Idiopathic osteonecrosis, hypofibrinolysis, high plasminogen activator inhibitor, high lipoprotein(a), and therapy with Stanozolol.
In five patients with idiopathic osteonecrosis (ON) of the hip, four having hypofibrinolysis mediated by high plasminogen activator inhibitor (PAI-Fx), and one with high Lp(a), our specific aim was to determine whether therapy (Rx) with the anabolic-androgenic steroid, Stanozolol (6 mg/day), would normalize PAI-Fx and Lp(a) and thus potentially ameliorate ON. Prior to Rx, none of the four patients with high PAI-Fx could normally elevate tissue plasminogen activator (tPA-Fx) after 10 min venous occlusion at 100 mm Hg. After 12-18 weeks on Rx, PAI-Fx and stimulated tPA-Fx normalized in all four patients. Prior to Rx, mean (SD) stimulated tPA-Fx was low, 0.4 +/- 0.3 IU/ml (lower limit of normal 2.28 IU/ml). On Rx, stimulated tPA-Fx normalized, rising to 2.83 +/- 1.9 IU/ml, P = .004. Prior to Rx, mean (SD) basal PAI-Fx was high, 99 +/- 68 (upper limit of normal 26.9 U/ml), and fell on Rx to 22.5 +/- 22, P = .004. In two of the five patients normalization of hypofibrinolysis or high Lp(a) was accompanied by major symptomatic improvement. Prior to Rx, and 2 years after onset of unilateral hip pain, one of the four patients with high PAI-Fx and low stimulated tPA-Fx could walk only one block painfully. After 8 weeks on Stanozolol Rx, and continuing through 54 weeks on Rx, he walked 2 miles per day without pain, despite radiographic progression of ON. In three of the four patients with high PAI and with osteonecrosis present 0.3, 2, and 6 years prior to Stanozolol Rx, there was no clinical improvement after 14-156 weeks of Rx despite normalization of stimulated tPA-Fx and PAI-Fx. The fifth patient, 1 month after onset of disabling hip pain, had normal PAI-Fx but high Lp(a) (27 mg/dl), and MRI evidence of bone marrow edema ("transient osteoporosis").(ABSTRACT TRUNCATED AT 250 WORDS)
Glueck
C J
CJ
Cholesterol Center Jewish Hospital, Cincinnati, OH 45229, USA.
Freiberg
R
R
Glueck
H I
HI
Tracy
T
T
Stroop
D
D
Wang
Y
Y
D000328:Adult; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects; D005500:Follow-Up Studies; D006615:Hip / Q000473:pathology; D006801:Humans; D017270:Lipoprotein(a) / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010020:Osteonecrosis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D015849:Plasminogen Inactivators / Q000097:blood*; D013197:Stanozolol / Q000627:therapeutic use*
D017270:Lipoprotein(a); D015849:Plasminogen Inactivators; D013197:Stanozolol