» Osseointegrated prostheses provide a rehabilitation option for amputees offering greater mobility, better satisfaction, and higher use than traditional socket prostheses. » There are several different osseointegrated implant designs, surgical techniques, and rehabilitation protocols with their own strengths and limitations. » The 2 most prominent risks, infection and periprosthetic fracture, do not seem unacceptably frequent or insurmountable. Proximal amputations or situations leading to reduced mobility are exceptionally infrequent. » Osseointegrated implants can be attached to advanced sensory and motor prostheses.

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.

Transcutaneous osseointegration for amputees (TOFA) refers to an intramedullary metal endoprosthesis which passes transcutaneously to connect with a limb exoprosthesis. The first recognizably modern experiments and attempts occurred in the 1940s. Multiple researchers using a plethora of materials and techniques over the following 50 years identified principles and obstacles which informed the first long-term successful surgery in 1990. Unfortunately, the current mainstream TOFA literature presents almost exclusively subsequent developments, generally omitting prior research, leading to some historical mistakes being repeated. Given the increasing interest and surgical volume of TOFA, this literature review was performed to delineate TOFA’s basic science and surgical origins and to integrate these early efforts within the contemporary understanding. Studying this research could protect and benefit future patients, surgeons, and implant developers as TOFA is entering a phase of increased attention and innovation. The aim of this article is to provide a focused reference of foundational research, much of which is difficult to identify and retrieve, for clinicians and researchers.

Toll-like receptor (TLR) ligands have been explored as vaccine adjuvants for tumor and virus immunotherapy, but few TLR ligands affecting schistosoma vaccines have been characterized. Previously, we developed a partially protective DNA vaccine encoding the 26-kDa glutathione S-transferase of Schistosoma japonicum (pVAX1-Sj26GST). In this study, we evaluated a TLR7/8 ligand (R848) and a TLR9 ligand (CpG oligodeoxynucleotides, or CpG) as adjuvants for pVAX1-Sj26GST and assessed their effects on the immune system and protection against S. japonicum. We show that combining CpG and R848 with pVAX1-Sj26GST immunization significantly increases splenocyte proliferation and IgG and IgG2a levels, decreases CD4⁺CD25⁺Foxp3⁺ regulatory T cells (Treg) frequency in vivo, and enhances protection against S. japonicum. CpG and R848 inhibited Treg-mediated immunosuppression, upregulated the production of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-4, IL-10, IL-2, and IL-6, and decreased Foxp3 expression in vitro, which may contribute to prevent Treg suppression and conversion during vaccination and allow expansion of antigen-specific T cells against pathogens. Our data shows that selective TLR ligands can increase the protective efficacy of DNA vaccines against schistosomiasis, potentially through combined antagonism of Treg-mediated immunosuppression and conversion. There is evidence that TLR activation can block Treg cell responses and thereby break tolerance to self-antigens. It is expected that the use of TLR ligands as vaccine adjuvants will induce potent anti-pathogen immune responses and simultaneously overcome immune inhibition mediated by Tregs. However, the impact of TLR ligands on schistosomiasis vaccines is unclear. Here, we demonstrate that the use of a TLR7/8 ligand (R848) and a TLR9 ligand (CpG) as adjuvants in combination with the S. japonicum vaccine pVAX1-Sj26GST improves disease protection. The combination of CpG and R848 administered after vaccination causes an immune response marked by an upregulation of splenocyte proliferation and IgG and IgG2a levels that also coincides with a decreased proportion of CD4⁺CD25⁺ Tregs in mice. We also show that combined adjuvant use of CpG and R848 may impair Treg development and function by promoting the secretion of proinflammatory cytokines and reducing Foxp3 expression. Our findings suggest that in combination with the vaccine, TLR ligands may protect the effector response from Treg-mediated suppression, thereby eliciting the appropriate immune response to improve vaccine efficacy. Immunization combined with the TLR ligands CpG and R848 thus represents a promising new approach for the design of schistosoma vaccines.

Transcutaneous osseointegration post amputation (TOPA),¹ a procedure that creates a direct linkage between residual bone and an external prosthetic limb, continues to gain momentum as a viable rehabilitation alternative to traditional compression and suction prostheses. Osseointegration provides improved mobility and quality of life compared with traditional prostheses for most patients with lower extremity amputation.^2,3 As with any major elective orthopedic surgical procedure, there are inherent risks to balance against the potential benefits,^4,5 with 1 potential risk being associated mortality. It is therefore imperative to investigate this risk so that clinicians may provide better information and patients may make better-informed decisions regarding this method of surgical reconstruction.