Heparanase role in the treatment of avascular necrosis of femur head.
BACKGROUND
Idiopathic avascular necrosis (AVN) of bone causes significant morbidity in adults although the pathophysiology is unknown. The present treatment options include systemic biphosphonate therapy and local bone drilling decompression, ameliorating the healing process and their by render the weight bearing femur head less vulnerable to collapse. In the present study we demonstrate the involvement of heparanase in AVN and in the acceptable treatments.


METHODS
56 female rats were studied. In 8 control rats AVN was induced by ligamentum teres ligation of the right femur while the left femur remained intact. In the rest of the rats, in addition to right femur AVN, treatment was added by subcutaneous biphosphonate therapy, femoral head drilling or combination of the treatments. All rats were scarified after 6weeks. Immunostaining of the femur heads were performed to heparanase, tissue factor pathway inhibitor (TFPI), tissue factor (TF) and hematoxylin-eosin.


RESULTS
Staining of heparanase, TFPI and TF were most prominent in the bone-marrow tissue of the femur heads. Staining by hematoxylin-eosin revealed damaged femur heads with prominent heparanase and TFPI staining in the femur with AVN compared to the contra lateral side of the same rat. No difference was found in the TF staining between the two sides. In the drilling and / or biphosphonate therapy groups, in contrast to the control group, femur heads were preserved with no significant difference in heparanase and TFPI staining between the two sides.


CONCLUSIONS
Heparanase and TFPI are locally elevated in the process of AVN and are normalized by the acceptable treatments. Inhibition of heparanase by heparins can potentially improve the nowadays therapy modalities.
Department of Orthopedic B, Rambam Health Care Campus, Haifa, Israel.
Eli
E
Peled
Matthew
M
Davis
Elena
E
Axelman
Doron
D
Norman
Yona
Y
Nadir
D019386:Alendronate / Q000008:administration & dosage*; D000818:Animals; D050071:Bone Density Conservation Agents / Q000008:administration & dosage*; D003131:Combined Modality Therapy; D019299:Decompression, Surgical / Q000379:methods*; D004195:Disease Models, Animal; D005260:Female; D005270:Femur Head / Q000187:drug effects* / Q000201:enzymology / Q000601:surgery*; D005271:Femur Head Necrosis / Q000097:blood / Q000188:drug therapy / Q000201:enzymology / Q000601:surgery / Q000628:therapy*; D005966:Glucuronidase / Q000378:metabolism*; D006487:Hemostasis; D007150:Immunohistochemistry; D007279:Injections, Subcutaneous; D008074:Lipoproteins / Q000378:metabolism; D019637:Orthopedic Procedures; D051381:Rats; D017207:Rats, Sprague-Dawley; D013194:Staining and Labeling / Q000379:methods; D013925:Thromboplastin / Q000378:metabolism; D013997:Time Factors; D000099175:Heparanase
D019386:Alendronate; D050071:Bone Density Conservation Agents; D005966:Glucuronidase; D008074:Lipoproteins; D013925:Thromboplastin; D000099175:Heparanase; C051928:lipoprotein-associated coagulation inhibitor