Several bisphosphonates are now available for the treatment of osteoporosis. Porous hydroxyapatite/collagen (HA/Col) composite is an osteoconductive bone substitute which is resorbed by osteoclasts. The effects of the bisphosphonate alendronate on the formation of bone in porous HA/Col and its resorption by osteoclasts were evaluated using a rabbit model. Porous HA/Col cylinders measuring 6 mm in diameter and 8 mm in length, with a pore size of 100 μm to 500 μm and 95% porosity, were inserted into a defect produced in the lateral femoral condyles of 72 rabbits. The rabbits were divided into four groups based on the protocol of alendronate administration: the control group did not receive any alendronate, the pre group had alendronate treatment for three weeks prior to the implantation of the HA/Col, the post group had alendronate treatment following implantation until euthanasia, and the pre+post group had continuous alendronate treatment from three weeks prior to surgery until euthanasia. All rabbits were injected intravenously with either saline or alendronate (7.5 μg/kg) once a week. Each group had 18 rabbits, six in each group being killed at three, six and 12 weeks post-operatively. Alendronate administration suppressed the resorption of the implants. Additionally, the mineral densities of newly formed bone in the alendronate-treated groups were lower than those in the control group at 12 weeks post-operatively. Interestingly, the number of osteoclasts attached to the implant correlated with the extent of bone formation at three weeks. In conclusion, the systemic administration of alendronate in our rabbit model at a dose-for-weight equivalent to the clinical dose used in the treatment of osteoporosis in Japan affected the mineral density and remodelling of bone tissue in implanted porous HA/Col composites.
We present a series of 30 uncemented total hip replacements performed between June 1985 and January 2002 with a mean follow-up of seven years (5 to 20) in 27 patients who had previously undergone a valgus intertrochanteric osteotomy. No further osteotomy was undertaken to enable hip replacement. We used a number of uncemented modular or monoblock femoral components, acetabular components and bearings. The patients were followed up clinically and radiologically. We report 100% survival of the femoral component. One acetabular component was revised at five years post-implantation for aseptic loosening. We noted cortical hypertrophy around the tip of the monoblock stems in six patients. We believe that modular femoral components should be used when undertaking total hip replacement in patients who have previously undergone valgus femoral osteotomy.
The purpose of this study was to investigate the possible relationship between matrix metalloproteinase-3 (MMP-3) promoter 5A/6A polymorphism and intervertebral disc (IVD) degeneration in the older generation. One of the important steps in IVD degeneration is disc matrix degradation by matrix degrading enzymes such as MMPs. MMP-3 is one of the potent proteoglycan degrading enzymes and has been suggested to play an important role in IVD degradation. A common 5A/6A polymorphism in the promoter region of the human MMP-3 gene has been identified. This polymorphism was reported to be involved in the regulation of MMP-3 gene expression (the 5A allele has 2-fold higher promoter activity than 6A). We now hypothesize that IVD degeneration is associated with MMP-3 promoter 5A/6A polymorphism. Forty-nine elderly Japanese volunteers (mean age 74.3 years, range 64–94 years) were studied. Each lumbar disc was graded according to the radiographic classification system of IVD degeneration described by Kellgren and Lawrence. The 5A/6A polymorphism was determined with both single strand conformation polymorphism (SSCP) and polymerase chain reaction with allele-specific primers (AS-PCR). Two subjects (4%) with 5A5A genotype, 16 (33%) with 5A6A, and 31 (63%) with 6A6A were observed. Genotype was totally independent of age and sex. There was a significantly larger number of IVDs graded 2 and higher in the 5A/5A+5A/6A than in the 6A/6A (p<
0.05). The degenerative scores of lumber discs were also distributed more highly in the 5A/5A+5A/6A than in the 6A/6A (p=0.0029). Many environmental factors have been reported to accelerate IVD degeneration. Recently, genetic factors have also been highlighted as possible risk factors. The 5A allele of the human MMP-3 promoter is a possible risk factor for acceleration of IVD degeneration in people aged over 64 years old. We conclude that MMP-3 plays a key role in the degeneration of IVD in the older generation.
A hydroxyapatite/type I collagen(HAp/Col) composite, in which the hydroxyapatite nanocrystals align along the collagen molecules, has been prepared. The bio-compatibility, osteoconductive activity and efficacy as a carrier of rhBMP-2 of this novel biomaterial were examined. Following three studies were performed – (1) The composite materials (4×4×1mm3) were implanted in the back of Wistar rats, and specimens collected for histological observations until week 24. (2) The composite materials (5×5×10mm3) containing rhBMP-2(0, 200, 400μg/ml) were grafted in radii and ulnae in beagle dogs. X-ray images were prepared, and specimens collected for histological observation at week 8 and 12. (3) The implants(15mm in diameter and 20mm in length) containing rhBMP-2 (0, 400 mg/ml) were implanted in tibiae in beagle dogs and fixed with Ilizarov method. Soft x-ray images were prepared each week. The bone mineral density was measured and the implants were harvested at 12, 18 and 24 weeks after surgery. The period until bone union after implantation of the HAp/Col implant was between 10 and 12 weeks after operation, and approximately the same as that of autogenous bone graft. Histological analysis revealed that osteoclasts appeared in a Howship’s lacunae-like structure formed on the composite and osteoblasts arranged on the newly formed bone. These findings suggest that the HAp/Col composite has a character similar to that of natural bone. X-ray images and histological findings for the composites support the idea that HAp/Col has a high osteoconductive activity and is able to induce bone-remodeling units. In cases where the implants are grafted at weight bearing sites, treatment with rhBMP(400μg/ml) may be useful to shorten the time until bone union.
We carried out a prospective, randomised study of 62 patients to determine the efficacy of a foot sole pump (the A-V Impulse System) for the prevention of pulmonary embolism (PE) after hip surgery. PE was assessed by pulmonary perfusion scintigraphy before and after operation. We defined a PE as any new scintigraphic defect which was larger than a bronchopulmonary segment. The incidence of PE was 55% in the control group and 21% in the treatment group. The foot sole pump significantly reduced the incidence of PE (p = 0.008) and we encountered no side-effects from its use.
It has been suggested that matrix metalloproteinase-3 (MMP-3, stromelysin-1) has an important role in the degeneration of intervertebral discs (IVDs). A human MMP-3 promoter 5A/6A polymorphism was reported to be involved in the regulation of MMP-3 gene expression. We suggest that IVD degeneration is associated with 5A/6A polymorphism. We studied 54 young and 49 elderly Japanese subjects. Degeneration of the lumbar discs was graded using MRI in the younger group and by radiography in the elderly. 5A/6A polymorphism was determined by polymerase-chain reaction-based assays. We found that the 5A5A and 5A6A genotype in the elderly was associated with a significantly larger number of degenerative IVDs than the 6A6A (p <
0.05), but there was no significant difference in the young. In the elderly, the IVD degenerative scores were also distributed more highly in the 5A5A and 5A6A genotypes (p = 0.0029). Our findings indicate that the 5A allele is a possible risk factor for the acceleration of degenerative changes in the lumbar disc in the elderly.
We treated 31 hips in 30 patients with advanced osteoarthritis of the hip secondary to acetabular dysplasia, by valgus-extension femoral osteotomy. The mean follow-up was 12.7 years (10 to 17). Acetabuloplasty was added in ten severely dysplastic hips. In 28 hips, radiological widening of the joint space was seen three years after operation, but in 12 had narrowed again by ten years. Survivorship analysis showed that the rate of survival was 82% using the pain score as the index of failure, and 72% based on radiological findings at ten years. Better long-term results were obtained in hips which had an acetabular head index greater than 70% or a roof osteophyte more than 5 mm in length three years after operation. Acetabuloplasty should be added for the hip which is severely dysplastic and with a poorly developed roof osteophyte.