title: Effects of resveratrol supplementation on bone growth in young rats and microarchitecture and remodeling in ageing rats.
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.
authors.affiliation: Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA 5001, Australia. alice.lee@unisa.edu.au.
authors.forename: Alice M C
authors.initials: AM
authors.lastname: Lee
authors.affiliation: Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA 5001, Australia. tetyanas@geneworks.com.au.
authors.forename: Tetyana
authors.initials: T
authors.lastname: Shandala
authors.affiliation: Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA 5001, Australia. long.nguyen@unisa.edu.au.
authors.forename: Long
authors.initials: L
authors.lastname: Nguyen
authors.affiliation: Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA 5001, Australia. Beverly.Muhlhausler@adelaide.edu.au.
authors.forename: Beverly S
authors.initials: BS
authors.lastname: Muhlhausler
authors.affiliation: Institute of Orthopaedics, Lanzhou General Hospital, Lanzhou Command of People's Liberation Army, Lanzhou 730050, China. chenkm@lut.cn.
authors.forename: Ke-Ming
authors.initials: KM
authors.lastname: Chen
authors.affiliation: Clinical Nutrition Research Centre, University of Newcastle, Callaghan, NSW 2308, Australia. peter.howe@newcastle.edu.au.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Howe
authors.affiliation: Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA 5001, Australia. cory.xian@unisa.edu.au.
authors.forename: Cory J
authors.initials: CJ
authors.lastname: Xian
mesh_terms: D050156:Adipogenesis / Q000187:drug effects; D000375:Aging; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D001846:Bone Development / Q000187:drug effects*; D016723:Bone Remodeling / Q000187:drug effects*; D024042:Collagen Type I / Q000097:blood; D019587:Dietary Supplements; D008297:Male; D023421:Models, Animal; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000077185:Resveratrol; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D024042:Collagen Type I; D013267:Stilbenes; D015675:Osteocalcin; D000469:Alkaline Phosphatase; C488368:Sirt1 protein, rat; D056564:Sirtuin 1; D000077185:Resveratrol