From the Guidelines
Denosumab is the safest osteoporosis medication option for patients with creatinine clearance under 35 ml/min, as it does not require dose adjustments and is not cleared by the kidneys. According to the study 1, denosumab may be administered to patients with impaired renal function or even patients on hemodialysis, although the risk for severe hypocalcemia and hypophosphatemia is greater. Key considerations for using denosumab in this population include:
- Correcting hypocalcemia before starting denosumab
- Monitoring serum calcium levels
- Optimizing vitamin D and calcium supplementation In contrast, zoledronic acid should be held for creatinine clearance <30 mL/min due to the risk of accumulation and further kidney damage 1. Other osteoporosis medications, such as bisphosphonates, may also be problematic in patients with severe renal impairment due to potential accumulation and toxicity. Therefore, denosumab is the preferred option for patients with creatinine clearance under 35 ml/min.
From the Research
Osteoporosis Medications and Renal Safety
- The safety of osteoporosis medications in patients with creatinine clearance under 35 ml/min has been evaluated in several studies 2, 3, 4, 5, 6.
- Bisphosphonates, a class of osteoporosis medications, are eliminated from the body by the kidney and may pose a risk to patients with severe renal impairment 2, 3.
- However, studies have shown that oral bisphosphonates, such as alendronate, may be safe for use in patients with creatinine clearance under 35 ml/min, with no significant deterioration in renal function or increased incidence of osteoporotic fractures or acute kidney injury 5.
Bisphosphonate-Specific Safety Profiles
- Zoledronic acid, an intravenous bisphosphonate, should be avoided in patients with GFR levels <35 ml/min due to the risk of acute kidney injury 2, 4.
- Ibandronate, another intravenous bisphosphonate, has not been reported to induce acute changes in serum creatinine concentrations, but the lack of head-to-head comparative data with zoledronic acid precludes knowing if one is safer than the other 2, 6.
- Alendronate, an oral bisphosphonate, may be safe for use in patients with creatinine clearance under 35 ml/min, with no significant deterioration in renal function or increased incidence of osteoporotic fractures or acute kidney injury 5.
Clinical Practice Recommendations
- Physicians should follow guidelines for bisphosphonate therapies administration at all times, taking into account the patient's renal function and other comorbidities 3, 6.
- Estimated glomerular function (eGFR) may be used to predict acute kidney injury in patients treated with zoledronic acid, and may be at least as good a predictor as creatinine clearance (CrCl) 4.
- Patients with creatinine clearance under 35 ml/min should be closely monitored for signs of acute kidney injury and other adverse events when treated with bisphosphonates 2, 3, 4, 5, 6.