Mr Muhammad Adeel Akhtar
BSc, MBBS, MRCSEd, Dip SEM (UK), PG Dip CAOS, MFSEM, MFSTEd, MD (Res), FEBOT, FRCSEd (Trauma & Orthopaedics)
Consultant Trauma and Orthopaedic Surgeon with Special interest in Lower Limb Arthroplasty, Arthroscopy, Trauma and Sports Injuries, NHS Fife.
Honorary Clinical Senior Lecturer, Deanery of Clinical Sciences, College of Medicine & Veterinary Medicine, University of Edinburgh.
Honorary Clinical Senior Lecturer, School of Medicine, University of St Andrews.
Ethan Gilmour, Medical Student, St Andrews University, Scotland.
Background
Amputation may be indicated for a variety of reasons such as trauma, vascular disease, or cancer treatment. The resultant limb loss can have a severe negative impact on a patient’s physical and mental state. It can also result in significant reduction in the functional ability, independence, confidence, and overall quality of life of amputees (1).
The traditional treatment for amputees is a socket prosthesis however complications can lead to limited use (3) or potential abandonment of their prosthesis (2). Complications following the use of traditional socket prosthesis (TSP) are reported between one third (4) and three quarter (5) of amputees using TSP. This high rate is in part due to the lack of adaptation of the residuum to weight bear, and the socket-residuum interface (6). Examples of common complications include skin and soft tissue problems like ulceration or irritation (6), hyper perspiration (5), pain and poor fit (7). There is also an issue for patients with shorter residuums, as they may not be able to achieve the same level of success with TSP, thus an alternative is required.
Osseointegration
Osseointegration is utilised as an alternative option to socket prostheses in amputee rehabilitation and allows direct attachment of the prosthetic limbs to the skeleton via a percutaneous abutment. Osseointegration specifically refers to bone growing into and binding onto titanium implants, creating a functional structural connection (8). Per-Ingvar Brånemark discovered osseointegration in rabbits (9), and used it for dental implants in 1965, and later for other purposes such as auricular implants and facial reconstruction (6). It was first used in amputees in 1990 by his son, Rickard Brånemark (5).
In 1999, a standardised protocol, “osseointegrated prosthesis for the rehabilitation of amputees”, OPRA, was developed. Like the dental implants, it utilised a threaded retention system, and allowed bone to grow onto the surface. The implant was fitted in a two-step procedure, separated by 6 months, to allow osseointegration to occur before weight bearing started (10). The first step involved implantation of the threaded intramedullary component. The second step consisted of stoma formation and abutment connection. After completion, there was a 6-month rehabilitation program (11).
Newer systems have attempted to improve retention by utilising press fit methods, adapted from joint replacements (11). These novel implant systems can be implanted using either a single or two step procedure, as press fit implants results in immediate retention (5). This allows for quick rehabilitation and a shorter interval before full weight bearing is allowed. The newer systems have also redesigned the surface so that bone grows into the implant, rather than onto it like the OPRA system (4), theoretically providing a more intimate and thus superior structural connection. These include the Osseointegrated Prosthetic Limb (OPL) and the Integral Leg Prosthesis (ILP).
Osseointegrated implants comprise of two main components. Firstly, an intramedullary component where the osseointegration occurs, with a biocompatible metal surface designed to maximise surface area for osseointegration (5). Secondly, this component is connected distally to the percutaneous abutment, which attaches to the prosthesis, this has a polished surface to minimise skin adhesion and irritation (12). Due to potential large force transfer, the connector sometimes contains a failsafe mechanism (13). After surgery, rehabilitation begins with axial load bearing, through a short training prosthesis where initially 20kg load is applied which is increased incrementally to 50kg or 50% body weight. The patients then undertake exercises to improve stability and gait, and when ready the final prosthesis is fitted and they ambulate using assists, which are scaled down over time (14).
Osseointegration is primarily used in amputees unable to use traditional socket prostheses due to socket-related complications. Osseointegrated prostheses avoid these problems thus allowing increased prosthesis use and improved quality of life. Osseointegration also has the added advantages of increased prosthesis control, donning and doffing speed and movement efficiency (9). It also provides osseoperception, which is the ability to detect stimuli, like vibration, through the bone from the prosthesis (11).
The main disadvantage of osseointegration is the risk of infection due to the stoma, potentially allowing pathogens into the internal environment. This may lead to deep infection and implant failure. Periprosthetic fracture risk (15) and long rehabilitation times have also been identified as potential risks.
Patient reported outcomes are often measured with the following tests: Timed Up and Go (TUG) and 6 Minute Walk Test (6MWT) which are functional measures assessing physical ability, as well as the Questionnaire for Persons with Transfemoral Amputation (Q-TFA) and Short Form Health Survey 36 (SF-36) which are function, mobility, prosthesis use and quality of life questionnaires.
We report an overview of the outcomes using the most commonly available Osseointegration implants from the literature for amputee rehabilitaion.
OPRA (osseointegrated prosthesis for the rehabilitation of amputees)
Li and Lindeque (16), reported results from 51 patients treated with the OPRA system in Sweden between 1999 and 2007. This patient group was included in a previous paper and also included in the papers by Tillander (17) and Hagberg (10). Significant improvements in daily prosthesis use (89% vs 57% preop), all Q-TFA scores and SF-36 physical component scores were reported. They also reported 28 patients experiencing superficial infections, mainly treated with oral antibiotics, and 4 patients requiring component replacement due to mechanical damage.
Hagberg et al. (10) followed 111 unilateral transfemoral amputees treated with the OPRA system between January 1999 and December 2017, for up to 15 years. Improvements were shown in all Q-TFA domains at 10 years follow up and some at 15 years. They reported 18 implant failures, 7 from infection, 6 from aseptic loosening and 5 due to fracture. The revision free survival rate of the implant was reported as 92% at 2 years, 89% at seven years and 72% at 15 years. The study reported 61 (55%) patients experiencing at least one mechanical complication and found an association between activity level and number of complications.
A study by Matthews et al. (18) included 18 transfemoral amputees treated with the OPRA system in the UK between 1997 and 2008. This study included 5 patients who were treated before the OPRA protocol was created, for whom implant survival was 60% at 11.4 years and 40% at 18.6 years (final follow up), whereas survival rates in the post-OPRA group were 92% at 11.2 years and 80.21% at 15.9 years (final follow up). These results suggest a significant improvement in implant survival resulting from advances in OPRA technique. The infection rate was 94% (17 patients), 5 of these lead to implant removal but most were controlled with oral antibiotics. It should be noted that most of the removals were in the pre-OPRA group, and this may have been influential. Both the Q-TFA and SF-36 at 2- and 5-years post-op, showed significant improvements vs pre-op, but not between follow up timepoints.
Tillander et al. (17) retrospectively investigated osteomyelitis risk in OPRA patients over a mean follow up of 7.9 years. A total of 96 patients with 102 implants were included in the study, including 27 pre-OPRA patients and 69 OPRA patients. There were 16 cases of osteomyelitis, 10 of which resulted in implant removal, 7 of these patients were in the pre-OPRA group, which suggested that the advances made in the protocol may have resulted in a lower rate of osteomyelitis. The authors used data up to the 10-year mark to calculate the risk of osteomyelitis and implant removal due to osteomyelitis, which were 20% and 9% respectively.
ILP (Integral Leg Prosthesis)
A prospective case series was carried out by Al Muderis et al. (13) investigating complications in 86 transfemoral amputees (91 implants), treated with the ILP. Infections occurred in 34% patients; however, most infections were superficial, mild, and treated with oral antibiotics alone (87%), with none leading to implant failure. While this suggests that most infections are a minor complication, it should be noted that due to the young age of patients undergoing osseointegration, many studies, including this one, have exclusion criteria which preclude patients at increased risk of infection like diabetics, from participating in these studies. This paper therefore may show a more favourable picture than would be true for the entire population. Two significant associations were discovered, between increased risk of severe infection and female sex, as well as increased risk of recurrent infection and smoking. The two most common non-infection related adverse effects were hypergranulation (20%) and irritation of the stoma caused by excess soft tissue (16%). The protocol has been updated to prevent excess soft tissue related issues.
OPL (Osseointegrated Prosthetic Limb)
Another study by Al Muderis (4), presented the results of the retrospective analysis of 22 patients treated with the OPL system with a mean follow up of 14 months. This study showed 12 patients (55%) experiencing an infection which was low grade and responded to antibiotic therapy alone. The study also showed improvements in outcomes, with 2 measures for quality of life and function showing significant improvements. While this study had a low number of patients, it was the first for this implant system and its results are promising and support further use and research, particularly assessing long term results.
A retrospective case series by McMenemy et al. (19) of 7 bilateral transfemoral amputees, treated with the OPL, showed significant improvements in all outcome measures in all patients. However, superficial infections also occurred in all patients, with a minimum of 1 antibiotic course being prescribed per patient. This infection rate is higher than other reported studies, however this may be due to the bilateral nature of this population. No implants were removed, and all other complications were managed without further issue. While a small number of patients were included, the results indicate significant benefits to this population, without serious complications. These results merit further research, as there is potential to significantly improve function in this population.
OGAAP (Osseointegration Group of Australia Accelerated protocol)
A novel Australian protocol, the Osseointegration Group of Australia Accelerated protocol-1 (OGAAP-1), has allowed for a reduction in the duration of the rehabilitation period. In a prospective cohort study by Al Muderis (20) of 50 transfemoral amputees treated with the ILP or OPL systems using a two-stage method, significant improvements were observed in all outcome measures. Complications occurred in 27 patients and the major complication was superficial infection in 21 patients (11) treated with oral antibiotics and did not result in implant failure. Another study by Al Muderis (21) reported outcomes of the use of the OGAAP-1 with the ILP/ OPL systems. The study included 37 patients with unilateral transfemoral amputation and reported significantly improved values across all outcome measures. The study reported infections in 16 patients, 14 of whom were treated with oral antibiotics only. Other adverse events included 1 peri-prosthetic fracture, which was managed without implant removal, and 6 soft tissue revision surgeries.
Total duration for the OPRA system from initial surgery to unrestricted ambulation has been reported as 9-12 months (11), however the OGAAP-1 allows for unassisted ambulation after a period of between 2.5 and 5 months (median 4.5) (20). To further decrease this duration the same group who created the OGAAP-1 have created the OGAAP-2 for single stage implantation of the OPL system and a rehabilitation period of 3-6 weeks. They have published a protocol for a study investigating its use (14). This reduction in time between initial surgery and unassisted ambulation is a significant advance in osseointegration. It results in a much shorter overall rehabilitation time, decreasing the time before patients can regain their independence, functionality, and ability to return to work.
Hoellwarth et al. (15) investigated peri-prosthetic fracture in 458 patients with 518 implants of either the ILP or OPL system, treated between 2010 and 2018. Peri-prosthetic fractures were reported in 22 patients, all of which occurred in the femur. This resulted in a fracture rate of 4.2% (22/518). The fractures were all reported to have occurred after a fall, and none resulted in implant failure or removal. This fracture rate was also compared to the rate for socket prostheses reported in previous studies (2-3%). The difference between these rates is small and considering the benefits osseointegration can provide, unlikely to be a contraindication.
The fractures did not decrease the mobility of the patients (K-level) and 21 patients who experienced a fracture still reported increased prosthesis use compared with their previous socket prosthesis. This study also identified two groups at increased risk of peri-prosthetic fracture. Females were found to be at almost 4 times greater risk, while patients whose weight exceeded 80kg were at a slightly increased risk per kg over. This group is the largest study population in the literature reported in this review and is the most diverse in terms of amputation type. On the other hand, lower limb amputees far outnumbered the upper limb amputees, therefore the results may not show the true balance of fracture rates between these groups. The comparably low fracture rate is promising and indicates that osseointegration does not cause a significantly increased risk in most patients.
Three studies featured wheelchair bound patients (4, 20, 21), all of whom, non-prosthetic factors excluded, were able to walk independently at the end of the study. This demonstrates a very significant improvement in function and suggests that this may be a population where osseointegration can have the greatest benefit.
Conclusion:
The available evidence base for osseointegration shows effectiveness however, evidence for the risk of infection and other adverse events is still developing. Much of the available literature, even when filtered for the most recent papers, was made up of low evidence, primarily case series, with low study population sizes.
Another limitation of much of the current evidence is short follow up periods, particularly as this is a life-long implant, however this is likely due to the relative novelty of the procedure when compared with longstanding treatments like total hip and total knee replacements.
Considering osseointegration is still relatively new, it has shown a promising level of success so far and the advances that have already been made to the designs have helped to favour this option as an alternate to traditional socket prosthesis. It is very likely that new techniques and designs, will further improve outcomes and minimise complications, so that Osseointegration can become a mainstream treatment option for amputee rehabilitation.
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