Inhibitors of hydroxymethylglutaryl-coenzyme A reductase and risk of fracture among older women

Lancet. 2000 Jun 24;355(9222):2185-8. doi: 10.1016/S0140-6736(00)02400-4.


Background: Inhibitors of hydroxymethylglutaryl-coenzyme A reductase (statins) increase new bone formation in rodents and in human cells in vitro. Statin use is associated with increased bone mineral density of the femoral neck. We undertook a population-based case-control study at six health-maintenance organisations in the USA to investigate further the relation between statin use and fracture risk among older women.

Methods: We investigated women aged 60 years or older. Exposure, outcome, and confounder information was obtained from automated claims and pharmacy data from October, 1994, to September, 1997. Cases had an incident diagnosis of non-pathological fracture of the hip, humerus, distal tibia, wrist, or vertebrae between October, 1996, and September, 1997. Controls had no fracture during this period. We excluded women with records of dispensing of drugs to treat osteoporosis.

Findings: There were 928 cases and 2747 controls. Compared with women who had no record of statin dispensing during the previous 2 years, women with 13 or more statin dispensings during this period had a decreased risk of non-pathological fracture (odds ratio 0.48 [95% CI 0.27-0.83]) after adjustment for age, number of hospital admissions during the previous year, chronic disease score, and use of non-statin lipid-lowering drugs. No association was found between fracture risk and fewer than 13 dispensings of statins or between fracture risk and use of non-statin lipid-lowering drugs.

Interpretation: Statins seem to be protective against non-pathological fracture among older women. These findings are compatible with the hypothesis that statins increase bone mineral density in human beings and thereby decrease the risk of osteoporotic fractures.

Publication types

  • Comparative Study
  • Multicenter Study

MeSH terms

  • Age Factors
  • Aged
  • Aged, 80 and over
  • Bone Density / drug effects
  • Case-Control Studies
  • Chronic Disease
  • Confidence Intervals
  • Confounding Factors, Epidemiologic
  • Female
  • Fractures, Bone / epidemiology*
  • Hip Fractures / epidemiology
  • Humans
  • Humeral Fractures / epidemiology
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Hypolipidemic Agents / therapeutic use*
  • Massachusetts / epidemiology
  • Middle Aged
  • Odds Ratio
  • Osteogenesis / drug effects
  • Patient Admission / statistics & numerical data
  • Population Surveillance
  • Protective Agents / therapeutic use
  • Risk Factors
  • Spinal Fractures / epidemiology
  • Tibial Fractures / epidemiology
  • Wrist Injuries / epidemiology


  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Hypolipidemic Agents
  • Protective Agents