title: Serum bone formation marker correlation with improved osseointegration in osteoporotic rats treated with simvastatin.
abstract: OBJECTIVE
  Simvastatin has been shown to enhance osseointegration of pure titanium implants in osteoporotic rats. This study aimed to evaluate the relationship between the serum level of bone formation markers and the osseointegration of pure titanium implants in osteoporotic rats treated with simvastatin.
  
  
  METHODS
  Fifty-four female Sprague-Dawley rats, aged 3 months, were randomly divided into three groups: Sham-operated group (SHAM; n = 18), ovariectomized group (OVX; n = 18), and ovariectomized with simvastatin treatment group (OVX + SIM; n = 18). Fifty-six days after ovariectomy, screw-shaped titanium implants were inserted into the tibiae. Simvastatin was administered orally at 5 mg/kg each day after the placement of the implant in the OVX + SIM group. The animals were killed at either 28 or 84 days after implantation and the undecalcified tissue sections were processed for histological analysis. Total alkaline phosphatase (ALP), bone-specific alkaline phosphatase (BALP) and bone Gla protein (BGP) were measured in all animal sera collected at the time of euthanasia and correlated with the histological assessment of osseointegration.
  
  
  RESULTS
  The level of ALP in the OVX group was higher than the SHAM group at day 28, with no differences between the three groups at day 84. The level of BALP in the OVX + SIM group was significantly higher than both OVX and SHAM groups at days 28. Compared with day 28, the BALP level of all three groups showed a significant decrease at day 84. There were no significant differences in BGP levels between the three groups at day 28, but at day 84, the OVX + SIM group showed significantly higher levels than both the OVX and SHAM groups. There was a significant increase in BGP levels between days 28 and 84 in the OVX + SIM group. The serum bone marker levels correlated with the histological assessment showing reduced osseointegration in the OVX compared to the SHAM group which is subsequently reversed in the OVX + SIM group.
  
  
  CONCLUSIONS
  The results from this study indicate that the serum level of bone formation markers, especially BALP and BGP, could be correlated with the degree of osseointegration around titanium implants in osteoporotic rats treated with simvastatin.
authors.affiliation: Department of Oral Implants, Affiliated Stomatological Hospital of Fujian Medical University, Fuzhou, China.
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Du
authors.forename: Jiang
authors.initials: J
authors.lastname: Chen
authors.forename: Fuhua
authors.initials: F
authors.lastname: Yan
authors.forename: Nghiem
authors.initials: N
authors.lastname: Doan
authors.forename: Saso
authors.initials: S
authors.lastname: Ivanovski
authors.forename: Yin
authors.initials: Y
authors.lastname: Xiao
mesh_terms: D000469:Alkaline Phosphatase / Q000097:blood*; D000818:Animals; D015415:Biomarkers / Q000097:blood; D015921:Dental Implants; D005260:Female; D020007:Implants, Experimental; D016348:Osseointegration / Q000187:drug effects*; D015675:Osteocalcin / Q000097:blood*; D010012:Osteogenesis / Q000187:drug effects*; D010024:Osteoporosis / Q000097:blood / Q000188:drug therapy; D010052:Ovariectomy; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D019821:Simvastatin / Q000494:pharmacology*; D013977:Tibia / Q000601:surgery*
chemical_list: D015415:Biomarkers; D015921:Dental Implants; D015675:Osteocalcin; D019821:Simvastatin; D000469:Alkaline Phosphatase