Introduction. Tunnelwidening in failed anterior cruciate ligament reconstruction (ACLR) can result in the staged revision procedures with a need for bone transplantation prior to revision reconstruction. Limited knowledge exist regarding to quality of different transplantation methods. The present study used CT-scanning to evaluate tunnel bone density after allogenic bone chips and bone cylinder transplantation. We hypothesized that bone chips transplantation resulted in higher bone density than bone cylinder transplantation due to possible voids between individual cylinders in the tunnels. Methods. The records of 24 patients operated for 1st stage revision ACLR from April 2003 to march 2010 were included in the study. twelve patients had their tunnels transplanted with bone chips and twelve patients with bone cylinders from allogenic femoral heads. Bone chips were created by fine bone milling and cylinders were extracted by 7–8 mm core drilling. Bone density 3–4 months after transplantation were evaluated by CT scanning reconstruction slides with 5 mm intervals throughout the tunnel length using histomorphometry. Results. There were 15 females and 9 males with an average age of 32 yrs. Using bone chips the bone density in the tibial tunnels was 55% and the femoral tunnels the bone density was 68% Using bone cylinders bone density was 60% in the tibial tunnels and 53% in the femoral tunnels. The femoral bone density in the bone chip group was significantly higher than the bone cylinders (p < 0.05). Conclusion. Transplantation with bone chips results in superior bone quality in the femoral tunnels where as no difference where demonstrated in the tibial tunnels

Background. The treatment of femoral neck fracture with internal fixation (IF) is recommended in younger patients and has compared to arthroplasty the advantage of retaining the femoral head. A big problem with osteosynthesis is though failure. Finding predictors for fixation failure is still an ongoing process and osteoporosis has been suggested as a predictor. Aim. To correlate bone mineral density (BMD) in regard to failure of IF in osteosynthesized femoral neck fractures. Material and method. In a health technology assessment study from 2005–2006 at Odense University Hospital, Department of Orthopaedic Surgery and Traumatology, 175 patients with femoral neck fractures accepted DEXA - scanning of the hip and lumbar spine assessing BMD. Final follow-up were 01.08.2010 and 141 patients with IF comprised the final cohort. The cohort consisted of 105 females and 36 males with a mean (CI) age of 77,2 (75,4–79,0). Failure is defined as revision surgery or new fracture. Results. 69 patients had a t-score (total hip) below −2,5 SD as defined for osteoporosis. At 1 year the overall (dislocated) failure rate was 34,5 % (44,7 %), at 2 years 45,4 % (60,0 %) and at end of follow-up 49,6 % (62,8 %). In the cox regression analysis the following factors for failure were significant: dislocated fracture, osteosynthesis placement and prior fracture. There were no associations for total hip BMD, neck BMD, age, sex, quality of fracture reduction, walking disability, independent living, alcohol or smoking. A cox regression sub analysis of the undisplaced fractures showed significant result only for osteosynthesis placement. Conclusion. There is no association between BMD and failure of internal fixation in osteosynthesized femoral neck fractures

Low-energy fractures of the proximal humerus indicate osteoporosis and it is important to direct treatment to this group of patients who are at high risk of further fracture. Data were prospectively collected from 79 patients (11 men, 68 women) with a mean age of 69 years (55 to 86) with fractures of the proximal humerus in order to determine if current guidelines on the measurement of the bone mineral density at the hip and lumbar spine were adequate to stratify the risk and to guide the treatment of osteoporosis. Bone mineral density measurements were made by dual-energy x-ray absorptiometry at the proximal femur, lumbar spine (L2-4) and contralateral distal radius, and the T-scores were generated for comparison. Data were also collected on the use of steroids, smoking, the use of alcohol, hand dominance and comorbidity. The mean T-score for the distal radius was −2.97 (. sd. 1.56) compared with −1.61 (. sd. 1.62) for the lumbar spine and −1.78 (. sd. 1.33) for the femur. There was a significant difference between the mean lumbar and radial T scores (1.36 (1.03 to 1.68); p < 0.001) and between the mean femoral and radial T-scores (1.18 (0.92 to 1.44); p < 0.001). The inclusion of all three sites in the determination of the T-score increased the sensitivity to 66% compared with that of 46% when only the proximal femur and lumbar spine were used. This difference between measurements in the upper limb compared with the axial skeleton and lower limb suggests that basing risk assessment and treatment on only the bone mineral density taken at the hip or lumbar spine may misrepresent the extent of osteoporosis in the upper limb and the subsequent risk of fracture at this site. The assessment of osteoporosis must include measurement of the bone mineral density at the distal radius to avoid underestimation of osteoporosis in the upper limb

Fractures of the distal forearm are widely regarded as the result of “fragility”. We have examined the extent to which patients with Colles’ fractures have osteopenia. We measured the bone mineral density (BMD) in the contralateral radius of 235 women presenting with Colles’ fractures over a period of two years. While women of all ages had low values for ultra-distal BMD, the values, in age-matched terms, were particularly low among premenopausal women aged less than 45 years. This result was not due to the presence of women with an early menopause. This large survey confirms and extends the findings from earlier small studies. We consider that it is particularly important to investigate young patients with fractures of the distal forearm to identify those with osteoporosis, to seek an underlying cause and to consider treatment

A total of 63 women who had an operation for a fracture of the hip was randomly allocated to one year of treatment either with anabolic steroids, vitamin D and calcium (anabolic group) or with calcium only (control group). The thigh muscle volume was measured by quantitative CT. The bone mineral density of the hip, femur and tibia was assessed by quantitative CT and dual-energy x-ray absorptiometry and of the heel by quantitative ultrasound. Quantitative CT showed that the anabolic group did not lose muscle volume during the first 12 months whereas the control group did (p< 0.01). There was less bone loss in the proximal tibia in the anabolic group than in the control group. The speed of gait and the Harris hip score were significantly better in the anabolic group after six and 12 months. Anabolic steroids, even in this moderate dose, given in combination with vitamin D and calcium had a beneficial effect on muscle volume, bone mineral density and clinical function in this group of elderly women

Objective. To compare regional body composition, bone mineral density (BMD), and clinical outcome in patients with two different shoulder arthroplasty designs. Materials and Methods. This cross-sectional study included 54 patients with a total of 63 shoulder arthroplasties. There were 18 men and 45 women with a mean age of 68.9 years SD ± 10.5. Mean follow-up time was 39.2 months SD ± 14.4. The patients were divided into three groups according to their history: 22 patients were diagnosed with a proximal humeral fracture and treated with a stemmed hemi arthroplasty, 11 patients were diagnosed with osteoarthritis and treated with a stemmed hemi arthroplasty, and 30 patients were diagnosed with osteoarthritis and treated with a resurfacing arthroplasty. All patients underwent a one-day protocol: Regional Dual X-ray Absorptiometri (DXA) was used to measure BMD of the distal third of humerus and regional body composition of the upper arm. The clinical outcome was measured using Western Ontario Osteoarthritis of the Shoulder index (WOOS) and Constant-Murley score. Results. All three groups were comparable regarding demographic data. Mean BMD of the distal third of humerus was 1.029 g/cm2 SD ± 0.204, mean tissue mass of the upper arm was 2.6 kg SD ± 0.7 and mean muscle mass was 1.4 kg SD ± 0.6. BMD of the distal third of humerus, tissue mass and muscle mass were significantly higher in the group diagnosed with osteoarthritis and treated with a resurfacing arthroplasty compared to the group diagnosed with a proximal humeral fracture and treated with a stemmed hemi arthroplasty, P = 0.03, P = 0.01 and P = 0.02 respectively. Median Constant score was 45.0, range 6–89, median WOOS 633, range 28–1824, and median strength 7.0 units, range 0–25. There were no significant differences between the three groups. Nevertheless, there was a trend towards a higher Constant-Murley score and muscle strength in the group of patients diagnosed with osteoarthritis and treated with a resurfacing arthroplasty compared to the group of patients diagnosed with a proximal humeral fracture and treated with a stemmed hemi arthroplasty. Conclusion. After shoulder arthroplasty BMD of the distal third of humerus and body composition are apparently more dependent on diagnosis rather than arthroplasty design. However, a larger number of patients diagnosed with osteoarthritis and treated with a stemmed hemi arthroplasty are needed to support this

Introduction. Several short femoral stems have been introduced in primary total hip arthroplasty, supposedly in order to save proximal bone stock. We intended to analyse primary stability, changes in periprosthetic bone mineral density (BMD), and clinical outcome after insertion of the uncemented collum femoris preserving (CFP)-femoral device. Methods. A prospective cohort study on 30 patients scheduled for receiving the CFP-stem combined with an uncemented cup was carried out. Stem migration was analysed by radiostereometry (RSA). Preoperative total hip BMD and postoperative periprosthetic BMD in Gruen zones 1–7 was investigated by DXA, and the Harris hips score (HHS) was determined. The patients were followed up to 12 months. Results. 2 patients were intraoperatively excluded because their proximal femur was found to be unsuitable for insertion of the studied implant, 1 patient was later revised due to a deep infection. This left 27 patients for final analysis. RSA showed that only very little migration of the implant occurred, with the largest amplitude found in rotation around the y-axis (1.8°, SD 0.6, after 12 mths), representing minimal stem retroversion. DXA after 12 mths demonstrated substantial BMD loss in Gruen zones 7 (−30.8%), 6 (−19.1%) and 2 (−13.3%, p-values for all described changes <0.001 when comparing with baseline BMD determined immediately postoperatively). There was a moderate correlation of low preoperative total hip BMD with a higher amount of bone loss in Gruen zones 2 (Pearson correlation coefficient r = 0.6, p = 0.001), 6 (r = 0.5, p = 0.005) and 7 (r = 0.6, p = 0.003). In contrast, we found no correlation of periprosthetic bone loss in any of the Gruen zones 1–7 with logarithmically transformed maximal total point translation (MTPT) of the stem (p > 0.05 for all regions), neither after 3 nor after 12 mths. The mean HHS increased from 49 (SD 15) preoperatively to 99 (SD 2) after 12 mths. Interpretation. Based on these short-term data, we conclude that i) the studied implant seems to be stable within the first year, ii) substantial loss in periprosthetic BMD - with a predominance in the calcar region - occurs, iii) low preoperative total hip BMD predisposes towards greater loss of periprosthetic BMD after 12 months, iv) postoperative loss in periprosthetic BMD does not correlate with increased stem migration. Clinical results are excellent so far. Continuing follow-up will reveal whether this novel stem remains stable in the medium and long term, and whether the loss in BMD in the regions mentioned above can be recovered with time or whether it continues

Background

Though less common than in females, osteoporosis and osteoporosis-related fractures are not uncommon in males. Our primary objectives were (1) to compare the rates of osteoporosis and osteopenia in adult Brazilian males versus females, 55 years old and over and presenting for bone mineral densitometry (BMD); and (2) to compare males and females as to past osteoporosis screening and management.

Aims. Osseointegrated prosthetic limbs allow better mobility than socket-mounted prosthetics for lower limb amputees. Fractures, however, can occur in the residual limb, but they have rarely been reported. Approximately 2% to 3% of amputees with socket-mounted prostheses may fracture within five years. This is the first study which directly addresses the risks and management of periprosthetic osseointegration fractures in amputees. Methods. A retrospective review identified 518 osseointegration procedures which were undertaken in 458 patients between 2010 and 2018 for whom complete medical records were available. Potential risk factors including time since amputation, age at osseointegration, bone density, weight, uni/bilateral implantation and sex were evaluated with multiple logistic regression. The mechanism of injury, technique and implant that was used for fixation of the fracture, pre-osseointegration and post fracture mobility (assessed using the K-level) and the time that the prosthesis was worn for in hours/day were also assessed. Results. There were 22 periprosthetic fractures; they occurred exclusively in the femur: two in the femoral neck, 14 intertrochanteric and six subtrochanteric, representing 4.2% of 518 osseointegration operations and 6.3% of 347 femoral implants. The vast majority (19/22, 86.4%) occurred within 2 cm of the proximal tip of the implant and after a fall. No fractures occurred spontaneously. Fixation most commonly involved dynamic hip screws (10) and reconstruction plates (9). No osseointegration implants required removal, the K-level was not reduced after fixation of the fracture in any patient, and all retained a K-level of ≥ 2. All fractures united, 21 out of 22 patients (95.5%) wear their osseointegration-mounted prosthetic limb longer daily than when using a socket, with 18 out of 22 (81.8%) reporting using it for ≥ 16 hours daily. Regression analysis identified a 3.89-fold increased risk of fracture for females (p = 0.007) and a 1.02-fold increased risk of fracture per kg above a mean of 80.4 kg (p = 0.046). No increased risk was identified for bilateral implants (p = 0.083), time from amputation to osseointegration (p = 0.974), age at osseointegration (p = 0.331), or bone density (g/cm2, p = 0.560; T-score, p = 0.247; Z-score, p = 0.312). Conclusion. The risks and sequelae of periprosthetic fracture after press-fit osseointegration for amputation should not deter patients or clinicians from considering this procedure. Females and heavier patients are likely to have an increased risk of fracture. Age, years since amputation, and bone density do not appear influential. Cite this article: Bone Joint J 2020;102-B(2):162–169

Aims. Ankle fractures are common injuries and the third most common fragility fracture. In all, 40% of ankle fractures in the frail are open and represent a complex clinical scenario, with morbidity and mortality rates similar to hip fracture patients. They have a higher risk of complications, such as wound infections, malunion, hospital-acquired infections, pressure sores, veno-thromboembolic events, and significant sarcopaenia from prolonged bed rest. Methods. A modified Delphi method was used and a group of experts with a vested interest in best practice were invited from the British Foot and Ankle Society (BOFAS), British Orthopaedic Association (BOA), Orthopaedic Trauma Society (OTS), British Association of Plastic & Reconstructive Surgeons (BAPRAS), British Geriatric Society (BGS), and the British Limb Reconstruction Society (BLRS). Results. In the first stage, there were 36 respondents to the survey, with over 70% stating their unit treats more than 20 such cases per year. There was a 50:50 split regarding if the timing of surgery should be within 36 hours, as per the hip fracture guidelines, or 72 hours, as per the open fracture guidelines. Overall, 75% would attempt primary wound closure and 25% would utilize a local flap. There was no orthopaedic agreement on fixation, and 75% would permit weightbearing immediately. In the second stage, performed at the BLRS meeting, experts discussed the survey results and agreed upon a consensus for the management of open elderly ankle fractures. Conclusion. A mutually agreed consensus from the expert panel was reached to enable the best practice for the management of patients with frailty with an open ankle fracture: 1) all units managing lower limb fragility fractures should do so through a cohorted multidisciplinary pathway. This pathway should follow the standards laid down in the "care of the older or frail orthopaedic trauma patient" British Orthopaedic Association Standards for Trauma and Orthopaedics (BOAST) guideline. These patients have low bone density, and we should recommend full falls and bone health assessment; 2) all open lower limb fragility fractures should be treated in a single stage within 24 hours of injury if possible; 3) all patients with fragility fractures of the lower limb should be considered for mobilisation on the day following surgery; 4) all patients with lower limb open fragility fractures should be considered for tissue sparing, with judicious debridement as a default; 5) all patients with open lower limb fragility fractures should be managed by a consultant plastic surgeon with primary closure wherever possible; and 6) the method of fixation must allow for immediate unrestricted weightbearing. Cite this article: Bone Jt Open 2024;5(3):236–242

Objectives. Because of the contradictory body of evidence related to the potential benefits of helical blades in trochanteric fracture fixation, we studied the effect of bone compaction resulting from the insertion of a proximal femoral nail anti-rotation (PFNA). . Methods. We developed a subject-specific computational model of a trochanteric fracture (31-A2 in the AO classification) with lack of medial support and varied the bone density to account for variability in bone properties among hip fracture patients. Results. We show that for a bone density corresponding to 100% of the bone density of the cadaveric femur, there does not seem to be any advantage in using a PFNA with respect to the risk of blade cut-out. On the other hand, in a more osteoporotic femoral head characterised by a density corresponding to 75% of the initial bone density, local bone compaction around the helical blade provides additional bone purchase, thereby decreasing the risk of cut-out, as quantified by the volume of bone susceptible to yielding. Conclusions. Our findings indicate benefits of using a PFNA over an intramedullary nail with a conventional lag screw and suggest that any clinical trial reporting surgical outcomes regarding the use of helical blades should include a measure of the femoral head bone density as a covariable

Aims. Osteopetrosis (OP) is a rare hereditary disease that causes reduced bone resorption and increased bone density as a result of osteoclastic function defect. Our aim is to review the difficulties, mid-term follow-up results, and literature encountered during the treatment of OP. Methods. This is a retrospective and observational study containing data from nine patients with a mean age of 14.1 years (9 to 25; three female, six male) with OP who were treated in our hospital between April 2008 and October 2018 with 20 surgical procedures due to 17 different fractures. Patient data included age, sex, operating time, length of stay, genetic type of the disease, previous surgery, fractures, complications, and comorbidity. Results. The mean follow-up period was 92.5 months (25 to 140). Bony union was observed in all of our patients. Osteomyelitis developed in two patients with femoral shaft fractures, and two patients had peri-implant stress fractures. Conclusion. Treatment of fractures in OP patients is difficult, healing is protracted, and the risk of postoperative infection is high. In children and young adults with OP who have open medullary canal and the epiphyses are not closed, fractures can be treated with surgical techniques such as intramedullary titanium elastic nail (TENS) technique or fixation with Kirschner (K)-wire. Cite this article: Bone Joint J 2020;102-B(8):1082–1087

The results of meta-analysis show a revision rate of 33% for internal fixation of displaced fractures of the femoral neck, mostly because of nonunion. Osteopenia and osteoporosis are highly prevalent in elderly patients. Bone density has been shown to correlate with the intrinsic stability of the fixation of the fracture in cadaver and retrospective studies. We aimed to confirm or refute this finding in a clinical setting. We performed a prospective, multicentre study of 111 active patients over 60 years of age with a displaced fracture of the femoral neck which was eligible for internal fixation. The bone density of the femoral neck was measured pre-operatively by dual-energy x-ray absorptiometry (DEXA). The patients were divided into two groups namely, those with osteopenia (66%, mean T-score −1.6) and those with osteoporosis (34%, mean T-score −3.0). Age (p = 0.47), gender (p = 0.67), delay to surgery (p = 0.07), the angle of the fracture (p = 0.33) and the type of implant (p = 0.48) were similar in both groups. Revision to arthroplasty was performed in 41% of osteopenic and 42% of osteoporotic patients (p = 0.87). Morbidity (p = 0.60) and mortality were similar in both groups (p = 0.65). Our findings show that the clinical outcome of internal fixation for displaced fractures of the femoral neck does not depend on bone density and that pre-operative DEXA is not useful

It is becoming increasingly common for a patient to have ipsilateral hip and knee replacements. The inter-prosthetic (IP) distance, the distance between the tips of hip and knee prostheses, has been thought to be associated with an increased risk of IP fracture. Small gap distances are generally assumed to act as stress risers, although there is no real biomechanical evidence to support this. The purpose of this study was to evaluate the influence of IP distance, cortical thickness and bone mineral density on the likelihood of an IP femoral fracture. A total of 18 human femur specimens were randomised into three groups by bone density and cortical thickness. For each group, a defined IP distance of 35 mm, 80 mm or 160 mm was created by choosing the appropriate lengths of component. The maximum fracture strength was determined using a four-point bending test. The fracture force of all three groups was similar (p = 0.498). There was a highly significant correlation between the cortical area and the fracture strength (r = 0.804, p <  0.001), whereas bone density showed no influence. This study suggests that the IP distance has little influence on fracture strength in IP femoral fractures: the thickness of the cortex seems to be the decisive factor. Cite this article: Bone Joint J 2014;96-B:1378–84

Aims

To determine if patient ethnicity among patients with a hip fracture influences the type of fracture, surgical care, and outcome.

Aims

Despite limited clinical scientific backing, an additional trochanteric stabilizing plate (TSP) has been advocated when treating unstable trochanteric fractures with a sliding hip screw (SHS). We aimed to explore whether the TSP would result in less post operative fracture motion, compared to SHS alone.

Introduction. Osteoporosis is a metabolic disease of the bone responsible for a loss of bone resistance and an increase in fracture risk. World Health Organization (WHO) estimations are about 6.3 millions of femoral neck fractures in the world by 2050. These estimations make osteoporosis a real problem in term of public health. Knowledge in biological tissues mechanical behaviour and its evolution with age are important for the design of diagnosis and therapeutic tools. From the mechanical aspect, bone resistance is dependent on bone density, bone architecture and bone tissue quality. If the importance of bone density and bone architecture has been well explored, the bone tissue quality still remains unstudied because of the lack of biomechanical tools suitable for testing bone at this microscopic dimension. Therefore the goal of this study is to estimate the osteoporotic cancellous bone tissue mechanical behaviour at its microscopic scale, using an approach coupling mechanical assays and digital reconstruction. Materials and methods. The experimental study is based on cancellous bone tissue extracted from human femoral head. Forty 8mm diameters bone cylinders have been removed from femoral head explanted after a femoral neck fracture treated by arthroplasty. These cylinders have been submitted to a digitally controlled compressive trial. Before and after the trials, microscanner analyses with an 8 μm spatial resolution have been realized in order to determine the micro structural parameters. The cylinders have been rebuilt with the digital model-building in order to estimate the mechanical behaviour and the bone quality. Results. The results will be presented from a macroscopic and microscopic point of view and will show the relationship between gender and age of the patients. At the macroscopic scale, we will look at that apparent young modulus heterogeneity and the cracking strength. At the microscopic scale, we will confirm that the cancellous bone tissue mechanical behaviour is close to the Haversian bone tissue mechanical behaviour. Finally, the parametric study will permit us to point out the main microstructural components influencing cancellous bone tissue quality. Conclusion. This study allows a precise estimation of the osteoporotic cancellous bone tissue mechanical behaviour. It seems to be a great step in the understanding of this disease and it could probably lead to great improvements in the diagnosis, prognostic, medical and surgical approaches of osteoporosis

Background. Skeletal stem cells (SSCs) have been used for the treatment of osteonecrosis of the femoral head to prevent subsequent collapse. In isolation SSCs do not provide structural support but an innovative case series in Southampton, UK, has used SSCs in combination with impaction bone grafting (IBG) to improve both the biological and mechanical environment and to regenerate new bone at the necrotic site. Aims. Analysis of retrieved tissue-engineered bone as part of ongoing follow-up of this translational case series. Methods. With Proof-of-Concept established in vitro and in vivo, the use of a living bone composite of SSCs and allograft has been translated to four patients (five hips) for treatment of osteonecrosis of their femoral heads. Parallel in vitro culture of the implanted cell-graft construct was performed. Patient follow-up was by serial clinical and radiological examination. In one patient collapse occurred in both hips due to more advanced disease than was originally appreciated. This necessitated bilateral hip arthroplasty, but allowed retrieval of the femoral heads. These were analyzed for Type 1 Collagen production, bone morphology, bone density and mechanical strength by micro computed tomography (CT), histology (A/S stain, Collagen Type 1 immunostain, biorefringence) and mechanical testing. Representative sections of cortical, trabecular and tissue engineered bone were excised from the femoral heads using a diamond-tipped saw-blade and tested to failure by axial compression. Results. Parallel in vitro analysis demonstrated sustained cell growth and viability on the allograft. Three patients currently remain asymptomatic at up to three year follow-up. Histological analysis of the two retrieved femoral heads demonstrated, critically, Type 1 collagen production in the regenerated tissue as well as mature trabecular architecture, indicative of de novo tissue engineered bone. The trabecular morphology of regenerated bone was evident on CT, and this had a bone density of 1400 Grey scale units, (compared to 1200 for natural trabecular bone and 1800 for cortical bone). On axial compressive testing the regenerated bone on the left showed a 24.8% increase in compressive strength compared to ipsilateral normal trabecular bone, and a 22.9% increase on the left. Conclusions. Retrieval analysis data has demonstrated the translational potential of a living bone composite, while ongoing clinical follow-up shows this to be an effective new treatment for osteonecrosis of the femoral head. Regeneration of the necrotic bone may prevent subsequent collapse, thereby delaying, or possibly avoiding, the need for hip arthroplasty in early stage osteonecrosis. Evaluation of this tissue engineering construct has confirmed the potential for clinical treatment of bone defects using SSC based strategies

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

Introduction. Osteoporosis (OP), osteoarthrosis (OA), and rheumatoid arthritis (RA) are the most common age-related degenerative bone diseases, and major public health problems in terms of enormous amount of economic cost. RA is considered as a major cause of secondary osteoporosis. At late stage, OP often leads to skeletal fractures, and OA and RA result in severe joint disability. Over the last a few decades, much significant research on the properties has been carried out on these diseases, however, a detailed comparison of the microarchitecture of cancellous bones of these diseases is not available. In this study, we investigated three-dimensional (3-D) microarchitectural properties of OP, OA and RA cancellous bone. We hypothesized that there were significant differences in microarchitecture among OP, OA and RA bone tissues that might lead to different bone quality. Materials and Method. Twenty OP, fifty OA, and twelve RA femur heads were harvested from patients undergone total hip replacement surgery. Cubic cancellous bone samples (8∗8∗8 mm3) were prepared and scanned with a high resolution microtomographic system (vivaCT 40, Scanco Medical AG., Brüttisellen, Switzerland). Then micro-CT images were segmented using individual thresholds to obtain accurate 3-D data sets. Detailed microarchitectural properties were evaluated based on novel unbiased, model-free 3-D methods. For statistical analysis, one-way ANOVA was used, and a p<0.05 was considered significant. Results. Significant differences in the microarchitecture of cancellous bone were observed among the OP, OA and RA groups. Compared with the other groups, OP cancellous bone had lowest density, thinner, typical rod-like structure and less connectivity (all p<0.01). Interestingly, there were no significant differences in the microarchitectural properties measured between the OA and RA cancellous bones. Both OA and RA cancellous bones had significant higher bone volume fraction and were thicker, typical plate-like structure compared with the OP group (all p<0.01), even though there was clearly bone erosion observed in RA cancellous bone. Discussion. Quantification of the alterations in bone properties and quality will help to gain more insights into the pathogenesis of degenerative bone diseases and to target and develop novel approaches for the intervention and treatment, and for the design, fixation and durability of total joint prosthesis. Our study demonstrated that there were significant differences in the microarchitecture of the OP, OA and RA femur head cancellous bone. The OA and RA cancellous bone had similar bone density and microarchitecture despite apparent bone erosion in the RA cancellous bone. These results from femur head did not support the traditional notion that RA and OP had similar low bone density. Thus, whether femur head bone tissues from these diseases have similar bone collagen, mineral and mechanical properties, more importantly bone quality, should be clarified in the future