At what Glomerular Filtration Rate (GFR) should bisphosphonates be avoided?

GFR Threshold for Avoiding Bisphosphonates

Bisphosphonates should not be prescribed in patients with GFR <30 mL/min/1.73 m² unless there is a strong clinical rationale. 1

Evidence-Based Recommendations

• Bisphosphonates are eliminated from the body by the kidney through both glomerular filtration and proximal tubular secretion 2
• KDOQI guidelines specifically recommend against prescribing bisphosphonate treatment in people with GFR <30 mL/min/1.73 m² (GFR categories G4-G5) without a strong clinical rationale 1
• For intravenous zoledronic acid specifically, it should be avoided in patients with GFR levels <35 mL/min due to reports of acute changes in serum creatinine concentrations post-infusion 2
• Oral bisphosphonates have not been shown to adversely affect kidney function, even in post-hoc analyses of clinical trials with patients having estimated GFR as low as 15 mL/min 2

Renal Considerations by Administration Route

Oral Bisphosphonates

• Oral bisphosphonates appear to be safer for the kidneys than intravenous formulations 3
• Risedronate may be a safer choice for patients with severe CKD who have no signs of renal osteodystrophy, but requires strict monitoring of renal function and PTH 4
• No renal pathology has been specifically associated with oral administration of bisphosphonates 5

Intravenous Bisphosphonates

• Intravenous zoledronic acid should be administered with an infusion rate no faster than 15 minutes to minimize renal risk 2
• Short-term increases in serum creatinine have been observed in a subset of patients 9-11 days post-infusion with zoledronic acid 2
• Patients receiving IV bisphosphonates should be well-hydrated and avoid concomitant use of any agents that may impair renal function 2

Special Considerations for CKD Patients

• In patients with GFR <30-35 mL/min, the diagnosis of osteoporosis becomes more complex as other forms of renal bone disease need to be excluded 2
• For patients on hemodialysis, administration during the hemodialysis session is recommended 5
• When bisphosphonates are given to patients with CKD stage 4-5, it is reasonable to reduce the dose to 50% of the standard dose 5
• If suppressed bone turnover (adynamic bone disease) is suspected, bone biopsy is mandatory before initiating bisphosphonate therapy 5

Alternative Therapies for Osteoporosis in Severe CKD

• Denosumab with regular monitoring of calcium and adequate vitamin D levels may be considered as an alternative 4
• Raloxifene is another possible alternative for patients with severe renal impairment 4
• Nearly 3.59% of osteoporotic women would not be recommended for bisphosphonate treatment due to severe renal impairment, highlighting the need for alternative therapies 6

Clinical Implications

• Physicians should always check renal function before prescribing bisphosphonates 3
• For patients with moderate renal impairment (GFR 30-59 mL/min), bisphosphonates can generally be used with appropriate monitoring 6
• All bisphosphonate therapies carry warnings for use in patients with severe renal impairment 3
• Following administration guidelines is critical to prevent adverse renal outcomes, particularly with intravenous formulations 3

The evidence clearly establishes GFR <30 mL/min/1.73 m² as the threshold below which bisphosphonates should generally be avoided, with a slightly higher threshold of <35 mL/min for intravenous zoledronic acid specifically.