Kjeld Søballe

Remodeling of cortical bone allografts mediated by adherent rAAV-RANKL and VEGF gene therapy

Structural allograft healing is limited because of a lack of vascularization and remodeling. To study this we developed a mouse model that recapitulates the clinical aspects of live autograft and processed allograft healing. Gene expression analyses showed that there is a substantial decrease in the genes encoding RANKL and VEGF during allograft healing. Loss-of-function studies showed that both factors are required for autograft healing. To determine whether addition of these signals could stimulate allograft vascularization and remodeling, we developed a new approach in which rAAV can be freeze-dried onto the cortical surface without losing infectivity. We show that combination rAAV-RANKL- and rAAV-VEGF-coated allografts show marked remodeling and vascularization, which leads to a new bone collar around the graft. In conclusion, we find that RANKL and VEGF are necessary and sufficient for efficient autograft remodeling and can be transferred using rAAV to revitalize structural allografts.

Transforming growth factor-β enhances fracture healing in rabbit tibiae

The ability of exogenous Transforming Growth Fac- densitometry. Increased maximal bending strength tor4 (TGF-D) to stimulate bone formation in fracture and callus formation were demonstrated in the healing was investigated. TGF-O was continuously groups receiving TGF-O. TGF-D had no effect on applied in doses of 1 and 10 pg/day for 6 weeks to 2 bending-stiffness, bone mineral content, cortical groups of adult rabbits with unilateral plated midtibial thickness or haversian canal diameter. We conclude osteotomies. A group receiving solvent without TGF- that local application of exogenous TGF-O may O served as control. Fracture healing was evaluated enhance fracture healing in rabbits. by mechanical tests, bone morphometry and bone

Accelerated perioperative care and rehabilitation intervention for hip and knee replacement is effective: A randomized clinical trial involving 87 patients with 3 months of follow-up

Background Approximately 12,000 hip and knee replacements were performed in Denmark in 2005. Accelerated perioperative interventions are currently implemented, but there is conflicting evidence regarding the effect. We therefore performed an efficacy study of an accelerated perioperative care and rehabilitation intervention in patients receiving primary total hip replacement, and both total and unicompartmental knee replacement. Methods A randomized clinical trial was undertaken in which 87 patients were randomized to either a control group receiving the current perioperative procedure, or an intervention group receiving a new accelerated perioperative care and rehabilitation procedure. Outcome measures were length of stay (LOS) in hospital, and gain in quality of life (QOL) using EQ-5D from baseline to 3-month follow-up. Results Mean LOS was reduced (p < 0.001) from 8 days (95% CI: 7.1–8.4) in the control group to 5 days (95% CI: 4.2–5.6) in the intervention group. This was accompanied by a greater gain in QOL of 0.08 (95% CI: 0.004–0.16) in the intervention group (p = 0.03). Interpretation An accelerated perioperative care and rehabilitation intervention in patients undergoing primary total hip replacement, and total or unicompartmental knee replacement is indeed effective—and of advantage to both the hospital and the patient.

The stabilizing effect of the ligamentous structures in the sinus and canalis tarsi on movements in the hindfoot An experimental study

Three-plane kinesiology of hindfoot instability was stud ied after lesions to the ligamentous structures in the sinus and canalis tarsi in 20 amputation specimens. Neither a lesion of the cervical ligament nor of the interosseous talocalcaneal ligament resulted in an in crease in the total range of movements above 2.6° in any of the three planes. However, the percentage in crease in the total range of movements after cutting of the ligaments was generally largest in the talocalcaneal joint compared to the increase in the total hindfoot joint complex. The largest percentage increase (43%) in the talocalcaneal joint occurred at dorsiflexion after cutting the interosseous talocalcaneal ligament. The demonstrated minor instability after experimental lesions of the ligamentous structures in the sinus and canalis tarsi may have a clinical identity in the sinus tarsi syndrome. Patients with that syndrome rarely present an objective hindfoot instability, although a major complaint is a feeling of hindfoot instability.

Hydroxyapatite and fluorapatite coatings for fixation of weight loaded implants.

Survivor analysis of total hip replacement recently has shown disappointing results in younger patients. To improve this, ceramic coatings have been applied to prostheses for cementless use. A new fluorine containing coating, fluorapatite, has been shown to increase bone ingrowth compared with hydroxyapatite in unloaded models. In a weight loaded model, the effects of hydroxyapatite and fluorapatite coated implants on implant fixation and bone ingrowth were evaluated. Eight hydroxyapatite and fluorapatite coated implants with porous surface were inserted into the medial femoral condyles of 8 mature dogs in a paired design. The implants initially were surrounded by a gap communicating with the joint space and were loaded during each gait cycle. After 25 weeks, no differences in pushout data or bone ingrowth between hydroxyapatite and fluorapatite coated implants were found. An important finding was the absence of foreign body reaction in the bone. Neither hydroxyapatite nor fluorapatite coatings delaminated during implantation or as a result of the pushout test. Bone repair activity remained in the initial gap zone, but most of the bone was of the lamellar type. No difference in bone remodeling between the hydroxyapatite and fluorapatite coated implants was found in the initial gap zone. Microprobe analysis showed no increase in fluorine content around the fluorapatite coated implants. The hydroxyapatite and fluorapatite coatings seem efficacious after a 25-week implantation period under weight loaded conditions.

Fixation of titanium and hydroxyapatitecoated implants in arthritic osteopenic bone

Retrieval studies of porous-coated prostheses have demonstrated deficient bony ingrowth in high percentages. Possible reasons for this are lack of initial mechanical stability and the presence of osteopenia. The authors studied ingrowth of osteopenic bone into titanium alloy (Ti) porous-coated implants with and without hydroxyapatite (HA) coating in an experimental dog model. Unilateral osteopenia of the knee with a 20% reduced bone density as judged by computed tomography (CT) scanning (P less than .001) was induced in 12 mature dogs by weekly intraarticular injections of Carragheenin into the right knee for 12 weeks, with the left knee serving as control. Ti porous-coated cylinders were inserted in press-fit bilaterally in the lateral femoral condyles in six dogs. HA-coated titanium plugs were implanted similarly in another sex-, age-, and weight-matched group of six dogs. Bony ingrowth after 4 weeks was significantly reduced for Ti implants in osteopenic bone compared to control bone, but HA-coated implants were covered by equal amounts of bone tissue. Bone-implant shear strength of Ti implants also was reduced in osteopenic bone compared to control bone. In control bone, the anchorage of Ti implants was stronger than HA-coated implants, whereas the fixation of Ti and HA-coated implants was equal in the osteopenic bone. The results demonstrate that the bony fixation of Ti porous-coated implants is weakened by the presence of experimentally induced osteopenia. However, the fixation of HA-coated implants was not affected by the osteopenic condition in the surrounding bone. The fixation of Ti and HA-coated implants was equal in osteopenic bone, whereas the fixation of Ti porous-coated implants was superior to that of HA-coated implants in control bone.

Effectiveness of accelerated perioperative care and rehabilitation intervention compared to current intervention after hip and knee arthroplasty. A before-after trial of 247 patients with a 3-month follow-up

BackgroundIn Denmark, approximately 12,000 hip and knee arthroplasties were performed in 2006, and the hospital costs were close to US

Soaking morselized allograft in bisphosphonate can impair implant fixation

110,000,000. In a randomized clinical trial, we have recently demonstrated the efficacy of accelerated perioperative care and rehabilitation intervention after hip and knee arthroplasty compared to current intervention under ideal circumstances. We do not, however, know whether these results could be reached under usual circumstances of healthcare practice. We therefore investigated whether length of stay after implementation of accelerated perioperative care and rehabilitation after hip and knee arthroplasty could be reduced in a normal healthcare setting, and how the achieved results matched those observed during the randomized clinical trial.MethodsAn effectiveness study as a before-after trial was undertaken in which all elective primary total hip and total knee arthroplasty patients were divided into a before-implementation group receiving the current perioperative procedure, and an after-implementation group receiving the new accelerated perioperative care and rehabilitation procedures as provided by a new multi-disciplinary organization. We used the Breakthrough Series Collaborative Model for implementation. The primary outcome measure was in hospital length of stay (LOS), and the secondary outcome measure was adverse effects within 3 months postoperatively.ResultsWe included a total of 247 patients. Mean LOS was significantly (P < 0.001) reduced by 4.4 (95% CI 3.8–5.0) days after implementation of the accelerated intervention, from 8.8 (SD 3.0) days before implementation to 4.3 (SD 1.8) days after implementation. No significant differences in adverse effects were observed. LOS in this effectiveness study was significantly lower than LOS reported in the efficacy study.ConclusionAccelerated perioperative care and rehabilitation intervention after hip and knee arthroplasty was successfully and effectively implemented. Results obtained during usual hospital circumstances matched the results achieved under ideal circumstances in this group of patients.

Comparison of trabecular metal cups and titanium fiber-mesh cups in primary hip arthroplasty: A randomized RSA and bone mineral densitometry study of 50 hips

The use of impacted, morselized allograft is a well-established way to provide initial stability of revision joint replacements. We investigated whether rinsing morselized allograft in bisphosphonate and subsequently impacting it around experimental titanium-coated implants would further facilitate biomechanical implant fixation and graft incorporation. In 10 dogs, a pair of titanium implants surrounded by a 2.5-mm gap was inserted into the proximal part of each humerus during two separate surgeries to allow two observation periods. The gap was filled with impacted, morselized allograft soaked in either bisphosphonate (alendronate, 2 mg/mL) or saline (control). Unbound alendronate was not rinsed away. During the first surgery, one pair of implants (alendronate and control) was inserted into one humerus. Eight weeks later, a second pair of implants was inserted into the contralateral humerus. The first pair of implants was observed for 12 weeks and the second pair for 4 weeks. Implants were evaluated by histomorphometry and biomechanical pushout test. We found substantially decreased biomechanical implant fixation for all implants surrounded by impacted, morselized allograft that had been soaked in alendronate. Furthermore, the alendronate treatment blocked formation of new bone and inhibited resorption of the graft material. Although limited by the specific dose of alendronate used and the omission of rinsing away excess bisphosphonate, this study warrants caution and calls for further experimental research before impacting alendronate-soaked morselized allograft around clinical joint replacements.

Superior sealing effect of hydroxyapatite in porous- coated implants : experimental studies on the migration of polyethylene particles around stable and unstable implants in dogs

Background Trabecular metal has shown promising results in experimental studies of bone ingrowth. Several clinical studies support these results. However, until now, no randomized clinical radiostereometric analysis (RSA) studies have been published. In this randomized RSA trial, we compared a new acetabular cup with a surface made of tantalum trabecular metal and a cup with a titanium fiber-mesh surface. Patients and methods Between 2004 and 2006, we operated 60 patients with noninflammatory hip arthritis. The patients were randomized to receive either an uncemented cup with a titanium fiber-mesh surface (Trilogy cup) or a cup with a trabecular tantalum surface (Monoblock cup). After 2 years, 50 patients had completed the study. The primary endpoint was cup migration within the first 2 years after surgery; the secondary endpoints were change in bone mineral density and Harris hip score at 3 months. Results Both cup types showed excellent fixation. RSA revealed minimal translation and rotation at 2 years. There was no statistically significant difference between the cup types with regard to translation. However, less rotation along the transverse axis was seen in the trabecular metal cups than in the fiber mesh cups: mean –0.01º (95% CI: –0.11 to 0.12) for trabecular metal cups and –0.60º (–0.72 to –0.48) for fiber-mesh cups (p = 0.04). The degree of periprosthetic bone loss was similar between the cup types in any of the regions of interest at 2 years of follow-up. 3 months postoperatively, we found a similar increase in Harris hip score in both groups: from around 50 to over 90. Interpretation We found promising early results concerning fixation of trabecular metal components to the acetabular host bone. However, we recommend a longer observation period to evaluate the outcome of this new cup design.