Osseointegration for Lower and Upper Limbs

Number: 1045

Table Of Contents

Policy
Applicable CPT / HCPCS / ICD-10 Codes
Background
References

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Policy

Scope of Policy

This Clinical Policy Bulletin addresses osseointegration surgery.

1. Experimental, Investigational, or Unproven

   Aetna considers osseointegration surgery and/or prosthesis (including the Osseoanchored Prostheses for the Rehabilitation of Amputees (OPRA) Implant System, and the Axor II connection device) experimental, investigational, or unproven because its effectiveness has not been established.

2. Policy Limitations and Exclusions

   This policy does not apply to osseointegrated devices such as brainstem auditory devices as prosthetic devices or osseointegrated implants to the mastoid process of the temporal bone and auditory brainstem devices.

   Consistent with DME MAC policy:

   Treating practitioner means physician (MD or DO) or physician assistant, nurse practitioner, or clinical nurse specialist. A prosthetist, orthotist, orthotic fitter, pedorthotist, physical therapist, or occupational therapist is not considered a treating practitioner.

   A new prescription from the treating practitioner is required each time a new device or repair is requisitioned.

   There must be sufficient medical information included in the medical record to demonstrate that all applicable coverage criteria are met.

   Consistent with DME MAC policy:

   Supplier prepared statements and physician attestations by themselves do not provide sufficient documentation of medical necessity, even if signed by the ordering physician.

   "Neither a practitioner’s order, nor a supplier-prepared statement, nor a practitioner’s attestation by itself provides sufficient documentation of medical necessity, even though it is signed by the treating practitioner or supplier. There must be information in the member’s medical record that supports the medical necessity for the item and substantiates the information on a supplier-prepared statement or treating practitioner’s attestation (if applicable)."

   "Forms are subject to corroboration with information in the medical record."

   Records from suppliers or healthcare professionals with a financial interest in the claim outcome are not considered sufficient by themselves for the purpose of determining that an item is reasonable and necessary. 

   Consistent with DME MAC policy:

   A Standard Written Order (SWO) must be communicated to the supplier before a claim is submitted. If the supplier bills for an item addressed in this policy without first receiving a completed SWO, the claim shall be denied as not medically necessary.

   The SWO must contain all the following elements:

   • Member's name or identification number
   • Order date
   • General description of the item
     
     
     • The description can be either a HCPCS code, a HCPCS code narrative, or a brand name/model number
     • In addition to the description of the base item, the SWO must include all concurrently ordered options, accessories or additional features that are separately billed or require an upgraded code (List each separately).
     • For supplies - in addition to the description of the base item, the order/prescription must include all concurrently ordered supplies that are separately billed (list each separately)
       
       
   • Each item or service requested must individually list the HCPCS code (Procedure code) and quantity to be dispensed
   • Treating practitioner name and national provider identifier (NPI)
   • Treating practitioner's signature.

3. Related Policies 

   • CPB 0578 - Lower Limb Prostheses

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Table:

CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
CPT codes not covered for indications listed in the CPB:
Osseointegration surgery for lower and upper limbs –no specific code
HCPCS codes not covered for indications listed in the CPB:
Osseointegration/osseoanchored prostheses –no specific code
L5991	Addition to lower extremity prostheses, osseointegrated external prosthetic connector
ICD-10 codes not covered for indications listed in the CPB (not all-inclusive):
Z47.81	Encounter for orthopedic aftercare following surgical amputation
Z89.9	Acquired absence of limb, unspecified

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Background

Osseointegration denotes bone ingrowth into a metal implant; it is most commonly used in dental implants as well as joint (e.g., lower and upper limbs) replacement surgery.  An artificial implant is surgically anchored and integrated into bone, which then grows into the implant.  Osseointegration limb replacement (e.g., the Osseoanchored Prostheses for the Rehabilitation of Amputees [OPRA] Implant System, see Appendix for indications and contraindications) is supposedly helpful for amputees who are having a poor experience with their conventional socket prosthesis.  The implant is expected to last for many years after successful osseointegration with the bone.  Connection parts with the prosthetic may, over time, need to be changed by the prosthetist.  The risks of osseointegration limb replacement include fracture, infection, and implant loosening; and revision surgery may be needed in these cases.

The OPRA Implant System is installed with 2 surgical procedures.  In the 1st procedure, a cylinder-shaped fixture is implanted into the central canal of the remaining thigh bone.  Approximately 6 months later, after tissue has grown to anchor the fixture and the skin tissue has healed, a 2nd surgery is carried out to attach additional device components of the OPRA Implant System to the fixture from the previous surgery.  The OPRA Implant System extends through the skin at the bottom of the patient’s residual limb and connects to the prosthesis.  After the 2nd surgery, the patient works with a trained physical therapist to gradually place weight on the OPRA Implant System using a training prosthesis.  Patients need about 6 months of training and rehabilitation following the 2nd surgery, before being fitted with their own customized prosthesis by a trained prosthetist.  The OPRA Implant System is surgically anchored and integrated into the patient’s remaining thigh bone to allow connection to an external prosthetic limb.  A conventional leg prosthesis uses a specially fitted, cup-like shell called a socket that fits over the remaining portion of the patient’s leg (the residual limb remaining after amputation) to secure the device to the leg.

The Axor II is an osseointegrated external prosthetic connection device that provides a standard connection between the OPRA Implant System implantable components and other external prosthetic components, specifically the prosthetic knee and foot.  The Axor II osseointegrated external prosthetic connection device is designed to protect the OPRA Implant System from damage caused by overloads.  It connects the osseointegrated implant and skin penetrating abutment to a standard external prosthetic knee and foot.  In the event of excessive twisting or bending of the prosthesis, the Axor II osseointegrated external prosthetic connection device releases the prosthesis to prevent damage to the bone-anchored fixture.

There is a clinical trial entitled “e-OPRA Implant System for Lower Limb Amputees” that is active, but not recruiting.  The e-OPRA Implant System, is a further development of the OPRA Implant System, approved under HDE (Humanitarian Device Exemption) H080004.  The e-OPRA Implant system is an implant system for direct skeletal anchorage of amputation prostheses.  The added feature in the e-OPRA Implant system, is a bi-directional interface into the human body that allows permanent and reliable communication using implanted electrodes.  These electrodes will provide long-term stable bioelectric signals for an improved control of the prosthetic limb.  The purpose of this trial is to examine the feasibility of a lower limb amputee with the e-OPRA Implant System exhibiting full neural control over a neuro-mechanical prosthetic system.  A maximum of 6 subjects will be enrolled.  Each subject will undergo a surgery where the e-OPRA Implant System will be implanted.  The subjects will participate in follow-up sessions of which the last one occurs approximately 24 months after the surgery.  This is a prospective, non-randomized, uncontrolled study.  The estimated study completion date is January 17, 2025. 

Tsikandylakis et al (2014) stated that osseointegrated percutaneous implants provide direct anchorage of the limb prosthesis to the residual limb.  These implants have been used for the rehabilitation of trans-humeral (TH) amputees in Sweden since 1995 using a 2-stage surgical approach with a 6-month interval between the stages; however, results on implant survival, adverse events (AEs), and radiologic signs of osseointegration (OI) and adaptive bone re-modeling in TH amputees treated with this method are still lacking.  In a retrospective study, these investigators reported on 2- and 5-year implant survival, AEs, and radiologic signs of OI and bone re-modeling in TH amputees treated with osseointegrated prostheses.  Between 1995 and 2010, these researchers carried out 18 primary osseointegrated percutaneous implants and 2 implant revisions in 18 TH amputees; of those, 16 patients were available for follow-up at a minimum of 2 years (median of 8 years; range of 2 to 19 years).  These included all TH amputees who have received osseointegrated prostheses and represented approximately 20 % of all TH amputees evaluated by these investigators for potential OI during that time; general indications for this approach included TH amputation resulting from trauma or tumor, inability to wear or severe problems wearing a conventional socket prosthesis (e.g., very short residual limb, and compliant patients).  Medical charts and plain radiographs were retrospectively evaluated.  The 2- and 5-year implant survival rates were 83 % and 80 %, respectively; 2 primary and 1 revised implant failed and were removed because of early loosening.  A 4th implant was partially removed because of ipsilateral shoulder osteoarthritis (OA) and subsequent arthrodesis.  The most common AE was superficial infection of the skin penetration site (15 infections in 5 patients) followed by skin reactions of the skin penetration site (n= 8), incomplete fracture at the 1st surgery (n = 8), defective bony canal at the 2nd surgery (n = 3), avascular skin flap necrosis (n = 3), and deep implant infection (n = 1).  The most common radiologic finding was proximal trabecular buttressing (10 of 20 implants) followed by endosteal bone resorption and (7 of 20), cortical thinning (5 of 20), and distal bone resorption (3 of 20).  The authors concluded that the implant system presented a survivorship of 83 % at 5 years and a 38 % 5-year incidence of infectious complications related to the skin penetration site that were easily managed with non-operative treatment, which made it a potentially attractive alternative to conventional socket arm prostheses.  Osseointegrated arm prostheses have so far only been used in TH amputations resulting from either trauma or tumor.  Their use has not been tested; and thus, is not recommended in TH amputations resulting from vascular disease.  This method could theoretically be superior to socket prostheses, especially in TH amputees with very short residual humerus in which the suspension of a conventional prosthesis is difficult.  These researchers stated that comparative studies are needed to support its potential superiority.  Moreover, the radiological findings in this study need to be followed over time because some of them were of uncertain long-term clinical relevance.

The authors stated that this study had several drawbacks.  The number of patients was small (n = 18), and the study was retrospective.  The patient cohort was selected by a multi-disciplinary team (orthopedic surgeon, occupational therapist, prosthetist, and coordinator) based on the patient’s reason for amputation (trauma or tumor), wish for better function, and estimated compliance without randomization and represented approximately 20 % of all TH amputees who were referred to the authors’ center.  Therefore, highly motivated patients with good compliance were more likely to be selected for OI.  However, the observer who reviewed the medical charts and plain radiographs was not part of this multi-disciplinary team or active in the treatment and follow-up of the amputees.  Moreover, no comparison was made between the OI cohort and amputees with socket arm prostheses.  Furthermore, the study did not include any patient-reported outcomes (PROs) for pain, function, and prosthetic use, which made it difficult to make any conclusions regarding the superiority of one or the other method.  In some instances, the patients missed their follow-up appointment resulting in potential AEs being registered at the next follow-up.  In these instances, the exact time when the AE had occurred was not registered in the medical charts.  Because a part of the implant is in direct contact with the outer environment and therefore contaminated by bacteria, it was difficult to draw a distinct line between skin reactions as a result of inflammation of the soft tissues of the skin penetration site and manifest bacterial superficial infections.  Clinical signs of inflammation, positive bacterial cultures, and antibiotic treatment given were used as criteria for infection trying to distinguish infection from inflammation.  Bacterial contamination has however previously been found in 50 % of asymptomatic patients with an osseointegrated percutaneous implant.  Bacteria may be commensals, mutualistic, or pathogenic and potential “pathogens” may or may not actually produce infection.  Presumably some inflammatory skin reactions have been registered as superficial infections and vice-versa.  All radiographs were not available for examination and moreover the assessment of radiologic changes was made by 1 observer without calculating intra-observer error.

This implant system had a 2- and 5-year survival rate of 83 % and 80 %, respectively, in TH amputees, which appeared lower than the 2-year survival rate (92 %) of the same implant system in trans-femoral (TF) amputees in the OPRA study.  These researchers believed that this difference could be explained by the higher experience of their center in TF amputees and that the use of custom-designed components could increase the risk of not having optimal primary stability at implant insertion.  In contrast to endoprostheses such as hip and knee prostheses, aseptic loosening cannot practically be diagnosed because the system is open to the outer environment and any failed osseointegration inevitably led to contamination of the bone-fixture interface.  The importance of good primary stability of the fixture at 1^st operation was highlighted because poor primary stability could compromise osseointegration and was reported in 2 implant failures.  No mechanical problems of the implant systems occurred, in contrast to TF amputees in whom bending or fracture of the abutment or the abutment screw has been reported.

Hebert et al (2017) noted that traditional socket prostheses are not a viable option for all lower-limb prosthetic users.  Discomfort, pain in the residual limb, and problems related to the fit of the socket are common and have been shown to negatively impact quality of life (QOL) and mobility.  Osseointegrated or bone-anchored prosthetic implants have evolved over the past 20 years as a promising alternative for patients who are experiencing substantial issues with socket prostheses.  These investigators carried out a review of the literature to identify studies focusing on the evolution, clinical outcomes, success rates, and complications of osseointegrated lower-limb prostheses.  Articles were summarized according to the implant type, amputation level, and study characteristics, with rating of the Level of Evidence.  Information on patient selection criteria, outcomes, and complications was extracted.  A total of 14 articles (with Level-II, III, or IV evidence) met the inclusion criteria.  Infection and soft-tissue irritation at the stoma were the most common complications.  It was evident that, over the years, changes in implant design, surgical technique, peri-operative and post-operative care, and rehabilitation protocols have resulted in improvements in functional outcomes and health-related QOL (HR-QOL), and reduction in rates of complications.  The authors concluded that osseointegration for limb amputation has become an established clinical therapeutic option for individuals with lower-limb amputation not tolerating traditional socket prostheses.  Osseointegration could provide substantial benefits regarding function and QOL for appropriately selected patients who accept the documented risks.  Moreover, these researchers stated that as with any new technology, ongoing incremental iteration to optimize outcomes is expected through this clinical evolutionary phase.  Adopting a standard classification system for tracking outcomes and complications would greatly assist in ongoing and future evaluation of implant techniques.  Furthermore, these investigators stated that there is insufficient evidence to address the cost-effectiveness of osseointegrated prostheses, and further longitudinal study is needed.

Atallah et al (2020) described safety and functional 1-year follow-up outcomes of individuals with lower limb amputation treated with bone-anchored prostheses using titanium press-fit osseointegration implants.  All consecutive individuals treated between March 2015 and June 2018 with curved osseointegration femur implant (OFI-C) indicated for a long femoral remnant, gamma osseointegration femur implant (OFI-Y) indicated for a short femoral remnant, or osseointegration tibia implant (OTI) were eligible for this study.  All AEs were evaluated, infections were graded as follows: grade 1 and 2: low- and high-grade soft tissue infection, respectively, grade 3: deep bone infection, grade 4: septic implant failure.  Functional outcome measures included prosthesis wearing time (PUS), health-related quality of life (GS), and the overall situation as an amputee (GS Q3); evaluated with the Questionnaire of persons with trans-femoral amputation (Q-TFA) before surgery and at 1-year follow-up.  A total of 90 of 91 individuals were included (mean age of 54 ± 14 years, 26 women); treated with 53, 16, and 21 OFI-C, OFI-Y and OTI, respectively.  Soft tissue infections (grade 1: 11 events, grade 2: 10 events) were treated successfully with antibiotics except in 2 (OFI-C and OFI-Y), who required additional surgery due to recurrent stoma irritation and peri-stoma abscess drainage.  One individual with dysvascular amputation (OTI) developed septic implant loosening and occlusion of the femoral artery resulting in a TF amputation.  No aseptic loosening’s occurred.  One individual (OFI-Y) required stoma surgical re-fashioning due to soft tissue redundancy.  At baseline mean ± SD and median (25th to 75th PCTL) Q-TFA PUS and GS were 52 ± 39, 52 (7 to 90) and 40 ± 19, 42 (25 to 50) and improved significantly to 88 ± 18, 90 (90 to 100), and 71 ± 15, 75 (67 to 83) at 1-year follow-up.  The GS Q3 improved over time.  The authors concluded that the findings of this study showed that press-fit OI’s could be safely used in individuals with different levels of amputations, resulting in an improvement in performance and acceptable complication rates at 1-year follow-up.  These findings may contribute to inform individuals with a lower extremity amputation and medical professionals of the risks and benefits of OI treatment so they can make an educated choice.  Moreover, these researchers stated that further investigation with longer follow-up period is needed and currently on-going.  Future research should be carried out to gain more insight in the effects of load bearing, during the rehabilitation time, and in daily living with regard to AEs such as component breakages, and the effects of modifications of soft tissue surgical technique of the stoma with regard to soft tissue AEs.

The authors stated that this study had several drawbacks.  First, the short follow-up period of 1 year precluded these researchers from definitive conclusions regarding implant survival on a long-term.  Second, AEs were collected retrospectively based on patient reports, and no general practitioners were contacted; which may have resulted in an under-estimation of the total number of AEs.  Third, the infectious complications were graded using an earlier developed system that is not validated; therefore may lead to inter-rater variability.  Fourth, a subset of individuals was treated with single-stage surgery while the rest was treated with 2-stage surgery.  This may have led to misinterpretation of the results, while there is still a lack of knowledge with regards to the safety of single-stage surgery, especially in individuals with a trans-tibial (TT) amputation.  Fifth, there was little insight in confounders such as loading during daily living or alignment of components used, possibly associated with certain AEs; such as the 4 dual cone adapter (DCA) breakages that occurred.  Earlier research in individuals treated with screw-type implants showed potential limitations of load monitoring, differences in loading compliance, as well as benefits of using certain instruments to monitor static load bearing.

Hoellwarth et al (2020) stated that 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 peri-prosthetic fracture -- do not appear unacceptably frequent or insurmountable.  Proximal amputations or situations resulting in reduced mobility are exceptionally infrequent.  Osseointegrated implants can be attached to advanced sensory and motor prostheses. 

Diaz Balzani et al (2020) noted that the conventional use of prosthetic custom-design socket is affected by discomfort related to well-known problems: sweating, sores or skin irritation, excessive weight and harness, impaired body image, that result in a high rate of abandonment.  Osseointegrated prosthetic implants for limb amputation are progressively evolving to overcome limitations of socket.  In a systematic review, these investigators examined the use, safety in terms of rate of infection and complications, and reported outcomes of upper and lower limb (UE and LE) osseointegrated prosthetic implants.  They carried out a systematic search for studies that examined outcomes of OI technique in case of UL and LE amputees according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement with a PRISMA checklist and algorithm.  MINORS (methodological items for non-randomized studies) score was used for methodologic assessment.  A total of 17 studies regarding the treatment of patients with UE or LE amputation treated with an osseointegrated prosthesis were included.  The overall rate of infections was 32 %.  All the clinical outcomes reported were related to LE.  No clinical data for UE was found.  The post-operative mean value of mental component summary (MCS) and physical component summary (PCS) of Short Form 36 (SF-36) Health Survey, and questionnaire for persons with a trans-femoral amputation (Q-TFA) was 55.1, 45.4 and 73.8, respectively, while 6-minute walk test (6MWT) and the timed up and go (TUG) test scored an average value of 388 meters and 11.5 seconds, respectively.  MINORS score ranged from 5 to 13, with a median of 11 [interquartile range (IQR), 9 to 11].  The OI was associated to a high rate of post-operative complications; however, significant improvement in clinical outcomes compared to pre-operative time were shown.  The authors concluded that available evidence was limited, but suggested good clinical outcomes and significant survivorship of the implants.  Moreover, these researchers stated that further clinical studies are needed to establish which kind of implant is associated to higher clinical performance and lower rate of post-operative complications and infections.

Overmann and Forsberg (2020) stated that transdermal osseointegrated amputation surgery is an evolving concept in amputee care.  The successful anchorage of a percutaneous metal implant requires optimization of the host bone, the implants surface, and the skin-implant interface.  Osseointegration will not occur without synergy between these 3 components.  This treatment has the potential to benefit amputees worldwide, who would otherwise not be able to tolerate a traditional prosthesis.  Osseointegration must be approached with caution and carried out under the supervision of a multi-disciplinary team of surgical and rehabilitation specialists.  The life-long clinical challenges of OI, including infection and loss of integration, require constant surveillance to combat.  Emerging sensor technologies leverage the percutaneous nature of the metal implant to examine its internal environment.  These sensors could provide the real time status of the endosteal surface.  These researchers stated that while some laboratory studies showed promising results of these proof-of-concept (POC) technologies, more investigation is needed to show that these sensors would be both safe and effective in clinical application.

Black et al (2023) stated that LE osseointegrated prostheses are a novel alternative to traditional socket-suspended prostheses, which are often associated with poor fit, soft tissue damage, and pain.  Osseointegration eliminates the socket-skin interface and allows for weight-bearing directly on the skeletal system; however, these prostheses can also be complicated by post-operative issues that can negatively impact mobility and QOL.  Little is known regarding the incidence of or risk factors for these complications as few centers currently perform the procedure.  These researchers carried out a retrospective analysis on all patients who underwent single-stage LE osseointegration at the authors’ center between 2017 and 2021.  Patient demographics, medical history, operative data, and outcomes were collected.  Fisher exact test and unpaired t-tests were conducted to identify risk factors for each adverse outcome, and time-to-event survival curves were generated.  A total of 60 patients met the inclusion criteria: 42 men and 18 women with 35 TF and 25 trans-tibial (TT) amputations.  The cohort had an average age of 48 years (range of 25 to 70 years) and follow-up period of 22 months (range of 6 to 47 months).  Indications for amputation were trauma (n = 50), prior surgical complication (n = 5), cancer (n = 4), and infection (n = 1).  Post-operatively, 25 patients developed soft tissue infections, 5 developed osteomyelitis, 6 had symptomatic neuromas, and 7 required soft tissue revisions.  Soft tissue infections were positively correlated with obesity and female sex.  Neuroma development was associated with increased age at OI.  Neuromas and osteomyelitis were both associated with decreased center experience.  Subgroup analysis by amputation etiology and anatomic location did not show significant differences in outcomes.  Notably, hypertension (n = 15), tobacco use (n = 27), and prior site infection (n = 23) did not correlate with worse outcomes; 47 % of soft tissue infections occurred in the 1st month following implantation, and 76 % occurred in the first 4 months.  The authors concluded that these data provided preliminary insights into risk factors for post-operative complications arising from LE osseointegration.  These factors are both modifiable (body mass index [BMI], center experience), and unmodifiable (sex, age).  These researchers stated that as this procedure continues to expand in popularity, such results are needed to generate best practice guidelines and optimize outcomes.  They stated that further prospective studies are needed to confirm the above trends.

Hoellwarth et al (2024) noted that UL amputation is disabling.  ULs are necessary for many domains of life, and few effective motor and sensory replacements are accessible.  Approximately 41,000 individuals in the U.S. have UL amputation proximal to the fingers, 2/3 of (all) traumatic amputations are UL4, and 80 % of UL amputations are carried out for trauma-related etiologies.  Socket prosthesis (SP) abandonment remains high because of the lack of sensation, limited prosthesis control, perceived weight, and difficulty in comfortably wearing the SP.  Transcutaneous OI surgically inserts a bone-anchored implant, passed through a transcutaneous portal to attach a terminal device, improving amputee rehabilitation by reducing perceived weight, conferring osseo-perception, and increasing wear time.  Without the socket, all residual skin and musculature remain available for transcutaneous myo-electrodes.  These researchers described single-stage radius and ulna press-fit OI (PFOI) after TF amputation.  This technique resembles a LE PFOI.  More importantly, at-risk nerves and vessels are different, and implant impaction must be gentler as a result.  The surgery is indicated for patients who are dissatisfied with SP rehabilitation or declining alternative rehabilitative options, and who are motivated and enabled to procure, train with, and use a forearm prosthesis.  An engaged prosthetist is critical.  Surgical steps are exposure, bone-end and canal preparation, first implant insertion, purse-string muscle closure, confirmation that radius-ulna motion remains, performing the prior steps for the other, and closure (including potential nerve reconstruction, soft-tissue contouring, and portal creation).  Although the patient in this case did not require nerve procedures to address pain or to create targets for transcutaneous myo-electrodes, targeted muscle reinnervation or a regenerative peripheral nerve interface procedure could be performed following exposure.  The authors noted that only 3 trans-forearm OI publications totaling 10 limbs could be identified, limiting the ability to determine generalizable outcomes.  These investigators stated that OI prostheses, being skeletally anchored, feel lighter to patients than SPs, which should confer better outcomes.  In 1 patient, multiple implant fractures and infection prompted additional surgeries.  Peri-prosthetic bone fractures and non-infectious loosening have not been documented for UL osseointegration.  Moreover, these researchers stated that prostheses must be individualized to the patient's elbow flexion and radioulnar rotation.  An attentive prosthetist must be ensured pre-operatively.  Achieving the demonstrated outcomes requires more therapy and retraining than walking with an OI lower-extremity prosthesis.  Patients must expect at least several months of spending multiple hours daily engaging in self-directed rehabilitation.

Rehani et al (2024) stated that bone-anchored prostheses (BAP) are an advanced reconstructive surgical approach for individuals who had TF amputation and are unable to use the conventional socket-suspension systems for their prostheses.  Access to this technology has been limited in part due to the lag between the start of a new procedure and the availability of evidence that is needed before making decisions regarding widespread provision.  In a systematic review, these investigators presented as a single-resource up-to-date information on aspects most relevant to decision makers, i.e., clinical efficacy, safety parameters, patient experiences, and health economic outcomes of this technology.  They carried out a systematic search of the literature using PubMed, Medline, Embase, CINAHL, Cochrane Library, the Core Collection of Web of Science, CADTH's Grey Matters, and Google Scholar up until May 31, 2023.  Peer-reviewed original research studies on the outcomes of clinical effectiveness (HR-QOL, mobility, and prosthesis usage), complications and AEs, patient experiences, as well as health economic outcomes were included.  The quality of the studies was assessed using the Oxford Centre for Evidence-Based Medicine Levels of Evidence and ROBINS-I, as appropriate.  A total of 50 studies met the inclusion criteria, of which 12 were excluded; 38 studies were finally included in this review, of which 21 reported on clinical outcomes and complications, 9 case-series studies, and 1 cohort study focused specifically on complications and AEs, and 2 and 5 qualitative studies reported on patient experience and health economic assessments, respectively.  The most common study design was a single-arm trial (pre-/post-intervention design) with varying lengths of follow-up.

The authors concluded that the effectiveness of this technology is evident in selected populations.  Overall, patients reported increased health-related quality of HR-QOL, mobility, and prosthesis usage post-intervention.  The most common complication is a superficial or soft-tissue infection, and more serious complications are rare.  Patient-reported experiences have generally been positive.  These researchers stated that the evidence points to the cost-effectiveness of this technology for those who suffer poor outcomes with standard-of-care socket prostheses, although further work is needed to collect sufficient data for rigorous health economic analysis.  These investigators stated that standardizing outcome-tracking would aid in synthesizing evidence across centers.  In addition, these researchers stated that this technology may offer no additional advantage to those who are functioning well with their socket-suspended prostheses.

Osseointegrated Prosthesis for Trans-Femoral Amputees

Cano et al (2018) examined the effect of a distal weight-bearing implant (DWBI) on well-being in patients with TF amputations using the visual analog scale (VAS).  A total of 29 patients from 5 hospitals with previous TF amputations were surgically implanted with an osseoanchored implant with a distal spacer that allows a direct load on the residuum over the distal surface of the socket.  Patients were followed for a 14-month period and evaluated pre-surgically and post-surgically using the VAS.  The Wilcoxon test was used to examine the differences between variables.  VAS mean scores improved significantly after intervention.  The authors concluded that significant and clinically meaningful improvements in the VAS score suggested overall improvement in well-being for patients after receiving a DWBI.  Moreover, these researchers stated that further studies in larger clinical trials, over longer follow-up periods, and using a wider range of relevant outcome measures are needed to confirm the improvements observed.

The authors stated that this study had several drawbacks.  First, the total number of patients included in this study was small (n = 23); however, given the design of the clinical trial where each patient acted as his/her own reference, the internal validity of the trial was very high.  The complication rate of 17 % was not small and further reduced their already small starting sample size.  Complications were due to uncontrollable circumstances and could continue to present a problem.  The 2nd drawback was the heterogeneity of the sample, given mainly by the causes of amputation.  The different etiologies of amputation were linked with different co-morbidities and patient characteristics.  Third, the socket used after implant was the same for all patients and not the same as they previously used; thus, it could account for some of the decrease in pain.  However, the type of socket used was possible owing to the DWBI, so therefore, the decrease in pain in the end is caused by the use of the DWBI.

Matthews et al (2019) noted that amputation of a limb impacts on patients' self-perception and quality of life (QOL).  Prostheses directly anchored to the skeleton are being examined, aiming to avoid soft tissue complications.  These investigators reported outcome data for the United Kingdom Trial of the OPRA Implant System with a minimum of 9-year follow-up.  A total of 18 TF amputees received unilateral implants between 1997 and 2008; 5 were implanted before a formalized protocol called OPRA was developed.  Mean follow-up of the Pre-OPRA group was 11.4 years (1.8 to 18.6 years), while for the Post-OPRA group it was 12.3 years (2.9 to 15.9 years).  The Kaplan-Meier cumulative survivorship was 40 % for the Pre-OPRA group and 80.21 % for the Post-OPRA group.  Five implants (28 %) have been removed, 3 (17 %) for deep infection, 1 (5.6 %) for chronic pain, later proven to be infected, and 1 (5.6 %) due to implant fracture secondary to loosening due to infection.  Two patients (11 %) had peri-implant infections suppressed with oral antibiotics; 11 cases (61 %) of superficial infection were successfully treated with antibiotics; 36-SF Health Survey and Q-TFA showed significant improvements in QOL up to 5 years following implantation.  The authors concluded that this small cohort of patients demonstrated osseointegrated prosthesis allowed prolonged usage and improved patients' QOL compared to conventional prostheses.  They stated that these prostheses may provide a future gold standard for amputees and this study provided the first outcome data over such a time period to be reported from outside of the developers group.

In a cohort study, Hagberg et al (2020) described implant and PRO in patients with a unilateral TFA treated with a bone-anchored, transcutaneous prosthesis.  All patients with a unilateral TFA treated with the OPRA implant system in Sahlgrenska University Hospital, Gothenburg, Sweden, between January 1999 and December 2017 were included.  The cohort comprised 111 patients (78 male (70 %)), with a mean age 45 years (17 to 70).  The main reason for amputation was trauma in 75 (68 %) and tumors in 23 (21 %).  Subjects answered the Q-TFA before treatment and at 2, 5, 7, 10, and 15 years' follow-up.  A prosthetic activity grade was assigned to each patient at each time-point.  All mechanical complications, defined as fracture, bending, or wear to any part of the implant system resulting in removal or change, were recorded.  The Q-TFA scores at 2, 5, 7, and 10 years showed significantly more prosthetic use, better mobility, fewer problems, and an improved global situation, compared with baseline.  The survival rate of the osseointegrated implant part (the fixture) was 89 % and 72 % after 7 and 15 years, respectively.  A total of 61 patients (55 %) had mechanical complications (mean of 3.3 (SD 5.76)), resulting in exchange of the percutaneous implant parts.  There was a positive relationship between a higher activity grade and the number of mechanical complications.  The authors concluded that compared with before treatment, the PRO was significantly better and remained so over time.  Although osseointegration and the ability to transfer loads over a 15-year period have been demonstrated, a large number of mechanical failures in the external implant parts were found.  Since these were related to higher activity, restrictions in activity and improvements to the mechanical properties of the implant system are needed.

Mortazavi et al (2025) noted that TF amputees face significant functional limitations with traditional socket prostheses.  In a retrospective study, these researchers examined the safety and effectiveness of the OPRA implant system in improving the QOL for these patients.  This trial was carried out on 22 TF amputees (20 men, 2 women; mean age of  44.6 years) who underwent OPRA implant surgery between 2019 and 2021.  Participants were evaluated pre-operatively and followed for 2 years post-surgery.  Outcomes were measured using the Q-TFA, pain scores, and complication rates.  At 2-year follow-up, significant improvements were observed in Q-TFA scores for prosthetic use (30.41 ± 10.90 to 87.68 ± 11.42, p < 0.001), mobility (44.36 ± 15.57 to 71.45 ± 13.72, p < 0.001), problem score (52.40 ± 10.22 to 25.81 ± 9.66, p < 0.001), and global score (43.45 ± 10.87 to 74.95 ± 21.82, p < 0.001).  Mean daily prosthesis usage increased from 3.77 ± 2.59 hours to 13.43 ± 3.76 hours (p < 0.001).  Complications included minor discharge (67.5 %), significant discharge requiring surgical intervention (13.6 %), prosthesis removal (9 %), as well as peri-prosthetic fracture (4.5 %).  The authors concluded that the OPRA implant system significantly improved functional outcomes and QOL for TF amputees over 2 years.  While complication rates were notable, most were manageable with conservative treatment.  These researchers stated that these findings suggested that osseointegrated prostheses offer a promising alternative to socket prostheses for suitable candidates, although further investigations with larger cohorts are needed to confirm long-term safety and effectiveness.

Osseointegrated Prosthesis for Trans-Tibial Amputees

Pitkin and Frossard (2021) noted that osseointegrated implants for direct skeletal attachment of TT prosthesis carry risks that are yet to be fully resolved, such as early loosening, mechanical failure of percutaneous and medullar parts of implant, peri-prosthetic issues, and infections.  Under-loading could lead to early loosening and infection; and over-loading might compromise the bone-implant interface; thus, Goldilocks loading regimen applied by TT bone-anchored prostheses is critical for safe and efficient development of OI around the implant during rehabilitation and beyond.  In a retrospective study, these researchers hypothesized that Goldilocks loading could be achieved when ambulating with a so-called anthropomorphic prosthetic ankle showing moment-angle relationship similar to a sound ankle.  Quantitative characteristics of the moment-angle curve of the sound ankle during dorsiflexion phase of a free-pace walking were extracted for 4 able-bodied subjects (experiment 1).  A slope of the moment-angle curve (stiffness) was calculated twice: for the 1st half, and for the 2nd half of the moment-angle curve.  The difference of stiffnesses (those at the 2nd half minus at the 1st half) was called the index of anthropomorphicity (IA).  By definition, positive IA was associated with concave shape of the moment-angle curve, and the negative IA was associated with convex shape.  In experiment 2, the same recordings and calculations were carried out for 3 subjects fitted with TT osseointegrated fixation during walking with their usual feet and the Free-Flow Foot (Ohio Willow Wood).  The Free-Flow Foot was selected for its anthropomorphicity demonstrated in the previous studies with amputees using traditional socket attachment.  The IA was 5.88 ± 0.93 for the able-bodied subjects, indicating that the stiffness during the 1st part of the dorsiflexion phase was substantially fewer than during the 2nd parts, as the calf muscles resisted to angulation in ankle substantially less than during the 2nd part of dorsiflexion phase.  For amputees fitted with Free-Flow Foot, IA was 2.68 ± 1.09 and −2.97 ± 2.37 for the same amputees fitted with their usual feet.  The authors concluded that IA, while of different magnitude, were positive in control able-bodied group and in the amputee group wearing Free-Flow Foot, which was qualitatively associated with concave shape of their moment-angle curves.  The 3 usual feet worn by the subjects were classified as non-anthropomorphic as their individual moment-angle curves were convex and the corresponding IAs were negative.  Furthermore, this study showed that a foot with anthropomorphic characteristics tended to decrease maximal loads at the bone-implant interface as compared to the non-anthropomorphic feet and possibly may minimize the risks to compromise the integrity of this interface.  These researchers stated that this study should be considered as a stepping-stone for manufacturers of components, prosthetic care providers, and decision-makers developing international standards and guidelines toward better evidence-based prescription of safe prosthetic components to growing population of individuals with TT amputation fitted with osseointegrated fixation worldwide.  They stated that future longitudinal studies should compare ankle stiffness with various prosthetic constructs (e.g., components, alignment) for a larger cohort of individuals fitted with a TT prosthesis.  This could provide a better understanding of intra- and inter-variability inherent to design of components and daily activities.  Subsequent cross-sectional studies could establish a link between ankle stiffness outcomes and additional 3D biomechanical (e.g., dynamics, kinematics, joint work, and power), physiological (e.g., EMG of residuum muscles, metabolic energy consumption, development of OI, and skin damages), and subjects’ experience (e.g., PEQm, TAPES-M) information.

The authors stated that this study presented the typical drawbacks of a retrospective, preliminary study comparing kinematic and kinetic data collected with 2 small and unrelated series.  As these investigators reported Frossard et al (2019), the interpretation of differences in stiffness outcomes between prostheses was limited mainly because of unknown effects of confounders (e.g., individual length of residuum, distal position of transducer, short acclimation with Free-Flow Foot, foot size, and footwear).  Unknown were also differences in spatiotemporal gait characteristics (e.g., speed of walking, walking base, step, and stride length), kinematics (e.g., trunk bending, knee flexion, and hip range of movement) and kinetics (e.g., knees and hips joint power information.  Furthermore, the comparison on stiffness between series of able-bodied and individuals with TT amputation was limited by the discrepancies in measurements of ankle angle of dorsiflexion (e.g., automated 3D Vicon motion capture versus manual 2D Kinovea movement analysis) and bending moment (e.g., inverse dynamics using fixed force plates versus direct measurement using wearable load cell).

Donnelley et al (2021) synthesized extant literature on the cost-effectiveness of prosthetic interventions and examined applicability to low- and middle-income country (LMIC) settings.  These investigators carried out a systematic literature review using subject headings including "prosthetics", "amputation" and "cost analysis" with PubMed, Embase, and Web of Science search engines, yielding 1,194 articles.  An additional 22 articles were identified via backward citation searching for 1,144 total after duplicate removal.  The search was last run in May 2019.  Studies were included if they conducted an economic analysis of a UE or LE prosthetic device.  Studies were excluded if full text was unavailable in English; study was a systematic review or meta-analysis; or study did not have a prosthetic comparison group.  Using DistillerSR software, 2 authors independently conducted title and abstract screening.  One author conducted full-text screening.  The proportion of initially identified studies that met final inclusion criteria was 1 % (12 of 1,144).  Data were dually extracted by 2 authors and reviewed by 3 additional authors.  All included studies (n = 12) examined LE amputations comparing advanced technology.  No studies were carried out in LMICs.  Comparable data between studies demonstrated the cost-effectiveness of microprocessor- over non-microprocessor-controlled knees TF amputation in high-income settings; equivocal findings regarding osseointegrated versus socket-suspended prostheses; and increased cost for ICEX and modular socket systems over patellar tendon-bearing socket systems with no functional improvement.  The authors concluded that there are few prosthetic cost analyses in the literature; additional analyses are needed to determine the direct and indirect costs associated with prosthetic acquisition, fitting, and maintenance; the costs of amputee rehabilitation; and long-term economic and QOL benefits.  Such studies may guide future prosthetic and rehabilitative care, especially in resource-austere settings where prosthetic needs are greatest.

Akhtar et al (2021) noted that the management of peripheral vascular disease (PVD) can require amputation; and OI surgery is an emerging rehabilitation strategy for amputees.  These investigators reported on the findings of 6 patients who had PVD requiring TT amputation (PVD-TTA) and either simultaneous or subsequent OI (PVD-TTOI).  A total of 6 patients (aged 36 to 84 years) with TTA and pre-existing PVD underwent OI between 2014 and 2016 and were followed-up for 3 to 5 years.  Pre- and post-operative clinical and functional outcomes (pain, prosthesis wear time, mobility, walking ability, and QOL) and AEs (including infection, fracture, implant failure, revision surgery, additional amputation, and death) were prospectively recorded.  All patients' mobility improved following OI; 3 patients initially had required the use of a wheelchair, precluding baseline walking tests; the other 3 were classified as K level 1 or 2, with mean baseline TUG test = 14.0 ± 2.2 s and 6MWT = 262 ± 75 m.  At the time of the latest follow-up, all patients were K level 2 or 3; mean TUG = 12.7 ± 7.2 s and 6MWT = 353 ± 148 m; 4 patients wore their prosthesis for 16 hours or more daily; 3 patients had superficial soft-tissue infections; 1 other patient experienced recurrent infections 2.8 years after OI requiring debridement and TF amputation; the patient died 2 days following surgery from myocardial infarction (MI) caused by coronary atherosclerosis.  The authors concluded that all 6 patients who underwent PVD-TTOI in this case-series survived through 2 years.  Patients who initially had used a wheelchair achieved and maintained independent, unaided ambulation until PVD-related impairments in the contralateral leg occurred in 1 patient.  Patients previously using a traditional socket prosthesis reported improvement in mobility and QOL.  One patient's death underscored the importance of careful patient selection.  However, marked improvement in the other 5 patients suggested cautious optimism that PVD-TTA is not an absolute OI contraindication; conscientious further investigation appeared appropriate. 

The authors stated that the main drawback of this trial was the small cohort (n = 6 patients).  Furthermore, there were multiple differences among the patients -- 3 patients were long-term amputees, while 3 had primary amputation with simultaneous OI.  There was also variation in specific dysvascular etiologies, age, co-morbidities, and potentially other likely relevant factors, such as employment and depression status, that were not evaluated.

Akhtar et al (2022) stated that management of total knee replacement (TKR) infection may sometimes prompt knee fusion (KF) or TF amputation (TFA), both associated with low mobility and QOL.  Transcutaneous OI for amputees (TOFA) provides superior mobility and QOL versus traditional socket prostheses but has not been studied for patients with a history of infected TKR.  These investigators tested the following hypothesis: Patients who have had TFA or KF following infected TKR achieve better mobility and QOL following TF osseointegration.  They carried out a retrospective evaluation of the prospectively maintained registry identified 10 patients who had prior infected TKR.  The mobility assessments (patient daily prosthesis wear time, K-level, TUG, 6MWT) and QOL surveys (Questionnaire for Persons with a Transfemoral Amputation Global, Mobility, and Problem scores) were compared pre-operatively and after at least 2 years.  Complications requiring an additional surgery were also evaluated.  Daily wear hours, K-level, and 6MWT and Questionnaire for Persons with a Transfemoral Amputation Global and Problem scores significantly improved (p < 0.05).  Through 1 year, 4 patients (40 %) had additional surgeries.  After several years, 7 patients (70 %) had at least 1 additional surgery, and 5 (50 %) had multiple, for an average of 1 debridement and 1.3 soft-tissue re-fashioning per patient; and 1 patient died of newly diagnosed cancer 1 year after transcutaneous OI for amputees.  The authors concluded that TF osseointegration provided significantly better mobility and QOL versus KF or a TFA with traditional socket prostheses following infected TKR.  Furthermore, technique improvements to prevent subsequent surgeries may provide an increasingly streamlined experience.

The authors stated that the main drawback of this study was the small cohort of 10 subjects.  There was also considerable heterogeneity in the demographic characteristics and prior surgical history among the patients: Some patients had KF, whereas others had TFA, for various durations before TOFA.  The merits of this study included the minimum 2-year follow-up for all subjects (except the deceased patient), along with the attention to mobility and also QOL data metrics.  There were several potential sources of bias.  TOFA remains relatively obscure and financially expensive, limiting potential patient awareness and access.  Furthermore, highly functional and satisfied patients with KF or TFA may not seek TOFA, potentially biasing the selection in this study.  No patients were lost to follow-up, so reporting bias was limited.  The team’s high-volume TOFA experience may also bias the reproducibility of the results.

Mohamed et al (2022) stated that septic loosening and stem breakage due to metal fatigue is a rare but well-known cause of orthopedic implant failure.  This may also affect the components of the osseointegrated implant system for individuals with TFA who subsequently undergo revision.  Identifying risk factors is important to minimize the frequency of revision surgery following implant breakage.  In a retrospective, comparative study, these investigators determined: What proportion of patients who received an osseointegrated implant following TFA underwent revision surgery, and what were the causes of those revisions?  What factors were associated with revision surgery when stratified by the location of the mechanical failure and (septic) loosening (intra-medullary stem versus dual cone adapter).  Between May 2009 and July 2015, these researchers treated 72 patients with an osseointegrated implant.  Inclusion criteria were a minimum follow-up of 5-years and a standard press-fit cobalt-chromium-molybdenum (CoCrMb) TF osseointegrated implant.  Based on that, 83 % (60 of 72) of patients were eligible; a further 3 % (2 of 60) were excluded because of no received informed consent (n = 1) and loss to follow-up (n = 1).  Eventually, the authors included 81 % (58 of 72) of patients for analysis in this trial.  They compared patient characteristics (gender, age, and BMI), implant details (diameter of the intra-medullary stem, length of the dual cone, and implant survival time), and event characteristics (infectious complications and distal bone resorption).  The data were retrieved from the electronic patient file and from the authors’ cloud-based database and analyzed by individuals not involved in patient care.  Failures were categorized as: mechanical failures, defined as breakage of the intra-medullary stem or dual-cone adapter, or (septic) loosening of the osseointegrated implant.  A total of 34 % (20 of 58) of patients had revision surgery.  In 12 % (7 of 58) of patients, the reason for revision was due to intra-medullary stem failures (6 breakages, 1 septic loosening), and in 22 % (13 of 58) of patients it was due to dual-cone adaptor failure (10 weak-point breakages and 4 distal taper breakages; 1 patient broke both the weak-point and the dual-cone adapter).  Smaller median stem diameter (failure: 15 mm [inter-quartile range (IQR) 1.3], non-failure: 17 mm; IQR 2.0, difference of medians 2 mm; p < 0.01) and higher median number of infectious events (failure: 6; IQR 11, non-failure: 1; IQR 3.0, difference of medians -5; p < 0.01) were associated with revision intra-medullary stem surgery.  No risk factors could be identified for broken dual-cone adapters.  The authors concluded that possible risk factors for system failure of this osteointegration implant included small stem diameter and high number of infectious events.  These researchers did not find factors associated with dual-cone adapter weak-point failure and distal taper failure, most likely because of the small sample size.  When treating a person with a LE amputation with a CoCrMb osseointegrated implant, these researchers recommended avoiding a small stem diameter.  They stated that further investigation with longer follow-up is needed to study the success of revised patients.  

Black et al (2022) noted that patients with TF and TT amputations generally rely on socket-suspended (SS) prostheses for ambulation.  The use of these aids can be complicated by poor fit, leading to tissue damage, pain at the socket-limb interface, and inability to ambulate.  Osseointegrated implants directly anchor a prosthesis to the patient's residual limb, eliminating these issues.  However, they require customized components and additional surgeries.  In a retrospective, chart review, these researchers carried out the 1st cost-benefit analysis of OI prostheses compared to SS prostheses for LE amputees in the U.S.  This study was conducted on all patients who received unilateral lower limb OI prostheses at the authors’ institution.  Costs were calculated in a bottom-up approach using Current Procedural Terminology (CPT) codes; utilities and SS prosthesis costs were derived from previous studies.  A Monte Carlo model was used to project costs and lifetime quality-adjusted life years (QALY) for OI and SS prostheses, and the incremental cost-effectiveness ratio (ICER) of OI compared SS prostheses was determined.  A total of 25 patients (12 female) were included in the study.  The mean follow-up was 17 months post-implantation.  The average cost of OI surgery was $54,463; 20 % of patients required pre-implantation soft tissue revision surgery ($49,191).  Complication rates per year and average costs were as follows: soft tissue infection (29 %, $435), bone/implant infection (11 %, $11,721), neuroma development (14 %, $14,659), and mechanical failure (17 %, $46,513); and the ICER was $44,660.  A cost-effectiveness acceptability curve demonstrated that OI was favored over SS in 78 % of cases at a willingness-to-pay of $100,000 per QALY.  In a 1-way sensitivity analysis, the ICER was most sensitive to the mechanical failure rate, mechanical failure cost, and prior SS prosthesis costs.  The authors concluded that the model showed that OI prostheses provided a higher QOL at affordable costs when compared to poorly tolerated SS prostheses in patients with LE amputations in the U.S.  The cost-effectiveness was largely determined by the patient's previous SS prosthesis costs and was limited by the frequency and costs of OI mechanical failure.  These researchers stated that more research is needed to understand the long-term benefits and risks of OI prostheses.

In a retrospective study, Orgel et al (2022) examined differences in functional outcome and satisfaction of patients treated with a transcutaneous osseointegrated prosthetic systems (TOPS) and patients using socket prosthesis after TFA.  This analysis included patients from a single center; and was carried out between February 2017 and December 2018.  A total of 139 patients with prosthesis were included and they were divided into 2 comparable groups (socket and TOPS group).  Incomplete data sets were excluded.  This led to n = 36 subjects for the socket group, and n = 33 for the TOPS group.  Functional outcome and satisfaction were evaluated by PROMs.  The used PROMs included Q-TFA, EQ5D-5L, Satisfaction with Prosthesis Questionnaire (SAT-PRO), Prosthesis Mobility Questionnaire (PMQ 2.0) and Functional Independence Measure (FIM).  Significant results in favor of TOPS patients were identified for the EQ-5D 5L (p = 0.004), Q-TFA (p = 0.000), SAT-PRO (p = 0.000) and PMQ 2.0 (p = 0.000).  For FIM, no statistical significance was found (p = 0.318).  The authors concluded that in this study, TF amputees treated with a TOPS showed significantly higher scores for mobility and satisfaction, showing the high potential of TOPS in the prosthetic treatment of patients with TF amputation with regard to their functional abilities in daily life.

This analysis had several drawbacks.  These researchers stated that the high percentage of excluded data due to incomplete information should be critically noted.  Many patients often did not fill out the entire questionnaires.  This circumstance was because some of the subjects only visited the outpatient clinic once.  They returned the incomplete questionnaire, so that the missing information only became apparent during the anonymous retrospective analysis.  These investigators then no longer had the opportunity to complete the data.  Moreover, this was a retrospective study with a small collective, even though it was also a large number of cases for this topic compared to the current literature.  Furthermore, the data inconsistency of the descriptive data concerning the socio-cultural sector should also be highlighted.  This inconsistency could be explained by the fact that these were discrete and personal topics on which not every subject wanted to give information.  A further limitation of the study was the study design itself.  It is well known that prospective study designs offer much more value; however, this dataset was created retrospectively.

Association Between Blood Markers and the Progression of Osseointegration in Percutaneous Prostheses Patients

Miller et al (2024) stated that patients implanted with OI prosthetic systems have reported vastly improved UE and LE prosthetic function compared with their previous experience with socket-suspension systems.  However, OI systems have been associated with superficial and deep-bone infections and implant loosening due, in part, to a failure of the OI process.  Although monitoring the OI using circulating biomarkers has clinical relevance for understanding the progression of OI with these devices, it has yet to be established.  In a pilot study, a total of 10 patients were enrolled.  Blood samples were collected at pre-selected times, starting before implantation surgery, and continuing to 12 months after the 2nd surgery.  Bone formation markers, bone resorption markers, and circulating amino acids (AAs) were measured from blood samples.  A linear mixed model was generated for each marker, incorporating patient ID and age with the normalized marker value as the response variable.  Post-hoc comparisons were made between 1 week before Stage 1 Surgery and all subsequent time-points for each marker, followed by multiple testing corrections.  Serial radiographic imaging of the residual limb containing the implant was obtained during follow-up, and the cortical index (CI) was calculated for the bone at the porous region of the device.  Two markers of bone formation, specifically bone-specific alkaline phosphatase (Bone-ALP) and amino-terminal pro-peptide of type I procollagen (PINP), exhibited significant increases when compared with the baseline levels of unloaded residual bone before the initial surgery, and they subsequently returned to their baseline levels by the 12-month mark.  Patients who experienced clinically robust OI experienced increased cortical bone thickness at the porous coated region of the device.  A medium correlation was observed between Bone-ALP and the porous CI values up to PoS2-M1 (p = 0.056), while no correlation was observed for PINP.  The authors concluded that an increase in bone formation markers and the lack of change observed in bone resorption markers likely reflected increased cortical bone formation induced by the end-loading design of the Utah OI device used in this study.  These researchers stated that a more extensive study is needed to validate the correlation observed between Bone-ALP and porous CI values.

The authors stated that this study had several drawbacks.  First, enrollment for the current study was capped at 10 patients due to the nature of the FDA early pre-feasibility study requirements from which these samples were obtained.  This limitation was amplified given that 2 patients experienced device failure, effectively reducing the sample size at later time-points in the study.  Second, all patients enrolled in this study were male indicating these results may not generalize to females undergoing percutaneous OI device implantation.  Third,, during the implantation of the endoprosthesis in these patients, it was noted that some of them did not achieve complete seating on the implant shoulder.  This lack of seating likely contributed to the distal rounding observed in these patients, which hindered the ability to obtain consistent measures of the CI at the distal end of the femur.

Muderis et al (2024) noted that most patients use a traditional socket prosthesis (TSP) to ambulate independently following TT amputation; however, these patients usually require prosthesis repairs more than twice-yearly and an entirely new prosthesis every 2 years.  In addition, TT amputation patients have 4 times the skin ulceration rate of TF patients, prompting more frequent prosthesis re-fitting as well as diminished use. Trans-tibial OI (TT-OI) is a promising technique to address the limitations of TSP; however, this approach remains under-studied with only 4 cohorts totaling 41 total procedures reported previously.  Continued concerns regarding the risk of infection and questions as to functional capacity post-operatively have slowed adoption of TT-OI globally.  In a retrospective, observational cohort study, these researchers reported the changes in mobility, quality of life (QOL), and the safety profile of the largest described cohort of patients with unilateral TT-OI following traumatic amputation.  The cohort consisted of patients with data outcomes collected before and after OI intervention.  Subjects were 21 skeletally mature adults (14 [67 %] were male, 1 [5 %] smoked, 3 [14 %] had diabetes mellitus) who had failed socket prosthesis rehabilitation, with at least 2 years of post-OI follow-up.  Mobility was evaluated by K-level, TUG, and 6MWT.  QOL was assessed by survey: daily prosthesis wear hours, prosthesis problem experience, general contentment with prosthesis, and SF-36; AEs included any relevant unplanned surgery such as for infection, fracture, implant loosening, or implant failure.  All patients showed statistically significant improvement following OI surgery with respect to K-level, TUG, 6MWT, prosthesis wear hours, prosthesis problem experience, general prosthesis contentment score, and SF-36 Physical Component Score (p < 0.01 for all); 3 patients had 4 unplanned surgeries: 2 soft tissue re-fashioning, and 1 soft tissue debridement followed eventually by implant removal.  No deaths, post-operative systemic complications, more proximal amputations, or peri-prosthetic fractures occurred.  The authors concluded that  TT-OI is likely to confer mobility and QOL improvements to patients dissatisfied with TSP rehabilitation following unilateral traumatic TT amputation; and AEs were relatively infrequent and not further disabling.  These researchers stated further use of TT-OI for judiciously selected patients appeared reasonable and warranted further prospective investigations.  Level of Evidence = II.

The authors stated that the principal drawback of this trial was the sample size, and the difficulty in generalizing these results.  At 21 patients, it was not large enough to definitively understand TT-OI outcomes or fully establish definitive indications or contraindications for OI reconstruction, although it was substantially larger than any TT-OI study to-date.  Second, the focus on traumatic TT amputation patients may have limited generalizability to other TT amputation cohorts, though the narrowly selected cohort aided in understanding outcomes for these specific patients.  Lastly, this study examined multiple perspectives of rehabilitation by surveying patient self-reported experience (SF-36 and self-assessments) and quantified mobility using both clinician-reported (K-level) and objective modalities (TUG, 6MWT).

Simon et al (2025) stated that recent advancements in powered prosthetic leg devices offer enhanced potential for mobility for individuals with lower limb amputations; however, challenges persist, especially for individuals with TF amputations and short residual limbs.  In a single-case study, these investigators examined the combination of a bone-anchored prosthetic interface via OI and a powered knee-ankle prosthesis, aiming to evaluate initial feasibility, functionality, as well as user experience.  This case entailed a 39-year-old woman with a very short residual limb; she used the Hybrid Knee and Polycentric Ankle powered leg connected to an osseointegrated implant.  Training involved level-ground and incline walking, stair climbing, and sit-to-stand weight transfers.  Results showed successful ambulation across all activities, with the subject demonstrating ease in reciprocal stair climbing and improved ease of sit-to-stand movements compared to her prescribed, passive prosthesis.  User feedback highlighted the benefits of level-walking knee swing assist and powered ankle plantarflexion, and stair ascent and sit-to-stand knee extension power, although cosmesis and weight remained areas of preference for her prescribed device.  The authors concluded that this case underscored the potential of combining osseointegration and powered prostheses to enhance functionality and mobility, paving the way for further research on this promising technology.

In a pre-post, observational, single-cohort study, Hendershot et al (2025) examined functional outcomes at 12 months and 24 months after TF-OI using established performance-based assessments.  A total of 47 service members (mean age ± SD, 38 ± 9 years) with traumatic unilateral (n = 22) and bilateral (n = 25) lower limb loss were included in this study.  Before OI, n = 2 unilateral; and n = 7 bilateral were not ambulatory on full-length prostheses; subjects received TF-OI (2-stage threaded implant).  Main outcome measures included 6MWT, TUG, 4 Square Step Test (4SST), (Bilateral) Amputee Mobility Predictor ([B]AMP), and Comprehensive High-level Activity Mobility Predictor (CHAMP).  For both unilateral and bilateral cohorts, the median performance-based functional outcomes were similar at 12 months and 24 months after versus before OI: 6MWT (373 m and 385 m versus 417 m; p > 0.31), TUG (9.7 s and 9.6 s versus 9.8 s; p > 0.53), 4SST (9.5 s and 10.6 s versus 10.8 s; p > 0.11), and CHAMP (12.6 and 10.6 versus 12.3; p > 0.44).  Median BAMP scores were greater at 12 months (p = 0.029) and 24 months (p = 0.014) after versus before OI among the bilateral cohort (30 and 35 versus 16); median AMP scores were similar (p > 0.10) among the unilateral cohort across time-points (39 and 43 versus 40).  Among the 9 subjects not ambulating with full-length prostheses before OI, 8 became capable of ambulation on full-length prostheses 24 months after OI.  The authors concluded that while a lack of improvement in these particular outcomes was not exclusively suboptimal, especially considering the median scores at baseline reported here generally exceeded those of other cohorts (both before and sometimes even after OI), these findings contrasted with previous self-reported improvements in function following OI among service members with traumatic lower limb loss.  As such, these data appeared to emphasize the importance of a comprehensive approach with both subjective and objective (multi-disciplinary) outcomes to more fully characterize OI, especially within unique patient populations like young service members with traumatic lower limb loss.

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Appendix

The OPRA Implant System was approved by the Food and Drug administration (FDA) via humanitarian device exemption (HDE; H080004) on July 16, 2015.  It is indicated for patients who have trans-femoral amputation due to trauma or cancer and who have rehabilitation problems with, or cannot use, a conventional socket prosthesis. The OPRA Implant System is intended for skeletally mature patients who failed to receive benefit from socket prostheses due to problems such as:

• A short stump preventing the use of socket prosthesis
• Extensive area of skin grafting
• Pain
• Recurrent skin infections and ulcerations in the socket contact area
• Restricted mobility
• Socket retention problems due to excessive perspiration
• Soft tissue scarring
• Volume fluctuation in the stump.

The contraindications for the OPRA Implant System are:

• The patient’s skeletal growth is incomplete; completed skeletal growth is defined through the finding of generally closed epiphyseal zones on X-ray;
• The patient has atypical skeletal anatomy that may affect treatment with OPRA;
• Examples of atypical skeletal anatomy:
  
  
  • Skeletal dimensions outside defined interval
  • Developmental anomalies
  • Conditions which are not amenable to device insertion such as deformities, fracture, infection;
    
    
• The patient would have less than 2 mm of remaining cortex bone available around the implant, if implanted;
• The patient has osteoporosis;
• The patient is older than 65 years or younger than 22 years;
• The patient’s body weight is higher than 220 lbs including the prosthesis;
• Do not treat patients with the following concurrent diseases:
  
  
  • Severe peripheral vascular disease
  • Diabetic mellitus with complications
  • Skin disorders involving the residual extremity
  • Neuropathy or neuropathic disease and severe phantom pain
  • Active infection or dormant bacteria;
    
    
• The patient is pregnant;
• The patient is not expected to be able to comply with treatment and follow-up requirements.

Note: Clinical studies of the OPRA implant have shown that higher activity grades (corresponding to K3/K4 levels) were positively correlated with increased mechanical complications (Hagberg, et al., 2020).

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References