Transcutaneous bone-anchoring prosthesis with hip replacement: A novel treatment for amputees

Background Over the last two decades, Transcutaneous Bone-Anchored Prosthesis (TCBAP) has proven to be an effective alternative for prosthetic attachment for above knee amputees, particularly for individuals suffering from socket interface related complications. [1-17] Amputees with a very short femoral residuum (<15 cm) are at a considerable higher risk for these complications as well as high risk of implant failure, if they underwent a typical TCBAP due to the relatively small bony-implant contact leading to a need of a novel technique. Aim A. To describe the surgical procedure combining THR with TCBAP for the first time; and B. To present preliminary data on potential risks and benefits with assessment of clinical and functional outcomes at follow up Method We used a TCBAP connected to the stem of a Total Hip Replacement (THR) prosthesis enabling the femoral residuum and the hip joint to act as weight sharing structures by transferring the load directly to the pelvis. We performed a tri-polar THR connected to a custom made TCBAP at the first stage followed by creating a skin implant interface as a second stage. We retrospectively reviewed three cases of transfemoral amputations presenting with extremely short femoral residuum. Patients were assessed clinically and functionally including standard measures of health-related quality of life, amputee mobility predictor tool, ambulation tests and actual activity level. Progress was monitored for 6-24 months. Results Clinical outcomes including adverse events show no major complications. Functional outcomes improved for all participants as early as 6 months follow up. All cases were wheelchair bound preoperatively (K0 – AMPRO) improved to walking with One stick (K3 – AMPRO) at 3 months follow up. Discussion & Conclusion THR and TCBAP were combined for the first time in this proof-of-concept case series. The preliminary outcomes indicated that this procedure is potentially a safe and effective alternative despite the theoretical increase in risk of ascending infection through the skin-implant interface to the external environment for this patient group. We suggest larger comparative series to further validate these results.

Meta-analysis of genome-wide studies identifies MEF2C SNPs associated with bone mineral density at forearm

Background Forearm fractures affect 1.7 million individuals worldwide each year and most occur earlier in life than hip fractures. While the heritability of forearm bone mineral density (BMD) and fracture is high, their genetic determinants are largely unknown. Aim To identify genetic variants associated with forearm BMD and forearm fractures. Methods BMD at distal radius, measured by dualenergy x-ray absorptiometry, was tested for association with common genetic variants. We conducted a metaanalysis of genome-wide association studies for BMD in 5866 subjects of European descent and then selected the variants for replication in 715 Mexican American samples. Gene-based association was carried out to supplement the single-nucleotide polymorphism (SNP) association test. We then tested the BMD-associated SNPs for association with forearm fracture in 2023 cases and 3740 controls. Results We found that five SNPs in the introns of MEF2C were associated with forearm BMD at a genome-wide significance level (p<5×10-8) in meta-analysis (lead SNP, rs11951031[T] -0.20 SDs per allele, p=9.01×10-9). The gene-based association test suggested an association between MEF2C and forearm BMD ( p=0.003). The association between MEF2C variants and risk of fracture did not achieve statistical significance (SNP rs12521522[A]: OR=1.14 (95% CI 0.92 to 1.35), p=0.14). Meta-analysis also revealed two genome-wide suggestive loci at CTNNA2 and 6q23.2. Conclusions These findings demonstrate that variants at MEF2C were associated with forearm BMD, implicating this gene in the determination of BMD at forearm.

Genetic determinants of bone density and fracture risk: State of the art and future directions

Context: Osteoporosis is a common, highly heritable condition that causes substantial morbidity and mortality, the etiopathogenesis of which is poorly understood. Genetic studies are making increasingly rapid progress in identifying the genes involved. Evidence Acquisition and Synthesis: In this review, we will summarize the current understanding of the genetics of osteoporosis based on publications from PubMed from the year 1987 onward. Conclusions: Most genes involved in osteoporosis identified to date encode components of known pathways involved in bone synthesis or resorption, but as the field progresses, new pathways are being identified. Only a small proportion of the total genetic variation involved in osteoporosis has been identified, and new approaches will be required to identify most of the remaining genes.

Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture

Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10−8). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10−4, Bonferroni corrected), of which six reached P < 5 × 10−8, including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.

The development of a component to improve the loading safety of bone-anchored prostheses

Use of socket prostheses Currently, for individuals with limb loss, the conventional method of attaching a prosthetic limb relies on a socket that fits over the residual limb. However, there are a number of issues concerning the use of a socket (e.g., blisters, irritation, and discomfort) that result in dissatisfaction with socket prostheses, and these lead ultimately a significant decrease in quality of life. Bone-anchored prosthesis Alternatively, the concept of attaching artificial limbs directly to the skeletal system has been developed (bone anchored prostheses), as it alleviates many of the issues surrounding the conventional socket interface.Bone anchored prostheses rely on two critical components: the implant, and the percutaneous abutment or adapter, which forms the connection for the external prosthetic system (Figure 1). To date, an implant that screws into the long bone of the residual limb has been the most common intervention. However, more recently, press-fit implants have been introduced and their use is increasing. Several other devices are currently at various stages of development, particularly in Europe and the United States. Benefits of bone-anchored prostheses Several key studies have demonstrated that bone-anchored prostheses have major clinical benefits when compared to socket prostheses (e.g., quality of life, prosthetic use, body image, hip range of motion, sitting comfort, ease of donning and doffing, osseoperception (proprioception), walking ability) and acceptable safety, in terms of implant stability and infection. Additionally, this method of attachment allows amputees to participate in a wide range of daily activities for a substantially longer duration. Overall, the system has demonstrated a significant enhancement to quality of life. Challenges of direct skeletal attachment However, due to the direct skeletal attachment, serious injury and damage can occur through excessive loading events such as during a fall (e.g., component damage, peri-prosthetic fracture, hip dislocation, and femoral head fracture). These incidents are costly (e.g., replacement of components) and could require further surgical interventions. Currently, these risks are limiting the acceptance of bone-anchored technology and the substantial improvement to quality of life that this treatment offers. An in-depth investigation into these risks highlighted a clear need to re-design and improve the componentry in the system (Figure 2), to improve the overall safety during excessive loading events. Aim and purposes The ultimate aim of this doctoral research is to improve the loading safety of bone-anchored prostheses, to reduce the incidence of injury and damage through the design of load restricting components, enabling individuals fitted with the system to partake in everyday activities, with increased security and self-assurance. The safety component will be designed to release or ‘fail’ external to the limb, in a way that protects the internal bone-implant interface, thus removing the need for restorative surgery and potential damage to the bone. This requires detailed knowledge of the loads typically experienced by the limb and an understanding of potential overload situations that might occur. Hence, a comprehensive review of the loading literature surrounding bone anchored prostheses will be conducted as part of this project, with the potential for additional experimental studies of the loads during normal activities to fill in gaps in the literature. This information will be pivotal in determining the specifications for the properties of the safety component, and the bone-implant system. The project will follow the Stanford Biodesign process for the development of the safety component.

Hip power analysis in individuals with transfemoral amputation: A different strategy different from stabilisation during gait stance

Introduction and Objectives Joint moments and joint powers during gait are widely used to determine the effects of rehabilitation programs as well as prosthetic fitting. Following the definition of power (dot product of joint moment and joint angular velocity) it has been previously proposed to analyse the 3D angle between both vectors, αMw. Basically, joint power is maximised when both vectors are parallel and cancelled when both vectors are orthogonal. In other words, αMw < 60° reveals a propulsion configuration (more than 50% of the moment contribute to positive power) while αMw > 120° reveals a resistance configuration (more than 50% of the moment contribute to negative power). A stabilisation configuration (less than 50% of the moment contribute to power) corresponds to 60° < αMw < 120°. Previous studies demonstrated that hip joints of able-bodied adults (AB) are mainly in a stabilisation configuration (αMw about 90°) during the stance phase of gait. [1, 2] Individuals with transfemoral amputation (TFA) need to maximise joint power at the hip while controlling the prosthetic knee during stance. Therefore, we tested the hypothesis that TFAs should adopt a strategy that is different from a continuous stabilisation. The objective of this study was to compute joint power and αMw for TFA and to compare them with AB. Methods Three trials of walking at self-selected speed were analysed for 8 TFAs (7 males and 1 female, 46±10 years old, 1.78±0.08 m 82±13 kg) and 8 ABs (males, 25±3 years old, 1.75±0.04, m 67±6 kg). The joint moments are computed from a motion analysis system (Qualisys, Goteborg, Sweden) and a multi-axial transducer (JR3, Woodland, USA) mounted above the prosthetic knee for TFAs and from a motion analysis system (Motion Analysis, Santa Rosa, USA) and force plates (Bertec, Columbus, USA) for ABs. The TFAs were fitted with an OPRA (Integrum, AB, Gothengurg, Sweden) osseointegrated implant system and their prosthetic designs include pneumatic, hydraulic and microprocessor knees. Previous studies showed that the inverse dynamics computed from the multi-axial transducer is the proper method considering the absorption at the foot and resistance at the knee. Results The peak of positive power at loading response (H1) was earlier and lower for TFA compared to AB. Although the joint power is lower, the 3D angle between joint moment and joint angular velocity, αMw, reveals an obvious propulsion configuration (mean αMw about 20°) for TFA compared to a stabilisation configuration (mean αMw about 70°) for AB. The peaks of negative power at midstance (H2) and of positive power at preswing / initial swing (H3) occurred later, lower and longer for TFA compared to AB. Again, the joint powers are lower for TFA but, in this case, αMw is almost comparable (with a time lag), demonstrating a stabilisation (almost a resistance for TFA, mean αMw about 120°) and a propulsion configuration, respectively. The swing phase is not analysed in the present study. Conclusion The analysis of hip joint power may indicate that TFAs demonstrated less propulsion and resistance than ABs during the stance phase of gait. This is true from a quantitative point of view. On the contrary, the 3D angle between joint moment and joint angular velocity, αMw, reveals that TFAs have a remarkable propulsion strategy at loading response and almost a resistance strategy at midstance while ABs adopted a stabilisation strategy. The propulsion configuration, with αMw close to 0°, seems to aim at maximising the positive joint power. The configuration close to resistance, with αMw far from 180°, might aim at unlocking the prosthetic knee before swing while minimising the negative power. This analysis of both joint power and 3D angle between the joint moment and the joint angular velocity provides complementary insights into the gait strategies of TFA that can be used to support evidence-based rehabilitation and fitting of prosthetic components.

Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution

Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10−9 to P = 1.8 × 10−40) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10−3 to P = 1.2 × 10−13). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.

Dislocation after total hip replacement: there is no such thing as a safe zone for socket placement with the posterior approach

Introduction Malorientation of the socket contributes to instability after hip arthroplasty but the optimal orientation of the cup in relation to the pelvis has not been unequivocally described. Large radiological studies are few and problems occur with film standardisation, measurement methodology used and alternative definitions of describing acetabular orientation. Methods A cohort of 1,578 patients from a single institution is studied where all patient data was collected prospectively. Risk factors for patients undergoing surgery are analysed. Radiological data was compared between a series of non-dislocating hips and dislocating cases matched 2:1 by operation type, age and diagnosis. Results The overall dislocation rate for all 1,578 cases was 3.23% but the rate varied according to the type of surgery performed. The rate in uncomplicated primary cases was 2.4% which increased to 9.3% for second stage implantation for a two stage procedure for infection. There was no significant difference in the variability of the dislocating and non-dislocating groups for either inclination (p = 0.393) or anteversion (p = 0.661). Conclusions A “safe zone” for socket orientation to avoid dislocation could not be defined. The cause of dislocation is multifactorial, re-establishing the anatomic centre of rotation, balancing soft tissues and avoidance of impingement around the hip are important considerations.

Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture

The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF fractures, and has been previously associated with common genetic variants, as well as rare, population-specific, coding variants. Here we identify novel non-coding genetic variants with large effects on BMD (ntotal = 53,236) and fracture (ntotal = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (n = 2,882 from UK10K (ref. 10); a population-based genome sequencing consortium), whole-exome sequencing (n = 3,549), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (n = 26,534), and de novo replication genotyping (n = 20,271). We identified a low-frequency non-coding variant near a novel locus, EN1, with an effect size fourfold larger than the mean of previously reported common variants for lumbar spine BMD (rs11692564(T), MAF = 1.6%, replication effect size = +0.20 s.d., Pmeta = 2 x 10(-14)), which was also associated with a decreased risk of fracture (odds ratio = 0.85; P = 2 x 10(-11); ncases = 98,742 and ncontrols = 409,511). Using an En1(cre/flox) mouse model, we observed that conditional loss of En1 results in low bone mass, probably as a consequence of high bone turnover. We also identified a novel low-frequency non-coding variant with large effects on BMD near WNT16 (rs148771817(T), MAF = 1.2%, replication effect size = +0.41 s.d., Pmeta = 1 x 10(-11)). In general, there was an excess of association signals arising from deleterious coding and conserved non-coding variants. These findings provide evidence that low-frequency non-coding variants have large effects on BMD and fracture, thereby providing rationale for whole-genome sequencing and improved imputation reference panels to study the genetic architecture of complex traits and disease in the general population.

Status on pre-surgical deformation apparatus for fracture fixation plates

Purpose: This paper reviews the apparatus used for deformation of bone fracture fixation plates during orthopaedic surgeries including surgical irons, pliers and bending press tools. This paper extends the review to various machineries in non-medical industries and adopts their suitability to clinics-related applications and also covers the evolution of orthopaedic bone plates. This review confirms that none of the studied machineries can be implemented for the deformation of bone fracture fixation plates during orthopaedic surgeries. In addition, this paper also presents the novel apparatus that are designed from scratch for this specific purpose. Several conceptual designs have been proposed and evaluated recently. It has been found that Computer Numerical Control (CNC) systems are not the golden solution to this problem and one needs to attempt to design the robotic arm system. A new design of robotic arm that can be used for facilitating orthopaedic surgeries is being completed.

The Exeter Contemporary flanged cemented acetabular component in primary total hip arthroplasty

Aims: We report on the outcome of the Exeter Contemporary flanged cemented all-polyethylene acetabular component with a mean follow-up of 12 years (10 to 13.9). This study reviewed 203 hips in 194 patients. 129 hips in 122 patients are still in situ; 66 hips in 64 patients were in patients who died before ten years, and eight hips (eight patients) were revised. Clinical outcome scores were available for 108 hips (104 patients) and radiographs for 103 hips (100 patients). Patients and Methods: A retrospective review was undertaken of a consecutive series of 203 routine primary cemented total hip arthroplasties (THA) in 194 patients. Results: There were no acetabular component revisions for aseptic loosening. Acetabular revision was undertaken in eight hips. In four hips revision was necessitated by periprosthetic femoral fractures, in two hips by recurrent dislocation, in one hip for infection and in one hip for unexplained ongoing pain. Oxford and Harris hip scores demonstrated significant clinical improvement (all p < 0.001). Radiolucent lines were present in 37 (36%) of the 103 acetabular components available for radiological evaluation. In 27 of these, the line was confined to zone 1. No component had migrated. Conclusion: Kaplan–Meier survivorship, with revision for aseptic loosening as the endpoint, was 100% at 12.5 years and for all causes was 97.8% (95% confidence interval 95.6 to 100) when 40 components remained at risk. The Exeter Contemporary flanged cemented acetabular component demonstrates excellent survivorship at 12.5 years. Take home message: The Exeter Contemporary flanged cemented acetabular component has excellent clinical outcomes and survivorship when used with the Exeter stem in total hip arthroplasty.

Morbid obesity in total hip arthroplasty: Redefining outcomes for operative time, length of stay, and readmission

Background The incidence of obesity amongst patients presenting for elective Total Hip Arthroplasty (THA) has increased in the last decade and the relationship between obesity and the need for joint replacement has been demonstrated. This study evaluates the effects of morbid obesity on outcomes following primary THA by comparing short-term outcomes in THA between a morbidly obese (BMI ≥40) and a normal weight (BMI 18.5 - <25) cohort at our institution between January 2003 and December 2010. Methods Thirty-nine patients included in the morbidly obese group were compared with 186 in the normal weight group. Operative time, length of stay, complications, readmission and length of readmission were compared. Results Operative time was increased in the morbidly obese group at 122 minutes compared with 100 minutes (p=0.002). Post-operatively there was an increased 30-day readmission rate related to surgery of 12.8% associated with BMI ≥40 compared with 2.7% (p= 0.005) as well as a 5.1 fold increase in surgery related readmitted bed days - 0.32 bed days per patient for normal weight compared with 1.64 per patient for the morbidly obese (p=0.026). Conclusion Morbidly obese patients present a technical challenge and likely this and the resultant complications are underestimated. More work needs to be performed in order to enable suitable allocation of resources.