{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T12:55:21Z","timestamp":1787144121945,"version":"build-2736575974"},"reference-count":38,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2006,7,11]],"date-time":"2006-07-11T00:00:00Z","timestamp":1152576000000},"content-version":"vor","delay-in-days":4119,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[1995,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In five patients with idiopathic osteonecrosis (ON) of the hip, four having hypofibrinolysis mediated by high plasminogen activator inhibitor (PAI\u2010Fx), and one with high Lp(a), our specific aim was to determine whether therapy (Rx) with the anabolic\u2010androgenic steroid, Stanozolol(6 mg\/day), would normalize PAI\u2010Fx and Lp(a) and thus potentially ameliorate ON. Prior to Rx, none of the four patients with high PAI\u2010Fx could normally elevate tissue plasminogen activator (tPA\u2010Fx) after 10 min venous occlusion at 100 mm Hg. After 12\u201018 weeks on Rx, PAI\u2010Fx and stimulated tPA\u2010Fx normalized in all four patients. Prior to Rx, mean (SD) stimulated tPA\u2010Fx was low, 0.4 \u00b1 0.3 IU\/ml (lower limit of normal 2.28 IU\/ml). On Rx, stimulated tPA\u2010Fx normalized, rising to 2.83 \u00b1 1.9 IU\/ml, <jats:italic>P<\/jats:italic> = 0.004. Prior to Rx, mean (SD) basal PAI\u2010Fx was high, 99 \u00b1 68 (upper limit of normal 26.9 U\/ml), and fell on Rx to 22.5 \u00b1 22, <jats:italic>P<\/jats:italic> = 0.004. 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\u2010Fx and low stimulated tPA\u2010Fx 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\u2010156 weeks of Rx despite normalization of stimulated tPA\u2010Fx and PAI\u2010Fx. The fifth patient, 1 month after onset of disabling hip pain, had normal PAI\u2010Fx but high Lp(a) (27 mg\/dl), and MRI evidence of bone marrow edema (\u201ctransient osteoporosis\u201d). After 3 weeks on Rx, Lp(a) normalized (14 mg\/dl) and there was marked amelioration of symptoms. For the subsequent 11 weeks on Rx, this patient's Lp(a) was 5 mg\/dl, and he became totally asymptomatic and remains asymptomatic 14 months later. We speculate that when ON is diagnosed prior to segmental collapse of the femoral head, it may be possible to reverse hypofibrinolysis, and\/or to arrest the progression of ON. We postulate that high PAI or high Lp(a) lead to inadequate lysis of venous thrombi in bone, impaired bone venous circulation, venous hypertension of bone, and subsequent, potentially reversible development of ON. \u00a9 1995 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajh.2830480402","type":"journal-article","created":{"date-parts":[[2007,2,21]],"date-time":"2007-02-21T13:55:39Z","timestamp":1172066139000},"page":"213-220","source":"Crossref","is-referenced-by-count":73,"title":["Idiopathic osteonecrosis, hypofibrinolysis, high plasminogen activator inhibitor, high lipoprotein(a), and therapy with stanozolol"],"prefix":"10.1002","volume":"48","author":[{"given":"Charles J.","family":"Glueck","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Freiberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen I.","family":"Glueck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trent","family":"Tracy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davis","family":"Stroop","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,7,11]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199205283262206"},{"key":"e_1_2_1_3_2","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1097\/00003086-199204000-00006","article-title":"Intravascular coagulation and osteonecrosis","volume":"277","author":"Jones JP","year":"1992","journal-title":"Clin Orthop"},{"key":"e_1_2_1_4_2","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1097\/00003086-198909000-00028","article-title":"A microangiographic study of idiopathic osteonecrosis of the femoral head","volume":"246","author":"Atsumi T","year":"1989","journal-title":"Clin Orthop"},{"key":"e_1_2_1_5_2","first-page":"1545","volume-title":"Arthritis and Allied Conditions: A Textbook of Rheumatology","author":"Jones JP","year":"1989"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.2830440405"},{"key":"e_1_2_1_7_2","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1055\/s-0038-1651633","article-title":"Familial high plasminogen activator inhibitor with hypofibrinolysis, a new pathophysiologic cause of osteonecrosis?","volume":"69","author":"Glueck CJ","year":"1993","journal-title":"Thromb Haemost"},{"key":"e_1_2_1_8_2","first-page":"195","article-title":"Familial idiopathic osteonecrosis mediated by familial hypofibrinolysis with high levels of plasminogen activator inhibitor","volume":"71","author":"Glueck CJ","year":"1994","journal-title":"Thromb Haemost"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.2830450212"},{"key":"e_1_2_1_10_2","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1097\/00003086-198806000-00005","article-title":"Osteonecrosis of the femoral head. 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