Mathias Bostrom

Posterior Approach to Total Hip Replacement Using Enhanced Posterior Soft Tissue Repair

The two senior authors (PMP, RP) independently began using an identical enhanced posterior soft tissue repair after total hip replacement through a posterior approach. In the first authors experience, a dislocation rate of 4% in 395 patients before using the enhanced closure was reduced to 0% in 395 patients in whom the enhanced closure was performed. In the second authors experience, 160 total hip replacements had a dislocation rate of 6.2% before the enhanced closure whereas 124 total hip replacements had a dislocation rate of 0.8% after the enhanced closure. These results are highly statistically significant.

Use of bone morphogenetic protein-2 in the rabbit ulnar nonunion model.

The ability of the osteoinductive protein and recombinant human bone morphogenetic protein-2, combined with polylactic glycolic acid porous microspheres and autologous blood clot to heal a large segmental defect was tested in a rabbit diaphyseal defect model. Two centimeter nonuniting defects were surgically created in the bilateral ulnae of 50 male New Zealand white rabbits. Each defect was then implanted with a pastelike polylactic glycolic acid/blood clot combination that was mixed with 5 different concentrations of recombinant human bone morphogenetic protein-2. The forearms were radiographically assessed on a biweekly schedule for 8 weeks. At 8 weeks, all animals were sacrificed and forearms radiographed. Radiographs were then scored by 3 independent observers for bone formation and union rates. United limbs were tested in torsion for mechanical strength using a Burstein torsion tester. All nonunited limbs were analyzed histologically as were 2 united limbs from each dosage group. Radiographic evaluation revealed that there was a dose dependent response in healing of the ulnar defect with a higher bone formation rate in the 2 higher dose limbs than in the lower dose limbs. Union was achieved in 100% of the highest dose limbs, whereas only 50% of the lowest dose limbs achieved bony union. No defects implanted with carrier alone achieved union. Biomechanical studies revealed significantly stiffer bone than age matched controls. Histologic analysis demonstrated normal bone formation with abundant normal appearing osteoid. These dose response data further support the role of recombinant human bone morphogenetic protein-2 as a potent morphogen in bone regeneration.

A Novel Tetracycline Labeling Schedule for Longitudinal Evaluation of the Short‐Term Effects of Anabolic Therapy With a Single Iliac Crest Bone Biopsy: Early Actions of Teriparatide

We describe a quadruple tetracycline labeling method that allows longitudinal assessment of short‐term changes in bone formation in a single biopsy. We show that 1 month of hPTH(1‐34) treatment extends the bone‐forming surface, increases mineral apposition rate, and initiates modeling‐based formation.

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.

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.

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 pre-clinical 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.

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.

Effects of Alendronate on Particle-Induced Osteolysis in a Rat Model

Background: Particle-induced osteolysis is currently a major problem affecting the long-term survivorship of total joint replacements. Alendronate is a third-generation bisphosphonate that blocks osteoclastic bone resorption. The objective of this study was to determine whether alendronate could prevent particle-induced osteolysis or restore (reverse) bone loss in established osteolysis.Methods: A rat model of particle-induced osteolysis was used. A specially designed polyethylene implant was placed in the proximal part of the right tibia of seventy-two animals. Following four weeks of healing, the animals were randomized into control groups, a prevention group, or a treatment group. In the prevention group, animals received intra-articular injections of high-density polyethylene particles (mean size, 2 m; all <10 m) at four, six, and eight weeks postoperatively. Alendronate (0.01 mg/kg/day) was administered concomitantly through an implantable pump from the fourth week through the tenth week. In the treatment group, animals were also exposed to polyethylene particles at four, six, and eight weeks, to establish bone loss, but they received alendronate subsequently, from the tenth week through the sixteenth week, to treat the bone loss. Positive (particle-only) and negative (saline-solution-only) control groups were assessed as well. Tissues were harvested at ten weeks in the prevention group and at sixteen weeks in the treatment group. Histological analyses and histomorphometric determinations of the periprosthetic bone volume were carried out.Results: Histological examination showed a rim of new bone (neocortex) around the implant in the untreated and saline-solution-treated control animals (no polyethylene particles). Treatment with saline solution (no polyethylene particles) did not affect periprosthetic bone. Animals exposed to polyethylene particles had bone loss. In those that received alendronate, the bone loss was either prevented or reversed, and the quantity of neocortical and trabecular bone was increased compared with that of the controls. Alendronate effectively preserved periprosthetic bone in both the prevention and treatment groups.In the prevention arm, the mean periprosthetic bone volume of the neocortex and the surrounding trabecular bone, as determined with histomorphometry, was 21.5% %plusmn; 6.5% in the saline-solution-treated controls (no particles), 13.1% %plusmn; 5.9% in the particle-treated animals, and 32.6% %plusmn; 6.4% in the alendronate-treated animals (p < 0.001). In the treatment arm, the mean periprosthetic bone volume was 27.2% %plusmn; 5.6% in the saline-solution-treated controls, 17.7% %plusmn; 6.2% in the particle-treated animals, and 30.2% %plusmn; 5.9% in the alendronate-treated animals (p = 0.002).Conclusions: In our model, the intra-articular injection of polyethylene particles caused substantial bone loss around a loaded implant. Alendronate effectively prevented and treated the particle-induced periprosthetic bone loss.Clinical Relevance: Alendronate may be useful in preventing particle-induced osteolysis around total joint implants. It may also elicit bone formation in established osteolytic lesions.

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.

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.