Oliver Birke

The incorporation of strontium and zinc into a calcium-silicon ceramic for bone tissue engineering.

In this study we developed novel scaffolds through the controlled substitution and incorporation of strontium and zinc into a calcium-silicon system to form Sr-Hardystonite (Sr-Ca(2)ZnSi(2)O(7), Sr-HT). The physical and biological properties of Sr-HT were compared to Hardystonite (Ca(2)ZnSi(2)O(7)) [HT]. We showed that Sr-HT scaffolds are porous with interconnected porous network (interconnectivity: 99%) and large pore size (300-500 microm) and an overall porosity of 78%, combined with a relatively high compressive strength (2.16+/-0.52 MPa). These properties are essential for enhancing bone ingrowth in load-bearing applications. Sr-HT ceramic scaffolds induced the attachment and differentiation of human bone derived cells (HOB), compared to that for the HT scaffolds. Sr-HT scaffolds enhanced expression of alkaline phosphatase, Runx-2, osteopontin, osteocalcin and bone sialoprotein. The in vivo osteoconductivity of the scaffolds was assessed at 3 and 6 weeks following implantation in tibial bone defects in rats. Histological staining revealed rapid new growth of bone into the pores of the 3D scaffolds with the Sr-HT and HT, relative to the beta-tricalcium phosphate (beta-TCP). In vivo, HT and Sr-HT produced distinct differences in the patterns of degradation of the materials, and their association with TRAP positive osteoclast-like cells with HT appearing more resistant compared to both Sr-HT and beta-TCP.

Myogenic progenitors contribute to open but not closed fracture repair

BackgroundBone repair is dependent on the presence of osteocompetent progenitors that are able to differentiate and generate new bone. Muscle is found in close association with orthopaedic injury, however its capacity to make a cellular contribution to bone repair remains ambiguous. We hypothesized that myogenic cells of the MyoD-lineage are able to contribute to bone repair.MethodsWe employed a MyoD-Cre+:Z/AP+ conditional reporter mouse in which all cells of the MyoD-lineage are permanently labeled with a human alkaline phosphatase (hAP) reporter. We tracked the contribution of MyoD-lineage cells in mouse models of tibial bone healing.ResultsIn the absence of musculoskeletal trauma, MyoD-expressing cells are limited to skeletal muscle and the presence of reporter-positive cells in non-muscle tissues is negligible. In a closed tibial fracture model, there was no significant contribution of hAP+ cells to the healing callus. In contrast, open tibial fractures featuring periosteal stripping and muscle fenestration had up to 50% of hAP+ cells detected in the open fracture callus. At early stages of repair, many hAP+ cells exhibited a chondrocyte morphology, with lesser numbers of osteoblast-like hAP+ cells present at the later stages. Serial sections stained for hAP and type II and type I collagen showed that MyoD-lineage cells were surrounded by cartilaginous or bony matrix, suggestive of a functional role in the repair process. To exclude the prospect that osteoprogenitors spontaneously express MyoD during bone repair, we created a metaphyseal drill hole defect in the tibia. No hAP+ staining was observed in this model suggesting that the expression of MyoD is not a normal event for endogenous osteoprogenitors.ConclusionsThese data document for the first time that muscle cells can play a significant secondary role in bone repair and this knowledge may lead to important translational applications in orthopaedic surgery.Please see related article: http://www.biomedcentral.com/1741-7015/9/136

Experience with the Fassier-Duval telescopic rod: first 24 consecutive cases with a minimum of 1-year follow-up.

Background The new Fassier-Duval Telescopic IM System (FD-rod) has the advantage of a single entry point over the traditional telescopic rods such as the Bailey-Dubow or Sheffield rods. Although encouraging early results were presented by the originators of the technique at international meetings, there is no formal publication in the literature as yet. Methods We performed a chart and x-ray review of the first 24 consecutive FD-rod insertions in 15 patients (age, 1.5 to 12.5 y) with a minimum of 1-year follow up (1 to 2.4 y) after implantation of femoral and/or tibial FD-rods. Diagnoses included with osteogenesis imperfecta (OI) (15 cases, 9 patients), and other conditions such as congenital tibial pseudarthrosis (CPT) in neurofibromatosis type 1 (NF1) (2 cases), and epidermal naevus syndrome (1 case). In patients with hypophosphataemic rickets (6 cases, 2 patients) the FD-rods were combined with an Ilizarov frame. Results We found the OI patient group associated with a 13% reoperation rate (2 of 15 cases) for proximal rod migration and a 40% complication rate (6 of 15 cases): rod migration and limited telescoping (5) and intraoperative joint intrusion (1). There were no infections. All the NF1 CPT (2) and epidermal naevus syndrome (1) cases required several reoperations for nonunion, loss of fixation, shortening (negative telescoping), migration, and/or joint intrusion—mainly due to the severe underlying pathology with insufficient longitudinal or torsional stability and diminished healing capacity. In hypophosphataemic rickets (combined with Ilizarov frame fixation) we found a 50% complication rate (3 of 6 cases) and a 17% reoperation rate (1 of 6): 2 FD-rods did not telescope and 1 case of peroneal neuropraxia required neurolysis. Conclusions In our experience the technique of using FD rods is demanding and associated with some intraoperative and postoperative pitfalls. We are happy to continue its use in OI patients when there is longitudinal stability and sufficient bone healing. However, in circumstances of insufficient stability and bone healing potential, further stabilization that can be achieved with an Ilizarov frame may be beneficial. Level of Evidence Level IV.

Distal tibial fracture repair in a neurofibromatosis type 1-deficient mouse treated with recombinant bone morphogenetic protein and a bisphosphonate

Congenital pseudarthrosis of the tibia is an uncommon manifestation of neurofibromatosis type 1 (NF1), but one that remains difficult to treat due to anabolic deficiency and catabolic excess. Bone grafting and more recently recombinant human bone morphogenetic proteins (rhBMPs) have been identified as pro-anabolic stimuli with the potential to improve the outcome after surgery. As an additional pharmaceutical intervention, we describe the combined use of rhBMP-2 and the bisphosphonate zoledronic acid in a mouse model of NF1-deficient fracture repair. Fractures were generated in the distal tibiae of neurofibromatosis type 1-deficient (Nf1(+/-)) mice and control mice. Fractures were open and featured periosteal stripping. All mice received 10 μg rhBMP-2 delivered in a carboxymethylcellulose carrier around the fracture as an anabolic stimulus. Bisphosphonate-treated mice also received five doses of 0.02 mg/kg zoledronic acid given by intraperitoneal injection. When only rhBMP but no zoledronic acid was used to promote repair, 75% of fractures in Nf1(+/-) mice remained ununited at three weeks compared with 7% of controls (p < 0.001). Systemic post-operative administration of zoledronic acid halved the rate of ununited fractures to 37.5% (p < 0.07). These data support the concept that preventing bone loss in combination with anabolic stimulation may improve the outcome following surgical treatment for children with congenital pseudarthosis of the tibia and NF1.

Biomechanics of Slipped Capital Femoral Epiphysis: Evaluation of the Posterior Sloping Angle.

Background: The posterior sloping angle (PSA) has been shown to be an objective and reproducible predictor of the risk of patients developing contralateral slipped capital femoral epiphysis (SCFE); however, prophylactic fixation remains controversial. This in vitro study investigates the biomechanical basis of using a 15-degree PSA as a threshold for prophylactic fixation. Methods: Synthetic bone in vitro models of the proximal femur were constructed with a PSA of 10 degrees as a control (normal) group (n=6) by performing an osteotomy at the physis and gluing the head back onto the neck. SCFE groups were created with a PSA of 15, 20, 25, 30, 50, or 60 degrees, by excising a wedge from the posterior neck and gluing them back at the new angle with corresponding posterior translation proportional to the slip angle, and loaded superoinferiorly in compression, to failure. Ultimate strength, energy to failure, and stiffness were recorded. Results: Increasing the PSA from 10 to 15 degrees only reduced ultimate strength by 13% (P>0.05; CI, −0.21 to −0.06), though a significantly lesser energy to failure was required (−58%, P<0.05; CI, −0.68 to −0.48). Increasing the angle to 20 degrees resulted in a further significant decrease in strength (−19%, P<0.05; CI, −0.28 to −0.10) and energy to failure (−45%, P<0.05; CI, −0.53 to −0.84). The severe SCFE (60-degree PSA) was significantly weaker and less rigid that the control, and the mild and moderate SCFE models (P<0.01). Conclusions: These biomechanical data support the threshold of 15-degree PSA as an objective measure for prophylactic fixation of the contralateral hip in SCFE. Clinical Relevance: The number needed to treat with (minimally invasive) prophylactic fixation to prevent contralateral SCFE can be minimized if the above-mentioned threshold is used.

The effect of hip position upon the location of the sciatic nerve: an MRI Study.

Background Allowance for the positional changes of the sciatic nerve is important when considering the safest position of the leg to perform hip operations, specifically the ischial osteotomy during a pelvic triple or periacetabular osteotomy. As for its proximity to the osteotomy site the sciatic nerve can be injured during these operations with the consequence of severe functional impairment. This is the first in-vivo study that demonstrates the effect of hip position upon the location of the sciatic nerve. Methods We determined how altering the position of the hip moves the nerve toward or away from the infracotyloid groove, the desired starting point of the ischial osteotomy site just inferior to the acetabulum when performing a pelvic triple or periacetabular osteotomy. Magnetic resonance imaging scans of the left hip in 3 different positions (neutral/supine, 30 to 45 degrees flexion, 30 to 45 degrees flexion/abduction/external rotation) were performed in 11 healthy children (5 boys and 6 girls, age 7 to 17 y) without prior hip surgery. The distance between the sciatic nerve and the infracotyloid groove was measured on the magnetic resonance images. Distance ratios based on the neutral position were calculated for flexion and flexion/abduction/external rotation for each of the participants. Results The sciatic nerve moves toward the ischium osteotomy site in hip flexion without abduction (mean flexion: neutral ratio 0.79, P<0.01). However the nerve moves away from the osteotomy site when the hip is 30 to 45 degrees flexed, abducted, and externally rotated (mean flexion/abduction/external rotation: neutral ratio 1.34), meaning the distance from nerve to infracotyloid groove increases significantly (P<0.01). The mean distances were 14.8 mm (11 to 20 mm) in neutral, 11.8 mm (9 to 16 mm) in flexion, and 20.0 mm (9 to 30 mm) in flexion/abduction/external rotation. Conclusions The likely safest position of the hip/leg to perform the ischium osteotomy as part of a pelvic triple or periacetabular osteotomy is in flexion, abduction, and external rotation. In this position the osteotomy can be performed via a medial or anterior approach with the nerve the furthest away from the osteotomy site. Level of Evidence Level II.

Iatrogenic Hip Instability Is a Devastating Complication After the Modified Dunn Procedure for Severe Slipped Capital Femoral Epiphysis

BackgroundThe modified Dunn procedure facilitates femoral capital realignment for slipped capital femoral epiphysis (SCFE) through a surgical hip dislocation approach. Iatrogenic postoperative hip instability after this procedure has not been studied previously; however, we were concerned when we observed several instances of this serious complication, and we wished to study it further.Questions/purposesThe purpose of this study was to evaluate the frequency, timing, and clinical presentation (including complications) associated with iatrogenic instability after the modified Dunn procedure for SCFE.MethodsBetween 2007 and 2014, eight international institutions performed the modified Dunn procedure through a surgical dislocation approach in 406 patients. During the period in question, indications varied at those sites, but the procedure was used only in a minority of their patients treated surgically for SCFE (31% [406 of 1331]) with the majority treated with in situ fixation. It generally was performed for patients with severe deformity with a slip angle greater than 40°. Institutional databases were searched for all patients with SCFE who developed postoperative hip instability defined as hip subluxation or dislocation of the involved hip during the postoperative period. We reviewed in detail the clinical notes and operative records of those who presented with instability. We obtained demographic information, time from slip to surgery, type of fixation, operative details, and clinical course including the incidence of complications. Followup on those patients with instability was at a mean of 2 years (range, 1–5 years) after the index procedure. Complications were graded according to the modified Dindo-Clavien classification. Radiographic images were reviewed to measure the preoperative slip angle and the presence of osteonecrosis.ResultsA total of 4% of patients treated with the modified Dunn procedure developed postoperative hip instability (17 of 406). Mean age of the patients was 13 years (range, 9–16 years). Instability presented as persistent hip pain in the postoperative period or was incidentally identified radiographically during the postoperative visit and occurred at a median of 3 weeks (range, 1 day to 2 months) after the modified Dunn procedure. Eight patients underwent revision surgery to address the postoperative instability. Fourteen of 17 patients developed femoral head avascular necrosis and three of 17 patients underwent THA during this short-term followup.ConclusionsAnterolateral hip instability after the modified Dunn procedure for severe, chronic SCFE is an uncommon yet potentially devastating complication. Future studies might evaluate the effectiveness of maintaining anterior hip precautions for several weeks postoperatively in an abduction brace or broomstick cast to prevent this complication.Level of EvidenceLevel IV, therapeutic study.

Sclerostin antibody enhances bone formation in a rat model of distraction osteogenesis

Neutralizing monoclonal sclerostin antibodies are effective in promoting bone formation at a systemic level and in orthopedic scenarios including closed fracture repair. In this study we examined the effects of sclerostin antibody (Scl‐Ab) treatment on regenerate volume, density, and strength in a rat model of distraction osteogenesis. Surgical osteotomy was performed on 179 Sprague Dawley rats. After 1 week, rats underwent distraction for 2 weeks, followed by 6 weeks for consolidation. Two treatment groups received biweekly subcutaneous Scl‐AbIII (a rodent form of Scl‐Ab; 25 mg/kg), either from the start of distraction onward or restricted to the consolidation phase. These groups were compared to controls receiving saline. Measurement modalities included longitudinal DXA, ex vivo QCT, and microCT, tissue histology, and biomechanical four‐point bending tests. Bone volume was increased in both Scl‐Ab treatments regimens by the end of consolidation (+26–38%, p < 0.05), as assessed by microCT. This was associated with increased mineral apposition. Importantly, Scl‐Ab led to increased strength in united bones, and this reached statistical significance in animals receiving Scl‐Ab during consolidation only (+177%, p < 0.01, maximum load to failure). These data demonstrate that Scl‐Ab treatment increases bone formation, leading to regenerates with higher bone volume and improved strength. Our data also suggest that the optimal effects of Scl‐Ab treatment are achieved in the latter stages of distraction osteogenesis. These findings support further investigation into the potential clinical application of sclerostin antibody to augment bone distraction, such as limb lengthening, particularly in the prevention of refracture.