Unfavorable effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors on the skeletal system of nondiabetic rats

Londzin, Piotr; Brudnowska, Agata; Kurkowska, Katarzyna; Wilk, Katarzyna; Olszewska, Karolina; Ziembiński, Łukasz; Janas, Aleksandra; Cegieła, Urszula; Folwarczna, Joanna

doi:10.1016/j.biopha.2022.113679

Cited by 7 publications

(7 citation statements)

References 74 publications

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“…In a nondiabetic rat model, canagliflozin and dapagliflozin induced disorders of cancellous bone microarchitecture and bone mechanical properties. 225 In diabetic DBA/2J mice, canagliflozin improved blood glucose but did not affect streptozotocin-induced trabecular and cortical microarchitecture. However, in the control group, canagliflozin caused adverse effects on the femoral trabecular bone.…”

Section: Anti-sclerostin Antibody: Romosozumabmentioning

confidence: 91%

Cardiovascular Calcification Heterogeneity in Chronic Kidney Disease

Hutcheson

Goettsch

2023

Circulation Research

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Patients with chronic kidney disease (CKD) exhibit tremendously elevated risk for cardiovascular disease, particularly ischemic heart disease, due to premature vascular and cardiac aging and accelerated ectopic calcification. The presence of cardiovascular calcification associates with increased risk in patients with CKD. Disturbed mineral homeostasis and diverse comorbidities in these patients drive increased systemic cardiovascular calcification in different manifestations with diverse clinical consequences, like plaque instability, vessel stiffening, and aortic stenosis. This review outlines the heterogeneity in calcification patterning, including mineral type and location and potential implications on clinical outcomes. The advent of therapeutics currently in clinical trials may reduce CKD-associated morbidity. Development of therapeutics for cardiovascular calcification begins with the premise that less mineral is better. While restoring diseased tissues to a noncalcified homeostasis remains the ultimate goal, in some cases, calcific mineral may play a protective role, such as in atherosclerotic plaques. Therefore, developing treatments for ectopic calcification may require a nuanced approach that considers individual patient risk factors. Here, we discuss the most common cardiac and vascular calcification pathologies observed in CKD, how mineral in these tissues affects function, and the potential outcomes and considerations for therapeutic strategies that seek to disrupt the nucleation and growth of mineral. Finally, we discuss future patient-specific considerations for treating cardiac and vascular calcification in patients with CKD—a population in need of anticalcification therapies.

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Section: Anti-sclerostin Antibody: Romosozumabmentioning

confidence: 91%

Cardiovascular Calcification Heterogeneity in Chronic Kidney Disease

Hutcheson

Goettsch

2023

Circulation Research

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“…In the ITP, dietary canagliflozin (180 ppm) started at 7 months of age extended the lifespan of UM-HET3 male mice by 14% with no effect on females despite lower fasting glucose and improved glucose tolerance in both sexes [52]. Concerningly, canagliflozin use in patients with T2DM, UM-HET3 mice, and rats report adverse effects on bone health as evident by decreased bone mineral density and increased risk of fracture [185][186][187][188][189].…”

Section: Sglt2 Inhibitorsmentioning

confidence: 99%

“…More work is needed exploring the interaction between various exercise modalities and SGLT2i to determine if SGLTi can have favorable effects on exercise adaptations. Furthermore, there is a need to understand whether the osteogenic effects of exercise can protect against the decline in bone health with SGLT2i use [185][186][187][188][189]. The limited data to date in humans suggests SGLT2i may interfere with glucose control and insulin sensitivity but do not negatively impact several other health benefits of exercise.…”

Section: Sglt2i + Exercisementioning

confidence: 99%

Geroprotector drugs and exercise: friends or foes on healthy longevity?

Elliehausen,

Anderson,

Diffee

et al. 2023

BMC Biol

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Physical activity and several pharmacological approaches individually combat age-associated conditions and extend healthy longevity in model systems. It is tantalizing to extrapolate that combining geroprotector drugs with exercise could extend healthy longevity beyond any individual treatment. However, the current dogma suggests that taking leading geroprotector drugs on the same day as exercise may limit several health benefits. Here, we review leading candidate geroprotector drugs and their interactions with exercise and highlight salient gaps in knowledge that need to be addressed to identify if geroprotector drugs can have a harmonious relationship with exercise.

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“…The mechanical properties studies were performed on the left tibia (the proximal tibial metaphysis), left femur (the femoral diaphysis) and the proximal part of the right femur (the femoral neck) of each rat using Instron 3342 500 N apparatus (Instron, Norwood, MA, USA). The data were analyzed using Bluehill 2 software version 2.14 (Instron, Norwood, MA, USA) [58,[99][100][101].…”

Section: Bone Mechanical Properties Studiesmentioning

confidence: 99%

“…The mechanical properties of the proximal tibial metaphysis were evaluated after removing the proximal tibial epiphysis, using a three-point bending test [58,[99][100][101][102]. The two supporting points were the edge of the proximal tibial metaphysis and the location of the fibula attachment to the tibia.…”

Section: Bone Mechanical Properties Studiesmentioning

confidence: 99%

Effects of Donepezil on the Musculoskeletal System in Female Rats

Londzin

Trawczyński

Cegieła

et al. 2023

IJMS

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The extension of human life makes it more and more important to prevent and treat diseases of the elderly, including Alzheimer’s disease (AD) and osteoporosis. Little is known about the effects of drugs used in the treatment of AD on the musculoskeletal system. The aim of the present study was to investigate the effects of donepezil, an acetylcholinesterase inhibitor, on the musculoskeletal system in rats with normal and reduced estrogen levels. The study was carried out on four groups of mature female rats: non-ovariectomized (NOVX) control rats, NOVX rats treated with donepezil, ovariectomized (OVX) control rats and OVX rats treated with donepezil. Donepezil (1 mg/kg p.o.) was administered for four weeks, starting one week after the ovariectomy. The serum concentrations of CTX-I, osteocalcin and other biochemical parameters, bone mass, density, mineralization, histomorphometric parameters and mechanical properties, and skeletal muscle mass and strength were examined. Estrogen deficiency increased bone resorption and formation and worsened cancellous bone mechanical properties and histomorphometric parameters. In NOVX rats, donepezil decreased bone volume to tissue volume ratio in the distal femoral metaphysis, increased the serum phosphorus concentration and tended to decrease skeletal muscle strength. No significant bone effects of donepezil were observed in OVX rats. The results of the present study indicate slightly unfavorable effects of donepezil on the musculoskeletal system in rats with normal estrogen levels.

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Unfavorable effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors on the skeletal system of nondiabetic rats

Cited by 7 publications

References 74 publications

Cardiovascular Calcification Heterogeneity in Chronic Kidney Disease

Cardiovascular Calcification Heterogeneity in Chronic Kidney Disease

Geroprotector drugs and exercise: friends or foes on healthy longevity?

Effects of Donepezil on the Musculoskeletal System in Female Rats

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