title: The effects of strength training and raloxifene on bone health in aging ovariectomized rats.
abstract: The aim of this study was to investigate the effects of strength training (ST) and raloxifene (Ral), alone or in combination, on the prevention of bone loss in an aging estrogen-deficient rat model. Aging Wistar female rats were ovariectomized at 14months and allocated to four groups: (1) non-trained and treated with vehicle, NT-Veh; (2) strength training and treated with vehicle, ST-Veh; (3) non-trained and treated with raloxifene, NT-Ral; and (4) strength training and treated with raloxifene, ST-Ral. ST was performed on a ladder three times per week and Ral was administered daily by gavage (1mg/kg/day), both for 120days. Areal bone mineral density (aBMD), strength, microarchitecture, and biomarkers (osteocalcin, OCN; osteoprotegerin, OPG; and tartrate-resistant acid phosphatase, TRAP) were assessed. Immunohistochemistry was performed for runt-related transcription factor 2 (RUNX2), osterix (OSX), OCN, OPG, TRAP, and receptor activator of nuclear factor kappa-B ligand (RANKL). The rats that performed ST (ST-Veh) or were treated with Ral (NT-Ral) showed significant improvements in aBMD (p=0.001 and 0.004), bone strength (p=0.001), and bone microarchitecture, such as BV/TV (%) (p=0.001), BS/TV (mm(2)/mm(3)) (p=0.023 and 0.002), Conn.Dn (1/mm(3)) (p=0.001), Tb.N (1/mm) (p=0.012 and 0.011), Tb.Th (1/mm) (p=0.001), SMI (p=0.001 and 0.002), Tb.Sp (p=0.001), and DA (p=0.002 and 0.007); there was also a significant decrease in plasma levels of OCN (p=0.001 and 0.002) and OPG (p=0.003 and 0.014), compared with animals in the NT-Veh group. Ral, with or without ST, promoted an increased immunolabeling pattern for RUNX2 (p=0.0105 and p=0.0006) and OSX (p=0.0105), but a reduced immunolabeling pattern for TRAP (p=0.0056) and RANKL (p=0.033 and 0.004). ST increased the immunolabeling pattern for RUNX2 (p=0.0105), and association with Ral resulted in an increased immunolabeling pattern for OPG (p=0.0034) and OCN (p=0.0024). In summary, ST and Ral administration in aged, estrogen-deficient Wistar female rats is associated with a decrease in bone turnover marker plasma levels, increased activity of cells that promote osteoblastogenesis, and decreased activity of cells that promote osteoclastogenesis; these are correlated with higher aBMD, bone strength, and bone microarchitecture at the femoral neck. The results indicate that strength training and Ral are potential tools to reduce the risk of fractures at clinically relevant sites.
authors.affiliation: Programa Multicêntrico de Pós-Graduação em Ciências Fisiológicas. Electronic address: camilatami@foa.unesp.br.
authors.forename: Camila Tami
authors.initials: CT
authors.lastname: Stringhetta-Garcia
authors.affiliation: Programa Multicêntrico de Pós-Graduação em Ciências Fisiológicas.
authors.forename: Monique Patrício
authors.initials: MP
authors.lastname: Singulani
authors.affiliation: Programa Multicêntrico de Pós-Graduação em Ciências Fisiológicas.
authors.forename: Leandro Figueiredo
authors.initials: LF
authors.lastname: Santos
authors.affiliation: Programa Multicêntrico de Pós-Graduação em Ciências Fisiológicas; Faculdade de Medicina Veterinária de Araçatuba, UNESP - Univ Estadual Paulista, Campus de Araçatuba, Departamento de Apoio, Produção e Saúde Animal.
authors.forename: Mário Jefferson Quirino
authors.initials: MJ
authors.lastname: Louzada
authors.affiliation: Programa Multicêntrico de Pós-Graduação em Ciências Fisiológicas; Faculdade de Odontologia de Araçatuba, UNESP - Univ Estadual Paulista, Campus de Araçatuba, Departamento de Ciências Básicas.
authors.forename: Ana Cláudia Stevanato
authors.initials: AC
authors.lastname: Nakamune
authors.affiliation: Faculdade de Odontologia de Araçatuba, UNESP - Univ Estadual Paulista, Campus de Araçatuba, Departamento de Ciências Básicas.
authors.forename: Antonio Hernandes
authors.initials: AH
authors.lastname: Chaves-Neto
authors.affiliation: Faculdade de Odontologia de Piracicaba, UNICAMP - Univ de Campinas, Campus de Piracicaba, Departamento de Morfologia.
authors.forename: Ana Cláudia
authors.initials: AC
authors.lastname: Rossi
authors.affiliation: Faculdade de Odontologia de Araçatuba, UNESP - Univ Estadual Paulista, Campus de Araçatuba, Departamento de Ciências Básicas.
authors.forename: Edilson
authors.initials: E
authors.lastname: Ervolino
authors.affiliation: Programa Multicêntrico de Pós-Graduação em Ciências Fisiológicas; Faculdade de Odontologia de Araçatuba, UNESP - Univ Estadual Paulista, Campus de Araçatuba, Departamento de Ciências Básicas.
authors.forename: Rita Cássia Menegati
authors.initials: RC
authors.lastname: Dornelles
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects; D016723:Bone Remodeling / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects / Q000502:physiology*; D004958:Estradiol / Q000097:blood; D005260:Female; D005269:Femur / Q000187:drug effects; D021621:Imaging, Three-Dimensional; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D020849:Raloxifene Hydrochloride / Q000494:pharmacology*; D017208:Rats, Wistar; D055070:Resistance Training; D014599:Uterus / Q000187:drug effects
chemical_list: D015415:Biomarkers; D020849:Raloxifene Hydrochloride; D004958:Estradiol
keywords: Aging; Bone microarchitecture; Osteoporosis; Raloxifene; Strength training