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PubMed2003

Outcome of nonvascularized bone grafting for osteonecrosis of the femoral head.

Osteonecrosis is a disease with a wide-ranging etiology and poorly understood pathogenesis seen commonly in young patients. Various head-preserving procedures have been used for this disease to avert the need for total hip replacement. These include various vascularized and nonvascularized bone grafting procedures. We will describe the use of bone-grafting through a window at the femoral head-neck junction for the treatment of osteonecrosis of the femoral head. Bone morphogenetic protein (BMP)-enriched allograft was used to avoid donor site morbidity. Nineteen patients (21 hips) were followed up for a mean of 48 months (range, 36-55 months) after a bone grafting procedure in which the diseased bone was replaced by a bone graft substitute (combination of demineralized bone matrix, processed allograft bone chips, and a thermoplastic carrier). Eighteen of 21 hips (86%) were clinically successful at latest followup. Two of these patients have minimal radiographic progression (< 2 mm head collapse). This procedure is straightforward technically, led to low morbidity, and did not necessitate procurement of donor site bone graft. This procedure may be effective at avoiding or forestalling the need for total hip arthroplasty in young patients with early to intermediate stages of osteonecrosis of the femoral head.

Adult↗
PubMed1990

Subungual exostoses--clinicopathological and ultrastructural studies of three cases.

Three patients with subungual exostoses, two involving the great toe and one the fourth toe, are presented. Local excision was performed, and the specimens were processed for light and electron microscopy. Light-microscopic study revealed that the tumours consisted of a proliferative fibrocartilaginous cap that merged into mature trabecular bone at its base. Electron-microscopic examination revealed that the tumour was composed of two types of cells: one was rich in cell organelles including rough endoplasmic reticulum, well-developed Golgi apparatus, and glycogen granules; the other cell had few such cell organelles. The former cells seemed to be osteoblasts actively engaged in bone formation, and the latter to be osteocytes related to those situated deeper in bone matrix in normal bone. However, ossification or calcification in subungual exostosis is rather casual, and osteocytes in this disorder may lack the capacity to elaborate compact bone.

Adult↗
PubMed1989

Impact of streptozotocin-induced diabetes on rat blood and alveolar bone affected by occlusal stress.

Adult male and female rats were used as test animals. The experimental diabetes mellitus was provoked with one dose of i.v. injection of streptozotocin (65 mg/kg body weight), which interferes with the insulin release mechanism in pancreatic beta cells. After a follow-up period of 10 wk an average loss of 10% of body weight and an increase of 25% in the amount of blood obtained by decapitation was recorded in the test animals. The biochemical assays performed on the serum of the diabetic rats showed, for both sexes, a fourfold rise in the plasma glucose level, a threefold rise in plasma alkaline phosphatase activity and plasma alanine transferase activity as well as a 1.5-fold rise in plasma creatine value. The two latter values indicated systematic disorders reflected in the liver and the kidneys. An increase in serum total calcium and hydroxyproline values was also detected. The clinical studies of the gingiva showed diminished tissue resistance in diabetic rats. The histologic studies of alveolar bone revealed retarded formation of bone matrix and new bone in diabetic animals. However, the stimulated metabolism in alveolar bone, due to the artificially induced stress, increased marginal bone cell activity in both the diabetic and the control group, resulting in increased crestal resorption in the former group. The differences in tissue response observed among the diabetic animals affected and unaffected by stress originated from the disturbed recovering mechanism typically found in diabetic animals.

Animals↗
PubMed1995

Interaction of osteopontin with osteoclast integrins.

Mammalian osteoclasts express three integrin receptors--alpha v beta 3 (vitronectin receptor), alpha 2 beta 1 and alpha v beta 1. The vitronectin receptor recognizes bone matrix proteins, including bone sialoproteins, in an RGD-dependent manner, whereas adhesion to collagen involves beta 1 integrins. Interference with integrin function, by anti-receptor antibodies or RGD-peptides, blocks bone resorption. Data on the mechanism of osteoclast adhesion to sialoproteins and the differential synthesis of osteopontin and bone sialoprotein by osteoclasts is presented. Thus, osteoclasts adhere to both osteopontin and bone sialoprotein with a characteristic irregular morphology with numerous, peripherally placed, actin-rich podosomes. Adhesion is predominantly RGD and beta 3 dependent, though alpha v beta 1 may also be involved in adhesion to bone sialoprotein. KQAGD and AGDV, but not H12, fibrinogen peptides induce osteoclast 'rounding' on osteopontin suggesting there is an alternative anti-adhesive signal to 'RGD.' However, adhesion is not completely inhibited and is not specific for osteopontin as equivalent effects are seen with adhesion to serum. The role of sialoproteins in osteoclast adhesion in situ in the skeleton is complicated by the finding of endogenous synthesis of osteopontin, but not bone sialoprotein, by osteoclasts. The disposition of osteoclast integrins during resorption and the role of integrins and sialoprotein-derived peptides in osteoclast adhesion and function is also reviewed.

Amino Acid Sequence↗
PubMed2004

Geometric determinants to cement line debonding and osteonal lamellae failure in osteon pushout tests.

Cement lines are the boundaries between secondary osteons and the surrounding interstitial bone matrix in cortical bone. The interfacial properties of cement lines have been determined by osteon pushout tests. However, distinctively different material properties were obtained when osteon pushout tests were performed under different test geometries. In the present study, an axisymmetric two-dimensional finite element model was used to simulate an osteon pushout test using the test geometry of actual experiments. The results indicated that shear failure within the osteonal lamellae would occur when the osteon pushout test was performed under the condition of a thick specimen and large supporting hole. On the other hand, cement line debonding occurred when the osteon pushout test was performed using a thin specimen and small supporting hole. The finite element results were consistent with previous experiments of osteon pushout tests under different test geometries. Furthermore, the finite-element results suggest that a smoothly curved punch would most likely cause debonding at the cement line instead of osteonal lamellae.

Animals↗
PubMed1990

Receptors for insulin-like growth factors-I and -II in osteoblast-enriched cultures from fetal rat bone.

Insulin-like growth factors-I and -II (IGF-I and IGF-II) are produced by bone cells and stored in bone matrix, and stimulate bone cell DNA synthesis and type I collagen production. Earlier studies in cells from an assortment of tissues indicate that IGF-I binds to membrane receptors of various relative molecular mass (Mr), whereas IGF-II binds predominantly to the mannose-6-phosphate transferase. In the present studies we have examined the IGF receptor profile in osteoblast-enriched cultures prepared from fetal rat parietal bone. Scatchard binding kinetics with either 125I-IGF-I or 125I-IGF-II were curvilinear, indicating high and low affinity receptor classes for each ligand. Chemical cross-linking and polyacrylamide gel analysis revealed that 125I-IGF-I bound at Mr 130,000, 240,000, and 260,000, whereas 125I-IGF-II bound predominantly at Mr 240,000. Unlabeled IGF-I displaced 125I-IGF-I with high affinity at Mr 260,000 and 130,000 and with lower affinity at Mr 240,000. Unlabeled IGF-II preferentially displaced either radioactive ligand at Mr 240,000, but at high concentrations displaced 125I-IGF-I at all binding sites. Furthermore, mannose-6-phosphate enhanced binding by both 125I-IGF-I and 125I-IGF-II at Mr 240,000, and antibody to the rat IGF-II receptor prevented binding only at this location. The relative affinities of IGF-I and IGF-II for the primary IGF-I receptor correlate with their anabolic activities in bone cultures and suggest that the IGF-I receptor mediates the growth-promoting effects of both agents in bone.

Animals↗
PubMed2006

RANKL inhibition: a novel strategy to decrease femoral head deformity after ischemic osteonecrosis.

UNLABELLED: A novel therapeutic strategy to decrease the development of femoral head deformity after ischemic osteonecrosis was studied in a large animal model of total head infarction. RANKL inhibition through exogenous osteoprotegerin administration significantly decreased pathologic bone resorption and deformity during repair of the infarcted head. INTRODUCTION: Legg-Calvé-Perthes disease (LCPD) is a juvenile form of osteonecrosis of the femoral head that can produce permanent femoral head deformity (FHD) and premature osteoarthritis. The development of FHD in LCPD is closely associated with the repair process, characterized by a predominance of bone resorption in its early stage that produces a fragmented appearance and collapse of the femoral head. We present here a novel strategy to preserve the femoral head structure after ischemic osteonecrosis based on inhibition of interaction between RANK and RANKL using exogenous administration of osteoprotegerin (OPG-Fc) in a large animal model of ischemic osteonecrosis. MATERIALS AND METHODS: Ischemic osteonecrosis was surgically induced in 18 male piglets by placing a ligature tightly around the right femoral neck to disrupt the blood flow to the right femoral head. Two weeks after the induction of total head infarction, OPG-Fc or saline was administered subcutaneously to nine animals per group for 6 weeks. The contralateral, normal (left) femoral heads from the animals treated with saline served as normal, nondisease controls. All animals were killed at 8 weeks when severe FHD has been previously shown to occur because of the repair process dominated by osteoclastic bone resorption. Radiographic, histomorphometric, and immunohistochemical assessments were performed. RESULTS: Radiographic assessment showed significantly better preservation of the femoral head structure in the OPG-Fc group compared with the saline group. Epiphyseal quotient (the ratio of epiphyseal height to diameter) was significantly higher in the OPG-Fc group (0.41 +/- 0.09) compared with the saline group (0.24 +/- 0.08, p < 0.001). Histomorphometric assessment revealed a significant reduction in the number of osteoclasts present in the OPG-Fc group (5.9 +/- 5.3mm(-2)) compared with the saline group (39.6 +/- 13.8 mm(-2), p < 0.001). Trabecular bone volume, number, and separation were significantly better preserved in the OPG-Fc group compared with the saline group (p < 0.001). No significant difference in femoral length was observed between the OPG-Fc and saline groups. Immunostaining revealed the presence of OPG-Fc only within the blood vessels, with no apparent staining of bone matrix or trabecular bone surfaces. CONCLUSIONS: To our knowledge, this is the first study to show that RANKL inhibition decreases bone resorption and FHD after ischemic osteonecrosis. Because RANKL inhibitors do not bind to bone, their effects on resorption are reversible as the drug is cleared from circulation. The reversible nature of RANKL inhibitors is very appealing for treating pediatric bone diseases such as LCPD, where the resorptive stage of the disease lasts for 1-2 years.

Animals↗
PubMed1997

Concentration of the cross-linked carboxyterminal telopeptide of type I collagen in serum of young growing rats fed a low calcium and vitamin D-deficient diet.

Type I collagen is the main type found in mineralized bone. Specific radioimmunoassay for the cross-linked carboxyterminal telopeptide of type I collagen allows assessing the degradation of type I collagen in serum samples. The aim of the present investigation was to determine the concentration of cross-linked carboxyterminal telopeptide of type I collagen in serum of dietary calcium and vitamin D-deficient rats, a good model disease of decreased formation and mineralization of bone matrix and excessive bone resorption. The studies were carried out on 20 young growing Wistar rats. Serum concentration of the cross-linked carboxyterminal telopeptide of type I collagen was analyzed by the Rat Telopeptide [125I]ICTP Radioimmunoassay Kit obtained from Orion Diagnostica (Finland). The data obtained from biochemical analysis showed increased concentration of the cross-linked carboxyterminal telopeptide of type I collagen in the serum of rats fed a low calcium and vitamin D-deficient diet after 14 days of the experiment. At the end of the experiment (day 21), the concentration of carboxyterminal telopeptide of type I collagen in serum was still elevated in these animals. In conclusion, dietary calcium and vitamin D-deficiency in rats produces hypocalcaemia together with the increased concentration of the cross-linked carboxyterminal telopeptide of type I collagen in serum.

Animals↗
PubMed1995

Human demineralized freeze-dried bone: inadequate induced bone formation in athymic mice. A preliminary report.

The purpose of this study was to test the osteoinductive properties of demineralized freeze-dried bone (DFDBA) randomly purchased from four commercial bone banks. Twenty-five (25) milligrams of bone from each of the banks was implanted into the hindquarter muscles of athymic mice. Two samples from each of the banks were compared with samples from the other banks. A total of 16 implants were grafted into 8 mice. Two additional mice served as controls. One mouse received an implantation of deactived human cortical bone matrix (DBM) (negative control). The other mouse received an implant of human bone morphogenetic protein/non-collagenous proteins (hBMP/NCP) infused to surface demineralized human cortical bone (positive control). At 21 days the mice were killed, the hindquarters were photographed, and the tissues were prepared for histologic evaluation. Of the 16 commercial DFDBA implants, 12 were available for histologic evaluation. There was no radiographic evidence of bone formation for the DFDBA implanted mice or the DBM implants. Small bone ossicles were scarcely visible in the hindquarters of the mouse which received the hBMP/NCP infused bone. Histomorphometric analysis was used to determine the percentage of new and dead bone. The bone was measured in pixels. The predominant histologic feature of the DFDBA implants was non-vital bone chips with minimal amounts of new bone. The average amount of non-vital bone ranged from 78.4% to 92.5%. There was no evidence of bone formation for the DBM implants. The average amount of bone for the mouse which received hBMP/NCP was 96%. The results of this pilot study indicate that commercially-available DFDBA induced clinically insignificant amounts of bone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2003

The influence of alendronate on bone formation and resorption in a rat ectopic bone development model.

BACKGROUND: Most bone grafting techniques that include bone marrow, alloplastic materials, and extracellular bone matrix produce new bone mass, filling bone defects unpredictably. In most cases, the new bone undergoes resorption due to low local strains, resulting in significant bone loss. Recently, it was shown that alendronate and other bisphosphonates reduce bone loss when administered systemically or locally. The aim of this study was to investigate whether alendronate is effective on bone formation or bone resorption. METHODS: A total of 64 rats were divided into 2 main groups. In all the rats, fresh bone marrow removed from DA young rats was placed into demineralized rat femur cylinders (DBMC) and implanted into subcutaneous sites of host DA rats, to form new bone. Group A served as an alendronate treatment group, and group B served as a non-treated control. Group A received 100 microl of 1.5 mg/ml alendronate solution at 1, 2, and 3 weeks (group A1) and at 3, 4, and 5 weeks (group A2). At designated times, the rats were sacrificed, and the implanted DBMC was dissected out of the thorax and processed for histological and microradiography image analysis. RESULTS: Alendronate given at 1, 2, and 3 weeks (during the bone formation phase) did not increase the amount of bone or the visual bone density in comparison to the time-matched control, after 4 and 8 weeks. When alendronate was injected at 3, 4, and 5 weeks, the bone mass increased by 70% and by 166% after 6 and 10 weeks, respectively, in comparison to the untreated control. The visual bone density in group A2 was maintained at the level of 140 +/- 15 at 6 weeks and 152 +/- 15 at 10 weeks. The matched, non-treated control group B2 was significantly lower, 106 +/- 20 and 108 +/- 15, respectively. The histological sections showed that alendronate treatment at 3, 4, and 5 weeks maintained the normal appearance of the ossicle at 6 and 10 weeks in comparison to the osteopenic bone appearance in the matched controls. CONCLUSIONS: This study suggests that alendronate is effective in inhibiting bone loss, but ineffective during the bone formation phase. We suggest, therefore, that alendronate should be administered in procedures where bone resorption is expected.

Alendronate↗
PubMed1990

Intensive training in young athletes. The orthopaedic surgeon's viewpoint.

A young athlete's musculoskeletal system is unique, in that it is not only growing, but is giving support to the growing soft tissues as well. With this in mind, it is easily understood that the fastest growing areas of children skeletal system are at greater risk of injury. No controlled longitudinal studies have yet been performed about the long term effects of injuries occurring in intensively trained young athletes. During the growth spurt, a dissociation between bone matrix formation and bone mineralisation occurs, thus leaving the child with the risks of chronic moderate-to-high overloading, sudden great overload, and diminished bone strength. This may account for both acute and overuse bone injuries in this age group. Epiphyseal plate injuries can have disastrous consequences. About 10% of all skeletal trauma in children involves the epiphysis, but few long-lasting effects have been reported. It is not clear whether intensively trained young athletes are at greater risk of injury than children engaged in free-play activities. It is worrying, though, that about 20% of injuries in sports children require internal fixation. Few studies have addressed injuries to tendons, ligaments and the enthesis in young athletes. It seems that tendon injuries are mild, not requiring surgery, and with a low recurrence rate, but no prospective studies have been performed. Avulsion of the ligamentous insertion occurs more frequently than ligament ruptures in this age group, even though they seem on the increase. Osteochondritis dissecans affects weightbearing joints such as the hip, the knee and the ankle, but elbow lesions in gymnasts and throwers are also relatively frequent. If it occurs before epiphyseal fusion, long term effects are scarce. The centre of growth or ossification where a major tendon is attached may undergo chronic inflammation and avulsion of cartilage and bone, due to the stresses transmitted to it. Typical areas are the inferior pole of the patella, the tibial tubercle and the calcaneal apophysis. Sports activity contributes to the disease by excessive traction at the tendinous and fascial insertion, or as a result of direct pressure. The lumbar spine is subjected to enormous forces in some sports. The true incidence of lumbar disc lesions in sporting children is not known, but it seems that acute trauma may play a major role. With the increase of the intensity and duration of training programmes, degenerative changes may play an adjuvant role.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1998

Ethene oxide and bone induction. Controversy remains.

There is controversy as to whether ethene oxide ("ethylene oxide", EO) sterilization destroys the bone-inducing capacity of demineralized bone matrix (DBM) or not. Correctly performed studies seem to support both opinions. Bone conductive properties of fresh frozen, defatted bone grafts are greatly impaired by EO sterilization, whereas purified inductive proteins resist EO. Studies showing destruction of osteoinductive capacity used nonpulverized DBM, whereas the others used powder. This could be the key to resolving the controversy, because if EO treatment reduces the cells' ability to penetrate a cortical graft and to reach inductive proteins inside it, it may appear noninductive after EO sterilization, even though BMP molecules may be intact. On the other hand, cells could easily penetrate the powder implants. We compared the effect of EO sterilization on the inductive capacity of demineralized cortical bone with that of DBM powder, using allogeneic material in rats. Cortical pieces lost all inductive capacity by EO sterilization, whereas the powder yielded a calcium content which was at best one fourth of the unsterilized. The concentrations of residual EO, ethene chlorohydrin and ethene glucol at implantation were far below approved levels. Another difference between studies is the humidity during EO treatment. In our hands, humidification reduced bone yield by half. In conclusion, EO sterilization may impair the biological performance of bone inductive implants by reducing cell penetration into bulk material. However, DBM powder, when correctly sterilized, also yielded scanty amounts of bone.

Animals↗
PubMedDate not supplied

Ultrastructural findings of bone marrow in a case with malignant osteopetrosis following successful allogeneic bone marrow transplantation.

A nine-month-old female patient suffering from malignant osteopetrosis was evaluated by light and transmission electron microscopic study before and following allogeneic bone marrow transplantation (BMT). Bone marrow specimens were obtained from iliac crest biopsies. Before BMT, the bone marrow had an irregular appearance and was filled with bridging bony trabeculae devoid of cells. Following BMT, the marrow had an almost normal appearance with no myelofibrosis and a relatively regular distribution of hematopoletic cells. The osteocytes were visible in their lacunae in the bone matrix. Presence of bone resorbing and bone forming cell together demonstrated that the bone was beginning to gain its normal dynamic structure. These findings were in accordance with the clinical, laboratory and radiological data which showed the beneficial effect of the therapy.

Bone Marrow↗
PubMed1992

Aspects of bone healing and bone substitute incorporation. An experimental study in rabbit skull bone defects.

After an initial assessment of the experimental approach this experimental project was undertaken to study the regenerative response and incorporation of various implanted materials in calvarial bone defects in rabbits. Four 5-mm full-thickness defects were trephined in the frontal and parietal bones of the rabbits. After removal of the circular bone plugs the defects were used as recipient sites for inlay bone tissue and bone substitutes. In five separate studies the impact of bone regeneration of autogeneic bone grafts or eight bone substitutes were evaluated mainly by contact radiography, light microscopy and morphometry. The observation periods were four and 15 weeks. The main findings were: Autogeneic bone chips offered only minor advantages over controls in the model used and, also, differences in bone regeneration between diversified amounts of bone chips were negligible. In contrast, after bone paste implantation a cellular and mature bone was rapidly produced. Natural bone mineral (Bio-Oss) and synthetic dense hydroxylapatite ceramic proved to be biocompatible and a definite long term bone regeneration around all implants regardless of granulae size or resorbability was observed. Initial bone regeneration in and around the Bio-Oss particles was more extensive. Demineralized bone matrix of membranous and enchondral origins displayed extensive osteoinductive capacity and early bone production significantly exceeded that of control groups. The embryonic origin implied minor effects on the initial regenerative response only. Lyophilized bone allografts of two embryonic origins showed a low osteoinductive potential and a similar fashion of bone regeneration. No marked difference between these groups were displayed. HTR-polymer alone or combined with membraneous mineralized autogeneic bone chips showed a more rapid early bone regeneration than the groups containing lactomer beads, resorbable gel and controls. Also, the HTR-material proved to be a well-tolerated implant material by the recipient tissue bed.

Animals↗
PubMed2004

Effect of nano-hydroxyapatite/collagen composite and bone morphogenetic protein-2 on lumbar intertransverse fusion in rabbits.

OBJECTIVE: To investigate the effect of nano-hydroxyapatite/collagen (nHA/collagen) composite as a graft extender and enhancer when combined with recombinant human bone morphogenetic protein-2 (rhBMP-2) on lumbar intertransverse fusion in rabbits. METHODS: Sixty-four adult female New Zealand white rabbits, aged 1 year and weighing 3.5-4.5 kg, underwent similar posterolateral intertransverse process arthrodesis and were randomly divided into 4 groups based on different grafts: autogenous cancellous bone alone (ACB group), nHA/collagen alone (HAC group), half autogenous cancellous bone and half nHA/collagen (ACB+HAC group) and nHA/collagen combined with rhBMP-2 (HAC+BMP group). The fusion masses were analyzed by manual palpation, radiography, biomechanical testing and histological examination. RESULTS: Fusion was observed in 4 cases in the 6th week and in 5 cases in the 10th week after surgery in ACB group. No case showed fusion in HAC group. In ACB+HAC group, there was fusion in 3 cases in the 6th week and in 4 cases in the 10th week after surgery. In HAC+BMP group, fusion in 1 case was found in the 4th week, in 5 cases in the 6th week and in 6 cases in the 10th week after surgery. It suggested that ACB, ACB+HAC and HAC+BMP groups showed similar fusion ratio and mechanical strength in the 6th and 10th week after surgery. According to the microstructure analysis of the samples, nHA/collagen had no negative effect when implanted together with ilium autograft. In HAC+BMP group, new bone-like tissue was observed in the 2nd week postoperatively, and nearly all of the implanted composites were replaced by mature bone matrix and new bones in 10th week postoperatively. CONCLUSIONS: The nHA/collagen, especially combined with rhBMP-2, is a promising bone substitute, for it has quick biodegradation, fine bone-bending ability, and high osteoconductivity on posterolateral spinal fusion in rabbits.

Analysis of Variance↗
PubMed2005

[Vitamin D and bone quality].

Active vitamin D analogs such as alfacalcidol have been shown to reduce fracture risk in clinical trials in spite of its moderate effects on bone mass. It has been reported that active vitamin D analogs may improve bone quality, by amelioration of bone microarchitecture, by specific effect on cortical bones, by acceleration of calcification, and by effect on nature of bone matrix proteins. The bone quality assessments that clarify the effect on bone mechanical properties will become important for the positioning of osteoporosis drugs.

Animals↗