Surface-bound bisphosphonates enhance screw fixation in rats—increasing effect up to 8 weeks after insertion

Background?A bisphosphonate coating improves screw fixation 2 weeks after implantation in cancellous bone. This study on rats examined further development of fixation over time for screws inserted in cancellous and cortical bone.

Methods?SS screws were coated with a multiple layer of fibrinogen. Half of the screws were coated further with bisphosphonates, which were linked to the fibrinogen. The screws were inserted in cancellous and cortical bone in rats. The rats were killed after 5 h, 4 days, 1, 2, 4, 8, and 24 weeks, and fixation was evaluated by pullout test.

Results?There was a gradual increase in pull-out force over time in both cancellous and cortical bone. The bisphosphonate coating improved fixation. Moreover, the difference between the bisphosphonate and control groups increased with time. The pull-out force was almost twice that of the controls for screws inserted in cancellous bone at 8 weeks. Energy uptake was increased more than 3-fold.

Discussion?The energy uptake and pull-out force of a screw depends on the bone engaged with the threads. Thus, the presence of bisphosphonates increased the amount or quality of this bone by affecting the resorp-tion/formation in a positive way. The increased effect of the bisphosphonates with time thus suggests that bisphosphonate is retained within the remodeling bone, with a positive effect on its gradual adaptation to the implant.     

Systemic and local ibandronate enhance screw fixation.

The trauma involved with inserting implants into bone leads to an activation of the inflammatory response and an activation of osteoclasts. In addition, apoptosis of osteocytes in the surrounding area has been implicated in further activation of osteoclasts. If the balance between resorption and bone formation shortly after implantation favours resorption, an impairment of early fixation might ensue. Because bisphosphonates inhibit resorption, this study analyses whether they can improve early fixation. Stainless steel screws (M 1.7) were inserted into the tibiae of 76 male Sprague-Dawley rats. Daily subcutaneous injections of ibandronate (3 microg) or saline were given to 20 rats. The remaining rats received ibandronate or saline directly applied into the drill hole before the screw was inserted. Tibiae were harvested at 14 days. Mechanical tests were performed on 50 tibiae. Systemically treated tibiae were tested for pull-out strength alone. Locally treated tibiae were tested for either pull-out or torque resistance. The remaining 18 tibiae were prepared for histology. Systemic ibandronate increased the pull-out force at failure by 30% (p=0.04). Local treatment increased the force at failure by 15% (p=0.02) and stiffness by 28% (p=0.01). In the removal torque measurements, local ibandronate increased the torque-moment at failure by 60% (p=0.04), and the maximum friction moment by 51% (p=0.04). Energy for turning the screw 1/4 revolution was increased by 68% (p=0.02). These results demonstrate that early remodeling events plays an important role in screw fixation, and that systemic or local bisphosphonate treatment could be an effective pharmacological path to improve early implant fixation.     

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.     

Alendronate treatment in the revision setting, with and without controlled implant motion: an experimental study in dogs

Introduction Bisphosphonates have been proposed to delay or prevent loosening of joint replacement implants by reducing bone resorption. It is known, however, that implant motion prevents the bone anchorage necessary to maintain secure implant fixation.

Methods We used our experimental implant model with controlled motion to evaluate the relative effects of implant motion and bisphosphonate. We implemented our established 8-week experimental revision protocol to obtain a bony and soft tissue setting of revision joint replacement in 16 dogs. At 8 weeks, we had stabilized half of the implants. The other half of the implants continued pistoning. Half of the dogs were exposed to alendronate (oral).

Results Stabilization of the revision implant was more effective at improving fixation (higher shear strength) than administering alendronate. As expected, the fibrous membrane remained under unstable conditions, even with alendronate. With alendronate and stabilized implants, increased bone was observed near the sclerotic shell of the revision cavity, but it was reduced with alendronate when the implant was unstable.

Interpretation Our findings suggest that it may be difficult for alendronate administration alone to rescue implants that are already loose. In implants that have not progressed to loosening, alendronate may increase bone density at the border with the sclerotic shell, but the effect of this bone in delaying eventual loosening is not known.     

Screw positions in femoral neck fractures: Comparison of two different screw positions in cadavers

To evaluate the influence of different screw positions on the stability of fixation in femoral neck fractures, 30 cadaveric proximal femora were osteotomized and fixed with 2 cannulated screws. The proximal screw was placed either with a posterior cortical support in the femoral neck or centrally, supported only by cancellous bone. The distal screw rested on the femoral calcar. The specimens were tested in bending, using the force at 2 and 5 mm deflection at the osteotomy site and at fracture, as an expression of the stability of fixation. The test sequences were recorded on a x-y plotter and on videotape. Bone density measurements were made at the femoral neck, Ward's triangle, and the trochanter region.

Our findings indicate that a posterior position with cortical support for the proximal screw, compared to a central screw position with only cancellous bone support, increases the stability of femoral neck fractures.     

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.     

Acetabular reconstruction with the Burch-Schneider ring: an EBRA analysis of 40 cup revisions

Background Reconstruction of the bone stock and fixation of the implant remain challenging problems in revision surgery. In this retrospective study, we wanted to gain information on initial stability and wear after revision with the Burch-Schneider ring.

Patients and methods Between 1994 and 1998, we performed 70 reconstructions of the acetabulum with a Burch-Schneider ring in revision arthroplasty. 63 patients could be followed up clinically and radiographically. 40 cups were suitable for EBRA measurements whereas migration and wear could not be assessed by this method in 23 cases due to lack of comparability of pelvic radiographs. The mean follow-up time was 4.7 years.

Results 2 cups were re-revised and 14 cups had breakage or changes of position of the screws. 30 cups showed detectable migration and 18 cups detectable wear. The mean migration was 2.8 mm and the mean wear rate was 0.12 mm/year. 16 cups had detectable migration after 1 year; 11 of these 16 continued to migrate and 9 of them had screw breakage. Both re-revisions showed early migration. Early migration correlated with later screw breakage and the overall migration correlated with wear. The only risk factor found for early migration was the wear rate.

Interpretation The Burch-Schneider ring is an established and reliable implant for cup revision with good clinical results, but it seems to be difficult to maintain intraoperative stability. The implants with continuous migration may lead to late clinical failure and require further observation. Wear may contribute to migration and resorption of the bone graft. ▪     

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. ▪     

Interference screw fixation of cervical grafts: a biomechanical study of a new method of cervical fixation.

The dislodgement of anterior bone graft in the cervical spine is a frequent complication of attempted fusion following discectomy or corpectomy. It has been hypothesized that fixation augmented with interference screws may increase the pull-out strength of the construct and decrease the rate of these complications. Mechanical tests were conducted to compare interference screw fixation methods for enhancing the fixation between the bone graft and the adjacent vertebra. The anterior pull-out strengths of cervical bone grafts were compared using fixation with and without the addition of interference screws. Both discectomy and corpectomy graft models were examined in vitro. The mean pull-out force for a Smith-Robinson type bone graft alone was 58.1 N (SD +/- 11.4 N); for the graft augmented with two 3.5 mm cancellous bone screws, 153.9 N (+/- 58.9 N); for the graft with four 3.5 mm screws, 217.1 N (SD +/- 69.9 N). The pull-out strengths of the two and four 3.5 mm screw constructs were significantly greater than the strength of the graft alone (p less than 0.05). Similarly placed 2.7 mm cortical screws of the same length provided increased pull-out strength (123.7 N +/- 38.6 N and 142.5 N +/- 38.2 N for two and four screws, respectively); however, in comparison to the graft alone, these differences were not statistically significant. For both screw types, the four screw fixations were stronger than the two-screw fixations, although these differences were not statistically different.(ABSTRACT TRUNCATED AT 250 WORDS)     

Anterior screw fixation for an odontoid fracture using an Acutrak 4/5 screw: a case report

The direct anterior screw fixation of odontoid fractures by a single cancellous screw, especially for osteoporotic vertebrae, has a potential risk of leading to insufficient stability and implant failures. We experienced good results following surgery using a single Acutrak 4/5 screw to obtain sufficient stability for an odontoid fracture in a patient with osteopenia. The screw is a cannulated self-tapping headless screw and has a tapered profile and full threads with variable pitches, and it can yield sufficient compression force as the screw is inserted. The preoperative severe neck pain of the patient was diminished immediately after the surgery. The patient achieved bone union in a short time and had a good clinical result for at least 3 years. Some biomechanical studies showed that the compression force of Acutrak standard screws was stronger than that of both 4.0-mm cancellous screws inserted with the lag screw technique and Herbert screws, and other studies showed that the compression force of Acutrak 4/5 screws was equivalent to that of 4.5-mm cortical screws. However, there has been no clinical report of surgery using an Acutrak 4/5 screw for odontoid fractures. This is the first clinical report of fixation by an Acutrak 4/5 screw.     

Optimization of screw fixation in rat bone with extracorporeal shock waves

Screw fixation in osteoporotic patients is becoming an increasing problem in orthopaedic surgery as deterioration of cortical and cancellous bone hamper biomechanical stability and screw fixation. This might result in delayed weight‐bearing or failure of instrumentation. We hypothesized that local peri‐operative shock wave treatment can optimize osseointegration and subsequent screw fixation. In eight female Wistar rats, two cancellous and two cortical bone screws were implanted in both femora and tibiae. Immediately after implantation, 3.000 unfocused extracorporeal shock waves (energy flux density 0.3 mJ/mm²) were applied to one side. The other side served as non‐treated internal control. Evaluation of osseointegration was performed after 4 weeks with the use of microCT scanning, histology with fluorochrome labeling, and pull‐out tests of the screws. Four weeks after extracorporeal shock wave treatment, treated legs exhibited increased bone formation and screw fixation around cortical screws as compared to the control legs. This was corroborated by an increased pull‐out of the shock wave treated cortical screws. The cancellous bone screws appeared not to be sensitive for shock wave treatment. Formation of neocortices after shock wave therapy was observed in three of eight animals. Furthermore, de novo bone formation in the bone marrow was observed in some animals. The current study showed bone formation and improved screw fixation as a result of shock wave therapy. New bone was also formed at locations remote from the screws, hence, not contributing to screw fixation. Further, research is warranted to make shock wave therapy tailor‐made for fracture fixation. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:76–84, 2018.

     

Tartrate-resistant acid phosphatase 5b (TRAP 5b) as a marker of osteoclast activity in the early phase after cementless total hip replacement

Background After total hip replacement, increased bone metabolism is seen. A local periprosthetic osteopenia can be measured by dual-energy X-ray absorptiometry (DXA), but it is still unkown whether biochemical markers can be used to monitor the local remodeling at an earlier stage.

Patients and methods In this prospective study we compared the biochemical markers tartrate-resistant acid phosphatase 5b (TRAP 5b), bone ALP, osteocalcin and CrossLaps with periprosthetic DXA in 17 consecutive patients after uncemented total hip replacement.

Results We found a highly significant early increase in TRAP 5b after 2 weeks and 6 weeks, which was followed by a densitometrically detectable decrease in bone mineral density after 26 weeks, especially in periprosthetic section Gruen zone 7. Bone ALP and osteocalcin levels as markers of osteoblast activity, and also Cross-Laps as a further marker of osteoclast activity, did not appear to allow any significant prediction of local bone remodeling.

Discussion Our findings show that TRAP 5b is a sensitive parameter for monitoring of osteoclast activity after cementless total hip replacement, and may predict local osteopenia.     

Attachment of autogenous tendon graft to cortical bone is better than to cancellous bone

We analyzed the mechanical and histological variables after the attachment of an autogenous tendon graft to cortical or cancellous bone. We reconstructed the medial collateral ligament of the knee in 33 Japanese white rabbits, using a bone socket procedure. The floor of the bone socket was cortical bone in group A and cancellous bone in group B.

Mechanically, the pull-out test showed a tendency towards an increase in maximum failure load, with 10.9 N, 35 N and 37 N in group A, and 11 N, 18 N and 36 N in group B at 2, 4 (statistically significant difference) and 8 weeks after surgery, respectively. Histologically, the attachments were immature at 2 weeks. At 4 weeks, granulations had matured and Sharpey's fiber-like structures were seen. These fibers were more abundant in group A than in group B. At 8 weeks, the attachments in both groups were rather like the normal 4-zone structure. With time, tendon attachments matured in both groups.

Our study showed that reattachment of tendons to cortical bone may be bettter than to cancellous bone.     

Doxycycline-coated sutures improve the suture-holding capacity of the rat Achilles tendon

Background There is evidence of high matrix metalloproteinase (MMP) activity around sutures inserted into tendons. This probably results in tissue breakdown, allowing the suture to cut through the tendon, and thus contributes to repair-site elongation and gap formation. We therefore hypothesized that treatment with the MMP inhibitor doxycycline would improve the sutureholding capacity of tendon.

Animals, methods and results In the first sub-study, rats received a suture in the Achilles tendon. One group was treated with systemic doxycycline and the other received no treatment. At 3, 5, and 7 days, suture-holding capacity was measured mechanically. The pull-out force and energy were reduced in all tendons, at 3 days compared to freshly inserted sutures, but no further reduction was detected at later time points. Doxycycline- treated tendons showed improved suture-holding capacity as measured by higher energy uptake than in untreated tendons. Force at failure showed a trend towards improvement. The effect was most evident on day 3. In the second sub-study, sutures were coated with doxycycline. At 3 days, local doxycycline treatment caused improved suture-holding capacity—as measured by higher force at failure and higher energy uptake.

Interpretation We provide proof of a novel treatment principle. MMP inhibitor-coated sutures improve suture-holding capacity during early repair of collagenous tissues.     

Outcome of undisplaced and moderately displaced femoral neck fractures

Background The optimal treatment for femoral neck fracture is a matter of controversy. We compared the outcome of displaced fractures with good healing potential (moderately displaced fractures) to the outcome of undisplaced fractures treated by internal fixation with 2 parallel screws.

Methods In a consecutive series of hip fracture patients, the rates of reoperation and mortality for 225 undisplaced fractures were compared to those for 241 moderately displaced fractures. The patients were followed for 1-6 years.

Results The total rate of reoperation was 19% (9% because of healing complications) for the undisplaced fractures and 33% (20% because of healing complications) for the moderately displaced fractures. Fracture displacement was the main predictor of reoperation. There was no difference in mortality between the groups, and patient-related background parameters (rather than fracture displacement) were the main predictors of mortality.

Interpretation Undisplaced fractures should be treated by internal fixation. The best treatment for moderately displaced fractures remains to be determined.     

Enhancement of pedicle screw stability using calcium phosphate cement in osteoporotic vertebrae: in vivo biomechanical study

 We conducted an experimental study using female beagles with and without ovariectomy-induced osteoporosis to determine the effect of calcium phosphate cement (CPC) on the mechanical stability of inserted pedicle screws. A drill hole was created from the base of the transverse process to the vertebral body; CPC was injected into the hole, and then a screw was inserted into the same hole. In the presence of osteoporosis evidenced by dual X-ray absorptiometry, the stability of the inserted screw augmented by CPC against pull-out and cephalocaudal forces were significantly greater by 28% and 54% at 1 week after operation, 48% and 71% at 2 weeks, and 56% and 68% at 4 weeks compared with those without CPC. The pull-out strength increased progressively with time after surgery, probably reflecting new-bone growth from the surrounding cancellous bone, which was in direct contact with the CPC, as shown in the histologic study. At each time point the cephalocaudal rigidity was similar and the pull-out strength greater than that for the screws inserted without CPC in nonporotic dogs. These findings suggest that CPC augments the stability of the inserted pedicle screws and increases the stiffness of fixed osteoporotic motion segments using instrumentation. Received: September 9, 2002 / Accepted: January 6, 2003 RID="*" ID="*" Offprint requests to: Y. Taniwaki     

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.