ARCO Newsletter, December 1996
Osteonecrosis (ON) and the bone marrow edema syndrome (BMES) may not be completely separate and distinct conditions as many currently believe, but they may conceivably be related to a common cause, but express different pathophysiologic effects. I theorize that the causative pathway is an acute ischemic event, i.e. sudden fibrin-platelet thrombosis of an entire intraosseous vascular segment. Intravascular coagulation (IC) of the intraosseous microcirculation (capillaries and venous sinusoids) progressing to generalized venous thrombosis, and less commonly retrograde arterial occlusion, is suggested by me to the genesis of both ON and BMES.(1) (Fig.1). These thrombi originate from the activation of a coagulopathy by any one or more etiologic risk factors. For exeample, BMES (and transient osteoprosis of the hip) is associated with pregnancy, in which placental tissue factor (thromboplastin) may unexpectedly enter the maternal circulation and trigger IC.
In BMES; I hypothesize that initially there is subtotal ischemia, especially in those intraosseous locations with compromised collateral circulation. Ischemic hypoxia temporarily injures those cells within the marrow and trabeculae, but there is insignificant cellular necrosis. Because there is nearly complete fibrinolysis of the intraosseous (and extraosseous) thrombi within a few minutes to two hours after the acute ischemic event. Therefore, these marrow cells, osteoblasts, and osteocytes will eventually recover from this reversible ischemic event. I suspect that most BMES patients probably have rapid plasmin activation by a relatively competent fibrinolytic system. However, there is probably incomplete fibrinolysis in those BMES cases in the grey zone between classic BMES and classic ON, who may have significant hypofibrinolysis. (2)
With intraosseous reperfusion there is reactive hyperemia with both increased bone blood flow by hydrogen-washout studies and also increased intraosseous pressure in BMES. (3) Bone scintigraphy reveals global hypervascularity in BMES, often involving the entire femoral head to the subtrochanteric region. (4) However, the reperfusion of partially necrotic terminal arterioles results in hemorrhage and edema, associated with the reactive hyperemia and the acute post-ischemic inflammatory response. Theoretically, I suggest that it is the hypoxia that stimulates osteoid synthesis by the markedly proliferating osteoblasts which surround the affected trabeculae. (5) Throughout the clinical course of BMES, most of the trabeculae appear to be remain viable, since most of their osteocytes spontaneously recover from this reversible ischemic hypoxia. Usually within six months the osteoid mineralizes, and the radiolucent and "osteoporotic" lesion heals uneventfully, both radiographically and pathologically.
However, in ON there is only minimal fibrinolysis, resulting in irreversible and residual necrosis, especially affecting terminal intraosseous vascular regions, i.e. femoral and humeral heads. Many ON patients have significant hypofibrinolysis (6) with elevated plasminogen activator inhibitor type 1 (PAI-1), often with some other hypercoagulable and prothrombotic risk factors. Although these patients may be able to lyse fibrin thrombi from most of their arterioles, and perhaps even from their capillaries and sinusoids, there is usually residual fibrin-platelet thrombosis affecting their downstream veins. (7) Endothelial damage, intraosseous stasis, and increased hydrostatic back pressure result in sinusoidal dilatation, vascular hyperpermeability, and intraoseous edema. Reflow of the necrotic arterioles likewise results in hemorrhage around the periphery of these necrotic lesions.
I theorize that intraosseous hemorrhage and edema are very early secondary effects in both ON and BMES. Although there is increased intraosseous pressure about the periphery of these anoxic ON lesions, often extending to the intertrochanteric region, there is decreased or no flow within the necrotic lesion itself. This is in distinction to the extensive reactive hyperemia and increased flow in early BMES, which has also been confirmed by hydrogen washout studies. (3) ON lesions can either stay the same size, or they can partially revascularize and decrease in size, usually within the first ten months following a probable acute ischemic event. However, ON lesions do not get larger with time, as would be expected if intraosseous hypertension were a cause of BMES and ON, rather than an early, nonspecific secondary effect. (8) Since I believe that truth is often only achieved through the conflict of ideas, this hypothesis remains controversial in relation to currently accepted dogma.
1. Jones JP Jr: Intravascular coagulation and osteonecrosis. Clin Orthop 1992, 277: 41-53.
2. Van Veldhuizen PJ, Neff J, Murphey MD et al: Decreased fibrinolytic potential in patients with idiopathic avascular necrosis and transient osteoporosis of the hip. Am J Hematol 1993, 44: 243-248.
3. Nishino M, Matsumoto T, Fujii H, et al: Hemodynamic study in the femoral head at risk for osteonecrosis and bone marrow edema syndrome. ARCO96 Fukuoka abstract, page 44.
4. Staudenhertz A, Leitha T, Breitenseher MJ et al: Pattern recognition in the scintigraphic differential diagnosis of AVN, BME and other disorders of the hip. ARCO95 Vienna abstract, page 24.
5. Kubo T, Hirasawa Y, Yamamoto T, et al: The morphological sudies of transient osteoporosis of the hip. ARCO96 Fukuoka abstract, page 43.
6. Glueck CJ, Freiberg R, Glueck HI et al: Hypofibrinolysis: A common, major cause of osteonecrosis. Am J Hematol 1994, 45: 156-166.
7. Jones JP Jr: Concepts of etiology and early pathogenesis of osteonecrosis, in Schafter IM (ed): Instructional Course Lectures. Chicago, IL, Amer Acad Orthop Surg 1994, 43: 499-512.
8. Jones JP Jr: Osteonecrosis, in Koopman WJ (ed): Arthritis and Allied Conditions: A Textbook of Rheumatology, ed 13, Baltimore, MA, Williams and Wilkins. 1996 pp1677-1696.