Idiopathic osteonecrosis, hypofibrinolysis, high plasminogen activator inhibitor, high lipoprotein(a), and therapy with stanozolol

Abstract

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)

Hypofibrinolysis: A common, major cause of osteonecrosis

“…In a pilot study, we have given stanozolol (6 mg/day) to three of our nine patients with primary high PAI, inability to initiate fibrinolysis, and idiopathic osteonecrosis. In two patients, after 12 weeks of therapy, PAI-Ag and PAI-Fx were normalized, and stimulated tPA-Fx became normal [40]. Unexpectedly, but encouragingly, after 12 weeks of treatment, one of these two patients, who had been able to walk painfully for only one block prior to treatment, walked 2 miles every day despite radiographic progression of osteonecrosis [40].…”

“…Since PA1 can be reduced and fibrinolytic activity increased by the anabolic steroid stanozolol [38,39], we speculate that, when primary osteonecrosis is diagnosed early, prior to segmental collapse of the femoral head, it may be possible to treat defective fibrinolysis and, hence, to arrest progression or induce regression of osteonecrosis of the hip [40]. In a pilot study, we have given stanozolol (6 mg/day) to three of our nine patients with primary high PAI, inability to initiate fibrinolysis, and idiopathic osteonecrosis.…”

Bone marrow edema syndrome of the femoral head

“…With regard to pharmacological treatment, Boos [7] reported good clinical results with sympathetic nerve blockade with bupivacaine in three patients, but no improvement in pathological MRI signal patterns. Laroche [32] reported some pain reduction in a small controlled study with nifedipine, and Glueck [33] presented preliminary data using stanozolol in the treatment of avascular necrosis, but these studies were performed in patients with avascular necrosis only and were not followed up in the literature. Lakhanpal [34] found no beneficial effect with the use of calcitonin, antituberculosis drugs, prednisone and lumbar sympathectomy with bupivacaine.…”

Neuralgia induzida por cavitação osteonecrótica

“…In addition to etiological factors, NICO has worsening and hereditary factors associated to the disease. Researchers 13,15,16 have concluded that patients with such neuralgia have differences in coagulation factors which are common as hereditary forms of thrombophilia and hypofibrinolisis, also related to risk factos such as femoral head osteonecrosis. Seventy-one percent of NICO cases are caused by alcohol abuse, trauma, prednisone, estrogen, pregnancy, sickle cell anemia, lupus erythematosus and use of chemotherapy for malignant neoplasias.…”

“…Current studies describe ischemic alveolar bone marrow coagulation disorders as the cause for NICO, which may also be the result of thrombosis with or without hypofibrinolysis, which would obstruct vascular spaces impairing blood flow in the region [12][13][14] . So, it could be treated with anticoagulants or anabolic steroids [15][16][17][18] . Other therapeutic options would be regional osteotomy and curettage of the painful area, or osteotomy associated to local application of absorbable gelatine sponge associated to tetracycline, with tetracycline and cephalexin, or clindamicine with gentamicine [1][2][3][4]9 .…”