Osteoporosis is a major healthcare burden, responsible for significant morbidity and mortality. Manipulating bone homeostasis would be invaluable in treating osteoporosis and optimising implant osseointegration. Strontium increases bone density through increased osteoblastogenesis, increased bone mineralisation, and reduced osteoclast activity. However, oral treatment may have significant side effects, precluding widespread use. We have recently shown that controlled disorder nanopatterned surfaces can control osteoblast differentiation and bone formation. We aimed to combine the osteogenic synergy of nanopatterning with local strontium delivery to avoid systemic side effects. Using a sol-gel technique we developed strontium doped and/or nanopatterned titanium surfaces, with flat titanium controls including osteogenic and strontium doped media controls. These were characterised using atomic force microscopy and ICP-mass spectroscopy. Cellular response assessed using human osteoblast/osteoclast co-cultures including scanning electron microscopy, quantitative immunofluorescence, histochemical staining, ELISA and PCR techniques. We further performed RNAseq gene pathway combined with metabolomic pathway analysis to build gene/metabolite networks. The surfaces eluted 800ng/cm2 strontium over 35 days with good surface fidelity. Osteoblast differentiation and bone formation increased significantly compared to controls and equivalently to oral treatment, suggesting improved osseointegration. Osteoclast pre-cursor survival and differentiation reduced via increased production of osteoprotegrin. We further delineated the complex cellular signalling and metabolic pathways involved including unique targets involved in osteoporosis. We have developed unique nanopatterned strontium eluting surfaces that significantly increase bone formation and reduce osteoclastogenesis. This synergistic combination of topography and chemistry has great potential merit in fusion surgery and arthroplasty, as well as providing potential targets to treat osteoporosis.
The surgical treatment options for patients who have sustained an intra-capsular hip fracture can vary depending on a number of patient and fracture related factors. Currently most national guidelines support the use of cemented prostheses for patient undergoing hemi-arthroplasty surgery. Uncemented prostheses are commonly used for a variety of indications including those patients who have significant medical co-morbidities. To determine whether cemented hemi-arthroplasty is associated with a higher post operative mortality when compared to uncemented procedures. Data was extracted from the Scottish SMR01 database from 01/04/1997 from all patients who were admitted to hospital after sustaining a hip fracture. We investigated mortality at day 1, 2, 4, 7, 30, 120 and 1 year from surgery vs. that on day 0. In order to control for the effects of confounding variables between patients cohorts, 12 case-mix variable were used to construct a multivariable logistic regression analysis model to determine the independent effect of prosthesis fixation method. There were 64,979 patients were included in the study. Mortality for osteosynthesis of extra-capsular fractures was consistently lower when compared to that for surgical procedures for intra-capsular fractures. At day 0, uncemented hemi-arthroplasty operations had a lower associated mortality (p<0.001) when compared to cemented implant designs. Unadjusted figures showed an increased mortality equal to 1 extra death per 424 procedures. By day 1 this had become 1 extra death per 338 procedures. By day 7 cumulative mortality was less for cemented than for uncemented procedures though this did not reach significance until day 120. When compared to uncemented fixation techniques, cemented hemiarthroplasty is associated with a higher mortality in the immediate postoperative period. However, by day 120 and beyond the trend is reversed.
The surgical management of musculoskeletal tumours is a challenging problem, particularly in pelvic and diaphyseal tumour resection where accurate determination of bony transection points is extremely important to optimise oncologic, functional and reconstructive options. The use of computer assisted navigation in these cases could improve surgical precision and achieve pre-planned oncological margins with improved accuracy. We resected musculoskeletal tumours in ten patients using commercially available computer navigation software (Orthomap 3D, Stryker UK Ltd). Of the five pelvic tumours, two underwent biological reconstruction with extra corporeal irradiation, two endoprosthetic replacement (EPR) and one did not require bony reconstruction. Three tibial diaphyseal tumours had biological reconstruction. One patient with proximal femoral sarcoma underwent extra-articular resection and EPR. One soft tissue sarcoma of the adductor compartment involving the femur was resected with EPR. Histological examination of the resected specimens revealed tumour free margins in all cases. Post-operative radiographs and CT show resection and reconstruction as planned in all cases. Several learning points were identified related to juvenile bony anatomy and intra-operative registration. The use of computer navigation in musculoskeletal oncology allows integration of local anatomy and tumour extent to identify resection margins accurately. Furthermore, it can aid in reconstruction following tumour resection. Our experience thus far has been encouraging. Further clinical trials are required to evaluate its long-term impact on functional & oncological outcomes.
Recent studies have shown that random disorder nanotopography increases osteoblast differentiation and bone formation. This has great potential merit in producing surfaces where osteointegration is required such as spinal fusion surgery and arthroplasty. However, the long-term failure of orthopaedic implants is often related to osteoclast mediated osteolysis and loosening. It is vitally important that we understand the effect of nanotopography on osteoclast formation and bone remodeling. We developed an unique osteoblast/osteoclast co-culture system derived from human mesenchymal and haematopoetic stem cells. This was co-cultured on both nanopatterned and unpatterned polycarbonate substrates. We assessed the co-culture using electron microscopy (SEM), protein expression using immunofluorescence and histochemical staining and gene expression using polymerase chain reaction (PCR). Co-culture of both osteoclasts and osteoblasts was confirmed with mature bone nodules and resorption pits identified on both surfaces. Significantly increased osteoblast differentiation and bone formation was noted on disordered nanotopography. Antagonistic genes controlling osteoclast activity were both upregulated with no significant difference in osteoclast marker gene expression. Our results confirm successful co-culture of osteoblasts and osteoclasts using an unique method closely resembling the
The surgical treatment options for patients who have sustained an intra-capsular hip fracture can vary depending on a number of patient and fracture related factors. Currently most national guidelines support the use of cemented prostheses for patient undergoing hemiarthroplasty surgery. Uncemented prostheses are commonly used for a variety of indications including those patients who have significant medical co-morbidities. To determine whether cemented hemiarthroplasty is associated with a higher post operative mortality when compared to uncemented procedures. Data were extracted from the Scottish SMR01 database from 01/04/1997 from all patients who were admitted to hospital after sustaining a hip fracture. We investigated mortality at day 1,2,4,7,30, 120 and 1 year from surgery vs. that on day 0. In order to control for the effects of confounding variables between patients cohorts, 12 case-mix variable were used to construct a multivariable logistic regression analysis model to determine the independent effect of prosthesis design. There were 52283 patients included in the study. Mortality for osteosynthesis of extra-capsular fractures was consistently lower when compared to that for surgical procedures for intra-capsular fractures. At day 0, uncemented hemiarthroplasty had a lower associated mortality (p<0.001) when compared to cemented implant designs. However, this increased mortality was equal to 1 extra death per 2000 procedures. From day 1 onward mortality for cemented procedures was equal to or lower than that of uncemented. By day 4, cumulative mortality was less for cemented than for uncemented procedures. Complication and re-operation rate was significantly higher in the uncemented cohort. The use of uncemented hemiarthroplasty for the treatment of intra-capsular hip fractures cannot be justified in terms of early/late post-operative mortality.
Total hip arthroplasty is well established as a successful treatment modality for end stage arthritis, with a variety of components currently available. However, utilising traditional stemmed implants in patients with distorted proximal femoral geometry can be technically challenging with increased risk of complications. We present seven patients with distorted proximal femoral anatomy or failed hip arthroplasty in whom a technically challenging primary or revision operation was simplified by use of a Proxima stem. This is a short, stemless, metaphyseal loading implant with a pronounced lateral flare. At twelve months follow up there have been no complications with average improvement in Oxford and Harris scores of forty and forty-nine respectively. Radiological analysis shows all stems to be stable and well fixed. Designed primarily as a bone conserving implant for primary hip arthroplasty we propose that the Proxima prosthesis also be considered in cases where a conventional stemmed implant may not be suitable due to challenging proximal femoral anatomy. The use of the stemless Proxima implant provided a simple solution in seven difficult and potentially lengthy complex primary and revision hip arthroplasties with gratifying clinical and radiological outcomes.
