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Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_II | Pages 342 - 342
1 May 2006
Peled E Norman D Bejar J Boss J Levin D Ben-Noon H Zinman C
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Introduction: In avascular necrosis [AVN] of the femoral head the dead bone undergoes osteoclastic osteolysis and is replaced by newly synthesized, immature, weak bone, which cannot withstand the daily loads. The articular surface might caves in because of these changes, and osteoarthritic joint changes can develop. Alendronate interferes with the osteoclastic activities, it can slow-down the bone turnover of the necrotic bone and can differ these changes.

The aim of this study is to delay the speedy renewal of living epiphyses by alendronate medication in order to describe the effects of it on the fate of the necrotic femoral heads in rats.

Methods: Sixty female sprague-dawley rats, 6-month old weighing about 400–500 grams, underwent surgical AVN of the right femoral heads. Forty-four rats, the treated group, were treated with alendronate 200 μgm/kg/day. Sixteen rats, the control group, were treated with saline. Both groups were daily injected subcutaneously for six weeks and sacrificed. Both femoral heads were harvested and were evaluated microscopically and stained by H& E.

Results: The necrotic femoral heads of the control group, which were not treated by alendronate, were severely distorted with osteoarthrosis features as; collapse of the epiphysis, pannus formation, filling of spaces by chronically and mildly inflamed densely textured fibrous tissue which was polluted by numerous tiny particles of necrotic bone. Additionally, large chunks of necrotic articular cartilage were haphazardly scattered in the fibrous tissue. All hematopoietic and fat cells of the intertrabecular spaces of the epiphysis were replaced by fibrous tissue. More often than not, the cartilage of the physis was focally or entirely absent such that osseous trabeculae of the epiphysis and metaphysis linked with each other, forming so-called epiphyseal-metaphyseal bridges. The above described alterations were encountered in all animals, yet their severity varied.

The decisive difference between the necrotic femoral heads of otherwise untreated in opposition to the alendronate-medicated rats was the preservation of a hemispherical configuration of the femoral heads. There was no distortion of the femoral heads in the alendronate-treated animals and the femoral heads preserved their roundness.

All femoral heads of the non-operated left hips were microscopically normal.

Discussion: It has become clear that the degree of architectural distortion of the femoral epiphyses depends on the extent of bone turnover leading to resorption of all debris and its replacement by living osseous and soft tissues. The more rapidly and more extensively the reconstruction of living epiphyses progresses, the smaller is the prospect of reshaping a hemispherical or near-hemispherical femoral head. The recently rebuilt epiphyses cannot carry daily transarticular loads without caving in. The revascularization-related reconstitution of weak bony trabeculae is blamed for the collapse of the femoral heads. If this indeed is the case, the remodeling of the necrotic femoral heads should be delayed, rather than sped-up. Alendronate interferes with the osteoclastic activities and hence, slowing-down the bone turnover.

The osteoclastic activity is detrimental for the conservation of a hemispherical femoral head because of the rapidly occurring replacement of the necrotic bone by living tissues. Halting the activities of the osteoclasts by a biphosphonate would stop the hasty osteoneogenesis, which is responsible for the early femoral capital disfigurement and might delay the regeneration of osteo-arthiritic changes of the joint later on.


Orthopaedic Proceedings
Vol. 87-B, Issue SUPP_III | Pages 390 - 390
1 Sep 2005
Peled E Zinman C Boss J Seliktar D
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Introduction: The aim of the current investigation to study the inherent ability of biomaterial scaffolds to regenerate bone defects without osteoinductive growth factors. We have developed a biosynthetic hybrid scaffold that mimics the biofunctionality of the provisional fibrin matrix which regulated the initial stages of in vivo bone regeneration. The material is comprised of a fibrinogen backbone and polyethylene glycol (PEG) cross-links that regulate the strength, durability, and degradation of the matrix during the healing process. Precise control over the degradability of the hydrogel scaffold provides the ability to systematically regulate the cellular infiltration associated with fracture healing. Furthermore, improved physical strength (over purified native fibrin clots) enables superior handling properties and stable in situ fixation.

Materials & Methods: In the current study, a 7-mm critical size defect is created in the right tibia of female Sprague-Dawley rats (age 3–4 months); an external fixator is placed proximal and distal to the mid-section of the tibia. Pre-cast fibrinogen-PEG cylindrical hydro-gels (3-mm dia, 7-mm long) are placed into the site of the defect. Three different hydrogel compositions are tested: 1:1, 1:2, and 1:3 fibrinogen to PEG. Independent experiments demonstrate that higher concentrations of PEG give the hydrogels slower degradation kinetics. Radiographs, post operative and during follow-up, and histological evaluation were done.

Results & Discussion: Both radiography and histological evaluation reveals extensive and widespread periosteal new bone formation. Post-operative radiographs show the formation of a periosteal callus in the gap region of treated animals after five weeks compared to immediately following excision (Figure 1, right). Five weeks post-operatively, histological sections stained with H& E reveal a thick covering of newly formed and moderately differentiated lamellar-fibred bone alongside lengthy stretches of the original cortex. There are large amounts of closely packed trabeculae of recently deposited, woven-fibered bone wherever there are empty spaces of the hydrogel scaffold. These trabeculae join at their perimeters with the preexisting bone. We also demonstrate a clear relationship between the composition of the hydrogel and the synthesis of new bone in the defect site. In conclusion, we demonstrate the formation of newly synthesized bone in critical size defects in the rat tibia using a biomimetic hydrogel scaffold without the use of exogenous growth factors.