D with biochemical abnormalities of CKD-MBD and low BMD and/or fragility fractures, additional investigation with bone biopsy is suggested prior to therapy with antiresorptive agents 2
• The use of bisphosphonates in males with CKD G4-G5D is considered off-label 4

Monitoring and Precautions

Renal Function Monitoring

• Serum creatinine should be monitored prior to each dose of intravenous bisphosphonates (pamidronate or zoledronic acid) 2
• When bisphosphonates are given to CKD stage 4-5 patients, it is reasonable to reduce the dose to 50% 5
• The development of renal dysfunction warrants discontinuation of the drug until reversal of renal abnormalities occurs 2

Mineral Metabolism

• Hypocalcemia must be corrected before initiating therapy with bisphosphonates 1
• Serum calcium, electrolytes, phosphate, magnesium, and hematocrit/hemoglobin should be monitored regularly in CKD patients receiving bisphosphonates 2
• Treatment may induce hypocalcemia in CKD patients with secondary hyperparathyroidism, but vitamin D supplementation may ameliorate this effect 6

Special Considerations

Bone Turnover Disorders

• Bone biopsy should be considered before prescribing bisphosphonates in advanced CKD due to the increased possibility of low bone turnover disorders such as adynamic bone disease 6, 2
• Bisphosphonate treatment can improve both bone mineral density and vascular calcification, but this becomes less likely in patients with stage 3-4 CKD who have vascular calcification without decreased bone mineral density 6

Administration Methods

• For hemodialysis patients, administration during the hemodialysis session is recommended 5
• Infusion times less than 2 hours with pamidronate or less than 15 minutes with zoledronic acid should be avoided to reduce risk of renal toxicity 2

Efficacy in CKD

• Despite concerns, some data suggest that bisphosphonate treatment may reduce fracture risk without increasing adverse events in patients with CKD 7
• In patients with CKD, bisphosphonates have been shown to improve bone mineral density, with an average 2.65% greater gain in femoral neck BMD per year compared to non-users 8

Common Pitfalls and Caveats

• Underutilization of bisphosphonates in early CKD due to overly restrictive prescribing guidelines may deprive patients of effective osteoporosis treatment 7
• Differentiating between osteoporosis and CKD-MBD in patients with low bone mineral density is challenging and may require bone biopsy 6
• Prescribing bisphosphonates without proper monitoring of renal function and mineral metabolism can lead to worsening of kidney function and other complications 3, 2

In conclusion, while bisphosphonates can be used with appropriate caution in CKD stages 3a-3b, their use in advanced CKD (stages 4-5) requires careful consideration of risks and benefits, with bone biopsy recommended prior to therapy to rule out adynamic bone disease.