Transcutaneous osseointegration for amputees (TOFA) [Figure 1] consistently provides improved mobility and quality of life (QOL) for amputees compared to traditional socket prosthesis (TSP) rehabilitation. Conventionally, amputees provided this reconstructive procedure are relatively optimal candidates: Healthy, young patients with a transfemoral amputation. The force of patients' full body weight-bearing impact is transmitted through the prosthetic leg and into the intramedullary implant to the patient's skeleton, so a patient's bone must achieve sufficiently robust ingrowth to prevent the static and dynamic forces from dislodging the implant from the skeleton. The strength of the bone-implant interface is influenced by the quality and quantity of integration. The quality is affected by the implant material, its surface texture and topography, and the general metabolic health of the patient and the specific bone. The quantity is the total surface area and depth available for integration.
The quantity of the surface area is mostly determined by the diameter and length of the intramedullary canal and the implant. There is very limited capacity to modify the diameter aspect of the equation. First, the diameter of the patient's bone is difficult to substantially modify because the implant must impact into the cortical bone, and many amputees have relatively thin cortices, limiting the aggressiveness of reaming. Second, deeper implant channels provide minimal additional strength but require substantially more time to ingrow and, most importantly, have increasing failure risk due to limited vascular support capacity. Length, however, is modifiable via distraction histogenesis, made more convenient by motorized intramedullary lengthening nails (MILNs). An additional benefit of a longer residual bone is better prosthetic control.
Because reliable, excellent results are routinely achievable when the textured portions of the two commercially available press-fit osseointegration implants are fully seated, we counsel patients with the short residual bone to have lengthening to optimize the area available for integration and to improve their prosthesis control. While the implant lengths could be cut shorter to accommodate a shorter residual bone, it is unknown whether this reduced length provides adequate contact to achieve stability. The two implants our group uses are the Integrated Limb Prosthesis (ILP, Orthodynamic, Lubeck, Germany) whose standard stem length is 140 mm, and the Osseointegrated Prosthetic Limb (OPL, Permedica Medical Manufacturing, Lecco, Italy) whose standard stem length is 160 mm.
This study reports our experience with a consecutive series of the first 10 transfemoral amputees who sought osseointegration from us but had a residual bone of approximately the minimum implant length or less. These patients had MILN lengthening followed by TOFA. The primary purpose of this article is to evaluate the safety profile of "lengthening before osseointegration" as a reconstructive strategy for such patients. In addition, this article describes the change in mobility, QOL, and complications experienced by these patients between their presentation and their most recent follow-up visit.
Subjects and Methods
Following institutional ethics review, we retrospectively reviewed our prospectively maintained osseointegration database. In general, patients considered for osseointegration are skeletally mature adults who either (1) report pain or mobility dissatisfaction with their TSP; (2) have an intact limb with incapacitating pain, complex deformity, or profound distal weakness, whose functional capacity is considered likely to be improved by amputation; or (3) are recent amputees preferring osseointegration to TSP rehabilitation. Patients included in this study had MILN lengthening before osseointegration at our primary medical center; patients who did not have lengthening or whose procedures were performed at outreach locations were excluded. Table 1 summarizes the patients included in this study.
Amputees interested in TOFA were counseled about the typical risks and benefits of the reconstruction procedure; patients with residual bones shorter than the standard length of the implants were counseled that very few patients worldwide had such short limbs prior to osseointegration, limiting the knowledge available to provide specific counseling. It was recommended to increase the length of their residual bone to provide more surface area for ingrowth into the implant, which would be expected to confer a better likelihood of permanent stable ingrowth. Patients were informed this would require at least two surgeries: The first to insert the MILN, followed by a period of lengthening and consolidation which would take at minimum several months, followed by a second surgery to remove the MILN and insert the osseointegration implant. Patients were counseled that amputee lengthening was more challenging than lengthening patients with intact limbs, and additional surgeries could be necessary to address issues such as regenerate quality or implant malfunction. Patients were informed that each of these surgeries was rare worldwide, and there were no known reports of this combination of procedures.
MILN lengthening was performed using a 14 mm × 130 mm telescopic nail (Freedom Residual Limb Lengthening device, NuVasive, San Diego, CA). The techniques and considerations have been previously detailed and summarized as follows. The fundamental goal of MILN for these patients was to create a bone with at least 140 or 160 mm, to fit the standard sized implant. We predominantly used the ILP early in our experience, but preferred the OPL later on, as the OPL's titanium composition facilitates osseointegration better than cobalt-chrome, and the proportionally thicker inner diameter of the OPL being more robust against implant fracture. The surgical exposure for the MILN was via the distal residual limb. The osteotomy site was predrilled, retrogradely reamed, and the osteotomy completed with osteotomes. MILNs were generally inserted in an antegrade implant orientation, in a retrograde surgical approach from the amputated femur's distal end. There are several reasons for a retrograde approach. Most importantly, all osseointegration is performed from a retrograde direction, so a distal surgical approach would be necessary eventually. Second, a distal incision is often necessary to visualize the distal linkage of nail to lengthening fragment. It is also faster and more visible to approach retrograde. By not violating the piriformis fossa bone, it can offer a backup support in situations where bone that is osteopenic from long-term amputation may lose proximal cross screw purchase. Finally, less radiation from image intensification is needed to place and secure the nail. Multiple blocking screws were often used to reduce malorientation during lengthening. Bones shorter than the MILN required linkage techniques such as cables [Figure 2] or bent locking plates [Figure 3]. Lengthening commenced after 7 days, at a maximum amount of 1 mm daily in divided episodes. Radiographic follow-up was performed weekly or biweekly until the goal length or the nail's maximum stroke length was achieved. Regenerate was generally considered adequate for MILN exchange for osseointegration when four cortices were clearly confluent on perpendicular radiographs.
Data were gathered as follows. At the preoperative consultation, patients had their Medicare Functional Classification Level (K-level) determined by the surgeons. Research assistants administered QOL surveys (Questionnaire for Persons with a Transfemoral Amputation, [QTFA]) and formal mobility tests. Mobility was assessed by the Timed Up and Go (TUG) and 6-min walk test (6MWT). Following osseointegration, patients were followed up clinically at 3 weeks, 3 months, 6 months, and annually. Formal K-level, survey, and mobility data was determined at annual time points. Although we encourage every patient to complete the data metrics to optimize our care for them and others, osseointegration surgery was not withheld from patients who declined completing surveys and formal mobility tests at any time point. They were still enrolled in our registry to optimize follow-up efforts and track complications, and their missing data was excluded from statistical comparisons. Complications were defined as any unplanned surgery to the individual extremity, such as to address infection or implant issues. Frequency comparison was performed using Fisher's exact test (QuickCalcs, GraphPad Software, San Diego, CA), and means were compared using Student's t-test (Google Sheets, Alphabet Inc., Mountain View, CA); significance was defined as P < 0.05.
Table 2 summarizes the MILN experience. Patients 8 and 9 had starting lengths that were borderline adequate for a standard implant, but were lengthened to optimize the lever arm of the amputated limb. Four of the eight (50%) patients who were shorter than the standard implant length achieved the ideal minimum length. Seven patients (70%) experienced one complication each prompting unplanned surgery. The first three patients had an additional procedure to supplement radiographically meager regenerate with autograft bone; this topic will be expounded upon in the Discussion. Two patients (7 and 10) had nail malfunction prompting implant exchange. Patient 4's linkage cables broke, prompting plate stabilization with autograft [Figure 2]. Patient 9 had early consolidation prompting re-osteotomy. The duration of lengthening and therefore lengthening index are not reported due to the high rate of additional surgery, obfuscating the usefulness of such metrics.
Table 3 summarizes the osseointegration experience. All 10 patients (100%) successfully received their osseointegration implant and achieved unassisted ambulation. Eight of 10 (80%) had no postosseointegration complications. One patient had debridement with implant retention, and another patient developed infection which eventually prompted implant removal; revision osseointegration was not performed for this patient.
Table 4 reports the mobility performance of patients before lengthening and after osseointegration. Overall, there was improvement in all mobility metrics. The daily wear hours improved as a cohort, although not to significant confidence [Figure 4]. The improvements of K-level [Figure 5] and TUG [Figure 6] were significant. The 6MWT also improved as a cohort, but not to significant confidence [Figure 7]. It is notable that all the patients who started as wheelchair-bound gained and achieved independent ambulation capacity; the patient whose implant required removal did achieve independent ambulation, but following removal he did not have revision osseointegration and returned to being wheelchair-bound because he had pain related to attempted prosthesis wear along with irremediable socket fit problems. In addition, no K-levels decreased.
Table 5 reports the QOL survey data of patients before lengthening and after osseointegration. Patients 5 and 10 were excluded due to incomplete data availability. All three categories significantly improved: The global, mobility, and problem domains [Figure 8].
The most important finding of this study is that all patients successfully had the tandem procedures of lengthening followed by osseointegration and walked full weight on their prosthetic leg without any compromise of bone integrity. Intramedullary lengthening was an intense journey: The average time from the lengthening surgery until osseointegration was 1 year, and seven patients had additional surgery during lengthening. However, the resultant bone was conducive to osseointegration: Nine of the ten patients remain ambulatory on their osseointegrated prosthetic leg after 2–3.8 years. Importantly, the patients considered the journey worth the effort: QOL significantly improved in all three major domains of the QTFA. Mobility also improved: The K-level and TUG were significantly better, and the daily wear hours and 6MWT also increased, although not to a significant degree.
The literature regarding transfemoral osseointegration is consistent and clear. Patients who are dissatisfied with their TSP are very likely to have significantly improved mobility and QOL after osseointegration. The most common complications include infection (which may require oral or intravenous antibiotics, or irrigation and debridement with implant retention or implant removal), periprosthetic fracture (from which patients recover following internal fixation with implant retention), and implant fracture (which requires remnant implant removal and potential revision osseointegration). The basic science of osseointegration between titanium and normal healthy bone is well enough understood that clinically stable long-term osseointegration is achievable in nearly every patient, with almost all studies reporting on healthy transfemoral amputees. Therefore, two major frontiers remain in the early exploration of osseointegrated limb replacement: Achieving a near-zero infection rate, and better understanding to what extent various health morbidities present risks for long-term successful osseointegration. In just the last few years, it has been proven that osseointegration can be safe and beneficial for patients with disease which traditionally were assumed to be of unacceptable risk for major complications: Vascular disease, prior total knee infection, diabetes mellitus, and irradiated bone.
The current study investigated a different potential risk factor for osseointegration: A prohibitively short residual limb. The biologic phenomenon of osseointegration is defined as "a process whereby clinically asymptomatic rigid fixation of alloplastic materials is achieved, and maintained, in bone during functional loading." The osseointegration process of TOFA exactly what occurs for cementless total joint replacement: Bone grows exceptionally close to a properly surfaced biocompatible implant, achieving clinical stability. It is important to directly iterate that the bone does not directly grow "into" the implant the way creeping substitution incorporates allograft bone, or "onto" the implant using any sort of biological bonding, but instead interdigitates within a sub-micron distance of the implant. Many factors that affect the ability of cementless arthroplasty components and other osseointegrated implants to achieve stability also affect TOFA, such as implant-bone positioning, the implant's surface texture, the general metabolic health of the patient and the specific bone, and the total surface area available for bone-implant integration. Two challenges that are nearly unique for TOFA versus other medical instances of osseointegration are the permanent transcutaneous situation, which allows bacteria to invade (which is also a concern for bone-anchored hearing aids) and the mechanical tension force of the weight of the external prosthetic limb that the TOFA system must resist whenever patients lift their extremity (unlinked total joints do not experience similar direct tension forces but rather almost exclusively compressive forces which promote osseointegration between bone and implant). Although experiments and clinical experience have proven that textured titanium surfaces can achieve sufficient osseointegration to resist supraphysiologic pull-out forces, it is not established what the pull out strength is per area of contact. Further, the clinical reality is that despite even the most meticulous surgical technique, there is no confident way to accurately and precisely assess the amount of actual surface contact between bone and implant. Therefore, clinical intuition and judgment remains the guide for how to best treat patients with short residual bone. It is intuitive that if the intramedullary canal and implant can have matching geometry, then the greater the diameter and length of bone-implant overlap, the greater potential areas available for osseointegration, and therefore, the greater the potential strength to pull-out forces. Such judgment proved sufficient for all patients in this cohort: Regardless of their initial and final femur length, all achieved sufficient bone-implant osseointegration to walk with full weight and none experienced pull-out.
Because this study represents the first known report of distraction histogenesis prior to TOFA, and because of the paucity of directly relevant comparative literature, we feel it is important and appropriate to also share some subjective observations and insights of our experience with this process. First, we admit and emphasize that we are not certain what a minimum length or contact area must be to achieve clinically successful TOFA. It stands to reason that the minimum amount is shorter than our smallest patient's length, as none of these implants gave way or fell out. Since the bone-implant interface strength was never exceeded, by definition all patients had at least some redundant contact area. It is also therefore logical that, perhaps, lengthening may not have been absolutely necessary to optimize a successful outcome for any of all of these patients. The shortest bone at TOFA implantation was 90 mm, shorter than all but one of the initial lengths. Since that patient remained stable, perhaps 90 mm is already more than the minimum requirement, and instead of lengthening patients equivalent stability could have been achieved by instead using customized shorter implant lengths to match the existing patient bone length.
A second insight worthy of discussion is that of regenerate quality. Amputee lengthening is itself a rare procedure, and often fraught with complications. Indeed, we may have been the first to publish on amputee lengthening using intramedullary lengthening nails, with only one other identified study being a more recent case report. The most common complication we encountered was regenerate that appeared radiographically deficient (three patients), which is a potential issue even for patients with complete limbs with both intramedullary and external lengthening. For patients who have intact sensate limbs that can reach the ground, with solid bone and vascularized soft tissue on both sides of the regenerate, it is common to prescribe progressive loading via weight bearing in order to more rapidly strengthen the bone, often guided by the implant's weight limitations. Amputees do not have healthy biology on both sides of their lengthening segment and also cannot achieve partial loading as easily. Further, there was no precedent guiding us to be confident how robust regenerate bone had to be to exchange a lengthening device for an osseointegration implant. Regenerate that is too weak could collapse upon removal of the intramedullary nail. Additionally, although titanium is a bioinert material in and on which bone can grow very well, and the new bone regenerate is very biologically active, it was unknown whether poorly matured regenerate had sufficient biologic capacity to sufficiently mature on these implants' surfaces. Therefore, to prevent regenerate collapse and ensure a stable length for the maturation of the regenerate, we provided autograft supplementation along with plate stabilization across the lengthening. This strategy did succeed in achieving a sturdy osseointegrated implant, but the plate irritated all patients and required removal.
The limitations of this study are those inherent to observational research of a small cohort. In particular is selection bias: All patients who had residual femurs near or below the standard implant size were lengthened, without a control group of patients with a similarly sized femur which was not lengthened. It is again emphasized that a minimum length or area of bone necessary to support a full weight bearing lower extremity osseointegrated prosthesis is not known – these patients were lengthened to optimize the length available for bone ingrowth – and this study is not intended to establish a minimum necessary length or area. The most significant strength of this study is the complete follow-up of the studied cohort. All patients were followed at least 2 years after their osseointegration, in addition to their time spent lengthening. Although not all formal mobility and survey data was successfully elicited, no patients were lost to follow-up, and although improvements may be under-represented, complications are fully represented. Additionally, we believe the data provide early insight regarding an important question that has not been addressed before in the literature: How to approach osseointegrated reconstruction for amputees with residual lower extremity bones shorter than the standard implant length?
For patients with a residual femur length that is concerningly short for successful ingrowth into an osseointegration implant, surgical lengthening can be performed to increase the surface area available for implant-bone contact. This technique of lengthening-before-osseointegration proved successful: All patients achieved full weight bearing on their osseointegrated limb, with infection being the only reason to lose full weight bearing ability Amputees may experience more difficulty consolidating regenerate than patients with intact limbs. It must be reiterated that a true "minimum length" for sufficiently robust osseointegration to support full weight bearing is not known, and lengths shorter than those of this study may be adequate.
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Conflicts of interest
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