title: Sclerostin antibody and interval treadmill training effects in a rodent model of glucocorticoid-induced osteopenia.
abstract: Glucocorticoids have a beneficial anti-inflammatory and immunosuppressive effect, but their use is associated with decreased bone formation, bone mass and bone quality, resulting in an elevated fracture risk. Exercise and sclerostin antibody (Scl-Ab) administration have both been shown to increase bone formation and bone mass, therefore the ability of these treatments to inhibit glucocorticoid-induced osteopenia alone or in combination were assessed in a rodent model. Adult (4 months-old) male Wistar rats were allocated to a control group (C) or one of 4 groups injected subcutaneously with methylprednisolone (5mg/kg/day, 5 days/week). Methylprednisolone treated rats were injected subcutaneously 2 days/week with vehicle (M) or Scl-Ab-VI (M+S: 25mg/kg/day) and were submitted or not to treadmill interval training exercise (1h/day, 5 days/week) for 9 weeks (M+E, M+E+S). Methylprednisolone treatment increased % fat mass and % apoptotic osteocytes, reduced whole body and femoral bone mineral content (BMC), reduced femoral bone mineral density (BMD) and osteocyte lacunae occupancy. This effect was associated with lower trabecular bone volume (BV/TV) at the distal femur. Exercise increased BV/TV, osteocyte lacunae occupancy, while reducing fat mass, the bone resorption marker NTx, and osteocyte apoptosis. Exercise did not affect BMC or cortical microarchitectural parameters. Scl-Ab increased the bone formation marker osteocalcin and prevented the deleterious effects of M on bone mass, further increasing BMC, BMD and BV/TV to levels above the C group. Scl-Ab increased femoral cortical bone parameters at distal part and midshaft. Scl-Ab prevented the decrease in osteocyte lacunae occupancy and the increase in osteocyte apoptosis induced by M. The addition of exercise to Scl-Ab treatment did not result in additional improvements in bone mass or bone strength parameters. These data suggest that although our exercise regimen did prevent some of the bone deleterious effects of glucocorticoid treatment, particularly in trabecular bone volume and osteocyte apoptosis, Scl-Ab treatment resulted in marked improvements in bone mass across the skeleton and in osteocyte viability, resulting in decreased bone fragility.
authors.affiliation: EA4708 I3MTO, Orleans Regional Hospital, University of Orleans, Orleans, France. Electronic address: z_achiou@yahoo.com.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Achiou
authors.affiliation: EA4708 I3MTO, Orleans Regional Hospital, University of Orleans, Orleans, France. Electronic address: hechmi.toumi@univ-orleans.fr.
authors.forename: Hechmi
authors.initials: H
authors.lastname: Toumi
authors.affiliation: EA4708 I3MTO, Orleans Regional Hospital, University of Orleans, Orleans, France. Electronic address: jerome.touvier@laposte.net.
authors.forename: Jérome
authors.initials: J
authors.lastname: Touvier
authors.affiliation: EA4708 I3MTO, Orleans Regional Hospital, University of Orleans, Orleans, France. Electronic address: arnaud.boudenot@yahoo.fr.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Boudenot
authors.affiliation: Department of Microscopy, University of François Rabelais, Tours, France. Electronic address: rustuzbekov@aol.com.
authors.forename: Rustem
authors.initials: R
authors.lastname: Uzbekov
authors.affiliation: Metabolic Disorders, Amgen Inc., One Amgen Center Dr., Thousand Oaks 91320, CA, USA. Electronic address: mominsky@amgen.com.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Ominsky
authors.affiliation: EA4708 I3MTO, Orleans Regional Hospital, University of Orleans, Orleans, France. Electronic address: stephane.pallu@univ-orleans.fr.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Pallu
authors.affiliation: EA4708 I3MTO, Orleans Regional Hospital, University of Orleans, Orleans, France. Electronic address: eric.lespessailles@chr-orleans.fr.
authors.forename: Eric
authors.initials: E
authors.lastname: Lespessailles
mesh_terms: D000818:Animals; D000906:Antibodies / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects; D001696:Biomechanical Phenomena; D015519:Bone Density / Q000187:drug effects; D001851:Bone Diseases, Metabolic / Q000139:chemically induced / Q000503:physiopathology / Q000628:therapy*; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors* / Q000276:immunology; D016723:Bone Remodeling; D053148:Caspase 3 / Q000378:metabolism; D024042:Collagen Type I / Q000378:metabolism; D004195:Disease Models, Animal; D005269:Femur / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D005819:Genetic Markers / Q000276:immunology; D008297:Male; D008775:Methylprednisolone / Q000633:toxicity; D015675:Osteocalcin / Q000378:metabolism; D010011:Osteocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010455:Peptides / Q000378:metabolism; D010805:Physical Conditioning, Animal / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D055114:X-Ray Microtomography
chemical_list: D000906:Antibodies; D019485:Bone Morphogenetic Proteins; D024042:Collagen Type I; D005819:Genetic Markers; D010455:Peptides; C486031:Sost protein, rat; C052929:collagen type I trimeric cross-linked peptide; D015675:Osteocalcin; C505410:Casp3 protein, rat; D053148:Caspase 3; D008775:Methylprednisolone
keywords: Bone; Glucocorticoid; Microarchitecture; Sclerostin antibody