Chaim Zinman

Hyperbaric oxygen therapy as a treatment for stage-I avascular necrosis of the femoral head.

Avascular necrosis (AVN) of the head of the femur is a potentially crippling disease which mainly affects young adults. Although treatment by exposure to hyperbaric oxygen (HBO) is reported as being beneficial, there has been no study of its use in treated compared with untreated patients. We selected 12 patients who suffered from Steinberg stage-I AVN of the head of the femur (four bilateral) whose lesions were 4 mm or more thick and/or 12.5 mm or more long on MRI. Daily HBO therapy was given for 100 days to each patient. All smaller stage-I lesions and more advanced stages of AVN were excluded. These size criteria were chosen in order to compare outcomes with an identical size of lesion in an untreated group described earlier. Overall, 81% of patients who received HBO therapy showed a return to normal on MRI as compared with 17% in the untreated group. We therefore conclude that hyperbaric oxygen is effective in the treatment of stage-I AVN of the head of the femur.

Hypertonic Mannitol Ameliorates Intracompartmental Tamponade in Model Compartment Syndrome in the Dog

Acute compartment syndrome (ACS) is a devastating complication of rhabdomyolysis caused by muscle tamponade secondary to increased intracompartmental pressure (Pi). ACS requires emergency surgical decompression when Pi greater than 30 mmHg (normal less than 4.0 mmHg) and clinical signs exist. The present study was undertaken to examine whether mannitol which has been used extensively for prevention of acute renal failure in rhabdomyiolysis may also improve muscular hemodynamics in ACS. ACS was produced in dogs by injecting dog plasma into the anterolateral compartment of the hind limb. The Pi was directly monitored. Control dogs received saline, whereas experimental dogs received intravenously 20% mannitol (0.15 ml/min/kg) over a period of 1 h. The initial Pi was set arbitrarily at 100 mm Hg. Following the establishment of ACS, the spontaneous mean decrease in Pi in the control group was 40% of initial value over 60 min (n = 5) versus a decrease of 65%/60 min in the experimental (mannitol) group (n = 7, p less than 0.01). The net mean decompressive effect of mannitol treatments was approximately 28 mm Hg (mean control Pi minus mean experimental Pi at time 60 min). Extrapolated to man with ACS, such a decrease in Pi induced by mannitol theoretically could relieve compartmental tamponade noninvasively.

The effects of enoxaparin on the reparative processes in experimental osteonecrosis of the femoral head of the rat

The blood supply of one femoral head of 6‐month‐old rats was severed by incising the periosteum of the neck and cutting the ligamentum teres. The rats were killed on the 30th postoperative day and the femoral bones were obtained for semiquantification of the reparative processes in the necrotic heads. Fourteen rats were treated with enoxaparin and 14 untreated animals served as controls. Statistically, the amounts of necrotic bone in the epiphysis were less, the extent of remodeling of the femoral heads was milder, and the articular cartilage degeneration was slighter in the enoxaparin‐treated than untreated rats. There was no significant difference in the quantities of newly formed bone in femoral heads of treated and untreated rats. These findings are in agreement with the known effects of unfractionated and low‐molecular‐weight heparins which enhance osteoclastic bone resorption and angiogenesis and decrease osteoblastic bone formation. The former activities, operative in minimizing the structural distortion of the femoral head, oppose the crucial event in the pathogenesis of post‐osteonecrotic osteoarthritis.

Osteoarthritis-like disorder in rats with vascular deprivation-induced necrosis of the femoral head.

The reparative processes following vascular deprivation-induced necrosis of the femoral head were studied histologically in rats sacrificed 2, 7, 14, 21, 42 and 92 days postoperatively. The blood supply was severed by incision of the periosteum at the neck of the femoral head and transection of the ligamentum teres. Granulation tissue and a well-vascularized fibrous tissue originating from the joint capsule invaded the necrotic marrow spaces. With progressive resorption of the necrotic tissues and osteoneogenesis, both appositional and intramembranous, within the fibrotic intertrabecular spaces, the remodeling process led to a shift of the normal spongy architecture of the femoral head to a compacta-like one. In a few cases, osseous bridges bisected a necrotic physeal cartilage at the latest time intervals. The remodeling was associated with flattening of the femoral heads as well as with degenerative, regenerative and reparative alterations of the articular cartilage. In one of the two femoral heads obtained three months postoperatively, cystic spaces developed in the fibrous subchondral zone. Our findings are consistent with the view that ineffective attempts at restoring the prenecrotic state of the femoral head by replacing the necrotic with viable tissue triggers the collapse of the femoral head. Thickening and condensation of the subchondral bone, leading to increased stiffness of the subchondral zone, result in the osteoarthritis-like disorder. Mimicking the well-known phases of human osteonecrosis, the model readily allows for preclinical studies of therapeutic regimens.

Transphyseal osseous bridges in experimental osteonecrosis of the femoral head of the rat. Histologic study of the bony bridges connecting the epiphyseal with the metaphyseal bony trabeculae through gaps in the physeal cartilage.

In view of the lifelong persistence of the physis, the femoral head of rats may serve to model Perthes disease and slipped capital femoral epiphysis. To produce osteonecrosis, the blood supply of one femoral head of 133, 6-month-old animals was severed by circumferentially incising the periosteum of the neck and cutting the ligamentum teres. The rats were killed 7 days to 90 days postoperatively. Associated with resorption of the necrotic bone and marrow, remodeling of the epiphysis was characterized by an ingrowth of vascularized fibrous tissue, formation of new bone and some cartilage, architectural deformation and flattening of the head. In 22 of 83 rats killed 30 days or more postoperatively, gaps in the continuity of the physeal cartilage were occupied by osseous bridges, connecting newly formed epiphyseal bony trabeculae with either the preexisting or newly formed metaphyseal osseous trabeculae. This healing mode may follow ischemic death of physeal chondrocytes or be owing to another mechanism, e.g., release of mediatory substances of inflammation. These findings raise the possibility that fixation of the healing epiphysis of a childs previously necrotic femoral head to the metaphysis occurs by transphyseal osseous growth in cases in which the physis is involved in the necrotic process.

Patients Aged 80 and Older Undergoing Orthopedic or Urologic Surgery: A Prospective Study Focusing on Perioperative Morbidity and Mortality

Background: The population is progressively aging and an increasing number of elderly patients face surgical treatment. Objective: The current study was designed to examine the perioperative morbidity and mortality of elderly patients undergoing orthopedic or urologic surgery and look for predictors for adverse outcome. Methods: This is a prospective study of elderly patients, 80 years of age and older, who underwent elective or emergent orthopedic or urologic surgery in our institution during a 5-month period. Data were collected on age, gender, chronic diseases, number of regular medications, whether or not the patient was bedridden before surgery, American Society of Anesthesiologists (ASA) class, type of surgery and anesthesia, duration of hospitalization, and 30-day postoperative morbidity and mortality. We studied correlations between pre- and intraoperative parameters and postoperative complications. Results: During the study period, 39 patients underwent urologic surgery and 147 patients underwent orthopedic surgery. Age ranged from 80 to 98 years (85 ± 4.2 years, mean ± SD). One patient had an intraoperative complication, 5 patients had postoperative complications within 1 day of surgery, and 23 had complications within 1 month of surgery. Five (2.7%) patients, all of whom were operated urgently, died after surgery. Postoperative complications correlated significantly to poor ASA class (p = 0.01), urgency of the procedure (p = 0.03), and extent (p = 0.02) and duration (p = 0.01) of surgery. No significant correlation was found between outcome and any other pre- or intraoperative factors. Conclusions: Elderly surgical patients with poor ASA class or following urgent, extensive or long surgery are at a higher risk for postoperative morbidity and mortality, mandating special perioperative care.

Intraosseous conduit-induced enhancement of ingrowth of blood vessels into the necrotic femoral head of rats

Following severance of the blood supply to the left femoral head of 6-month-old rats by incising the periosteum of the neck and cutting the ligamentum teres, a 21-gauge needle, inserted into the foveola, was pushed forward in the direction of the neck up to the opposite cortical bone. Femora were obtained for histological examination on postoperative days 32 and 42, from 22 and 12 rats, respectively. The right femoral heads were normal. In addition to the usual reparative and regressive changes characteristic of the second month after induction of osteonecrosis, the left femoral heads showed, compared to the femoral heads of otherwise untreated rats, lavish ingrowth of blood vessels and proliferation of mesenchymal cells. Moreover, 16 of the 34 femoral heads disclosed additional distinctive lesions, namely, partial fibrous replacement, surface depression, intraosseous tunneling, and subtotal destruction of the epiphysis. The results of this experiment, an attempt at modeling core decompresssion in man, parallel the frequently reported unsatisfactory outcome of the procedure in patients with osteonecrosis of the femoral head. They as well indicate that any therapeutic effects of producing an epiphyseal-metaphyseal conduit for the ingrowth of vessels and cells may only be achieved at the cost of a reduction in the mechanical load-bearing capacity of the femoral head.

Postosteonecrotic osteoarthritis-like disorder of the femoral head of rats.

The femoral heads of 15 rats were studied histologically 3 months after the induction of ischaemic necrosis by incising the cervical periosteum and cutting the ligamentum teres. The epiphyses consisted of immature disorganized subchondral and trabecular bone. The inter-trabecular spaces contained fibrous or haematopoietic tissue. Residual necrotic bone was rare. There was marked osteoblastic and osteoclastic activity. The articular aspect of the heads showed a spectrum of changes, ranging from cartilaginous degeneration with fibrillation and loss of glycosaminoglycans to an eburnated and polished bony surface. In seven rats, transphyseal bridges connected the epiphyseal and metaphyseal bony trabeculae to each other. It is suggested that the postnecrotic reparative processes, including the resorption of the necrotic debris and its replacement by newly formed, weak bone, led to an osteoarthritis-like disorder. This healing pattern of the necrotic femoral head was reminiscent of the progressive remodelling that occurs in rings in femoral capital osteonecrosis of adult human patients and in Perthess disease of children.

Vasculature deprivation-induced osteonecrosis of rats’ femoral heads associated with the formation of deep surface depressions

BackgroundShallow or deep bowl-shaped depressions often develop after drilling an intraosseous conduit in the necrotic, avascular femoral head of rats. The etiopathogenesis of tissue loss at the articulation surface after a drilling procedure was elaborated in the authors’ previous reports.GoalsTo scrutinize a large collection of femoral heads of rats in order to search for similar changes in cases in which no drilling procedure was carried out.StudyThis retrospective study comprised the specimens of 386 rats with vessels-deprived osteonecrosis of the femoral heads, none of the animals having undergone a drilling procedure.ResultsShallow or deep bowl-shaped depressions were encountered at an incidence as low as 2.8% of the femoral heads of the above mentioned 386 rats. It is not feasible to distinguish histologically the “spontaneously” arising from and drilling-related depressions.ConclusionsNo assured explanation can be offered for the evolving depressions of the surface of femoral heads of rats, which have not undergone a drilling procedure. It is hypothesized that the synovial fluid forces its way via slits in the articulation surface and bores cavities in the substance of femoral heads, which display a postosteonecrotic osteoarthritis-like disorder. The rising pressure in the arthritic joints results, firstly, in an enlargement of these cavities and, secondly, loss of fibro-cartilaginous tissue such that the cavities come to communicate with the articular space.

Giant-cell reparative granuloma-like lesion in the femoral heads of rats during the early repair phase of osteonecrosis

We describe the unusual occurrence of giant-cell reparative granulomas in the rat. Cutting the ligamentum teres and incising the periosteum around the base of the femoral neck induced femoral capital necrosis. Giant-cell reparative granuloma-like lesions developed in ~0.8% of 366 rats during the early reparative stages of osteonecrosis. Resorption of the necrotic bone, hematopoietic tissue, and adipocytes was exceptionally widespread in these three rats. Overexpression of macrophage-fusing cytokines may account for the increased number of multinucleated giant cells, which on a plump stromal cell background imitate a giant-cell reparative granuloma of the bone.RésuméDescription d’un développement inhabituel de granulome de réparation à cellules géantes chez le rat. La section du ligament rond et l’incision du périoste à la base du col fémoral induit le développement d’une nécrose de la tête fémorale. Un granulome de réparation à cellules géantes se développe chez 0,8% de 366 rats durant la phase précoce de réparation de l’ostéonécrose. Une résorption de l’os nécrosé, du tissu hématopoéïtique et des adipocytes étaient largement présent et à titre exceptionnel chez ces 3 rats. Une sur-expression de cytokines créatrices de macrophages doit compter pour expliquer le grand nombre de cellules géantes, qui dans un environnement de stroma graisseux imitent un granulome à cellules géantes de réparation osseuse.