High calcium diet alleviates 5/6 nephrectomy-induced bone deteriorations of lumbar vertebrae in mice

Abstract

Abstract. Dietary calcium (Ca) supplementation has beneficial effects on bone health. However, it is not clear whether a high calcium diet (HCD) following 5/6 nephrectomy (5/6 Nx) is beneficial to bone health. The aim of the present study was to examine the effects of an HCD on bone metabolism using a chronic kidney disease (CKD) mouse model. Male C57BL/6J mice were divided into three groups: Sham group, 5/6 Nx group and 5/6 Nx + HCD group. Mice were sacrificed 12 weeks post-surgery. Calcium (Ca) and creatinine (Cr) were measured using standard colorimetric methods and picric acid methods, respectively. Bone metabolism-associated markers, FGF-23, PTH, ALP-b and TRAP-5b were measured using ELISA kits. Lumbar vertebrae histomorphological analysis was performed using hematoxylin and eosin staining. The expression of osteoprotegerin (OPG) and receptor activator of nuclear factor κB ligand (RANKL) mRNA was detected using reverse transcription-quantitative polymerase chain reaction. Impaired renal function and histopathological damage was indicated in 5/6 Nx mice. However, HCD had no significant effects on these changes in 5/6 Nx mice. Notably, mineral metabolism disorder and histopathological damage to lumbar vertebrae were markedly improved in HCD-treated 5/6 Nx mice. Compared with 5/6 Nx mice, HCD supplementation significantly elevated the ratio of OPG/RANKL and inhibited RANKL mRNA expression in lumbar vertebrae. To conclude, the present findings indicated that increased Ca intake is effective in increasing bone mineral content of the lumbar vertebrae in 5/6 Nx mice. These results may provide a basis for the clinical use of dietary Ca supplementation as a therapeutic approach to treat CKD-induced disturbance of mineral metabolism and bone loss.

Doxercalciferol Alleviates Bone Deteriorations and Cartilage Degeneration in Aging Mice

“…OPG and RANKL as the mainly regulators affect the activity of osteoclast. OPG as a competitive inhibitor to RANKL blocks RANKL binding to the RANK receptor on osteoclast cells, subsequently inhibiting bone resorption and osteoclastogenesis [13]. Previous study found that the ratio of RANKL to OPG is increased in ovariectomized rats, while attenuation of the RANKL/ OPG ratio can reduce bone loss [29].…”

“…Continuous PTH administration leads to the catabolism of bone, while intermittent PTH administration promotes anabolic effects on bone [10,11]. Numerous studies have validated that serum PTH level is up-regulated in a variety of animal models of osteoporosis, such as ovariectomized [12] and 5/6 nephrectomy [13]. A clinical investigation indicates that post-menopausal women have higher serum PTH and lower bone density of spine and femoral neck than premenopausal women, suggesting that elevated in intact PTH is related to age, but there is no evidence to validate that PTH is a mediator of age-related bone loss [14].…”

Mouse Models of Mineral Bone Disorders Associated with Chronic Kidney Disease

“…CKD degree was progressively increasing over time, mainly in genetic models of CKD. Surgical models were the most frequently used [ 19 , 20 , 21 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 ], as they offered the possibility to compare the phenotype before and after surgery and were described as stable over time. Subtotal nephrectomy, so-called 5/6th nephrectomy, mimics quite well the process of reduction in nephron mass occurring in humans during renal failure.…”

Diosmin, a citrus fruit-derived phlebotonic bioflavonoid protects rats from chronic kidney disease-induced loss of bone mass and strength without deteriorating the renal function

“…Thus, CKD-induced bone loss was caused by a combination of decreased osteoblast activity and enhanced osteoclast function, and the latter event appeared to be mediated by increased osteoblastic RANKL production. 78,79 Suppression of RANKL in the diosmin-treated CKD rats likely contributed to the inhibition of resorption reflected by the restoration of TRAcP-5b and osteoclast number and activity to the control levels.…”