Use of SGLT2 inhibitors may not increase fracture risk in patients with CKD
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Key takeaways:
- Canagliflozin showed beneficial results in serum phosphate, plasma FGF-23 and plasma PTH.
- The association between SGLT2i and fracture risk is inconclusive.
While SGLT2 inhibitors are often associated with bone and mineral metabolism irregularities, it remains unclear if these are linked to higher fracture risk in patients with chronic kidney disease, according to recently published research.
“[Chronic kidney disease] CKD is frequently associated with disorders of bone and mineral metabolism, including abnormal metabolism of calcium, phosphorus, parathyroid hormone or vitamin D; as well as abnormalities in bone mineralization, turnover, volume, linear growth and strength,” Arnaud D. Kaze, MD, MPH, and colleagues, wrote. “This review analyzes recent evidence on the safety of [SGLT2 inhibitors] SGLT2i with respect to bone and mineral metabolism ... and discusses potential underlying mechanisms and clinical implications.”
Researchers conducted a meta-analysis of recently published studies and found several indicate SGLT2i may increase serum phosphate level and potentially affect bone and mineral homeostasis.
Canagliflozin, for example, was associated with beneficial results in a placebo-controlled randomized crossover study of 25 healthy adults. Treatment was tied to increased levels of serum phosphate by 16%, plasma FGF-23 by 20% and plasma PTH by 25%. Canagliflozin also decreased levels of 1,25-dihydroxyvitamin D by 10%, according to the review.
“The increased renal tubular reabsorption of phosphate was noted within 2 to 4 hours after the administration of canagliflozin,” the researchers wrote. “Peak levels of FGF-23 were noted about 12 hours after the peak serum phosphorus level.”
Dapagliflozin and empagliflozin also showed similar effects on these markers. However, the changes in bone turnover markers have been inconsistent across different studies.
SGLT2i are an emerging class of antidiabetic medications with potentially positive cardiovascular and kidney effects in patients with CKD, according to the review. While use is “steadily increasing among patients with CKD, major professional organizations are recommending the use of this medication class in this patient population.”
The association between SGLT2i and fracture risk in patients with CKD, however, remains inconclusive. Some studies report no significant difference in fracture risk between SGLT2i users and non-users, while others show conflicting results, the researchers note.
As SGLT2i use continues to increase, it is crucial to monitor and evaluate the impact of these on bone health, Kaze and colleagues wrote. Further studies should assess the effect of SGLT2i on fracture risk in patients with CKD, particularly those at higher baseline risk.
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