Kidney Disease Improving Global Outcomes (KDIGO) 2017 Clinical Practice Guideline has recommended treatment decisions for patients with
chronic kidney disease (CKD) with
osteoporosis and/or high risk of fracture.
Bisphosphonates, the first-line anti-
osteoporosis drugs have the concern of worsening kidney functions. Moreover, despite impaired bone formation in CKD patients,
teriparatide, the formation-stimulating drug is not recommended. Thus, there is an urgent need for safe and effective treatment of
osteoporosis in CKD patients. Here, in CKD rats, we tested the osteoprotective effect of
diosmin, a citrus-derived
bioflavonoid used as a phlebotonic in chronic
venous insufficiency and has a renoprotective effect. CKD was developed by 5/6th
nephrectomy and
diosmin at the human equivalent dose (100 mg kg-1) did not advance
renal failure but reduced blood pressure to the level of
sham control.
Fibroblast growth factor-23 and
parathyroid hormone were increased in CKD and
diosmin suppressed both. CKD reduced bone mass and deteriorated the microarchitecture of trabecular bones, and
diosmin maintained both to control levels. Bone formation and strength were impaired in the CKD and
diosmin maintained these levels to control levels. Nanoindentation of bone showed that
diosmin significantly increased tissue hardness over the control.
Diosmetin, the metabolic surrogate of
diosmin had comparable pharmacokinetic profiles between the control and CKD groups. Furthermore,
diosmetin (50 mg kg-1) protected against CKD-induced bone loss. These data suggest that
diosmin and its metabolic surrogate,
diosmetin protect against CKD-induced
osteopenia. Since
diosmin has no renal adverse effect and protected bone mass and strength in CKD rats, we propose assessing its anti-
osteoporosis effect in CKD patients.