Prospective, double blind, randomized, controlled trial of simvastatin in human fracture healing.
Although statins are widely prescribed as cholesterol-lowering drugs, a number of studies suggest that these compounds may have anabolic effects on bone. Our aim was to assess whether simvastatin affects the rate of fracture healing in humans. A prospective, double-blind, randomized controlled trial was performed. Individuals who had sustained an undisplaced, extra-articular fracture of the distal radial metaphysis were recruited from a trauma clinic. Patients were randomized to receive simvastatin 20 mg once daily or a placebo. Regular clinical and radiological follow-up was undertaken for a 12 week period. Dual-energy X-ray absorptiometry assessment of bone mineral density was conducted at 2 and 12 weeks postinjury. Biochemical markers of bone turnover were assayed during the study period. Time to fracture union was defined as the time to cortical bridging in four cortices on plain radiographs. In addition, the rate of trabecular union was assessed. Eighty patients were recruited, of which 62 completed the study (31 in each group). Study cohorts were matched for age and gender. For patients receiving simvastatin therapy, the mean time to fracture union was 71.6 days (SD 22.2 days, SEM 3.8 days). This compared to 71.3 days (SD 21.3, SEM 4.1 days) for the control cohort (p = 0.6481). There was no significant difference between bone mineral density or bone biochemical markers between groups (p > 0.05). Despite promising results from in vivo and in vitro animal studies, simvastatin at a treatment dose of 20 mg once daily does not affect the rate of fracture healing in humans.
Patil
Sanjeev
S
Department of Orthopaedic and Trauma Surgery, Southern General Hospital, 1345 Govan Road, Glasgow, G51 4TF, United Kingdom.
Holt
Graeme
G
Raby
Nigel
N
McLellan
Alastair R
AR
Smith
Karen
K
O'Kane
Sarah
S
Beastall
Graham
G
Crossan
James F
JF
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004311:Double-Blind Method; D005260:Female; D017102:Fracture Healing / Q000187:drug effects*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011885:Radius Fractures / Q000188:drug therapy*; D019821:Simvastatin / Q000494:pharmacology / Q000627:therapeutic use*
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin