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Biomedical subjects

M P Bostrom

Publications and source records attributed to M P Bostrom.

At least 19 recordsLinked to original sources
PubMed2001

An unexpected outcome during testing of commercially available demineralized bone graft materials: how safe are the nonallograft components?

STUDY DESIGN: Radiographic and histologic analyses of commercially available bone graft materials were performed. OBJECTIVE: To compare the osteoinductive efficacy of commercially available demineralized bone matrix material. SUMMARY OF BACKGROUND DATA: The relative in vivo bone formation and toxicology of the nonallograft components the make up various commercially available demineralized bone matrix products are not known. METHODS: An in vivo bone formation model was used in 30 athymic rats. Six different bone grafting materials were tested in subcutaneous and intermuscular locations. After 4 weeks, radiographic and histologic testing of bone formation was performed. RESULTS: Eight of nine rats implanted with Grafton demineralized bone matrix products died 1 to 4 days after implantation of the bone graft material. None of the remaining 10 animals implanted with the four other grafting materials died. The experiment was modified and completed with a lower dose of bone graft material. Pathologic analysis indicated that the cause of death was hemorrhagic necrosis of the kidneys, most likely caused by a toxic effect on the glomeruli and tubules. A possible causative factor may have been the glycerol in the graft material. CONCLUSIONS: Although the volume of Grafton product per kilogram of body weight used in this study was approximately eight times the maximum volume used in humans, the authors believe that this data must be reported because this product is used substantially in clinical settings. In addition, the osteoinductive performance and relative safety of the nonallograft components in all commercially available demineralized bone grafts are not known.

Animals↗
PubMed2001

Combination of growth factors inhibits bone ingrowth in the bone harvest chamber.

Previous studies using bone harvest chambers have shown that bone morphogenetic protein-2 inhibits bone ingrowth. The authors hypothesized that the combination of bone morphogenetic protein-2 and a potent angiogenic factor, basic fibroblast growth factor, would result in increased bone formation in this model. Five New Zealand White rabbits were surgically implanted with bone harvest chambers in the proximal metaphyseal region of both tibias. The right leg of each rabbit was implanted with a bovine collagen sponge that was impregnated with recombinant human bone morphogenetic protein-2, basic fibroblast growth factor, or a combination of these factors. The left leg chamber was implanted with the collagen sponge with no growth factors as a control. The bone that grew into the chambers was harvested after 2 weeks, and histomorphologic analysis was performed to determine the amount of tissue and bone ingrowth. The tissue chambers were left empty for 2 weeks between test implants, and this tissue also was harvested, analyzed, and compared with the other samples. The results showed decreased bone formation for the bone morphogenetic protein-2, basic fibroblast growth factor, and combination of bone morphogenetic protein-2 and basic fibroblast growth factor treated groups when compared with the control and empty groups. The combination of bone morphogenetic protein-2 and basic fibroblast growth factor showed inhibition of bone formation that was greater than either growth factor individually. The reason for the inhibition of bone formation with the combination of factors is unknown.

Analysis of Variance↗
PubMed2001

Two-stage exchange hip arthroplasty for deep infection.

Although the risk of infection after total hip arthroplasty has decreased over the last three decades with the use of prophylactic antibiotics, laminar airflow operating rooms and whole-body exhaust suites, deep infection after total hip arthroplasty remains a serious complication. Significant morbidity to the patient and the cost to the health care system remain. During this period of time, diagnostic techniques also have improved including the use of polymerase chain reaction amplification. Treatment options now include: suppressive antibiotics, irrigation and debridement with retention of components, one-stage reimplantation, two-stage reimplantation, and salvage procedures. Based on the medical literature, the successful eradication of a total joint replacement infection with a two-stage reimplantation protocol is over 90% while the success rate with a one-stage protocol is approximately 80%. These success rates may decline however as the prevalence of antibiotic resistant organisms increases. Current controversies regarding two-stage reimplantation protocols include: duration of intravenous antibiotic therapy, timing of the reimplantation, the use of allograft bone in the reconstruction, the choice of fixation (cement versus cementless), and the use of antibiotic-loaded cement spacers.

Anti-Bacterial Agents↗
PubMed2000

Bone growth factors.

Osteoblastic culture models, experimental, and clinical models have revealed that bone growth factors influence cellular activity. Growth factors including bone morphogenetic proteins, transforming growth factor beta, platelet-derived growth factor, insulin-like growth factors I and II, and acidic and basic fibroblast growth factors, are powerful tools for fracture healing and bone grafting. Understanding the role that bone growth factors play in bone repair is necessary to apply these factors in a clinical setting.

Animals↗
PubMed2000

Parathyroid hormone-related protein analog RS-66271 is an effective therapy for impaired bone healing in rabbits on corticosteroid therapy.

A new class of parathyroid hormone-related protein (PTHrP) analogs has been developed that causes a rapid gain in both trabecular and cortical bone in models of osteopenia. This study investigates the efficacy of the PTHrP analog, RS-66271 ([MAP(1-10)]22-31 hPTHrP(1-34)-NH(2)), as systemic therapy for impaired bone healing in corticosteroid-treated rabbits. A 1 mm defect was created bilaterally in the ulnae of 30 rabbits. Delayed healing was induced by daily injections of prednisone (0.15 mg/kg) beginning 2 months prior to surgery and continuing until killing. Rabbits in the experimental group received daily subcutaneous injections of PTHrP analog RS-66271 (0.01 mg/kg) starting 1 day after surgery. Control animals received subcutaneous normal saline. At the 6 week timepoint, nine of ten ulnae from PTHrP-treated rabbits achieved radiographic union, whereas only two of ten limbs achieved union in control rabbits (p < 0.01). In a separate part of the study, 20 animals (10 control, 10 RS-66271-treated) were killed when radiographic union was achieved bilaterally. In this portion of the study, all limbs in animals treated with PTHrP achieved union by 6 weeks. In the control animals that were allowed to heal for 10 weeks, only 20% of the limbs achieved radiographic union. In addition, ulnae in the PTHrP-analog-treated rabbits showed greater radiographic intensity (20%-40%), larger callus area (209% anteroposterior view, 417% lateral view) (mean area on AP radiographs: control, = 387 +/- 276 mm(2); PTHrP analog, 1195 +/- 408 mm(2)), and greater stiffness (64%) and torque (87%) when compared with controls. RS-66271 was shown to be an effective therapy for preventing impaired bone healing caused by prednisone in a rabbit model.

Animals↗
PubMed1999

The short term outcome of elderly patients with hip fractures.

A prospective outcome study was performed of 100 hip fracture patients at an urban medical center in the United States. After hospitalization 19% were discharged to a rehabilitation facility and 59% were discharged home. At a mean follow-up of 8 months, 81% of patients lived at home, compared to 89% who lived at home prior to the fracture. At follow-up 71% of the patients were able to walk outside with one cane or no aids at all, and 81% were able to perform basic activities of daily living. Half of all patients did not require any home assistance at follow-up. Ten patients had died at follow-up. The goal of operatively treating the patient with a hip fracture is fixation of the fracture with a return to the patient's pre-fracture functional ability. This study illustrates that patients with hip fractures can be effectively treated and discharged home or to a short-term rehabilitation facility with restoration of their pre-fracture functional status.

Activities of Daily Living↗
PubMed1999

Osteoinductive growth factors in preclinical fracture and long bone defects models.

Fracture healing is a specialized form of the reparative process that the musculoskeletal system undergoes to restore skeletal integrity. This biologic process is a consequence of a complex cascade of biologic events that result in the restoration of bone tissue, allowing for the resumption of musculoskeletal function. Several growth-promoting substances have been identified at the site of skeletal injury and appear to play a physiologic role in fracture healing. This article reviews the effects of these osteoinductive growth factors on bone healing as elucidated by both preclinical in vivo fracture and diaphyseal defect healing models.

Animals↗
PubMed1999

Biosynthetic bone grafting.

The regeneration of bone remains an elusive yet important goal in the field of orthopaedic surgery. Despite its limitations, autogenous cancellous bone grafting continues to the most effective means by which bone healing is enhanced clinically. Biosynthetic bone grafts currently are being developed as an alternative to autogenous bone grafting. These grafts generally contain one or more of three critical components: (1) osteoprogenitor cells; (2) an osteoconductive matrix; and (3) osteoinductive growth factors. The importance of each of these components based on preclinical data supports their use in biosynthetic bone grafts. The use of growth factors such as bone morphogenetic proteins, transforming growth factor, platelet derived growth factor, and fibroblastic growth factor is reviewed in preclinical long bone defect and spinal fusion models. The use of bone marrow in preclinical and clinical settings is presented with specific emphasis given to the use of bone marrow as a source of osteoprogenitor cells and how the use of these cells can be enhanced with the use of bone morphogenetic protein-2. These data support the concept that although products that contain only one of the three key components of a bone graft may regenerate bone successfully, composites of the three key components will be more successful clinically.

Animals↗
PubMed1998

Expression of bone morphogenetic proteins in fracture healing.

Fracture healing involves a complex interaction of many local and systemic regulatory factors. Recently, the presence of several bone morphogenetic proteins and their receptors in the fracture healing process has been described. During the early stages of fracture healing, only a minimum number of primitive cells are expressing bone morphogenetic proteins in the fracture callus. As the process of endochondral ossification proceeds, the presence of bone morphogenetic proteins and their receptors increases dramatically, especially in the primitive mesenchymal and chondrocytic cells. While the cartilaginous component of the callus matures with a concomitant decrease in the number of primitive cells, there is a concomitant decrease in presence of bone morphogenetic protein expressing cells. As osteoblasts start to lay down woven bone on the chondroid matrix, these osteoblastic cells express bone morphogenetic proteins and their receptors. The presence of bone morphogenetic proteins decreases, however, as lamellar bone replaces the primitive woven bone. A similar observation is seen in the areas of the callus undergoing intramembranous ossification. Initially, within several days after the fracture, periosteal cells and osteoblasts show intense expression of bone morphogenetic proteins and their receptors. As the woven bone is replaced with mature lamellar bone, the expression of bone morphogenetic protein decreases. These data and the knowledge of bone morphogenetic proteins' strong osteoinductive capacities suggest that individual bone morphogenetic proteins play important yet different roles during fracture repair.

Animals↗
PubMed1998

Transforming growth factor beta in fracture repair.

Transforming growth factor betas are a group of polypeptide growth factors that have a wide range of activities in the musculoskeletal and immunological systems. They are thought to play an important role in the development, induction, and repair of bone. This family of closely related genes includes the five known transforming growth factor betas and also the bone morphogenetic proteins. With the development of new techniques to analyze gene expression, the broad range of cellular activities regulated by transforming growth factor beta is beginning to be understood. The critical role that transforming growth factor beta plays in the regulation and stimulation of mesenchymal precursor cells for chondrocytes, osteoblasts, and osteoclasts is now emerging based on a series of in vitro studies. Although transforming growth factor betas appear to stimulate proliferation of precursor cells, it appears that transforming growth factor betas have an inhibitory effect on mature cell lines. In vivo studies indicate the presence of transforming growth factor beta protein and transforming growth factor beta gene expression in normal fracture healing, whereas exogenous transforming growth factor beta administration stimulates the recruitment and proliferation of osteoblasts in fracture healing. Although the cascade of events that leads to bone formation and repair is not completely understood, transforming growth factor beta's central role in the regulation of fracture healing is not disputed.

Bone Morphogenetic Proteins↗
PubMed1998

Potential role of bone morphogenetic proteins in fracture healing.

Since their discovery, bone morphogenetic proteins have held the promise for use in various orthopaedic diseases. One of the largest areas of likely application is the area of fracture repair. Although millions of fractures occur annually and the majority heal satisfactorily, 5% to 10% go on to delayed union or nonunion. Bone morphogenetic proteins may be able to improve bony healing in these conditions and perhaps enhance the healing of fractures that otherwise heal satisfactorily. This study examines the preclinical data to support the concept of enhancing bony healing and discusses the preliminary data from clinical trials using bone morphogenetic proteins to augment bony healing. Although the potential clinical uses of bone morphogenetic proteins in fracture healing remain significant, this potential has yet to be realized.

Animals↗
PubMed1998

Enhancement of bone formation in the setting of repeated tissue deformation.

The purpose of this study was to investigate whether the osteoinductive recombinant human bone morphogenetic protein 2, combined with a collagen carrier, could enhance bone formation when exposed to controlled amounts of tissue deformation. Chambers that allow for the multiple harvestings of tissue specimen were used. The devices were implanted in the tibial metaphyses of skeletally mature New Zealand White rabbits. A tissue ingrowth canal in each device either was left empty or filled with a collagen carrier with or without 0.6 microgram of recombinant human bone morphogenetic protein 2. The tissue ingrowth canal was deformed cyclically during a period of 2 minutes daily, according to a previously described deformation protocol. The tissue that developed in the chambers was harvested every 3 weeks. Undecalcified histologic sections of each tissue sample were stained with trichrome and von Kossa stains and subjected to histomorphometric analysis. It was found that deformation decreased the area occupied by bone trabeculae in the empty chambers and carrier controls. The amount of bone formed in the chambers treated with bone morphogenetic protein 2 was significantly greater than that in the chambers subjected to micromotion and left empty or implanted with the collagen carrier. The amount of bone in chambers with motion and bone morphogenetic protein 2 was equal to that in chambers left empty and not subjected to micromotion. Qualitative histologic analysis of the bone formed with bone morphogenetic protein 2 revealed normal bone trabeculae. These findings indicate that bone morphogenetic protein 2 may be useful in augmenting bone formation in conditions that otherwise would favor the formation of fibrous tissue.

Animals↗
PubMed1997

Future directions. Augmentation of osteoporotic vertebral bodies.

Because current medical and surgical treatments of vertebral body fractures are less than adequate, there is a need for interventions that decrease the likelihood of occurrence of these fractures and improve the treatment options once they have occurred. One such broad category of intervention involves the fortification or augmentation of the vertebral bodies. In addition to prophylactically stabilizing osteoporotic vertebral bodies at risk for fracture, augmentation of vertebral bodies that have already fractured may prove to be useful by reducing pain, improving function, and preventing further collapse and deformity. Vertebral body augmentation can also be used as an adjunct to fixation of internal hardware--for example, pedicle screws-in osteoporotic spines. A number of products are now available or are in clinical trials. The most promising products are injectable materials-polymethylmethacrylate or mineral bone cement. The early clinical results using polymethylmethacrylate in percutaneous vertebroplasty for fractured vertebral bodies and the results in vitro using an injectable mineral cement for vertebral body fortification are encouraging. Although the principle of vertebral body augmentation remains encouraging, data to support the widespread use of these techniques remain sparse, and the indications for their use should be more clearly defined.

Bone Cements↗
PubMed1997

Use of bone morphogenetic protein 2 on ectopic porous coated implants in the rat.

The ability of recombinant human bone morphogenetic protein 2 to remain osteoinductive and stimulate appositional bone formation on a porous coated implant was tested in a rat quadriceps muscle pouch. Implants with or without hydroxyapatite were used to compare the effects on bone formation of two different does (23 micrograms or 46 micrograms) of recombinant human bone morphogenetic protein 2 against controls as evidenced by contact radiography, histologic examination, and backscatter scanning electron microscopic analysis. Cylindrical plasma sprayed porous titanium implants were placed bilaterally within a muscle pouch surgically created in 48 Lewis rats. Implants treated with recombinant human bone morphogenetic protein 2 formed significantly more bone than did control implants independent of the dose or presence of hydroxyapatite. In all implants with bone formation, osteoinduction via endochondral ossification began within 7 days. By 21 days, cartilage largely was replaced by bone and marrow. The results of this ectopic, nonweightbearing in vivo assay suggest that recombinant human bone morphogenetic protein 2 remains biologically active after application to a titanium implant and may be used to enhance appositional bone formation by direct application to the implant surface.

Analysis of Variance↗
PubMed1996

Cancellous bone screw thread design and holding power.

This study was designed to isolate and evaluate the parameters of host density, outer diameter (OD), root diameter (RD), and pitch in cancellous bone screw design and their effect on holding power. Special emphasis was placed on screw pitch, which has been evaluated infrequently in the literature. Three groups of stainless steel V thread screws (group I, OD 4.5 mm, RD 3.0 mm; group II, OD 6.4 mm, RD 3.5 mm; group III, OD 6.4 mm, RD 4.2 mm) were machined with progressive increases in pitch from 12 to 32 threads per inch (TPI). Two densities of synthetic cancellous bone material (Pedilen, Ottobock, Minneapolis, MN, U.S.A.), 0.15 g/ml and 0.22 g/ml, were then prepared and molded into sheets 1.9 cm thick and the screw threads completely engaged. Push-out tests were performed using a servohydraulic testing machine (MTS, Minneapolis, MN, U.S.A.). Fifteen trials of each screw were tested in each material. The effect on holding power of the different parameters of the custom screws in order of importance was (a) host material density, (b) OD (c) pitch, and (d) RD. The groups with a 6.4-mm OD had a much greater holding power than did the group with a 4.5-mm OD (p < 0.001). A decrease in screw pitch (increased threads per inch) did itself have a significant improved effect on fixation for all groups in both pedilen densities (p < 0.001). In the two 6.4-mm screw groups studied, the difference in the two root diameters (4.2 mm vs. 3.5 mm) showed the smaller root diameter to give a greater holding power in the less dense 0.15 g/ml pedilen (p < 0.001). In the more dense 0.22 g/ml pedilen there was no difference (p = 0.26) between the root diameters. To optimize holding power, cancellous screws may be designed with a decreased pitch (increased TPI) over those commercially available today. Cannulated screws must have a larger cancellous thread root diameter to leave room for the central cannulation; this may decrease their holding power in less dense cancellous bone but not in denser bone.

Biomechanical Phenomena↗
PubMed1996

Revision total knee arthroplasty due to aseptic failure.

Revision TKA for aseptic failure presents the surgeon with a variety of technical problems. The major problems include loss of bone stock and inadequacy of soft-tissue constraints. Historically, these patients have done poorly but when these problems are adequately addressed with the appropriate surgical technique and appropriate choice of implant, then the results are quite good.

Humans↗