title: The effects of improved metabolic risk factors on bone turnover markers after 12 weeks of simvastatin treatment with or without exercise.
abstract: OBJECTIVE
  Emerging evidence supports an association between metabolic risk factors and bone turnover. Statins and exercise independently improve metabolic risk factors; however whether improvements in metabolic risk factor affects bone turnover is unknown. The purpose of the present study was to: 1) evaluate the relationship between metabolic risk factors and bone turnover; and 2) determine if improvements in metabolic risk factors after 12 weeks of statin treatment, exercise or the combination affect bone turnover.
  
  
  METHODS
  Fifty participants with ≥2 metabolic syndrome defining characteristics were randomly assigned to one of three groups: statin (STAT: simvastatin, 40 mg/day), exercise (EX: brisk walking and/or slow jogging, 45 minutes/day, 5 days/week), or the combination (STAT+EX). Body composition and whole body bone mineral density were measured with dual energy X-ray absorptiometry. Serum markers of bone formation (bone specific alkaline phosphatase, BAP; osteocalcin, OC), resorption (C-terminal peptide of type I collagen, CTX) and metabolic risk factors were determined. Two-factor (time, group) repeated-measures ANCOVA was used to examine changes of metabolic risk factors and bone turnover. General linear models were used to determine the effect of pre-treatment metabolic risk factors on post-treatment bone turnover marker outcomes.
  
  
  RESULTS
  Participants with ≥4 metabolic syndrome defining characteristics had lower pre-treatment OC than those with 3 or fewer. OC was negatively correlated with glucose, and CTX was positively correlated with cholesterol. STAT or STAT+EX lowered total and LDL cholesterol. The OC to CTX ratio decreased in all groups with no other significant changes in bone turnover. Higher pre-treatment insulin or body fat predicted a greater CTX reduction and a greater BAP/CTX increase.
  
  
  CONCLUSIONS
  Metabolic risk factors were negatively associated with bone turnover markers. Short-term statin treatment with or without exercise lowered cholesterol and all treatments had a small effect on bone turnover.
authors.affiliation: Department of Nutrition & Exercise Physiology, University of Missouri-Columbia, Columbia, MO, USA, 65211.
authors.forename: Jun
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Nutrition & Exercise Physiology, University of Missouri-Columbia, Columbia, MO, USA, 65211.
authors.forename: Leryn J
authors.initials: LJ
authors.lastname: Boyle
authors.affiliation: Department of Nutrition & Exercise Physiology, University of Missouri-Columbia, Columbia, MO, USA, 65211.
authors.forename: Catherine R
authors.initials: CR
authors.lastname: Mikus
authors.affiliation: Department of Nutrition & Exercise Physiology, University of Missouri-Columbia, Columbia, MO, USA, 65211.
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Oberlin
authors.affiliation: Department of Nutrition & Exercise Physiology, University of Missouri-Columbia, Columbia, MO, USA, 65211.
authors.forename: Justin A
authors.initials: JA
authors.lastname: Fletcher
authors.affiliation: Department of Nutrition & Exercise Physiology, University of Missouri-Columbia, Columbia, MO, USA, 65211.
authors.forename: John P
authors.initials: JP
authors.lastname: Thyfault
authors.affiliation: Department of Nutrition & Exercise Physiology, University of Missouri-Columbia, Columbia, MO, USA, 65211. Electronic address: HintonP@missouri.edu.
authors.forename: Pamela S
authors.initials: PS
authors.lastname: Hinton
mesh_terms: D015502:Absorptiometry, Photon; D000328:Adult; D015415:Biomarkers / Q000097:blood; D016723:Bone Remodeling; D015444:Exercise; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D024821:Metabolic Syndrome / Q000188:drug therapy* / Q000503:physiopathology; D008875:Middle Aged; D010349:Patient Compliance; D012307:Risk Factors; D019821:Simvastatin / Q000627:therapeutic use*
chemical_list: D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin
keywords: Aerobic exercise; Bone turnover markers; Metabolic risk factors; Simvastatin; The metabolic syndrome