CKD progression risk ‘modest’ with bisphosphonate use

Adults with chronic kidney disease stage 3b were more likely to experience a worsening of renal function when prescribed bisphosphonate therapy, according to a database analysis published in the Journal of Bone and Mineral Research.
“We found an increasing risk for CKD progression associated with bisphosphonate use, equivalent to a number needed to harm of approximately 25 for a 5-year treatment regimen,” Victoria Strauss, Ph.D., a lead statistician with the Centre for Statistics in Medicine at the University of Oxford, U.K., told Healio. “However, no association was found between bisphosphonate use and acute kidney injury, gastrointestinal events, or severe hypocalcemia. Our research suggests that despite known bone fragility in people suffering from CKD, bisphosphonates should be used with caution, not only among those where bisphosphonates are contraindicated, such as those with an estimated glomerular filtration rate less than 30 mL/min/1.73 m², but also in patients with an eGFR between 30 mL/min/1.73 m² and 45 mL/min/1.73 m².”Strauss and colleagues analyzed data from two primary-care electronic record databases, the U.K. Clinical Practice Research Datalink (CPRD) GOLD (1997-2016) and Catalan Information System for Research in Primary Care (2007-2015). Both databases were linked to hospital records; the SIDIAP database was also linked to end-stage renal disease registry data.

Researchers identified patients with CKD stage 3b through stage 5, based on two or more eGFR measurements of less than 45 mL/min/1.73 m² who were aged at least 40 years; these patients were propensity-score matched with new bisphosphonate users (n = 2,447 in CPRD and 1,399 in SIDIAP) and with up to five non-users (n = 8,931 in CPRD and 6,547 in SIDIAP). The primary outcome was CKD stage worsening, defined as a decline in eGFR or renal replacement therapy. Secondary outcomes were acute kidney injury, gastrointestinal bleeding/ulcers and severe hypocalcemia.

Researchers found that bisphosphonate use was associated with a greater risk for CKD progression in the CPRD database (HR = 1.14; 95% CI, 1.04-1.26) and the SIDIAP database (HR = 1.15; 95% CI, 1.04-1.27).

There were no between-group risk differences for acute kidney injury, gastrointestinal bleeding/ulcers or hypocalcemia.

“Hence, we can conclude a modestly increased risk of CKD progression was identified in association with bisphosphonate use,” the researchers wrote. “No other safety concerns were identified.”

Strauss said future research should explore whether bisphosphonates increase the risk for CKD progression in CKD stage 3a patients.

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