Alendronate preserves femoral head shape and height/length ratios in an experimental rat model: A computer-assisted analysis.

BACKGROUND: Surgical osteonecrosis of the rat femoral head was induced by detaching the ligamentum teres and stripping the femoral neck periosteum. Bone and marrow necrosis were found from the fifth postoperative day and replaced by creeping substitution. Osteonecrosis of the femoral head results in the flattening to various degrees of roundness and osteoarthritic changes of the hip joint. Alendronate, an osteoclast inhibitor, slows down bone resorption and remodeling. The purpose of this study was to evaluate objectively the influence of alendronate treatment on the rat femoral head shape after six weeks of daily treatment, when compared with controls. MATERIALS AND METHODS: The blood circulation of right femoral head of 20 female Sprague-Dawley rats was interrupted. Twelve were treated by alendronate injections of 200 microg/kg/day and eight controls were treated with saline, both for a total of 42 days. Both femoral head specimens were obtained for computed-assisted morphometry. For each rat, the right operated head was compared with the left, and the alendronate treated group was compared with the control group. RESULTS: No differences were found in shape factor and femoral head height/length ratios in the alendronate treated femoral heads. Among the nontreated control group, shape-factor differences were found between the operated and the nonoperated femoral heads. CONCLUSION: Alendronate treatment prevented the distortion and destruction of the femoral head. Osteoclast inhibition might prolong the bone creeping substitution process and could enable secondary bone maturity and mineralization that increases bone strength. Alendronate preserved the femoral head architecture, which might reduce morbidity and disability due to femoral head collapse.

Prevention of distortion of vascular deprivation-induced osteonecrosis of the rat femoral head by treatment with alendronate.

INTRODUCTION: In animals with a disrupted blood supply and drainage of the femoral head, the dead epiphyseal bone undergoes osteoclastic osteolysis and is replaced by newly synthesized, immature, and weak bone, which cannot withstand the daily loads and, therefore, the articular surface caves in. METHODS: Female Sprague-Dawley rats with interrupted blood circulation of the femoral head were treated with alendronate and compared to controls. RESULTS: There was no distortion of the femoral heads in the alendronate-treated animals. INTERPRETATION: Alendronate medication interferes with osteoclastic activities, slowing down bone turnover. These observations verify our hypothesis that osteoclastic activity is detrimental to the conservation of a hemispherical femoral head because of the rapidly occurring replacement of the dead by living tissues. Hence, halting the activities of the osteoclasts by alendronate stops the hasty new bone formation which is responsible for early femoral capital disfigurement.

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

BACKGROUND: Shallow 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. GOALS: To 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. STUDY: This 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. RESULTS: Shallow 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. CONCLUSIONS: No 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.

Vasculature deprivation--induced osteonecrosis of the rat femoral head as a model for therapeutic trials.

EXPERIMENTAL OSTEONECROSIS: The authors' experience with experimentally produced femoral capital osteonecrosis in rats is reviewed: incising the periosteum at the base of the neck of the femur and cutting the ligamentum teres leads to coagulation necrosis of the epiphysis. The necrotic debris is substituted by fibrous tissue concomitantly with resorption of the dead soft and hard tissues by macrophages and osteoclasts, respectively. Progressively, the formerly necrotic epiphysis is repopulated by hematopoietic-fatty tissue, and replaced by architecturally abnormal and biomechanically weak bone. The femoral heads lose their smooth-surfaced hemispherical shape in the wake of the load transfer through the hip joint such that, together with regressive changes of the joint cartilage and inflammatory-hyperplastic changes of the articular membrane, an osteoarthritis-like disorder ensues. THERAPEUTIC CHOICES: Diverse therapeutic options are studied to satisfy the different opinions concerning the significance of diverse etiological and pathogenic mechanisms: 1. Exposure to hyperbaric oxygen. 2. Exposure to hyperbaric oxygen and non-weight bearing on the operated hip. 3. Medication with enoxaparin. 4. Reduction of intraosseous hypertension, putting to use a procedure aimed at core decompression, namely drilling a channel through the femoral head. 5. Medication with vascular endothelial growth factor with a view to accelerating revascularization. 6. Medication with zoledronic acid to decrease osteoclastic productivity such that the remodeling of the femoral head is slowed. Glucocorticoid-related osteonecrosis appears to be apoptosis-related, thus differing from the vessel-deprivation-induced tissue coagulation found in idiopathic osteonecrosis. The quantities of TNF-alpha, RANK-ligand and osteoprotegerin are raised in glucocorticoid-treated osteoblasts so that the differentiation of osteoclasts is blocked. Moreover, the osteoblasts and osteocytes of the femoral cortex mostly undergo apoptosis after a lengthy period of glucocorticoid medication.

Intramyofiber erythrocytes in skeletal muscle.

The authors describe the serendipitous discovery of clustered erythrocytes within myocytes in a biopsy obtained during repair of a torn tendon. Their perusal of the literature failed to uncover an analogous observation.

Pyogenic granuloma-like reaction in the necrotic, vessels-deprived femoral head of the rat.

Osteonecrosis of the femoral head was produced in rats by cutting the ligamentum teres and incising the cervical periosteum. As of the second postoperative week, fibrous tissue pervaded the necrotic epiphyses, macrophages and osteoclasts removed the debris, osteoblasts deposited lamellar-fibred and woven-fibred intramembranous bone, and remodeling began. In 16% of the rats killed during the 2nd postoperative week, the epiphyses contained big fragments of necrotic bone enclosed by densely packed, capillary-sized vessels. Ingrowth of this hypervascularized, pyogenic granuloma-like tissue is presumably due to the presence of excessive growth factors, reflecting an exaggerated pathophysiological reaction within the framework of organization of the necrotic epiphyses.

Liesegang rings in hemorrhagic urine.

Myriad Liesegang rings were encountered in the urine of a 43-year-old patient who was diagnosed as having idiopathic hematuria, emanating from the left ureter or kidney. Erythrocytes and the Liesegang rings spontaneously disappeared from the urine within 4 weeks. We are unaware of a report of a similar observation. Lack of descriptions may be due to underreporting or reflect true rarity of Liesegang rings in the urine. It is suggested that Liesegang rings may precipitate in the hemorrhagic urine as they do in diverse blood-imbibed tissues.

Fractal dynamics in the differential diagnosis of thyroideal follicular neoplasms.

In this study, we investigated the sensitivity, specificity, and predictive values of morphometric parameters of thyroideal follicular neoplasms based on concepts of fractal geometry. Thirty-seven follicular adenomas and 36 well-differentiated follicular carcinomas were assessed morphometrically. The nuclear area, nuclear area fraction, nuclear regularity factor, nuclear elongation factor, and slope setting (representing the ratio between the nuclear perimeter and nuclear regularity factor) were subjected to fractal dimensions analysis. By univariate analysis, the nuclear area, nuclear area fraction, nuclear regularity factor and slope values discriminate between adenomas and carcinomas. By multivariate analysis, the nuclear area, nuclear area fraction and slope values possess significant discriminatory powers in distinguishing between adenomas and carcinomas. Incorporating the nuclear area, nuclear area fraction, and slope values leads to a discriminatory power with 92% specificity and 83% sensitivity. The reciprocal relationships between the nuclear area, nuclear perimeter, and nuclear regularity factor of the cells of thyroideal adenomas and carcinomas may be expressed by fractal dimensions. Analysis limited to one parameter provides incomplete data. Expressing variations of the nuclear perimeter as a function of the nuclear regularity factor, the slope values constitute an independent attribute that significantly differentiates thyroideal adenomas from carcinomas.

The prognostic significance of the semiquantitatively determined estrogen receptor content of breast carcinomas. A clinicopathological study.

Response of breast carcinomas to tamoxifen treatment depends, among others, on the estrogen receptor status. The estrogen receptor content was semiquantitatively determined in immunostained sections of stage 1 and 2 cancers of patients who had undergone tumor excision, tamoxifen treatment, adjuvant chemotherapy and radiotherapy. Weighted scores of the estrogen receptor content of the tumors were established by calculating the arithmetic means of the intensity of stained nuclei and the number of positively stained nuclei. Statistically, a cut-off value of > or = 2.1 signified a good prognosis; all patients whose tumors disclosed a weighted score of > or = 2.1 were alive and free of disease at the 10-year postoperative follow-up examination. On the other hand, one third of the patients whose carcinomas had a weighted score of < 2.1 presented with locally recurrent cancer, distant metastases, or both during the follow-up observation period. The statistically significant association between the patients' 10-year event-free survival and carcinomas with a weighted score of > or = 2.1 may serve oncologists in their decision making with respect to hormonal treatment.

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.