Journal of nephrology · 2026
Effects of gliflozins on bone health of patients with chronic kidney disease: a systematic review.
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Cassani de Oliveira Mariana, Rufino Lorena, Mendes Lourenço Ana Laura, Corrêa Eric Aragão, Mac-Way Fabrice, Pelepenko Lauter Eston, Câmara Niels Olsen Saraiva, de Oliveira Rodrigo Bueno
Аннотация
BACKGROUND: Sodium-glucose co-transporter-2 inhibitors (SGLT2i) are a crucial therapy for chronic kidney disease (CKD), yet concerns persist regarding their impact on bone metabolism. This systematic review evaluates the skeletal safety and metabolic effects of SGLT2i in patients with CKD.
METHODS: A systematic review of randomized controlled trials (RCTs) and observational cohort studies was conducted. Data on study design, population characteristics, baseline kidney function, bone-related comorbidities, and outcomes (osteoporosis, fractures, falls, amputations, and bone mineral markers) were summarized. Risk of bias was evaluated according to the included category.
RESULTS: The analysis revealed that while one RCT and a cohort study reported a significantly increased risk of bone fracture and amputation, this finding was not replicated in other subsequent cohort studies and other RCTs, which generally showed non-significant differences. Of note, the reporting of bone-related outcomes was inconsistent throughout the literature, and a substantial proportion of the evidence derives from studies primarily designed for patients with type 2 diabetes, largely involving early-stage CKD subgroups. One study suggests that SGLT2i may favorably modulate markers of CKD-mineral bone disease (MBD), reporting reduced risk of hyperphosphatemia, hypocalcemia, high parathyroid hormone, and low vitamin D levels. The reviewed literature primarily included data on empagliflozin, canagliflozin, dapagliflozin, and ertugliflozin.
CONCLUSIONS: Mostly, SGLT2i demonstrated a possible reassuring skeletal safety profile in CKD. Initial safety concerns regarding fractures have not been consistently supported, although evidence in moderate-to-advanced CKD remains limited. Long-term, prospectively defined skeletal outcomes are needed to confirm these findings and clarify class effects.
METHODS: A systematic review of randomized controlled trials (RCTs) and observational cohort studies was conducted. Data on study design, population characteristics, baseline kidney function, bone-related comorbidities, and outcomes (osteoporosis, fractures, falls, amputations, and bone mineral markers) were summarized. Risk of bias was evaluated according to the included category.
RESULTS: The analysis revealed that while one RCT and a cohort study reported a significantly increased risk of bone fracture and amputation, this finding was not replicated in other subsequent cohort studies and other RCTs, which generally showed non-significant differences. Of note, the reporting of bone-related outcomes was inconsistent throughout the literature, and a substantial proportion of the evidence derives from studies primarily designed for patients with type 2 diabetes, largely involving early-stage CKD subgroups. One study suggests that SGLT2i may favorably modulate markers of CKD-mineral bone disease (MBD), reporting reduced risk of hyperphosphatemia, hypocalcemia, high parathyroid hormone, and low vitamin D levels. The reviewed literature primarily included data on empagliflozin, canagliflozin, dapagliflozin, and ertugliflozin.
CONCLUSIONS: Mostly, SGLT2i demonstrated a possible reassuring skeletal safety profile in CKD. Initial safety concerns regarding fractures have not been consistently supported, although evidence in moderate-to-advanced CKD remains limited. Long-term, prospectively defined skeletal outcomes are needed to confirm these findings and clarify class effects.