Reduced Kidney Function Attenuates BMD Gains in Bisphosphonate Treatment

Illustration of a man’s kidneys.
Gains in bone mineral density associated with bisphosphonate treatment in patients with osteoporosis are reduced with decreasing kidney function.

Gains in bone mineral density (BMD) associated with bisphosphonate treatment in patients with osteoporosis are reduced with decreasing kidney function, according to study results published in Bone.

Bisphosphonates used to treat osteoporosis are cleared by renal filtration and thus are not recommended in patients with reduced kidney function. Using data from the real-world observational Odense Bisphosphonate Safety Study, investigators aimed to identify the cutoff for renal function below which there is no benefit to BMD in bisphosphonate treatment.

A total of 1789 bisphosphonate users (81.0% women) and 3908 nonusers (79.0% women) who received both a measurement of estimated glomerular filtration rate (eGFR) and dual-energy x-ray absorptiometry scans within 1 year of index date were included in the analysis.

Bisphosphonate users exhibited progressively smaller gains in BMD with decreasing renal function. For patients with stage 1 chronic kidney disease (CKD), an annual 1% change in total hip BMD was observed, compared with 0.1% in patients with stage 3B CKD. For individuals with CKD stage 3A and better, annual increase in BMD was higher than in nonusers at similar levels of kidney function. The annual loss of BMD was not associated with kidney function down to stage 3B in nonusers.

Adherence to bisphosphonate therapy was the strongest predictor of BMD gains, and this effect of adherence on change in BMD was nonsignificantly attenuated when adjusted for eGFR.

No difference in safety events, including acute renal injury, glomerulonephritis, or dialysis, were observed between bisphosphonate users and nonusers. Hypocalcemia events were rare in both bisphosphonate users (0.80 per 1000 patient-years) and nonusers (0.75 per 1000 patient-years). No kidney transplantations occurred over the course of follow-up (up to 3 years) in nonusers, and the rate in bisphosphonate users was 0.26 per 1000 patient-years.

The investigators noted that the observational nature of the study represented a limitation, as treatment was based on provider recommendations rather than randomization.

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“We noted a gradual decrease in the absolute gains in BMD in oral bisphosphonate users with decreasing renal function,” the study authors concluded. “More data is needed on the efficacy and safety of bisphosphonates in CKD stage 3B to 5 and prescribers should reconsider the low use of [dual-energy x-ray absorptiometry] in patients with renal function impairment now that a wider range of treatment options have become available.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

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Abrahamsen B, Ernst MT, Smith CD, et al. The association between renal function and BMD response to bisphosphonate treatment: real-world cohort study using linked national registers [published online April 22, 2020]. Bone. doi:10.1016/j.bone.2020.115371