Abstract
Osteoporosis is a highly prevalent skeletal disorder in the elderly that causes serious bone fractures. Peak bone mass achieved at adolescence has been shown to predict bone mass and osteoporosis related risk fracture later in life. Resveratrol, a natural polyphenol compound, may have the potential to promote bone formation and reduce bone resorption. However, it is unclear whether it can aid bone growth and bone mass accumulation during rapid growth and modulate bone metabolism during ageing. Using rat models, the current study investigated the potential effects of resveratrol supplementation during the rapid postnatal growth period and in late adulthood (early ageing) on bone microarchitecture and metabolism. In the growth trial, 4-week-old male hooded Wistar rats on a normal chow diet were given resveratrol (2.5 mg/kg/day) or vehicle control for 5 weeks. In the ageing trial, 6-month-old male hooded Wistar rats were treated with resveratrol (20 mg/kg/day) or vehicle for 3 months. Treatment effects in the tibia were examined by μ-computer tomography (μ-CT) analysis, bone histomorphometric measurements and reverse transcription-polymerase chain reaction (RT-PCR) gene expression analysis. Resveratrol treatment did not affect trabecular bone volume and bone remodeling indices in the youth animal model. Resveratrol supplementation in the early ageing rats tended to decrease trabecular bone volume, Sirt1 gene expression and increased expression of adipogenesis-related genes in bone, all of which were statistically insignificant. However, it decreased osteocalcin expression (p = 0.03). Furthermore, serum levels of bone resorption marker C-terminal telopeptides type I collagen (CTX-1) were significantly elevated in the resveratrol supplementation group (p = 0.02) with no changes observed in serum levels of bone formation marker alkaline phosphatase (ALP). These results in rat models suggest that resveratrol supplementation does not significantly affect bone volume during the rapid growth phase but may potentially have negative effects on male skeleton during early ageing.
Highlights
Osteoporosis is a disease that is characterized by a progressive decrease in bone mass and subsequently an increase in fracture risk [1]
Effects of resveratrol supplementation at 2.5 mg/kg from 4 to 9 weeks of age on bone structure and volume were examined by μ-computer tomography (μ-CT) and histomorphometry. μ-CT analysis revealed no significant differences in trabecular bone structures and volume (BV/TV, %) between the resveratrol and control groups (Figure 1A–C)
While in vitro studies have shown that resveratrol can dose-dependently increase proliferation and differentiation of osteoblastic MC3T3-E1 cells [17] and can promote human mesenchymal stem cell commitment to the osteogenic lineage through the master osteogenic transcription factor RUNX2 [24,37], our current study demonstrated that resveratrol supplementation for 5 weeks during the rapid growth period in male rats had no significant effects on growth plate thickness, primary spongiosa heights and trabecular bone volume by the end of treatment, suggesting a lack of effect of resveratrol supplementation on the bone mass outcome in growing rats
Summary
Osteoporosis is a disease that is characterized by a progressive decrease in bone mass and subsequently an increase in fracture risk [1]. The importance of peak bone mass (accrued by late adolescence or young adulthood) in relation to fracture risk has been studied extensively, and developing strategies to enhance peak bone mass has been suggested to be an important means of reducing the risk of osteoporosis in later life. Epidemiological studies have shown that a 10% increase in peak bone mass could be predicted to reduce the risk of fracture by 50% in women after menopause [5,6,7]. Since bone loss continues with ageing, the bone mass of individuals later in life largely depends upon the original peak bone mass achieved during the skeletal growth phase and the subsequent rate of bone loss. Preventative means against osteoporosis should be aimed at increasing the peak bone mass during growth and reducing the rate of bone loss during ageing
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