Effects of simvastatin gels on murine calvarial bone.
BACKGROUND
The cholesterol-lowering drug simvastatin has been shown to stimulate murine calvarial bone growth after multiple injections. The purpose of this study was to test if similar bone stimulation could be induced by 2 single-dose drug delivery systems appropriate to periodontal therapy.


METHODS
ICR Swiss mice were treated with the following protocols: 1) injection of methylcellulose gel alone, subcutaneously over the calvarium (INJ-GEL; n = 8); 2) injection of gel with simvastatin (INJ-SIM; 2.2 mg, n = 16); 3) polylactide membrane (PLA) containing gel alone implanted over calvarium (MEM-GEL; n = 10); 4) implanted PLA membrane containing gel and simvastatin (MEM-SIM; n = 10); and 5) untreated mice (n = 12). Animals were sacrificed after 22 or 44 days, calvaria decalcified and stained with hematoxylin and eosin, and images digitized and measured for bone thickness and area. Data were compared using analysis of variance.


RESULTS
INJ-SIM stimulated a 53% (P = 0.02) increase at the thickest point of calvarial bone, while MEM-SIM caused a highly significant (P < or = 0.0005) increase in bone thickness (159% to 172%) and bone area (144% to 180%) compared to gel controls. Simvastatin gels caused soft tissue inflammation, which appeared to be related to bone increases. If INJ-SIM animals showing leakage of gel and/or no inflammation were excluded from analysis, INJ-SIM resulted in more bone (58% to 83%) than gel controls. An insignificant amount of SIM-stimulated bone was lost over the long term (44 days).


CONCLUSIONS
A single, high dose of simvastatin gel can stimulate murine cranial bone apposition, particularly when delivered under an occlusive membrane. Both approaches should be investigated further for possible development for periodontal therapy.
Thylin
Michael R
MR
Department of Surgical Specialties, University of Nebraska Medical Center, College of Dentistry, Lincoln 68583-0757, USA.
McConnell
Jay C
JC
Schmid
Marian J
MJ
Reckling
Ryon R
RR
Ojha
Junu
J
Bhattacharyya
Indraneel
I
Marx
David B
DB
Reinhardt
Richard A
RA
D000704:Analysis of Variance; D000818:Animals; D000924:Anticholesteremic Agents / Q000008:administration & dosage*; D015519:Bone Density / Q000187:drug effects; D016503:Drug Delivery Systems; D004343:Drug Implants; D005260:Female; D005782:Gels; D007267:Injections; D008567:Membranes, Artificial; D008747:Methylcellulose; D051379:Mice; D008813:Mice, Inbred ICR; D010012:Osteogenesis / Q000187:drug effects*; D011091:Polyesters; D019821:Simvastatin / Q000008:administration & dosage*; D012886:Skull / Q000187:drug effects
D000924:Anticholesteremic Agents; D004343:Drug Implants; D005782:Gels; D008567:Membranes, Artificial; D011091:Polyesters; C033616:poly(lactide); D008747:Methylcellulose; D019821:Simvastatin