Hypercholesterolemia promotes an osteoporotic phenotype

Am J Pathol. 2012 Sep;181(3):928-36. doi: 10.1016/j.ajpath.2012.05.034. Epub 2012 Jul 4.


A role for hypercholesterolemia in the development of osteoporosis has been suggested in published reports. However, few studies contain direct evidence of a role for maintenance of cholesterol homeostasis in bone health. Using isocaloric high-fat/high-cholesterol and low-fat/no-cholesterol diets in a 4-month feeding study combined with micro computed tomography analysis, we demonstrated in two different mouse strains that mice with hypercholesterolemia lose cortical and trabecular bone in the femurs and vertebrae (bone mineral density was decreased on average by ≈90 mg/mL in the cortical vertebrae in one strain) and cortical bone in the calvariae (bone mineral density was decreased on average by ≈60 mg/mL in one strain). Mechanical testing of the femurs demonstrated that loss of bone in the mice with hypercholesterolemia caused changes in the mechanical properties of the bone including loss of failure load (failure load was decreased by ≈10 N in one strain) and energy to failure. Serologic and histomorphologic analyses suggested that hypercholesterolemia promotes osteoclastogenesis. These studies support a role for hypercholesterolemia in the development of osteoporosis and provide a model with which to test intervention strategies to reduce the effects of hypercholesterolemia on bone health.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomechanical Phenomena
  • Body Weight
  • Bone Resorption / complications
  • Bone Resorption / diagnostic imaging
  • Bone Resorption / pathology
  • Bone Resorption / physiopathology
  • Dietary Fats / administration & dosage
  • Femur / diagnostic imaging
  • Femur / pathology
  • Femur / physiopathology
  • Hypercholesterolemia / blood
  • Hypercholesterolemia / complications*
  • Hypercholesterolemia / pathology*
  • Hypercholesterolemia / physiopathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Osteoclasts / pathology
  • Osteoporosis / blood
  • Osteoporosis / etiology*
  • Osteoporosis / pathology*
  • Osteoporosis / physiopathology
  • Phenotype
  • Radiography
  • Skull / diagnostic imaging
  • Skull / pathology
  • Skull / physiopathology
  • Spine / diagnostic imaging
  • Spine / pathology
  • Spine / physiopathology


  • Dietary Fats