Background: With regard to the pathogenesis of
corticosteroid-associated femoral head osteonecrosis, only intravascular and
extravascular factors have been discussed. Wall constriction of the lateral
epiphyseal arteries, which are the main supplying arteries within the femoral
head, has not previously been investigated. This study examined the effect of
long-term corticosteroid treatment on vasoconstriction of the lateral
epiphyseal arteries of the femoral head in a porcine model.
Methods: The immature female Danish Landrace pig was chosen as the
model for our study because femoral head osteonecrosis can be induced in this
animal and because the lateral epiphyseal arteries of the femoral heads are of
the appropriate size for myographic investigation. Twenty-four female Danish
Landrace pigs (two siblings from each of twelve litters for a total of twelve
sibling pairs) were divided by randomly separating the sibling pairs into two
groups, with a total of twelve pigs in each group. One group of twelve animals
received a daily dose of 100 mg of methylprednisolone orally for three months.
The other group of twelve pigs served as controls and received no
corticosteroids. After the animals were killed with an intravenous injection
of pentobarbital, the lateral epiphyseal arteries of the femoral head were
isolated from the cancellous bone. These arteries were mounted as ring
preparations on a small-vessel myograph for measurement of isometric force
development. The effects on the resected vessels of the vasoactive agents
endothelin-1, noradrenaline, bradykinin, substance P, and nitrous oxide were
Results: Vasoconstriction induced by increasing doses of
endothelin-1 was increased after three months of methylprednisolone treatment
compared with the vasoconstriction in vessels from control animals.
Sensitivity to noradrenaline was not altered by this treatment. After
submaximal precontraction by noradrenaline, vasorelaxation was elicited by
substance P, nitrous oxide, and increasing doses of bradykinin without
differences between the corticosteroid-treated and the control groups.
Conclusions: Endothelin-1-induced vasoconstriction of the epiphyseal
arteries of the femoral head was increased in this corticosteroid-treated pig
model. Such vasoconstriction may lead to a reduction in femoral head blood
flow and to local ischemia and thus may be a newly described factor in the
multifactorial pathomechanism of osteonecrosis of the femoral head.