title: Effects of anti-sclerostin antibody and running on bone remodeling and strength.
abstract: Sclerostin antibody (Scl-Ab) represents a promising therapeutic approach to treat patients with osteoporosis.
  
  
  OBJECTIVE
  The aim of this study was to investigate the effects of Scl-Ab, running and a combination of both on bone formation.
  
  
  METHODS
  Sixty female Wistar rats, aged 8 months were randomly assigned to five groups (subcutaneous injections performed twice a week): (1) (Sham): sedentary rats + saline, (2) (OVX): ovariectomized rats + saline, (3) (OVX + E): OVX rats + saline + treadmill training (5 times/week, 1 h/day), (4) (OVX + E + S): OVX rats + treadmill training + 5 mg/kg Scl-Ab and (5) (OVX + S): OVX rats + 5 mg/kg Scl-Ab. After 14 weeks, body composition, whole body and femoral BMDs were determined by DXA and serum was collected for analysis of osteocalcin and NTX. Bone microarchitecture was analyzed using μCT and bone strength was assessed at the femur mid-shaft in 3-point bending.
  
  
  RESULTS
  Running exercise decreased fat mass as well as the bone resorption marker NTX relative to the non-exercised control groups, effects that were associated with a prevention of the deleterious effects of OVX on whole body and femoral BMDs. Scl-Ab increased the bone formation marker osteocalcin, which resulted in robust increases in BMD and femoral metaphyseal bone volume to levels greater than in the Sham group. OVX + S + E group did not further impact on bone mass relative to the OVX + S group. At the cortical femur diaphysis, Scl-Ab prevented the decreases in bone strength after OVX, while exercise did not affect cortical strength.
  
  
  CONCLUSIONS
  We suggest that while running on a treadmill can prevent some bone loss through a modest antiresorptive effect, it did not contribute to the robust bone-forming effects of Scl-Ab when combined in an estrogen ablation model.
authors.affiliation: Service de Rhumatologie, Centre hospitalier régional d'Orléans, 1 rue Porte Madeleine, 45032 Orléans, France; University of Orléans, I3MTO Laboratory, EA 4708, Hospital of Orleans, 1 rue Porte Madeleine, F-45032 Orléans, France.
authors.forename: H
authors.initials: H
authors.lastname: Toumi
authors.affiliation: University of Orléans, I3MTO Laboratory, EA 4708, Hospital of Orleans, 1 rue Porte Madeleine, F-45032 Orléans, France.
authors.forename: D
authors.initials: D
authors.lastname: Benaitreau
authors.affiliation: University of Orléans, I3MTO Laboratory, EA 4708, Hospital of Orleans, 1 rue Porte Madeleine, F-45032 Orléans, France.
authors.forename: S
authors.initials: S
authors.lastname: Pallu
authors.affiliation: University of Orléans, I3MTO Laboratory, EA 4708, Hospital of Orleans, 1 rue Porte Madeleine, F-45032 Orléans, France.
authors.forename: M
authors.initials: M
authors.lastname: Mazor
authors.affiliation: Prisme Institute, MMH, 8, Rue Leonard de Vinci, 45072 Orleans Cedex 2, France.
authors.forename: R
authors.initials: R
authors.lastname: Hambli
authors.affiliation: Metabolic Disorders, Amgen Inc., One Amgen Center Dr., Thousand Oaks, 91320 CA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Ominsky
authors.affiliation: Service de Rhumatologie, Centre hospitalier régional d'Orléans, 1 rue Porte Madeleine, 45032 Orléans, France; University of Orléans, I3MTO Laboratory, EA 4708, Hospital of Orleans, 1 rue Porte Madeleine, F-45032 Orléans, France.
authors.forename: E
authors.initials: E
authors.lastname: Lespessailles
keywords: Anti-sclerostin antibody; Osteocyte; Osteoporosis; Physical exercise