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PubMed1998

Expression of human bone morphogenic protein 7 in primary rabbit periosteal cells: potential utility in gene therapy for osteochondral repair.

A commonly encountered problem in orthopedics is bone and cartilage tissue injury which heals incompletely or without full structural integrity. This necessitates development of improved methods for treatment of injuries which are not amenable to treatment using current therapies. An already large and growing number of growth factors which play significant roles in bone remodeling and repair have been identified in the past few years. It is well established that bone morphogenic proteins induce the production of new bone and cartilage. An efficient method of delivery of these growth factors by conventional pharmacological means has yet to be elucidated. We wished to evaluate the use of retroviral vector-mediated gene transfer to deliver genes of therapeutic relevance for bone and cartilage repair. To determine the feasibility of using amphotropically packaged retroviral vectors to transduce primary rabbit mesenchymal stem cells of periosteal origin, primary periosteal cells were isolated from New Zealand white rabbits, transduced in vitro with a retroviral vector bearing both the nuclear localized lacZ marker gene and the neo(r) gene, and selected in G418. We used a convenient model for analysis of in vivo stability of these cells which were seeded on to polymer scaffold grafts and implanted into rabbit femoral osteochondral defects. The nuclear localized beta-galactosidase protein was expressed in essentially 100% of selected cells in vitro and was observed in the experimental explants from animals after both 4 and 8 weeks in vivo, while cells transduced with a retroviral vector bearing only the neo(r) gene in negative control explants showed no blue staining. We extended our study by delivering a gene of therapeutic relevance, human bone morphogenic protein 7 (hBMP-7), to primary periosteal cells via retroviral vector. The hBMP-7 gene was cloned from human kidney 293 cell total RNA by RT-PCR into a retroviral vector under control of the CMV enhancer/promoter. Hydroxyapatite secretion, presumably caused by overexpression of hBMP-7, was observed on the surface of the transduced and selected periosteal cells, however, this level of expression was toxic to both PA317 producer and primary periosteal cells. Subsequently, the strong CMV enhancer/promoter driving the hBMP-7 gene was replaced in the retroviral vector by a weaker enhancer/promoter from the rat beta-actin gene. Nontoxic levels of expression of hBMP-7 were confirmed at both the RNA and protein levels in PA317 producer and primary periosteal cell lines and cell supernatants. This work demonstrates the feasibility of using a gene therapy approach in attempts to promote bone and cartilage tissue repair using gene-modified periosteal cells on grafts.

Animals↗

PubMed2002

Induced osteogenesis by periosteal distraction.

PURPOSE: The purpose of this project was to evaluate a novel technique for inducing osteogenesis through periosteal distraction in a rabbit model. MATERIALS AND METHODS: A periosteal distraction device was rigidly fixed to the lateral surface of the mandible in 10 adult rabbits. Periosteal distraction was started 7 days after placement of the periosteal distraction device. The periosteum was distracted 7 mm over 15 days. The unoperated, contralateral side of the mandible served as the control. The animals were killed at postoperative days 28, 35, 42, and 56. The specimens were then fixed, decalcified, and stained with hematoxylin and eosin. Histologic examination and histomorphometric analysis were performed on all specimens. RESULTS: Nine of 10 periosteal distraction devices remained rigidly fixed to the lateral surface of the mandible. On postoperative day 28, the histologic specimen from the experimental side showed periosteal proliferation and an increase in the number of osteoblasts. On postoperative days 35, 42, and 56, the experimental side showed an increase in the number of osteocytes per unit area, collagen fibers parallel to the vector of distraction, islands of osteoblasts surrounded by newly formed bone, and maturation of bone. An average of 2.86 +/- 0.56 mm of new bone height was formed. CONCLUSION: We report on a novel technique for generating bone by periosteal distraction. Our histologic analysis showed proliferation of the periosteum, an increase in the number of osteoblasts and osteogenesis.

Animals↗

PubMed2005

Articular cartilage defects in a rabbit model, retention rate of periosteal flap cover.

BACKGROUND: A periosteal flap is frequently used in procedures involving repair of articular cartilage defects. Hypertrophy of the repair tissue, probably from a retained periosteum, is a clinical problem but not much is known about this issue. The objective of the present experimental study was to investigate the retention rate of periosteal flaps with respect to various postoperative mobilization regimes and the introduction of bone marrow elements underneath the flap. METHOD: We created a chondral lesion (diameter 4 mm) in both patellas of 18 New Zealand white rabbits. The subchondral bone was left intact in one knee. In the other, the bone plate was perforated, allowing bone marrow elements to enter the defect. All defects were covered with a periosteal flap, sutured and glued to the rim of the cartilage defect. Postoperatively, the rabbits were allocated to one of three groups: A. rehabilitation in cages for 4 days, then killed; B. rehabilitation in cages for 7 days, then free activity on the floor of a 10 m2 room until the end of the second week, then killed; C. rehabilitation in cages for 2 weeks, then killed. RESULTS: 16 of 23 periosteal flaps became detached within 2 weeks (one knee was excluded because of clinical signs of infection), with no difference in the retention rate with respect to mobilization regime or established access to bone marrow elements in the defect. The periosteum still served as a cover of the defect in 10 of 12 knees at day 4. This figure decreased to 7 of 23 knees at day 14. CONCLUSION: Our study is the first to document the retention rate of periosteal flaps in a rabbit model. The low retention rate observed may explain why periosteal hypertrophy is not reported in experimental studies where the periosteal flap is sutured to the cartilage rim.

Animals↗

PubMed1998

Periosteal augmentation of the acetabulum.

The periosteum in children and especially infants has significant osteogenic potential. To determine the efficacy of periosteal flaps to assist in improving acetabular coverage in children with acetabular dysplasia, a series of experiments were designed using young rabbits. Three groups of five rabbits each had periosteal flaps fashioned and brought down from the anterolateral aspect of the innominate bone superior to the acetabulum and sutured to the capsule of the hip. The study was designed to examine the effects of the periosteal cambium layer in the formation of new bone to augment the acetabulum and to determine the effects of a periosteal flap plus cancellous bone graft. A control group of five rabbits underwent a sham operation of an open arthrotomy of the hip. Radiographic and histologic examination at 12 weeks revealed augmentation of the acetabulum with periosteal flaps that resulted in an average improvement of the acetabular index of 3.5 degrees and 6.6 degrees, without and with bone graft, respectively. New bone formation from the rim of the acetabulum averaged 3.9 mm with periosteal flaps alone and 4.6 mm with bone graft added. Periosteal augmentation of the acetabulum in conjunction with established procedures for augmenting acetabular coverage would appear to be a useful procedure for improving coverage of the femoral head in children with acetabular dysplasia.

Acetabulum↗

PubMed1999

Osteogenic ability of free periosteal autografts in tibial fractures with severe soft tissue damage: an experimental study.

OBJECTIVE: The present study was undertaken to assess whether free nonvascularized autologous periosteum transplants enhance bone healing in a rabbit fracture model designed to resemble a tibial fracture with severe soft tissue damage. DESIGN: Transplantation of free autologous periosteal grafts on the anteromedial site of the tibia (experimental group) was compared with nontransplantation on the contralateral tibia (control group). We produced a standardized transverse osteotomy of both tibial diaphyses in white male adult New Zealand rabbits. The endomedullary cavity was reamed and nailed, and then a one-centimeter segment of periosteum was excised from either side of the osteotomy. To prevent periosteal and extraosseous ingrowth at the osteotomy site, a silastic sheet was wrapped around two-thirds of the circumference of the tibia. In the first group, on the silastic-free bone window, we then spanned the osteotomy with a free, nonvascularized, longitudinally oriented autologous periosteum and sewed it to the adjacent periosteum both proximally and distally. In the second group, the periosteum was placed transversely, leaving a gap between it and the adjacent periosteum proximally and distally. Revascularization of the graft was determined with the colored microsphere technique. MAIN OUTCOME MEASUREMENTS: Histomorphometric analysis of the periosteal callus was done on a transparent grid superimposed on enlarged photographs of the histologic sections. RESULTS: Free, nonvascularized, longitudinally placed autologous periosteum in contact with intact periosteum produced significantly more periosteal callus than was seen in the control group, in which no periosteal graft was used. However, when transversely placed periosteal grafts were set in the silastic-free bone window and there was no contact with surrounding remnants of intact periosteum, no significant difference in callus production was noted when compared with the control. Revascularization of these grafts was seen within one week after transplantation. Bone healing occurred mainly through endochondral ossification. CONCLUSION: Our data suggest that orthotopically placed autologous nonvascularized periosteum retains its osteogenic potential in a poorly vascularized environment such as a tibial fracture with severe soft tissue damage. The effect is enhanced if the graft is in contact with intact periosteum. Histologically, callus formation after periosteal grafting resembles endochondral and intramembranous ossification.

Animals↗

PubMed1985

Studies on the osteogenic potential of vascularized periosteum: behavior of periosteal flaps transferred onto soft tissues.

We investigated the basic properties of vascularized periosteal autografts. A pleuro-periosteal flap based on the intercostal vessels was developed in a canine model. Fourteen animals had vascularized periosteal flaps rotated onto the soft tissues of the chest wall. These animals were killed at intervals of 7 to 90 days and the flaps were studied by tetracycline labeling and light microscopy. Four other animals had similar flaps transplanted onto the soft tissues of the neck by microvascular techniques. All harvested flaps showed periosteal bone production, leading to the following observations: Osteogenesis begins as early as 7 days after grafting; the rate and extent of periosteal osteogenesis is proportional to the vascular supply; bone formation starts in small foci of active osteoblasts that grow and become confluent; and intimate bony periosteal contact is not necessary for periosteal osteogenesis to take place, but it appears to influence the rate and amount of bone formation.

Animals↗

PubMed2005

Healing of a critical-sized defect in the rat femur with use of a vascularized periosteal flap, a biodegradable matrix, and bone morphogenetic protein.

BACKGROUND: The purpose of this study was to evaluate the osseous healing of a critical-sized femoral defect in a rat model with use of recombinant human bone morphogenetic protein-2 (rhBMP-2), a matrix fabricated of D,D-L,L-polylactic and hyaluronan acid (OPLA-HY), and a vascularized periosteal flap. METHODS: The carrier matrix OPLA-HY with or without rhBMP-2 was implanted in a 1-cm-long femoral defect and secured with a plate and screws. In some groups, a vascularized periosteal flap was harvested from the medial surface of the tibia. In group 1, the femoral defects in the animals were filled with the OPLA-HY matrix alone; in group 2, the OPLA-HY matrix was covered by the vascularized periosteal flap; in group 3, 20 mug of rhBMP-2 was added to the OPLA-HY matrix; and in group 4, the femoral defect containing the OPLA-HY matrix and 20 mug of rhBMP-2 was wrapped circumferentially by the vascularized periosteal flap. The presence and density of new bone formation in the femoral defect were evaluated radiographically, histologically, and with histomorphometry at four and eight weeks postoperatively. RESULTS: Groups 1 and 2, which were not treated with rhBMP-2, showed no radiographic or histologic evidence of mature bone formation at four or eight weeks. Both groups 3 and 4, which were treated with rhBMP-2, demonstrated excellent bone formation. However, with the periosteal flap, group 4 demonstrated more bone formation on histomorphometric analysis at eight weeks (43.1%) than did group 3 (28.3%) (p < 0.01). Additionally, heterotopic bone formed outside the boundaries of the defect in eight of the fifteen animals in group 3, which had no periosteal flap. CONCLUSIONS: Bone-tissue engineering with use of the OPLA-HY matrix and rhBMP-2 produced good bone formation in the rat femoral defect model. However, the addition of a vascularized periosteal flap significantly increased bone formation within the boundaries of the defect and prevented heterotopic ossification.

Animals↗

PubMed1978

Osteogenic capacity of periosteal grafts. A qualitative and quantitative study of membranous and tubular bone periosteum in young rabbits.

A standardized model, permitting only periosteal bone formation, has been applied for qualitative and quantitative studies on the osteogeneses from periosteal grafts. The periosteum from the tibia was grafted to the skull and vice versa. The investigation also included the study of periosteal bone formation combined with other osteogenic factors. A total of 78 operations were performed on the tibias and skulls of 43 growing rabbits. For qualitative studies ordinary histological methods were used. Tibial periosteal grafts to skull defects started bone formation already after 2 weeks and, via a very small amount of woven bone, compact bone and bone marrow was formed after 8-10 weeks. Combined epidural and subperiosteal bone formation gave a calvarial bone. Skull periosteal grafts to tibial defects started bone formation somewhat later, but, after more woven bone as an intermediate stage, the defect had healed with thick compact bone and bone marrow after about the same period. For quantitative studies the newly formed periosteal bone was removed, dry-weighted and ashed. The ashes were dissolved in HCl for spectrophotometric determination of total Ca content, which was used as a quantitative measure of bone amount. Tibial periosteum grafted to a calvarial defect halved its bone forming capacity but compared to the in situ skull periosteal potential, the capacity was tripled. This meant that the defect was completely healed. Calvarial periosteum was much less potent than was the tibial periosteum, when both were grafted to skull defects. However, when transplanted to a long bone defect the former increased its bone forming capacity 5 times compared to its original one as an in situ flap. Environmental functional demands seem to influence the type of bone formation and the final structure of the new bone. On the other hand, there are differences between long and membranous bone periosteum regarding the amount of bone formed.

Animals↗

PubMed2005

A rare case of periosteal osteoblastoma located in the frontal cranial bone.

Periosteal osteoblastoma is an extremely rare bone-forming neoplasm located on the surface of cortical bone. Of the fewer than 30 cases of periosteal osteoblastomas found in the literature, 2 have been reported to be located in cranial bone, and these have not been documented in detail with clinical history, radiographic findings, macroscopic features, and microscopic findings. Although the differential diagnoses of periosteal lesions include parosteal and periosteal osteosarcoma, periosteal chondroma and chondrosarcoma, osteochondroma, osteoid osteoma, periostitis ossificans, and myositis ossificans, an important differential diagnosis both radiologically and pathologically of such a lesion in the cranium is meningioma. We report an unusual case of periosteal osteoblastoma located in the frontal cranial bone that was radiologically consistent with a meningioma. The differential diagnosis of metaplastic meningioma with differentiation toward bone is discussed.

Adult↗

PubMed1991

[Vascularized periosteal transplant. A review of a new therapeutic possibility].

The idea of using vascularized periosteal flaps in reconstructing bone defects is more than one hundred years old. Up to now, experimental and clinical results regarding their osteogenic capacity have been a subject of debate. Experimental and clinical studies over the last ten years were able to demonstrate osteogenic capability of such vascularized periosteal flaps, provided the periosteum is well vascularized. To insure intact microcirculation, vascularized periosteal flaps must be freed up by sharp dissection. Small pieces of bone may be removed with the periosteum, whereas the periosteum must remain uninjured. There are many known donor sites in man: the iliac crest, the distal femur, the distal humerus and the tenth rib. There are no reports concerning donor site morbidity. Besides its osteogenic capacity, the periosteal flaps have "shape giving" and "space limiting" functions. The given volume within a periosteal flap rolled into a tube is the basis for the "Concept of the Given Space": the space within the tube defines where bone formation will occur, there being no loss of bone into the surrounding soft tissue. Because of the vascularized periosteal flap's fragility and the good results of other reconstructive procedures for segmental bone defects, there are few indications for extremity reconstruction using periosteal flaps: pseudarthrosis in the upper extremity is one example. In the lower extremity, a combination of vascularized periosteum with conventional and mainly vascularized bone grafts offers interesting possibilities for reconstruction.

Animals↗

PubMed1979

The role of periosteal tension in the growth of long bones.

Vertical or circumferential periosteal incisions were made over one tibia of anaesthetized rats, supplemented by localized periosteal stripping in two of the experimental groups. The rats were killed 5 weeks later and tibial lengths measured. Circumferential periosteal division plus periosteal elevation produced the greatest ipsilateral increase in tibial length. In this group of rats the alignment of cortical blood vessels provided evidence that sliding of the periosteum and a release of periosteal tension are associated with the gain in length. However, anisomelia, though not seen following vertical periosteal division alone, did occur after vertical division and periosteal stripping. This supports suggestions that both growth plate decompression and vascular phenomena influence skeltal growth rates after trauma.

Animals↗

PubMed1995

Anatomy and histophysiology of the periosteum: quantification of the periosteal blood supply to the adjacent bone with 85Sr and gamma spectrometry.

The periosteum or periosteal membrane is a continuous composite fibroelastic covering membrane of the bone to which it is intimately linked. Although the bone cortex is the main beneficiary of the principal anatomical and physiological functions of the periosteal membrane, the behavior of the entire bone remains closely influenced by periosteal activity. These principal functions are related to the cortical blood supply, osteogenesis, and muscle and ligament attachments. Through its elastic and contractile nature, it participates in the maintenance of bone shape, and plays an important role in metabolic ionic exchange and physiologic distribution of electro-chemical potential differences across its membranous structure. It has also been suggested that the periosteum may have its own specific proprioceptive property. This paper presents a study of the anatomy and histophysiology of the periosteum, and discusses in detail its main functions of cortical blood supply and osteogenesis. It also presents the third intermediary report on a current study of the quantification of cortical vascularization of femoral bone via the periosteum, using an isotonic salt solution containing 85 Strontium. The afferent-efferent (arterio-venous) flows of this solution in the thigh vascular system of guinea pigs were measured by gamma spectrometry after a series of selective macro- and micro-injections of radioactive salt into the femoral arterial system was carried out. Each vascular territory was meticulously selected and the injections were made according to size, starting with the larger vessels, with or without ligatures of neighboring vessels, going progressively to smaller and smaller vessels with diameters not exceeding 100 microns. The principal technical difficulty at this stage of experimentation was related to the identifying and acquiring of appropriate microcatheters. The study also includes a series of measurements after blockage of the transmuscular blood flow and the corresponding periosteal vascular system by selective ligation of the thigh muscles. The results clearly show the fundamental predominance of periosteal blood circulation to the bone cortex (70 to 80% of the arterial supply and 90 to 100% of venous return) compared with centromedullary vascularization. A quantitative formula related to the general blood circulation in the bone cortex and marrow, taking into account the two pathways, is presented. Although the application of these results (which concern a long-bone site in an animal) to the alveolar and maxillo-mandibular periosteum requires the conception of an appropriate human experimental model, the extrapolation of the findings seems plausible in the case of the mandible, where the osseous structures and the vascular network are comparable with those found in long bone. However, in the maxilla, where the general blood supply is more intense and anastomotic, the periosteal contribution may legitimately be considered less important than the centro-medullary circulation. Finally, the presentation analyzes the physio-pathology of an experimentally damaged periosteum either directly (by thermodestruction, squashing, and chemodestruction), or indirectly (by muscular pull and tear), leading to the inevitable chain reaction, i.e., "ischemia-necrosis-atrophy and partial regeneration" of the underlying bone and very frequently compromising the survival of an implant that had been placed within it. The report emphasizes the importance of impeccable soft tissue and periosteum management at the time of implant surgery and indicates a number of technical precautions that should be observed in order to avoid periosteal damage.

Animals↗

PubMed1998

Pathologic femoral fracture after periosteal excision and radiation for the treatment of soft tissue sarcoma.

BACKGROUND: Surgical resection and adjuvant radiation therapy are standard therapy for soft tissue sarcomas. When the tumor approximates bone, periosteal excision may be necessary. It was hypothesized that periosteal stripping and radiation therapy would increase the rate of pathologic fracture. METHODS: The soft tissue sarcoma data base at the Memorial Sloan-Kettering Cancer Center was used to identify a consecutive series of 205 patients who were treated over a 15-year period (1982-1997). All patients had a soft tissue sarcoma of the thigh, which was managed by limb-sparing surgery and radiation therapy. Patients who had bone invasion by tumor or bone resection were not included. RESULTS: Nine patients, including eight women and one man, developed a femoral fracture in an area of previous radiation and surgery. All nine patients had undergone periosteal excision. The risk of fracture, by Kaplan-Meier survivorship, was 29% at 5 years if the resection included periosteum (P < 0.0001). Cox multiple regression analysis showed that periosteal excision was the only independent prognostic factor for the entire set of 205 patients at risk. However, for the subset of 54 patients who had periosteal stripping, two factors were also found to be prognostically important: female gender (P=0.022) and chemotherapy (P=0.020). The risk of fracture was 47% and 45%, respectively. The treatment of the fractures was difficult. There were four nonunions and three delayed unions. CONCLUSIONS: Periosteal stripping and radiation therapy places the femur at high risk of pathologic fractures, especially for female patients and patients undergoing chemotherapy. When practical, the combination of periosteal stripping and radiation should be avoided.

Adult↗

PubMed1997

Ulcer osteoma and periosteal reactions to chronic leg ulcers.

OBJECTIVE: The purpose of this study was to describe the types of periosteal reaction seen in response to long-standing leg ulcers and to differentiate the types associated with osteomyelitis. MATERIALS AND METHODS: Over a 10-year span, we retrospectively evaluated the radiographs of 20 patients with lower leg soft-tissue ulceration and adjacent periosteal bone reaction of the tibia or fibula. Two of us evaluated the location and appearance of periosteal reaction, and one of us evaluated the patients' medical records for evidence of peripheral vascular disease, systemic illnesses, and osteomyelitis. RESULTS: Twelve patients had organized periosteal reactions that resulted in the appearance of ulcer osteoma. None of these patients subsequently developed osteomyelitis. Eight patients had interrupted lamellar nodular periosteal reactions; six of the eight patients had superimposed osteomyelitis. CONCLUSION: Our study showed two types of periosteal response to chronic leg ulcers: a solid organized type that over time formed an ulcer osteoma and a lamellar nodular type that was often associated with osteomyelitis. Both types of ulcers were seen in patients with peripheral vascular disease, IV drug abuse, sickle cell disease, and neurologic impairment.

Chronic Disease↗

PubMedDate not supplied

Periosteal readhesion after brow-lift in New Zealand white rabbits.

OBJECTIVES: To define the postoperative time interval required for elevated periosteum to readhere to the skull and regain its preoperative strength, and to evaluate whether fixation of the periosteum affects this interval or the strength of postoperative readhesion. DESIGN: Prospective analysis of variance and covariance with repeated measures. SUBJECTS: Thirty-six New Zealand white rabbits, each serving as its own control. INTERVENTIONS: Subperiosteal elevation was performed on one side of the skull, leaving the contralateral periosteum untouched. The periosteum in half of the subjects was lifted and fixed to a resorbable screw, with the comparison group undergoing subperiosteal elevation only, without lifting and fixation. Several adhesion characteristics were subsequently examined at postoperative weeks 1, 3, 5, 7, 8, 9, 10, 11, and 12. Half of the subjects were assessed histologically to determine attachment of periosteum onto underlying bone. The other half underwent analysis of periosteal readhesion strength. RESULTS: The 3 independent measures of periosteal adherence to the skull all lacked significant differences between sides after the first postoperative week. Blinded histologic analysis showed no evidence of ongoing periosteal healing and demonstrated no difference between operated-on and nonoperated-on sides. Analysis of periosteal stiffness (P =.76) and energy density (P =.74) also demonstrated no significant differences between sides. CONCLUSIONS: Periosteal readhesion after surgical elevation is virtually complete by the seventh postoperative day. In addition, tension secondary to periosteal elevation with suspension has no influence on postoperative healing. These findings will contribute to the debate regarding the most appropriate brow-lift fixation technique.

Absorbable Implants↗

PubMed1994

Mechanical loading stimulates rapid changes in periosteal gene expression.

Although mechanical forces regulate bone mass and morphology, little is known about the signals involved in that regulation. External force application increases periosteal bone formation by increasing surface activation and formation rate. In this study, the early tibial periosteal response to external loads was compared between loaded and nonloaded contralateral tibia by examining the results of blot hybridization analyses of total RNA. To study the impact of external load on gene expression, RNA blots were sequentially hybridized to cDNAs encoding the protooncogene c-fos, cytoskeletal protein beta-actin, bone matrix proteins alkaline phosphatase (ALP), osteopontin (Op), and osteocalcin (Oc), and growth factors insulin-like growth factor I (IGF-I) and transforming growth factor-beta (TGF-beta). The rapid yet transient increase in levels of c-fos mRNA seen within 2 hours after load application indirectly suggests that the initial periosteal response to mechanical loading is cell proliferation. This is also supported by the concomitant decline in levels of mRNAs encoding bone matrix proteins ALP, Op, and Oc, which are typically produced by mature osteoblasts. Another early periosteal response to mechanical load appeared to be the rapid induction of growth factor synthesis as TGF-beta and IGF-I mRNA levels were increased in the loaded limb with peak levels being observed 4 hours after loading. These data indicate that the acute periosteal response to external mechanical loading was a change in the pattern of gene expression which may signal cell proliferation. The altered pattern of gene expression observed in the present study supports previous evidence of increased periosteal cell proliferation seen both in vivo and in vitro following mechanical loading.

Actins↗

PubMed2002

Suppression of prostaglandin synthesis with NS-398 has different effects on endocortical and periosteal bone formation induced by mechanical loading.

Prostaglandins mediate adaptive bone formation induced by mechanical loading. Inhibition of cyclooxygenase-2 (COX-2) with NS-398 effectively blocks loading-induced osteogenesis on the endocortical bone surface of the tibia. In this study, we compared the effects of selective inhibition of COX-2 with NS-398 on mechanically induced osteogenesis at the endocortical surface (tibia) with that on the periosteal surface (ulna). We further tested the effect of NS-398 administered at different times before (3 hrs or 30 min) or after (30 min) mechanical loading. Mechanical loading induced lamellar bone formation on the endocortical surface of the tibia and the periosteal surface of the ulna. Oral administration of either indomethacin or NS-398 3 hrs before loading significantly decreased loading-induced bone formation rate (BFR) and mineralizing surface (MS/BS), but not mineral apposition rate (MAR), at the endocortical surface of the tibia and the periosteal surface of the ulna. NS-398 reduced loading-induced MS/BS by 96% on the endocortical surface of the tibia, but only by 37% on the periosteal surface of the ulna (significantly different from endocortical, P <0.05). Indomethacin reduced MS/BS and BFR to a lesser extent than NS-398 and did not have different effects on the periosteal and endocortical surfaces. These data suggest that the endocortical bone adaptive response to mechanical loading is more dependent upon COX-2 activity than is the periosteal bone response. Intraperitoneal injection of NS-398 3 hrs before loading suppressed load-induced bone formation rate at the endocortical surface of the tibia significantly more (27%) than when administered 30 min before loading. When NS-398 was given 30 min after loading, bone formation was not significantly suppressed. These data suggest that a primary cellular mechanism of bone formation following brief bouts of mechanical loading involves release of prostaglandins from cells at the time mechanical loading is applied, rather than new prostaglandin synthesis associated with a mechanically induced COX-2 expression.

Animals↗

PubMed1996

Effect of periosteal stripping on cortical bone perfusion: a laser doppler study in sheep.

The goals of internal fixation are an accurate reduction and stable fixation in the presence of adequate bony vascularity. This can be achieved by a variety of means including plate fixation. A certain amount of periosteal stripping is necessary for proper open reduction of a fracture and for proper plate application. With displaced diaphyseal fractures, cortical bone perfusion (CBP) is already compromised. Further damage, in terms of periosteal stripping for plate fixation, may not be acceptable. Little information is available as to what extent the periosteum contributes to cortical bone perfusion. The purpose of this study was to determine the acute effects of periosteal stripping on cortical bone perfusion in a sheep tibia model. Twenty-three sheep were operated on and had the medial aspect of their right tibia exposed. Cortical bone perfusion measurements were obtained using laser Doppler flowmetry prior to periosteal stripping and after periosteal stripping. The results of this study show that the cortical bone perfusion significantly decreased by 20% after periosteal stripping over the entire length of the tibia. We therefore conclude that the periosteum contributes to diaphyseal bone perfusion and that it is important to preserve this source with fractures where blood supply is already significantly compromised.

Animals↗