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Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_3 | Pages 26 - 26
23 Feb 2023
George JS Norquay M Birke O Gibbons P Little D
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The risk of AVN is high in Unstable Slipped Capital Femoral Epiphysis (SCFE) and the optimal surgical treatment remains controversial. Our AVN rates in severe, unstable SCFE remained unchanged following the introduction of the Modified Dunn Procedure (MDP) and as a result, our practice evolved towards performing an Anterior Open Reduction and Decompression (AOR) in an attempt to potentially reduce the “second hit” phenomenon that may contribute. The aim of this study was to determine the early surgical outcomes in Unstable SCFE following AOR compared to the MDP.

All moderate to severe, Loder unstable SCFEs between 2008 and 2022 undergoing either an AOR or MDP were included. AVN was defined as a non-viable post-operative SPECT-CT scan.

Eighteen patients who underwent AOR and 100 who underwent MPD were included. There was no significant difference in severity (mean PSA 64 vs 66 degrees, p = 0.641), or delay to surgery (p = 0.973) between each group. There was no significant difference in the AVN rate at 27.8% compared to 24% in the AOR and MDP groups respectively (p = 0.732). The mean operative time in the AOR group was 24 minutes less, however this was not statistically significant (p = 0.084). The post-reduction PSA was 26 degrees (range, 13–39) in the AOR group and 9 degrees (range, -7 to 29) in the MDP group (p<0.001). Intra-operative femoral head monitoring had a lower positive predictive value in the AOR group (71% compared to 90%).

Preliminary results suggest the AVN rate is not significantly different following AOR. There is less of an associated learning curve with the AOR, but as anticipated, a less anatomical reduction was achieved in this group. We still feel that there is a role for the MDP in unstable slips with a larger remodelling component.


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_22 | Pages 93 - 93
1 Dec 2017
Mills R Schindeler A Little D
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Aim

Implant-associated infection remains one of the biggest challenges facing orthopaedics and there is an urgent clinical need to develop new prophylactic strategies. We have previously shown that CSA-90, a broad-spectrum antimicrobial, prevented infection in an infected open fracture model. In this study we developed a novel model of implant-associated infection, in which to further test the potential of CSA-90 as a prophylactic agent.

Method

All studies were approved by the local animal ethics committee. 3D-printed porous titanium implants were implanted into the distal femora of 18 week-old male Wistar rats under general anaesthesia. The treatment groups' (n=10) implants were pre-coated with 500μg CSA-90 in saline. Staphylococcus aureus* was inoculated either directly around the implant (1×104 CFU) or injected intravenously immediately post-operatively (1×105 CFU). No systemic antibiotic prophylaxis was used. The study ran for six weeks and animals were reviewed daily for signs of infection. An independent, blinded veterinarian reviewed twice-weekly radiographs, and rats demonstrating osteolysis and/or declining overall health were culled early at their instruction. The primary outcome was implant infection, incorporating survival, microbiological, radiological, and histological measures.


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_11 | Pages 2 - 2
1 Feb 2013
Quick T Carpenter C Gibbons P Little D Skowno J
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Aim

Vascular compromise following supracondylar fractures is frequently described. Near Infra-red Spectrometry (NIRS) is a technique through which real-time data can be gathered non-invasively on the oxygenation status of tissues. The drive now is to gain knowledge on how NIRS data can be interpreted and to validate its use in the clinical setting.

Methods

This ethically approved prospective study looks at volar forearm compartment oxygen saturation (StO2) in 20 patients with supracondylar fractures requiring operative intervention. Both the injured limb and the contra-lateral, uninjured limb were monitored. 20 patients from a cohort of 29 had full data sets and are thus presented.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XLI | Pages 12 - 12
1 Sep 2012
Birke O McDonald M Morse A Liu M Ke D Little D
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Sclerostin is a negative regulator of osteoblast differentiation and bone formation. Expressed by osteocytes, it acts through antagonising the Wnt/â-catenin pathway and/or BMP activity. Distraction osteogenesis, used for limb lengthening and reconstruction, can be complicated by disuse osteopenia and poor healing response, both of which would benefit from pro anabolic therapy.

We examined the effects of Sclerostin Antibody (Scl-AbIII, Amgen Inc.,) in a rat model of distraction osteogenesis. A femoral osteotomy was stabilized with an external fixator in male Sprague Dawley rats. After a week of latency, the gap was distracted twice daily for 14 days to a total of 7 mm. Saline or Scl-Ab was administered twice weekly throughout the distraction period and up to 4, 6 or 8 weeks post commencement of distraction. Three groups were examined: Saline, Continuous Scl-Ab throughout the study (C Scl-Ab), and Delayed Scl-Ab with commencement of Scl-Ab after distraction (D Scl-Ab).

Regenerate bone mineral content (BMC), determined by DEXA, was increased 36% at 4 weeks and 86% at 6 weeks with C Scl-Ab, resulting in a 65% increase in bone mineral density (BMD) at 6 weeks, compared with Saline (p<0.01). D Scl-Ab treatment showed a 41% increase in BMC and a 31% increase in BMD compared with Saline at 6 weeks (p<0.05). At 8 weeks, C Scl-Ab remained significantly increased over Saline (72% in BMC; 60% in BMD).

Micro-CT scans of the regenerate revealed increases in bone volume of 88% with C Scl Ab and 65% with D Scl-Ab compared with Saline at 6 weeks (p<0.05). By 8 weeks, these increases were 36% for C Scl-Ab (p<0.05) and 37% for D Scl-Ab compared with Saline (p<0.01). Importantly, mean moment of inertia was increased over two-fold in both Scl-Ab groups at 6 weeks compared with Saline (p<0.05). Histology at 6 weeks confirmed micro-CT data with 85–88% increases in bone volume/tissue volume (BV/TV) in the regenerate with both C Scl-Ab and D Scl-Ab compared with Saline (p<0.05). Analysis of bone formation at 6 weeks revealed increases in mineral apposition rate of 56% in C Scl-Ab and 52% in D Scl-Ab compared with Saline (p<0.05).

Scl-Ab treatment increased bone formation in this model of distraction osteogenesis, resulting in a larger regenerate callus (increased BMC and BV/TV). We expect further studies to reveal increases in mechanical strength. Scl-Ab may hold promise as a therapeutic to accelerate regenerate formation and consolidation in distraction osteogenesis for limb reconstruction.


Anatomic reduction (subcapital re-alignment osteotomy) via surgical hip dislocation – increasingly popular. While the reported AVN rates are very low, experiences seem to differ greatly between centres. We present our early experience with the first 29 primary cases and a modified fixation technique.

We modified the fixation from threaded Steinman pins to cannulated 6.5mm fully-threaded screws: retrograde guidewire placement before reduction of the head ensured an even spread in the femoral neck and head. The mean PSA (posterior slip angle) at presentation (between 12/2008 and 01/2011) was overall 68° (45–90°). 59% (17/29) were stable slips (mean PSA 68°), and 41% (12/29) were unstable slips unable to mobilise (mean PSA 67°). The vascularity of the femoral head was assessed postoperatively with a bone scan including tomography.

The slip angle was corrected to a mean PSA of 5.8° (7° anteversion to 25° PSA). We encountered no complications related to our modified fixation technique.

All cases with a well vascularised femoral head on the post-operative bone scan (15/17 stable slips and 8/12 unstable slips) healed with excellent short term results.

Both stable slips with decreased vascularity on bone scan (2/17, 12%) had been longstanding severe slips with retrospectively suspected partial closure of the physis, which has been described as a factor for increased risk of avascular necrosis (AVN). One of these cases was complicated by a posterior redislocation due to acetabular deficiency. In the unstable group, 4/12 cases (33%) had avascular heads intra-operatively and cold postoperative bone scans, 3 have progressed to AVN and collapse.

Anatomic reduction while sparing the blood supply of the femoral head is a promising concept with excellent short term results in most stable and many unstable SCFE cases. Extra vigilance for closed/closing physes in longstanding severe cases seems advisable. Regardless of treatment, some unstable cases inevitably go on to AVN.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XLI | Pages 11 - 11
1 Sep 2012
Little D El-Hoss J Sullivan K Schindeler A
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CPT is a uniquely difficult condition, often associated with Neurofibromatosis (NF1), where bone healing is compromised. Although rare, the severity of this condition and the multiple procedures often entailed in treating it, warrant research attention. As study material is limited, animal models of the disorder are desirable for testing new treatments.

We sought to create a model of CPT where both copies of the NF1 gene were ablated at the fracture site, as has been found in some clinical specimens. NF1 floxed mice had fracture surgery; both closed fracture and open osteotomy were performed. Either a Cre- or control GFP-adenovirus was injected into the fracture site at day zero. Recombination was confirmed in ZAP reporter mice. Additionally, cell culture studies were used to examine the possible responses of NF1+/+ (wild type) NF1+/− or NF1−/− to drugs which may rescue the dysregulated Ras/MAPK pathway in NF1.

In closed fractures, radiographic bridging was 100% in NF1+/+ calluses and <40% in NF1−/− calluses (P<0.05). In open fractures, radiographic bridging was 75% in NF1+/+ calluses and <30% in NF1−/− calluses (P<0.05). In both fracture repair models the NF1−/− state was associated with a significant up to 15-fold increase in fibrotic tissue invading the callus by week 3. In NF1−/− fractures, large numbers of TRAP+ cells were observed histologically in the fibrotic tissue. Closed fractures also showed a significant increase in BRDU labelled proliferating cells in the callus. In cell culture models of NF1 deficient osteogenesis, NF1−/− progenitors were found to be significantly impaired in their capacity to form a calcified matrix as measured by Alizarin Red S staining and osteogenic markers (Runx2, Osteocalcin, Alp expression). However, when differentiated calvarial NF1 floxed osteoblasts were treated with Cre adenovirus, mineralization was not affected, suggesting that NF1 impacts on osteogenic differentiation rather than mature cell function. Treatment with MEK inhibitor PD0325901 was found to rescue the NF1−/− progenitor differentiation phenotype and permit robust mineralization. Treatment with the JNK inhibitor SP600125 was also able to improve ALP activity and mineralization in NF1+/− osteoprogenitors compared to control cells.

This model of NF1 −/− induction at a fracture or osteotomy site closely replicates the clinical condition of CPT, with lack of bone healing and fibrous tissue invasion. Underlying defects in bone cell differentiation in NF1 deficiencies can be at least partially rescued by JNK and MEK inhibitors.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXIII | Pages 130 - 130
1 May 2012
Yu N Schindeler A Peacock L Mikulec K Little D
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A Ruys, School of Aerospace, Mechanical and Mechatronic Engineering, University of Sydney, Sydney

The effects of bone anabolics can be maximised by systemic co-treatment with an anti-catabolic. Local treatment may reduce the total drug required and produce superior outcomes, although high dose local bisphosphonate has been reported to impair bone formation. We have explored local co-delivery of anabolic/anti- catabolic bone drugs at different doses.

We manufactured biodegradable poly-D,L-lactic acid (PDLLA) polymer pellets containing 25g BMP-7 as an anabolic with or without 0.002mg-2mg Pamidronate (PAM) as an anti-catabolic. Polymer pellets were surgically implanted into the hind limb muscle of female C57BL6 mice. Animals were sacrificed at three weeks post- implantation and bone formation was assessed by radiography, microcomputed tomography (microCT) and histology. Histological staining on five Âm paraffin sections included haematoxylin/eosin, alcian blue/picrosirius red, and tartrate- resistant acid phosphatase (TRAP).

Radiographic and microCT data confirmed that 0.02mg and 0.2mg local PAM doses significantly augmented BMP-7 induced bone formation. In contrast, 2mg local PAM dramatically reduced the amount of bone present. This dose was comparable to that used by Choi et al who also reported impaired bone formation in a skull defect model.2 three-dimensional microCT and histological analyses of the ectopic bone and surrounding muscle showed a cortical shell covering the polymer pellet, which had not completely resorbed.

Histological analysis at the pellet/bone interface showed tissue granulation and no inflammation, suggesting a high biocompatibility of the PDLLA polymer. The presence of bisphosphonate also decreased the amount of fatty marrow tissue seen within between the cortical shell and the unresorbed polymer.

For the first time we can demonstrate synergy with local BMP/bisphosphonate. This study confirms that high local PAM doses can have negative effects, indicating a need to avoid overdosing. The lack of implant degradation suggests a need to optimise polymer degradation for bone tissue engineering application.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXIII | Pages 128 - 128
1 May 2012
Uzun H James B Dunstan C Wu C Ramaswamy Y Paschalidis A Zreiqat H Little D McDonald M
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Developing biomaterials for bone regeneration that are highly bioactive, resorbable and mechanically strong remains a challenge. Zreiqat's lab recently developed novel scaffolds through the controlled substitution of strontium (Sr) and zinc (Zn) into calcium silicate, to form Sr-Hardystonite and Hardystonite, respectively and investigated their in vivo biocompatibility and osteoconductivity

We synthesized 3D scaffolds of Sr-Hardystonite, Hardystonite and compared them to the clinically used tricalcium phosphate (micro-TCP) (6 × 6 × 6 mm) using a polyurethane foam template to produce a porous scaffold. The scaffolds were surgically implanted in the proximal tibial metaphysis of each tibia of Female Wistar rats. Animals were sacrificed at three weeks and six weeks post-implantation and bone formation and scaffold resorption were assessed by microcomputed tomography (micro-CT) histomorphometry and histology. Histological staining on undecalcified sections included Toluidine blue, tartrate-resistant acid phosphatase (TRAP) and alkaline phosphatase (ALP).

The bone formation rate and mineral apposition rate will be determined by analysing the extent and separation of fluorescent markers by fluorescent microscopy micro-CT results revealed higher resorbability of the developed scaffolds (Sr-Hardystonite and Hardystonite) which was more pronounced with the Sr-Hardystonite. Toluidine blue staining revealed that the developed ceramics were well tolerated with no signs of rejection, necrosis, or infection. At three weeks post implantation, apparent bone formation was evident both at the periphery and within the pores of the all the scaffolds tested. Bone filled in the pores of the Sr- Hardystonite and Hardystonite scaffolds and was in close contact with the ceramic. In contrast, the control scaffolds showed more limited bone ingrowth and a cellular layer separating the ceramic scaffolds from the bone. By six weeks the Hardystonite and Sr Hardystonite scaffolds were integrated with the bone with most pores filled with new bone. The control scaffold showed new bone formation in the plane of the cortical bone but little new bone where the scaffold entered the marrow space. Sr Hardystonite showed the greatest resorbability with replacement of the ceramic material by bone.

We have developed novel engineered scaffolds (Sr-Hardystonite) for bone tissue regeneration. The developed scaffolds resorbed faster than the clinically used micro- TCP with greater amount of bone formation replacing the resorbed scaffold.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXIII | Pages 131 - 131
1 May 2012
Liu R Peacock L Mikulec K Morse A Schindeler A Little D
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Bone morphogenetic proteins (BMPs) are able to induce osteogenic differentiation in many cells, including muscle cells. However, the actual contribution of muscle cells to bone formation and repair is unclear. Our objective was to examine the capacity of myogenic cells to contribute to BMP-induced ectopic bone formation and fracture repair.

Osteogenic gene expression was measured by quantitative PCR in osteoprogenitors, myoblasts, and fibroblasts following BMP-2 treatment. The MyoD-Cre x ROSA26R and MyoD-Cre x Z/AP mouse strains were used to track the fate of MyoD+ cells in vivo. In these double-transgenic mice, MyoD+ progenitors undergo a permanent recombination event to induce reporter gene expression. Ectopic bone was produced by the intramuscular implantation of BMP-7. Closed tibial fractures and open tibial fractures with periosteal stripping were also performed. Cellular contribution was tracked at one, two and three week time points by histological staining.

Osteoprogenitors and myoblasts exhibited comparable expression of early and late bone markers; in contrast bone marker expression was considerably less in fibroblasts. The sensitivity of cells to BMP-2 correlated with the expression of BMP receptor-1a (Bmpr1a). Pilot experiments using the MyoD-Cre x Rosa26R mice identified a contribution by MyoD expressing cells in BMP-induced ectopic bone formation. However, false positive LacZ staining in osteoclasts led us to seek alternative systems such as the MyoD-cre x Z/AP mice that have negligible background staining. Initially, a minor contribution from MyoD expressing cells was noted in the ectopic bones in the MyoD-cre x Z/AP mice, but without false positive osteoclast staining. Soft tissue trauma usually precedes the formation of ectopic bone. Hence, to mimic the clinical condition more precisely, physical injury to the muscle was performed. Traumatising the muscle two days prior to BMP-7 implantation: (1) induced MyoD expression in quiescent satellite cells; (2) increased ectopic bone formation; and (3) greatly enhanced the number of MyoD positive cells in the ectopic bone. In open tibial fractures the majority of the initial callus was MyoD+ indicating a significant contribution by myogenic cells. In contrast, closed fractures with the periosteum intact had a negligible myogenic contribution.

Myoblasts but not fibroblasts were highly responsive to BMP stimulation and this was associated with BMP receptor expression. Our transgenic mouse models demonstrate for the first time that muscle progenitors can significantly contribute to ectopic bone formation and fracture repair. This may have translational applications for clinical orthopaedic therapies.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_IV | Pages 60 - 60
1 Mar 2012
Zenios M Ramachandran M Milne B Little D Smith N
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The aims of this study were (1) to assess whether rotational stability testing in Gartland III supracondylar fractures can be used intra-operatively in order to assess fracture stability following fixation with lateral-entry wires and (2) to quantify the incidence of rotational instability following lateral-entry wire fixation in Gartland type III supracondylar humeral fractures in children.

Twenty-one consecutive patients admitted with Grade III supracondylar fractures at the Children's Hospital at Westmead were surgically treated according to a predetermined protocol. Following closed fracture reduction, 2 lateral-entry wires were inserted under radiographic control. Stability was then assessed by comparing lateral x-ray images in internal and external rotation. If the fracture was found to be rotationally unstable by the operating surgeon, a third lateral-entry wire was inserted and images repeated. A medial wire was used only if instability was demonstrated after the insertion of three lateral wires.

Rotational stability was achieved with two lateral-entry wires in 6 cases, three lateral-entry wires in 10 cases and with an additional medial wire in 5 cases. Our results were compared to a control group of 24 patients treated at our hospital prior to introduction of this protocol. No patients returned to theatre following introduction of our protocol as opposed to 6 patients in the control group. On analysis of radiographs, the protocol resulted in significantly less fracture position loss as evidenced by change in Baumann's angle (p<0.05) and lateral rotational percentage (p<0.05).

We conclude that the introduction of rotational stability testing allows intra-operative assessment of fracture fixation. Supracondylar fractures that are rotationally stable intra-operatively following wire fixation are unlikely to displace post-operatively. Only a small proportion (26%) of these fractures were rotationally stable with 2 lateral-entry wires. This may be a reflection of either the fracture configuration or inability to adequately engage the medial column.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_III | Pages 47 - 47
1 Feb 2012
Kiely P Ward K Chan S Bellemore M Little D
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Background

Distraction Osteogenesis can be complicated by regenerate insufficiency resulting in prolonged implant usage or regenerate failure with malalignment or fracture. Experimental evidence has demonstrated that bisphosphonates may mediate improved local limb BMD and regenerate strength.

Methods

A prospective series of 14 patients over 5 years. One cohort (Group A) of these cases presented with established regenerate insufficiency leading to consideration for surgical intervention. Patients received a therapeutic regime of intravenous bisphosphonate A further cohort (Group B) of 7 patients was commenced on bisphosphonate therapy at an earlier stage, prior to the regenerate maturation phase.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_I | Pages 140 - 140
1 Mar 2009
Ramachandran M Fox M Munns C Cowell C Brown R Little D
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Background: Traumatic femoral head osteonecrosis in adolescents has a poor prognosis due to collapse and subsequent degenerative change. There are currently no satisfactory treatments available for this condition. Bisphosphonate therapy has improved outcome in animal models of osteonecrosis. We have evaluated bisphosphonate therapy as a novel strategy for adolescent traumatic osteonecrosis.

Methods: We established a protocol of identification of adolescents with osteonecrosis utilizing bone scans immediately after surgical treatment for hips at risk of osteonecrosis after trauma. Of a consecutive group of twenty-eight patients with either unstable slipped capital femoral epiphyses (SCFE) (22), femoral neck fracture (4) or hip dislocation (2), seventeen patients with osteonecrosis were identified. These patients (13 boys and 4 girls, mean age 12.6 years) and their families consented for treatment with intravenous bisphosphonates based on animal experimental evidence. Of the patients with osteonecrosis, twelve had presented with unstable SCFE, four with femoral neck fractures and one following traumatic hip dislocation. The average length of bisphosphonate treatment was 20.3 months (range 7 to 39). All patients were followed for at least 2 years.

Results: At mean follow-up of 38.7 months, fourteen patients (82%) were pain free. Clinically, all patients had a good to excellent outcome. The mean Harris Hip Score was 91.1, the Iowa Hip Rating was 92.1 and the Global PODCI score was 91.5. On radiographs, nine patients (53%) were rated as Stulberg I–II, six (35%) as Stulberg III, and two (12%) as Stulberg V.

Conclusion: Bisphosphonates therapy may play an adjunctive role in the treatment of adolescents with traumatic osteonecrosis.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_I | Pages 137 - 137
1 Mar 2009
Ramachandran M Schindeler A Godfrey C McDonald M Little D
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Background: Recombinant bone morphogenic proteins (BMPs) are potent bone anabolic agents suggested for the treatment of orthopaedic complications associated with neurofibromatosis type 1 (NF1), in particular, congenital pseudarthrosis of the tibia. We have explored the effect of Nf1 haploinsufficiency on ex vivo and in vivo models of BMP-induced bone formation in Nf1+/− mice.

Methods: Using an Nf1+/− knockout mouse model, we expanded primary cell cultures from calvarial and long bone osteoblasts and measured osteogenic markers, such as alkaline phosphatase and mineralization using Alizarin Red staining, and the responses of these markers to BMP-2 treatment. We also developed an in vivo muscle pouch heterotopic ossification model to assess the ability of BMP-2 to form bone.

Results: Primary osteoblast cultures from Nf1+/− mice showed reduced ALP staining, ALP activity and mineralization, denoting an anabolic deficiency. Nf1+/− osteoblasts responded to BMP-2 treatment, although osteogenic markers were reduced compared to BMP-2 treated Nf1+/+osteoblasts. Heterotopic bone was induced in both genotypes by surgically implanting BMP-2, however less bone was formed in Nf1+/− mice than Nf1+/+ controls.

Conclusion: These data indicate that BMP therapies have potential utility in treating orthopaedic defects in children with NF1, but that dosing may need to be optimized for this patient subgroup or that catabolism may need to be also controlled.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_I | Pages 117 - 117
1 Mar 2006
Brown R Goergens E Cowell C Little D
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Traumatic osteonecrosis of the femoral head in adolescents has a poor prognosis due to collapse and degenerative change. We hypothesised that early bisphosphonate treatment to reduce osteoclast activity could allow revascularisation and repair with maintenance of joint congruity.

Nine patients with documented osteonecrosis were treated with intermittent intravenous pamidronate (Aredia, Novartis) commencing within a mean 1 month of diagnosis (range, 5 to 91days). The dosing protocol has evolved over two years with the current dose being 9 mg/kg/year for 18 months. Mean follow up is 19.8 months (range, 13 to 30 months) with all patients followed for more than one year. There were 6 patients, who presented after unstable SCFE. Of these the index procedure had failed in three, requiring multiple early operations. The other three patients had sustained an inter-trochanteric fracture with a pelvic fracture, a traumatic hip dislocation and a femoral neck fracture respectively.

Eight of the patients are painfree. Six have been instructed to fully weight bear, while two can partial weight bear and one is non-weight bearing. Seven of 9 patients do not show significant resorption of the femoral heads at the most recent follow up. Of the two patients with significant resorption, one patient began to resorb after his medication was ceased, so it was recommenced. He has subsequently undergone a realignment procedure. The other patient had resorption of a section of the femoral head, which had not re-vascularised by 18 months, and this was elevated and bone grafted. These two hips are considered functional in the short term as they are currently pain free, but their deformity is expected to bring about early osteoarthritis in adult life.

This early experience lays the foundation for prospective clinical trials of bisphosphonate therapy in adolescents with osteonecrosis. It appears that bisphosphonate treatment protocols for adolescents will need to be prolonged. Our current practice is for a duration of around 18 months with normalisation of uptake on bone scan as the end point for therapy.


Orthopaedic Proceedings
Vol. 86-B, Issue SUPP_IV | Pages 484 - 484
1 Apr 2004
Brown R Goergens E Cowell C Little D
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Introduction Traumatic osteonecrosis of the femoral head in adolescents has a poor prognosis due to femoral head collapse and degenerative change. We hypothesised that early bisphosphonate treatment to reduce osteoclast activity could allow revascularisation and repair with maintenance of joint congruity.

Methods Nine patients with documented osteonecrosis are presented. There were six patients, who presented after unstable SCFE. Of these the index procedure had failed in three, requiring multiple early operations. The other three patients had sustained an inter-trochanteric fracture with a pelvic fracture, a traumatic hip dislocation and a femoral neck fracture respectively. They were treated with intermittent intravenous pamidronate (Aredia, Novartis) commencing within a mean one month of diagnosis (range 5 to 91 days). The dosing protocol has evolved over two years with the current dose being 9 mg/kg/year for 18 months. Mean follow-up is 19.8 months (range 13 to 30 months) with all patients followed for more than one year.

Results Eight of the patients are painfree. Six have been instructed to fully weight bear, while two can partial weight bear and one is non-weight bearing. Seven of nine patients do not show significant resorption of the femoral heads at the most recent follow-up. Of the two patients with significant resorption, one patient began to resorb after his medication was ceased, so it was recommenced. He has subsequently undergone a realignment procedure. The other patient had resorption of a section of the femoral head, which had not re-vascularised by 18 months, and this was elevated and bone grafted. These two hips were considered functional in the short term as they were pain free, but their deformity was expected to bring about early osteoarthritis in adult life.

Conclusions This early experience lays the foundation for prospective clinical trials of bisphosphonate therapy in adolescents with osteonecrosis. It appears that bisphosphonate treatment protocols for adolescents will need to be prolonged. Our current practice is for a duration of around 18 months with normalisation of uptake on bone scan as the end point for therapy.

In relation to the conduct of this study, one or more of the authors is in receipt of a research grant from a non-commercial source.


Orthopaedic Proceedings
Vol. 85-B, Issue SUPP_III | Pages 266 - 266
1 Mar 2003
Williams P Smith N Briody J Cowell C Little D
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Objective: To evaluate the effects of a new potent bisphosphonate on the formation, mineralisation, density, and mechanical properties of bone in distraction osteogenesis.

Methods: Thirty immature New Zealand White rabbits had a 10.5 millimetre lengthening of their tibia performed over 2 weeks using an Orthofix M-100 fixator. Ten control rabbits received saline only; 10 received the new bisphosphonate at the time of surgery, and 10 received a second dose at the end of distraction. Bone mineral content (BMC) and density (BMD) measurements were made at two, four and six weeks. Quantitative CT analysis of regenerate, proximal and distal bone, and corresponding segments in the non-operated limb was performed after culling. Mechanical testing was by 4-point bending.

Results: Bone mineral accrual was significantly faster in both treatment groups (ANOVA p< 0.01). BMD increased in all treated animals (ANOVA p< 0.01). Cross sectional area of regenerate at six weeks was increased by 49% in the single dosed group versus controls and by 59% in the re-dosed group. (ANOVA p< 0.01). BMC of the regenerate was increased by 92% in the single dose group and by 111% in the re-dosed group (ANOVA p< 0.01). Moment of inertia of the regenerate was significantly increased in both treated groups (ANOVA p< 0.05). The difference between single dose and controls was significant (p< 0.05), the difference between re-dosed and single dosed was not (p=0.5).

Conclusion: Bisphosphonate therapy significantly increased new bone formation, bone mineralisation and mechanical properties. Osteoporotic effects were reversed. This effect could have wide ranging implications for many orthopaedic practices


Orthopaedic Proceedings
Vol. 85-B, Issue SUPP_III | Pages 267 - 267
1 Mar 2003
Uglo M Hile M Briody J Bilston L Little D
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Low intensity pulsed ultrasound (SAFHS, Exogen Inc.) was used to treat 15 immature New Zealand white rabbits following a mid diaphyseal tibial osteotomy and 1cm bone lengthening using an Orthofix M-100 device. Fifteen matched controls underwent an identical procedure but the ultrasound transducer was not switched on. At 4 and 6 weeks postoperatively the tibiae were analysed using DXA, QCT and 4 point bend mechanical testing. There were no differences identified between the active and control groups at 4 or 6 weeks with respect to bone mineral content or cross-sectional area of the regenerate, nor the bone proximal and distal to it. No improvement in strength of the regenerate was identified in either group. We cannot, therefore, support the use of the SAFHS to accelerate bone healing in patients undergoing limb lengthening.

Low intensity pulsed ultrasound has been shown to accelerate fracture healing in animals and humans. The mechanisms of action are discussed and we propose that the intensity of the ultrasound may need to be increased mechanically to stimulate a bone that is rigidly fixed using the M-100 fixator.


Orthopaedic Proceedings
Vol. 84-B, Issue SUPP_III | Pages 276 - 276
1 Nov 2002
Little D Williams P Briody J Cowell C
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The bisphosphonate, pamidronate, has been used successfully in our hospital for the management of osteogenesis imperfecta with an excellent safety profile in growing children. We have performed several research studies on distraction osteogenesis in New Zealand white rabbits showing significant increases in new bone formation and the abolition of stress shielding osteopaenia using both pamidronate and zoledronic acid. Recent studies have shown that bisphosphonates positively effect osteoblasts as well as inhibiting osteoclastic bone resorption.

We present a series of early cases where this research has been used in humans. Two cases of pamidronate assisted distraction osteogenesis are presented, one of which also had congenital pseudarthrosis of the tibia, which united after pamidronate administration.

Two cases of post-traumatic avascular necrosis have been successfully treated such that osteolysis and collapse of the necrotic femoral head did not occur. Bisphosphonates may act to slow bone resorption while simultaneously increasing new bone formation, such that the mechanical integrity of the necrotic segment can be maintained during revascularisation.

A randomised controlled trial of bisphosphonates in distraction osteogenesis at our hospital has now received ethical approval. Newer bisphosphonates have proven their clinical value in osteogenesis imperfecta and adult osteoporosis, but other potential roles are emerging for these compounds, which have extremely potent effects on bone.


Orthopaedic Proceedings
Vol. 84-B, Issue SUPP_III | Pages 276 - 276
1 Nov 2002
Little D Hile M Uglow M Briody J Bilston L
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Aim: To examine the effect of the low intensity ultrasound stimulation (SAFHS, Exogen) on new bone formation and stress shielding in a distraction osteogenesis model in New Zealand white rabbits.

Methods: Thirty male rabbits underwent a right tibial osteotomy at eight weeks of age. Distraction of the osteotomy by 0.75mm/day was performed for two weeks. Ultrasound stimulation commenced on the seventh day after wound healing. The ‘active’ group was stimulated for 20 minutes daily. The controls had identical dummy stimulators applied. Half of the animals were culled at four weeks and half at six weeks. Dual-energy x-ray absorptiometry scans evaluated BMC and BMD. Quantitative computerised tomography measured the cross-sectional areas. Four-point bend testing of distracted and non-operated tibiae was performed in a standardised fashion.

Results: No differences were identified between the active and control groups at four or six weeks with respect to BMD, BMC or cross-sectional area of the regenerated bone. Stress shielding osteopaenia was unaffected by ultrasound stimulation. No significant improvement in strength of the regenerate was identified in either group – there was a trend towards improved strength at four weeks.

Discussion: Low intensity pulsed ultrasound accelerates fracture healing in humans when immobilised by plaster of Paris. One published study purporting to show improvement in distraction osteogenesis is fatally flawed. We believe the intensity of the ultrasound may need to be increased to stimulate mechanically a bone rigidly fixed by an external fixator. Other interventions such as the use of growth factors or bisphosphonates provide much greater improvements in experimental animals and are much more convenient to apply.


Orthopaedic Proceedings
Vol. 84-B, Issue SUPP_III | Pages 276 - 276
1 Nov 2002
Little D Williams P Smith N Briody J Cowell C Bilston L
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Aim: To examine the effect of the bisphosphonate zoledronic acid in doses of 0.1mg/kg on new bone formation and stress shielding in a distraction-osteogenesis model in New Zealand white rabbits.

Method: Thirty male rabbits underwent a right tibial osteotomy at eight weeks of age. Distraction of the osteotomy by 0.75mm/day was performed for two weeks followed by four weeks for consolidation. Group I was given saline infusions, Group II zoledronic acid at surgery, and Group III received zoledronic acid at surgery and again at two weeks. DXA scans evaluated BMC and BMD. Quantitative computerised tomography measured the cross-sectional areas. Four-point bend testing of both distracted and non-operated tibiae was performed in a standardised fashion.

Results: Bone mineral accretion between two and four weeks was significantly higher in treated versus saline groups, and was better maintained at six weeks (P< 0.01 ANOVA). Stress shielding osteopaenia that was seen in surrounding bone segments in Group I (controls) was abolished in the treated groups. By six weeks there was a 49% and 59% increase in cross sectional area of new bone in Groups II and III respectively (P< 0.01 ANOVA). Group II tibiae were 29% stronger in four-point bending, while Group III were 89% stronger than Group I (P< 0.01 ANOVA). There was little detectable effect on the non-operated tibiae.

Conclusions: Zoledronic acid administration significantly increased the rate and amount of new bone formation and its mineralisation. The increases in bone formation and retention translated to a significant, dose-dependent increase in strength. Further research into the role of zoledronic acid in orthopaedic surgery is indicated.