Effect of Intermittent Fasting on Glucose Homeostasis and Bone Remodeling in Glucocorticoid-Induced Osteoporosis Rat Model

Abstract

Background: The present study examined the effect of intermittent fasting (IF) on bone mineral content (BMC) and bone mineral density (BMD) and the markers of bone remodeling in a glucocorticoid-induced osteoporosis (GIO) rat model.

Methods: Forty male rats were allocated to 4 groups (N=10 per group): control group of normal rats; control+IF group (normal rats subjected to IF for 16-18 hr daily for 90 days); dexamethasone (DEX) group: (DEX [0.5 mg i.p.] for 90 days); and DEX+IF group (DEX and IF for 90 days). By the end of the experiment, BMD and BMC in the right tibia were measured. Serum levels of the following were measured: glucose; insulin; triglycerides (TGs); total cholesterol; parathyroid hormone (PTH); osteoprotegerin (OPG); receptor activator of nuclear factor-κB (RANK); bone-resorbing cytokines, including bone deoxypyridinoline (DPD), N-terminal telopeptide of collagen type I (NTX-1), and tartrate-resistant acid phosphatase 5b (TRAP-5b); and bone-forming cytokines, including alkaline phosphatase (ALP) and osteocalcin (OC).

Results: DEX administration for 90 days resulted in significantly increased serum levels of glucose, insulin, TGs, cholesterol, PTH, OPG, DPD, NTX-1, and TRAP-5b and significantly decreased BMD, BMC, and serum levels of RANK, OC, and ALP (all P<0.05). IF for 90 days significantly improved all these parameters (all P<0.05).

Conclusions: IF corrected GIO in rats by inhibiting osteoclastogenesis and PTH secretion and stimulating osteoblast activity.

Keywords: Bone remodeling; Fasting; Glucocorticoids; Osteocalcin; Osteoporosis; Parathyroid hormone.

Fig. 1

Serum levels of fasting glucose (mg/dL) (A) and fasting insulin (μU/mL) (B) in different groups. Data were expressed as mean±standard deviation. *Significant vs. control group. ^#Significant vs. control+intermittent fasting (IF) group. ^$Significant vs. dexamethasone (DEX) group. P ≤ 0.05 is considered significant.

Fig. 2

Serum levels of triglycerides (TGs) (mg/dL) (A) and total cholesterol (mg/dL) (B). Data were expressed as mean±standard deviation. *Significant vs. control group. ^#Significant vs. control+intermittent fasting (IF) group. ^$Significant vs. dexamethasone (DEX) group. P≤0.05 is considered significant.

Fig. 3

Bone mineral density (BMD) (A), bone mineral content (BMC) (B) in different groups. Graphs of X-rays pictures from (C) control group, (D) control+intermittent fasting (IF) group, (E) dexamethasone (DEX) group and (F) IF+DEX group. Data were expressed as mean±standard deviation. *Significant vs. control group. ^#Significant vs. control+IF group. ^$Significant vs. DEX group. P≤0.05 is considered significant. ROI, region of interest.

Fig. 5

Serum level of parathyroid hormone (PTH) in different studied groups. Data were expressed as mean±standard deviation. *Significant vs. control group. ^#Significant vs. control+intermittent fasting (IF) group. ^$Significant vs. dexamethasone (DEX) group. P≤0.05 is considered significant.

Fig. 4

Histopathological examination of the proximal metaphysis of the tibia using hematoxylin and eosin (H&E) in different groups. The specimens from the control and intermittent fasting (IF)+control groups show a network of cancellous bone trabeculae with osteocytes within their lacunae within bone trabeculae (black arrows) (×200 magnification) (A, B), from the dexamethasone (DEX) group show loss of trabecular bone with bone marrow (BM) spaces and empty lacunae (blue arrows) (×200 magnification) (C), and from the IF+DEX group shows n normal trabecular bone architecture with osteoblasts at endosteal surface (black arrows) (×200 magnification) (D).

Fig. 6

Serum levels of osteoprotegerin (pg/mL) (A) and receptor activator of nuclear factor-κB (RANK) (ng/dL) (B) in different groups. Data were expressed as mean±standard deviation.*Significant vs. control group. ^#Significant vs. control+intermittent fasting (IF) group. ^$Significant vs. dexamethasone (DEX) group. P ≤0.05 is considered significant.

Fig. 7

Serum levels of deoxypyridinoline (DPD) (ng/mL) (A), tartrate-resistant acid phosphatase (TRAP)-5b (ng/mL) (B) and N-terminal telopeptide of collagen type I (NTX-1) (ng/mL) (C) as bone resorbing biomarkers in different groups. Data were expressed as mean±standard deviation. *Significant vs. control group. ^#Significant vs. control+intermittent fasting (IF) group. ^$Significant vs. dexamethasone (DEX) group. P ≤0.05 is considered significant.

Fig. 8

Serum levels of osteocalcin (pg/mL) (A) and alkaline phosphatase (ng/mL) (B) in different groups. Data were expressed as mean±standard deviation. *Significant vs. control group. ^#Significant vs. control+intermittent fasting (IF) group. ^$Significant vs. dexamethasone (DEX) group. P ≤ 0.05 is considered significant.