No positive effects of OP-1 device on the incorporation of impacted graft materials after 8 weeks: a bone chamber study in goats

Background Bone morphogenetic proteins (BMPs) have the potential to improve clinical outcome after hip revision surgery by improving graft incorporation and implant fixation. However, impaction of cancellous bone grafts and TCP/HA bone substitute mixed with OP-1 device in a bone chamber in goats in a previous study led to reduced fibrous tissue ingrowth after 4 weeks. New bone formation was not promoted by OP-1. In the current study we examined whether this reduction represented a final loss of ingrowth or was just a delay, and whether the reduction can be overcome and ultimately results in a better late ingrowth.

Methods Bone chambers with impacted allografts and impacted TCP/HA granules mixed with 2 doses of OP-1 device were implanted in proximal medial goat tibias. Impacted allografts and TCP/HA not treated with OP-1 served as controls. After 8 weeks, the incorporation was evaluated using histology and histomorphometry.

Results Histology revealed evidence of bone graft incorporation, which proceeded in a similar way in both allografts and TCP/HA, with and without the addition of OP-1. After 8 weeks, no difference in bone ingrowth was found between the OP-1 groups and their controls. It was only in the allografts that the addition of OP-1 resulted in more fibrous tissue ingrowth.

Interpretation We conclude that the previously observed delay in fibrous tissue ingrowth can be only partially overcome.     

Rinsing morselized allografts improves bone and tissue ingrowth

Bone defects in revision hip surgery can be reconstructed with impacted morselized bone grafts. Rinsing these trabecular allografts may enhance graft incorporation by washing out immunogenic factors present in blood, marrow, and fat. However, it has been proposed that impaction of the graft releases biologically active factors, which can provide sufficient activity to stimulate new bone formation. Rinsing before impaction could enhance bone allograft incorporation, but rinsing after impaction could diminish the incorporation process of impacted bone graft. To study the effect of rinsing and impaction of morselized bone grafts on bone ingrowth, a bone chamber study was done in goats. Autografts and allografts were divided into three treatment groups: (A) impacted; (B) rinsed and impacted; and (C) rinsed, impacted, rinsed, and impacted again. Ten goats received three bone chambers in each proximal tibia. The chambers were filled with either allograft or autograft, yielding six different implants per goat. After 6 weeks, histologic analyses were done and bone and tissue ingrowth were measured. New bone and total tissue ingrowth were higher in autografts than in allografts, especially in the nonrinsed group. With rinsing, total tissue ingrowth increased in the allograft group to approach that of autografts. Rinsing after impaction did not additionally alter bone ingrowth. The current findings show that incorporation of allografts can be improved by rinsing the grafts before impaction.     

Incomplete incorporation of morselized and impacted autologous bone graft: A histological study in 4 intracorporally grafted lumbar fractures

Morselized and impacted bone allografts are used successfully in hip and knee revisions, but experiments using bone chambers indicate that impaction actually can delay ingrowth of new bone into a graft. To understand the remodeling and incorporation process of morselized and impacted grafts, we studied the incorporation of morselized impacted autografts in lumbar fractures histologically.

4 patients were operated on for Th XII-LI fractures. The fractures were stabilized by VSP plates and transpedicular screws in the vertebrae above and below the fractured one. Autologous bone graft was packed into the fractured vertebral body through one of the pedicles. After 18-20 months, the plates were removed and biopsies were obtained from various locations in the fractured vertebra. All fractures were at this time clinically and radiographically healed. Histologically, in all cases, large areas of the autograft in the vertebral body were unvascularized and partially or entirely necrotic. As with morselized bone in hip revisions, evaluation of graft incorporation requires histological examination. Full osseous incorporation of a graft is not always necessary for a good clinical result.     

Systemic zoledronate precoating of a bone graft reduces bone resorption during remodeling

Background Cartilage degeneration often occurs after osteosynthesis of a devascularized intermediary fragment in a joint fracture, in mosaicplasty or in whole-joint toe-to-finger transplantation. Hypothetically, the degeneration is secondary to a collapse of the transferred subchondral bone as it remodels during high mechanical load. Bisphosphonates are used to reduce resorption of necrotic bone. We tested a systemic pretreatment before harvesting the graft in order to protect the bone and cartilage against collapse and secondary arthrosis.

Methods Rats were given one zoledronate injection and bone grafts were harvested. The grafts were frozen, thawed and placed into bone chambers, and implanted into another batch of rats. Graft resorption and new bone formation was measured by histomorphometric analysis and compared with untreated grafts.

Results In the remodeled area of the controls, the graft was almost totally resorbed and replaced by bone marrow. In the zoledronate-treated specimens, the graft remained and the graft trabeculas were lined with new bone. By histomorphometry, the total amount of bone (graft plus new bone) within the remodeled area was 16% in the zoledronate-treated grafts and 5% in the controls (p = 0.003).

Interpretation A bone graft can be pretreated with bisphosphonate and remain protected against resorption once implanted again. ▪     

Pulse-lavage washing is an effective method for defatting of morselized allograft bone in the operating theater

Background and purpose Incorporation of fresh-frozen allograft bone and safety aspects associated with this procedure can be improved by removing blood and lipids from the bone. We investigated in a quantitative manner how efficient pulse lavage might be for removal of adipose tissue from morselized allograft bone.

Methods Depending on the study, the washing was performed with an average of 0.8 L or 1.6 L of sterile saline at room temperature. Fat content of the morselized bone samples was determined using hexane elution. The efficiency of pulse lavage alone was compared with that after an additional wash in 12 L of warm water (55°C). Unprocessed controls were also included for comparison.

Results Pulse lavage with 0.8 L saline alone removed 80% of the fat from the bone, whereas 95% of the fat was removed when washing was performed with 1.6 L of saline. The cleansing efficacy was improved further when an additional wash with warm water was used.

Interpretation Our results indicate that pulse-lavage washing alone at room temperature is an effective method for defatting of morselized allograft bone, but an additional wash with warm water improves the cleansing efficiency. Pulse lavage is easily available and simple to use in the operating theater.     

Hamstring tendon autograft better than bone patellar-tendon bone autograft in ACL reconstruction: a cumulative meta-analysis and clinically relevant sensitivity analysis applied to a previously published analysis

Background Current debate on treatment options for anterior cruciate ligament (ACL) reconstruction complicate the choice between hamstring and bone patellartendon bone autografts. We hypothesized a priori that cumulative meta-analysis (a form of sensitivity analysis) might show that the evidence for reduction of morbidity by hamstring grafts could have been reached at an earlier time. Furthermore, we hypothesized a priori that modern state-of-the-art hamstring graft fixation technique would give similar results regarding stability as bone-patellar tendon-bone autografts.

Methods We performed a cumulative meta-analysis and sensitivity analysis based on femoral graft fixation techniques to compare hamstring autograft and bonepatellar tendon-bone autografts in ACL reconstruction derived from a previously published meta-analysis.

Results Cumulatively, that hamstring autograft reduces anterior knee pain had already reached statistical significance in 2001 (relative risk 0.49 (95%CI: 0.32-0.76; p = 0.001, I2 = 0%)). The modern endobutton hamstring graft fixation technique (2 studies) yielded similar stability in the Lachman test as bone-patellar tendon-bone grafts, with a relative risk of 1.1 (95%CI: 0.82-1.5; p = 0.6, I2 = 0%). Exclusion of the endobutton group explains the increased laxity in the hamstring graft group.

Interpretation Cumulative meta-analysis strengthens the evidence for reduced morbidity using hamstring tendon autograft for anterior cruciate ligament reconstruction. Sensitivity analysis focusing on state-of-the-art hamstring graft fixation techniques further weakens the evidence that bone-patellar tendon-bone autografts provide better stability.     

Influence of water and fat content on compressive stiffness properties of impacted morsellized bone: an experimental ex vivo study on bone pellets

Background The initial stability of an exchanged hip arthroplasty is crucial for the survival of the revised joint. Several factors can affect the outcome. The amount of liquid in morsellized bone has a major influence on the constrained stiffness properties of impacted bone applied in revision joint surgery.

Method To determine whether water or fat is the main contributing liquid, we performed an experimental study on impacted morsellized cortico-cancellous bovine bone to compare the constrained e-moduli in native bone and bone with modified water and fat content. The bone was impacted into bone pellets by a standardized method by which the construction procedure was monitored. Other stiffness properties were recorded during subsequent load testing.

Results Low water content significantly increased the constrained stiffness moduli during load, while high water content significantly reduced it. Low fat content increased stiffness significantly only during the initial phase of loading.

Interpretation Our findings indicate that the preparation and usage of morsellized bone in revision joint surgery should be performed under dry conditions to improve the initial stability of the revised prosthesis. ▪     

Long-standing increased bone turnover at the fixation points after anterior cruciate ligament reconstruction: a positron emission tomography (PET) study of 8 patients

Background A secure incorporation of the graft in a bone tunnel is a prerequisite for successful anterior cruciate ligament reconstruction. In this cross-sectional pilot study, we studied the healing process with positron emission tomography (PET) scanning.

Patients and methods 8 young patients underwent an anterior cruciate ligament reconstruction with a bonepatellar tendon-bone graft (BTB, n = 4) or a quadruple semitendinosus and gracilis graft (ST/G, n = 4). Regional bone turnover was quantified with an 18F-fluoride PET scan in each patient 1 day, 3 weeks, 7 months, or 22 months after surgery.

Results The highest activity level was found 3 weeks after surgery, but the activity at the femoral fixation points was markedly increased even after 7 months. The bone turnover was almost normalized 22 months after the operation.

Interpretation It would take at least 7 months until an anterior cruciate ligament graft, fixed with an interference screw, is completely incorporated. This finding is important for postoperative rehabilitation. Furthermore, PET is a feasible tool when studying new ways of fixing soft tissue to bone.     

Larger bone graft size and washing of bone grafts prior to impaction enhances the initial stability of cemented cups: experiments using a synthetic acetabular model

Background Bone defects after failed total hip arthroplasty can be reconstructed with impacted morselized bone grafts and a cemented cup. On the acetabular side, the effects on initial cup stability of washing bone grafts prior to impaction and bone graft size remain unclear. Related to these variables, cement penetration and inter-particle shear resistance have been suggested to be critical factors to ensure initial cup stability.

Methods Using a synthetic acetabular model, we studied the effects of (1) washing bone grafts prior to impaction, and (2) bone graft size on the initial stability of cemented cups. In addition, cement penetration was measured using CT scans.

Results Reconstructions with large, washed bone grafts provided the highest stability during mechanical compression and in a lever-out situation. Washing of the bone grafts had a positive effect on initial cup stability, but the size of the bone grafts appeared to be more important. Cement penetration was affected by bone graft size but not by washing.

Interpretation From a mechanical standpoint, large bone grafts that have been washed prior to impaction may be preferable in order to obtain optimal cup stability using the bone impaction grafting technique.     

Structural allografts for bone stock reconstruction in two-stage revision for infected total hip arthroplasty: good outcome in 16 of 18 patients followed for 5-14 years

Background The use of massive bone allografts in cases of revision of failed total hip arthroplasties (THAs) due to infection is controversial.

Patients and methods 18 patients presented with infection at the site of a THA and were treated with a two-stage protocol. In the first stage, the prosthesis was removed together with all necrotic tissues and cement material if present. A custom-made mold of Palacos R cement containing 1 g of gentamicin was then inserted in 17 of the 18 patients. Systemic antibiotics were used during the interval period. In the second stage, the patients had either acetabular or femoral reconstruction using bulk allograft bone.

Results Mean follow-up was 9 (5-14) years. 1 patient presented with recurrent infection and underwent a Girdlestone resection arthroplasty as definitive treatment. Another patient had a mechanical failure of the acetabular component, which was revised 10 years after the second stage of the reconstruction. The mean Harris Hip Score improved from 34 points preoperatively to 71 points at the last review. By our definition, 16/18 of the patients had a successful outcome.

Interpretation Our results support the use of massive allografts in staged reconstructions of infected THAs complicated by considerable bone loss. ▪     

Incomplete incorporation of morselized and impacted autologous bone graft: a histological study in 4 intracorporally grafted lumbar fractures

Morselized and impacted bone allografts are used successfully in hip and knee revisions, but experiments using bone chambers indicate that impaction actually can delay ingrowth of new bone into a graft. To understand the remodeling and incorporation process of morselized and impacted grafts, we studied the incorporation of morselized impacted autografts in lumbar fractures histologically. 4 patients were operated on for Th XII-LI fractures. The fractures were stabilized by VSP plates and transpedicular screws in the vertebrae above and below the fractured one. Autologous bone graft was packed into the fractured vertebral body through one of the pedicles. After 18-20 months, the plates were removed and biopsies were obtained from various locations in the fractured vertebra. All fractures were at this time clinically and radiographically healed. Histologically, in all cases, large areas of the autograft in the vertebral body were unvascularized and partially or entirely necrotic. As with morselized bone in hip revisions, evaluation of graft incorporation requires histological examination. Full osseous incorporation of a graft is not always necessary for a good clinical result.     

Effect of bone marrow grafting on the titanium porous-coated implant in bilateral total knee arthroplasty

Background and purpose Poor bone ingrowth into the porous coating of tibial components has been reported. We hypothesized that iliac marrow grafting might be useful to enhance bone ingrowth into a porous-coated implant. The first part of this study was to examine the presence of fibroblast colony-forming units (CFUF) containing osteogenic precursor cells in tibial bone marrow and iliac bone marrow. The second aim was to compare the clinical and radiographic results after bilateral total knee arthroplasty (TKA) with and without autologous bone marrow transplantation to the bone-implant interface.

Methods Simultaneous bilateral TKA was performed in 21 patients with osteoarthritis. Aspirated iliac bone marrow was transplanted to the interface of one randomly selected porous-coated tibial component in each patient, and contralateral knees served as controls. All of the 21 patients were followed for 5 years.

Results The average number of CFU-F was significantly lower in tibial marrow than in iliac marrow (p = 0.008). The final fluoroscopically-guided radiographs revealed a decrease in the number of knees with radiolucent lines after marrow grafting compared to those without grafting (p = 0.004).

Interpretation Iliac bone marrow is useful as a bone grafting material to enhance the biological fixation in porous-coated implants.     

Impaction bone grafting with freeze-dried irradiated bone. Part I. Femoral implant stability: cadaver experiments in a hip simulator

Processed freeze-dried irradiated allografts seem to be used less than instead of fresh-frozen allografts for impaction bone grafting in revision hip arthroplasties. Although biologically acceptable, their use is discouraged because of their questionable mechanical properties following freeze-drying and irradiation procedures. To address this question, we impacted freeze-dried grafts in 6 cadaveric femurs and loaded with a cemented Charnley prosthesis. The routinely used fresh-frozen allografts were used as controls in the contralateral side. These constructs were compared simultaneously in a walking hip simulator for their stability during 900,000 loading cycles. The mechanical parameters were axial inducible displacement and subsidence of the implant. The former parameter was lower in the implant mounted on freeze-dried impacted grafts than that mounted on the fresh-frozen bone. The latter parameter was also lower in the freeze-dried group. At the end of the test, we found no implant loosening in either group and their 'pull out' resulted in cement-prosthesis debonding, which showed the mechanical integrity of the impacted grafts. Freeze-dried grafts provide more stable fixation of the stem than fresh-frozen morselized grafts, when tested in a hip simulator.     

Impaction bone grafting with freeze-dried irradiated bone. Part I. Femoral implant stabilityCadaver experiments in a hip simulator

Processed freeze-dried irradiated allografts seem to be used less than instead of fresh-frozen allografts for impaction bone grafting in revision hip arthroplasties. Although biologically acceptable, their use is discouraged because of their questionable mechanical properties following freeze-drying and irradiation procedures. To address this question, we impacted freeze-dried grafts in 6 cadaveric femurs and loaded with a cemented Charnley prosthesis. The routinely used fresh-frozen allografts were used as controls in the contralateral side. These constructs were compared simultaneously in a walking hip simulator for their stability during 900,000 loading cycles. The mechanical parameters were axial inducible displacement and subsidence of the implant. The former parameter was lower in the implant mounted on freeze-dried impacted grafts than that mounted on the fresh-frozen bone. The latter parameter was also lower in the freeze-dried group. At the end of the test, we found no implant loosening in either group and their pull out resulted in cement-prosthesis debonding, which showed the mechanical integrity of the impacted grafts. Freeze-dried grafts provide more stable fixation of the stem than fresh-frozen morselized grafts, when tested in a hip simulator.     

Freeze-dried irradiated bone brittleness improves compactness in an impaction bone grafting model

Background?Defatted bone chips with or without freeze-drying and irradiation have mechanical advantages as compared to fresh-frozen controls in in vitro models of impaction. These improved results have been ascribed to replacement of viscous bone marrow by saline and embrittlement of the freeze-dried bone by irradiation.Material and methods?To determine which of these hypotheses is correct, we compared the development of stiffness and compactness of morselized bone graft that had been: 1) fat-reduced with saline, and 2) fresh-frozen, solvent-detergent defatted, 3) freeze-dried irradiated and 4) not irradiated. We used 12 osteo-arthrotic femoral heads to prepare these four batches of morselized bone, and impacted 18 samples from each batch in a cylinder. The frozen bone grafts were tested after thawing at room temperature for 2 hours and the freeze-dried grafts were tested after 30 minutes of rehydration. We monitored the development of compactness and stiffness of the material during impaction.Results?The stiffness of the freeze-dried irradiated bone was greater than that of the other three series after 10, 50 and 150 impactions. The freeze-dried bone chips that were not irradiated and the chips defatted with saline alone were less stiff than the fresh-frozen control after 150 impactions.Interpretation?The brittleness of freeze-dried irradiated bone, caused by loss of the capacity to absorb energy in a plastic way, increases the compactness and stiffness of the morselized grafts. Washing bone with saline alone or treating bone with solvent-detergent but no irradiation had no similar mechanical advantage and the bone did not impact better than fresh-frozen undefatted bone in our model.     

Freeze-dried irradiated bone brittleness improves compactness in an impaction bone grafting model

BACKGROUND: Defatted bone chips with or without freeze-drying and irradiation have mechanical advantages as compared to fresh-frozen controls in in vitro models of impaction. These improved results have been ascribed to replacement of viscous bone marrow by saline and embrittlement of the freeze-dried bone by irradiation. MATERIAL AND METHODS: To determine which of these hypotheses is correct, we compared the development of stiffness and compactness of morselized bone graft that had been: 1) fat-reduced with saline, and 2) fresh-frozen, solvent-detergent defatted, 3) freeze-dried irradiated and 4) not irradiated. We used 12 osteoarthrotic femoral heads to prepare these four batches of morselized bone, and impacted 18 samples from each batch in a cylinder. The frozen bone grafts were tested after thawing at room temperature for 2 hours and the freeze-dried grafts were tested after 30 minutes of rehydration. We monitored the development of compactness and stiffness of the material during impaction. RESULTS: The stiffness of the freeze-dried irradiated bone was greater than that of the other three series after 10, 50 and 150 impactions. The freeze-dried bone chips that were not irradiated and the chips defatted with saline alone were less stiff than the fresh-frozen control after 150 impactions. INTERPRETATION: The brittleness of freeze-dried irradiated bone, caused by loss of the capacity to absorb energy in a plastic way, increases the compactness and stiffness of the morselized grafts. Washing bone with saline alone or treating bone with solvent-detergent but no irradiation had no similar mechanical advantage and the bone did not impact better than fresh-frozen undefatted bone in our model.     

Platelet-rich plasma accelerated surgical angio-genesis in vascular-implanted necrotic bone: an experimental study in rabbits

Background Platelets contain many kinds of growth factors with the ability to accelerate angiogenesis. We analyzed whether a single injection of platelet-rich plasma (PRP) would accelerate surgical angiogenesis in necrotic bone implanted with vascular tissue.

Methods We used 24 Japanese White rabbits. PRP was refined from autologous blood by separation twice with centrifugation. A removed iliac bone was frozen in liquid nitrogen to ensure complete cellular necrosis. A narrow hole was made in the bone and the saphenous vascular bundle was passed through the hole. The bone was wrapped after injection of either 1 mL (1) PRP, or (2) saline solution into the hole, and was placed subcu-taneously in the thigh. In both groups, angiogenesis was compared 1 week and 2 weeks after surgery.

Result Angiogenesis was observed along the implanted vascular bundle in both groups. At 1 and 2 weeks after surgery, both the vessel density and the average length of newly formed vessels of the experimental group were significantly greater than in the control group. Both the vessel density and the length were greater after 2 weeks than after 1 week.

Interpretation A single injection of PRP accelerates surgical angiogenesis in vascular-implanted necrotic bone.     

Fibrous tissue armoring increases the mechanical strength of an impacted bone graft

Impacted, morselized bone allografts are used with good clinical results in revision of hip prostheses with loosening and osteolysis. The impacted bone graft appears radiographically to remodel, but histological analyses have shown a heterogeneous picture with a mixture of living and dead bone. Thus, complete remodeling of the graft may be neither a prerequisite nor a cause of the good clinical results. The present study concerns the mechanical effect of the mere armoring of the bone graft by ingrowing fibrous tissue. We compared the compression strength of freshly-impacted grafts to grafts that had been inserted into a bone chamber and thus were penetrated by fibrous tissue growing in between the graft trabeculae. The compressive strength was doubled after 4 weeks of fibrous ingrowth. We conclude that the mechanical properties of an impacted graft are enhanced by armoring with ingrowing fibrous tissue. Strengthening of the parts of the impacted grafts which have not yet remodeled, would be clinically relevant for the outcome of the operation, since these parts are at high stress during the whole remodeling period. Complete osseous remodeling may not be necessary to obtain a good clinical result with a morselized impacted graft.     

Fibrous tissue armoring increases the mechanical strength of an impacted bone graft

Impacted, morselized bone allografts are used with good clinical results in revision of hip prostheses with loosening and osteolysis. The impacted bone graft appears radiographically to remodel, but histological analyses have shown a heterogeneous picture with a mixture of living and dead bone. Thus, complete remodeling of the graft may be neither a prerequisite nor a cause of the good clinical results. The present study concerns the mechanical effect of the mere armoring of the bone graft by ingrowing fibrous tissue. We compared the compression strength of freshly-impacted grafts to grafts that had been inserted into a bone chamber and thus were penetrated by fibrous tissue growing in between the graft trabeculae. The compressive strength was doubled after 4 weeks of fibrous ingrowth. We conclude that the mechanical properties of an impacted graft are enhanced by armoring with ingrowing fibrous tissue. Strengthening of the parts of the impacted grafts which have not yet remodeled, would be clinically relevant for the outcome of the operation, since these parts are at high stress during the whole remodeling period. Complete osseous remodeling may not be necessary to obtain a good clinical result with a morselized impacted graft.