In 2005, there were approximately 1.6 million amputees in the United States, a prevalence of almost 1 in 200 people, and that number is expected to double by 20501. The global amputee census is difficult to establish2, but estimates have suggested that worldwide there is a lower-extremity amputation performed every 30 seconds for a patient with diabetes3. The current accepted standard for rehabilitation and mobility following amputation is a socket-mounted prosthesis. Unfortunately, problems are common. Up to three-quarters of patients undergoing a lower-extremity amputation experience skin ulcers or intolerable perspiration4, require frequent refitting5, or have prosthesis-fit issues due to residuum size fluctuation6; approximately 7% sustain a fracture in the residual limb7; and the majority have reported that they lack confidence with mobility8.
Osseointegration surgery of the appendicular skeleton for reconstruction in amputees is defined as a procedure in which a metal implant is directly anchored to the residual bone, which is then attached to a prosthetic limb using a transcutaneous connector through a small opening in the skin. This technique has gradually gained greater acceptance in the almost 30 years since the first osseointegration surgical procedure was performed in Sweden on May 15, 1990. On that date, a patient who had undergone bilateral traumatic transfemoral amputations a decade earlier had the first-stage titanium implant anchored to 1 of the femora9. This implant technology was based on the work of Per-Ingvar Brånemark, who first discovered that rabbit bone became strongly bound and inextricably linked with titanium implants, leading to him coining the term osseointegration and using titanium for human dental implants as early as 196510. Dental implant technology has shown successful outcomes with screw fixation devices because of the small size of the bone, the high vascularity of the jaw, substantial support by the surrounding teeth minimizing torsional forces that can lead to early loosening, and the dental implants experiencing mostly axial compression forces11. Joint replacement has shown success with press-fit implants that provide a high surface area of integration and substantial porosity and rely on maximum contact with inherent geometric features of the implant to provide rotational stability12. The principles of osseointegration for amputees are more comparable with the principles of arthroplasty than those of dentistry13. For clarity, the remainder of this article will use the term “osseointegration” to refer specifically to direct metal-to-bone anchorage in the appendicular skeleton as a means to reconstruct amputated limbs or digits.
Osseointegration surgery using titanium implants directly attached to bone was successful from the start. The initial efforts to cement transcutaneous implants into bone, by Dr. Vert Mooney and other surgeons at Rancho Los Amigos National Rehabilitation Center in Los Angeles in 1977, resulted in uniform loosening and infection, requiring early removal14, as did other earlier experiments15. The Brånemark technique is instead able to achieve intimate bone-titanium contact, and preliminary results were so encouraging that clinical trials soon expanded to patients who underwent upper-extremity amputation16. This demanding procedure requires meticulous attention to detail and skillfully merges hard-tissue and materials science principles from both dental and orthopaedic surgery, together with soft-tissue handling techniques more familiar to plastic surgeons. Perhaps due in part to this, only approximately 400 patients have been treated using this technique17.
Inspired by these preliminary outcomes, and with the goal of vastly increasing clinician adoption and patient access to this transformative prosthetic solution, Munjed Al Muderis began osseointegration with a different implant design, improved operative techniques, and accelerated rehabilitation strategies in 2009. Their goal was to make this technology more readily applicable for use by a wider community of surgeons, adhering to principles familiar to arthroplasty and reconstruction surgeons18. With the recent approval by the U.S. Food and Drug Administration (FDA) for osseointegration to be used in situations of humanitarian exemption19, and with the current FDA clinical trial spearheaded by the U.S. Department of Defense (ClinicalTrials.gov NCT03720171), global interest in osseointegration for amputees is expected to increase dramatically in the coming years.
The purposes of this article were to introduce and describe the current osseointegration implant designs, to identify key variations of surgical and rehabilitation concepts, to briefly summarize the salient benefits of and residual concerns with regard to osseointegration, and to forecast where osseointegration may be headed in the near future. In this article, we will focus attention on lower-extremity (transfemoral and transtibial) osseointegration, as it represents the overwhelming majority of current and immediate future surgical procedures in the United States1 and around the world20-23.
Currently Active Osseointegration Implant Systems
The currently active osseointegration implant systems are shown in Table I and are discussed individually below.
TABLE I -
Comparison of Osseointegration Implant Systems
||Long bones, digits
||Long bones, pelvis
||Czech hedgehog 1.5 mm
||Plasma-sprayed up to 0.5 mm
||Porous-coated, axial compression
|Months from implantation to full weight
||3 to 18
||2 to 3
||2 to 3
The Osseointegrated Prostheses for the Rehabilitation of Amputees (OPRA) (Integrum) has evolved from the first osseointegration surgical procedure in 1990 under the direction of Rickard Brånemark24. The OPRA has principally been implanted into patients with transfemoral amputations, with smaller numbers of transhumeral, transradial, finger or thumb, and transtibial amputations. The OPRA is detailed in Figure 1.
The Integral Leg Prosthesis (ILP) (Orthodynamics) evolved from the Endo-Exo implant (ESKA Orthopaedic Handels), which was introduced by Hans Grundei in Germany. The Endo-Exo and ILP are detailed in Figure 2.
The Osseointegrated Prosthetic Limb (OPL) (Permedica Manufacturing) evolved from the experience with the ILP. Al Muderis began designing the OPL in 2010, and it became commercially available in 201425. For all 3 types, immediate implant retention is achieved through press-fit interdigitation25. The OPL is detailed in Figure 3.
A percutaneous osseointegrated prosthesis (POP) (DJO Global) is still currently in the development phase26 and is detailed in Figure 4.
The Compress Device (Zimmer Biomet) was originally designed as a solution for large-gap limb salvage for patients with bone tumors, for which it is still used, and has since been modified to become a transcutaneous implant system. This device features a porous-coated titanium abutment with a narrow minimally contacting intramedullary shaft, anchoring the implant to bone by transverse cross-pins. Spring forces inherent in this design, both static and dynamic, promote bone remodeling continuously even when patients are not weight-bearing27,28. The Compress Device is detailed in Figure 5.
The Intraosseous Transcutaneous Amputation Prosthesis (ITAP) (Stryker Orthopaedics) is a device that recently completed its clinical trial (ClinicalTrials.gov NCT02491424) but will not be released. Its main goal was to replicate the skin-implant interface that is seen with animal antlers, a biologic example of a hard tissue protruding through skin while resisting infection. Although animal trials were promising29, human trials led to problems with the hydroxyapatite interface breaking down, leading to implant failure and infection. The ITAP is detailed in Figure 6.
Major Surgical and Rehabilitation Principles
The OPRA is the oldest extant osseointegration implant, and has been developed over 3 decades with continuous clinical use and research development. Of all osseointegration techniques, the OPRA has the longest patient follow-up data available30. The OPRA technique9 is characterized by 2 surgical events per bone, spaced 6 months apart. The goal of the first procedure is to implant the threaded intramedullary bone anchor. In brief, this is achieved by gently reaming the canal and then tapping the thread for the implant to later be screwed into position at least 20 mm deep, beyond the distal bone edge, as a buffer against potential bone resorption. After inserting the implant, the incision is then fully closed. If inadequate bone graft is harvested during the reaming, iliac crest bone can be auto-transplanted to plug the distal end below the fixture. Either the extremity remains non-weight-bearing, or patients may continue to walk in a traditional socket, to avoid bone loading during the initial osseointegration. Following an interval of 6 months to allow the implant to integrate with the host bone, the second surgical event is undertaken. This features the attachment of an abutment to the implanted fixture, the externalization of the abutment through the skin, and additional soft-tissue procedures to create a stoma at the skin-implant interface. The points of emphasis with this protocol include eliminating hair follicles surrounding the implant to reduce this potential source of infection and tightly securing soft tissue to limit movement, which can cause inflammation and provoke infection. Muscle endings should be sutured to the periosteum within 10 mm of the distal bone end, and the subcutaneous fat should be excised to promote skin adhesion directly to bone. The patient is then limited to non-weight-bearing, range-of-motion exercises for 10 to 12 days to promote soft-tissue healing. The routine postoperative protocol is detailed31 but may be summarized as non-weight-bearing for approximately 1 month following the second stage, with progressive weight-bearing limited to a few hours daily featuring a short training prosthesis attachment and increasing the amount of weight loaded through the prosthesis and the hours of weight-bearing each day through the initial 3 months. By month 4, patients are encouraged to increase prosthetic wear time and to then graduate to independent walking without crutches and full weight-bearing, possibly without a time limitation, by month 6. For patients with suboptimal bone quality, the recommended time to each milestone may be doubled. Approximately 400 OPRA have been implanted so far17.
The ILP was developed by Hans Grundei for 2-stage implantation. The first stage is implant placement via sequential broaching (without reaming) and insertion of the implant using a press-fit technique and a temporary plug inserted into the distal end of the implant. The wound is fully closed, and, 4 to 6 weeks later, a circular corer is used to open the skin over the abutment to create a stoma. The implant plug is then removed, and a dual cone adapter is inserted percutaneously. The rehabilitation protocol involves activity progression as tolerated, and permanent prosthetic limbs usually are attached within the first few weeks thereafter32.
The OPL was designed for single-stage implantation by Al Muderis, the first implant available specifically with this intent, and there have already been >800 implantations of the OPL worldwide33. For patients with prohibitively short residual bone (less than approximately 8 cm), lengthening of the residuum using an externally powered intramedullary magnetic telescopic nail can be performed34-36. Following a period of bone consolidation after attaining the desired length, routine osseointegration ensues. Using a guillotine or other incision as is best suited to address any existing skin compromise, first the distal bone end is prepared. This may include heterotopic ossification removal or resection and face reaming to a uniform surface using a calcar reamer. Flat reaming fits OPL type A implants and conical reaming fits OPL type B and C implants. The developing surgeon recommends tight purse-string cerclage closure of the muscular envelope around the bone-implant interface; there is no suturing to bone. Canal preparation is then performed using sequential flexible reamers, followed by sequential implant-specific broaches. Press-fit implantation is then performed until the collar solidly abuts the distal part of the femur. Further modification of the circumferential myodesis is performed, tightening the muscle so that it is directly apposed to both implant and bone. The subcutaneous tissue is then defatted, and the skin is secured to adjacent muscle before tightly closing the amputation incision. Finally, the circular coring device is used to create a stoma and to percutaneously insert the dual cone and endoprosthetic connection adapter. Since the development of the single-stage protocol in 2014, almost all patients have had a single-stage surgical procedure instead of a 2-stage surgical procedure37, followed by a standardized rehabilitation protocol38. Rehabilitation occurs in 3 distinct and progressive phases. The first day after the surgical procedure, the patients stand and axially load the operatively treated leg through a manual bathroom scale, increasing progressively by 5 kg each day until they achieve 50 kg or 50% of their body weight, which should occur by week 2. A lightweight training leg is then attached, and core strengthening and balance exercises are performed, as well as supervised ambulation. The final stage of rehabilitation consists of attachment of the final prosthetic limb, and weight-bearing as tolerated with crutches is recommended. This process usually completes by 6 weeks after osseointegration. Unrestricted body-weight loading and ambulation are encouraged, but patients are cautioned that regaining adequate proprioception usually takes close to a year or even more, so they must be mindful of their balance to limit the potential for inadvertent falls.
The POP and the Compress Device are newer systems and surgical technique or rehabilitation guidelines have not yet been published to establish the preferences of their development groups. The ITAP has been discontinued and will not be further detailed.
Clinical Aspects of Osseointegration: Indications, Expected Outcomes, and Concerns
No formal consensus indications exist for osseointegration. Early contraindications included peripheral vascular disease, diabetes, age of >70 years, ongoing chemotherapy, immunosuppressive medications, skeletal immaturity, irradiated limbs, pregnancy, and situations of questionable patient compliance or psychiatric stability31,38,39. On the basis of positive early experience, some surgeons have expanded indications or disproven supposed contraindications to osseointegration, improving the mobility of patients with peripheral vascular disease40, those who underwent total hip arthroplasty41 or total knee arthroplasty42, and elderly patients who underwent amputation decades ago43. Although both major designs have been implanted into patients who have undergone transhumeral and transradial amputations, only the OPL has demonstrated a high success rate with patients who have undergone transtibial amputation, perhaps due to its 3-dimensional printed customization to individual patient anatomy. The screw design of the OPRA system has shown a particular utility in small implants such as thumb amputations30 and penile epitheses44. As basic science understanding and clinical experience improve, it is likely that the indications will broaden and the contraindications will narrow.
The overwhelming majority of amputees who change from a traditional socket prosthesis to an osseointegrated prosthesis improve dramatically, both subjectively and objectively. One study showed that when amputees changed from a socket prosthesis to an osseointegrated prosthesis, there were improvements on the Questionnaire for Persons with Transfemoral Amputation (from 45.27 to 84.86 points), Short Form-36 Physical Component Summary (from 36.97 to 49.00 points), 6 Minute Walk Test (from 286.25 to 512.72 meters), and the Timed Up and Go test (from 13.86 to 9.12 seconds)45. Another group reported similar trends for those same metrics and also found that the oxygen requirement was reduced from 1,330 mL/min to 1,093 mL/min46. Laboratory gait analysis revealed that cadence, duration of the gait cycle, and support phases are closer to normal in patients with osseointegrated prostheses than in patients with socketed prostheses47,48. Sitting comfort and position are improved49. Prosthesis use is high, with 82% to 90% of patients reporting daily use50. The donning and doffing are quicker and easier51. Patients have also reported that osseointegrated prostheses provide a much more intimate and “part of me” experience than socket prostheses52.
An additional exciting phenomenon that improves the patient experience with an osseointegrated prosthesis is that of osseoperception. Osseoperception is defined as the mechanical stimulation of a bone‐anchored prosthesis that is transduced by mechanoreceptors likely located in the muscles, joints, skin, and other bone-adjacent tissues that travel to the central nervous system to cause passive awareness of a patient’s own sensorimotor position and function53. Osseoperception has been well studied in dental implants, in which mechanical and neurologic mechanisms have been identified54. Although relatively few studies focus on this aspect of appendicular skeletal osseointegration, it is clear that osseointegrated prostheses facilitate improved vibration detection in patients compared with socket prostheses55,56. This improved sensation may, in part, be due to innervation in the newly integrated bone57. Further studies are needed to further characterize the potential clinical utility and day-to-day impact of this phenomenon on the patient quality of life.
One potential risk of osseointegration is periprosthetic fracture, which might lead to further impairment or more proximal amputation. To date, safety studies have only briefly touched on that topic18,58. Although, to our knowledge, no currently available peer-reviewed article exists specifically addressing fractures adjacent to osseointegration implants, periprosthetic fractures are managed with device removal and potential replacement in cases involving OPRA9 and POP59 implants, whereas fractures adjacent to ILP and OPL implants are managed with implant retention and routine fracture techniques such as plating60. Infection continues to be the main challenge, although this is less common than many believe. Even in this early stage of development and exploration, infection requiring an additional surgical procedure occurs in only 5% to 8% of patients18,61. This risk appears to be reducing as soft-tissue management experience increases, especially with a single-stage surgical procedure, and the risk of implant removal due to infection is even less common. Curiously, the risk of osteomyelitis following osseointegration might be influenced by the implant design62. Currently published infection rates reflect the outcomes of relatively tightly controlled and highly selected cohorts of patients. Unfortunately, the vast majority of amputees worldwide have diabetes3 and would be expected to have an increased risk of deep infection.
The ideal implant likely should achieve stable fixation immediately to allow independent ambulation, would be short (perhaps 5 to 10 cm) to allow implantation into very short residual bones without pre-lengthening procedures, would be inexpensive to manufacture, would successfully scale to accommodate a variety of long bones with similar techniques, would incorporate neural connection technology, would limit the risk of infection, and would provide durable long-term osseointegration. Of all those goals, perhaps the least certain is how to address the implant-skin interface. The transcutaneous nature of the implant and the exposure to the external environment represent the most clinically important and obvious risk. Generally, stable skin is less likely to become inflamed than skin that is moved or stretched18,63. Detailed research with regard to the ideal skin-implant interface is actively being pursued, and creative innovations may be necessary.
The Future of Osseointegration
The field of osseointegration has existed for almost 30 years and now appears to be on the verge of greater acceptance and widespread implementation. Beyond providing an excellent mobility solution for an expanding spectrum of long bone amputees, some patients with a hip disarticulation, hemipelvectomy, or flail arm due to brachial plexus avulsion have already had their mobility or quality of life improved by relatively simple technical improvisations to the established fundamentals of osseointegration. Amputation and osseointegration may even prove to be a favorable alternative when compared with limb-salvage megaprostheses for patients with appendicular skeletal tumors64 or those who have debilitating chronic pain in an extremity such as persistent complex regional pain syndrome.
Osseointegration already provides direct skeletal anchorage for prosthetic limbs designed with both afferent and efferent neural integration, allowing patients to more intuitively control the force65,66, approaching the scenes depicted in science fiction movies only a generation ago. It may soon be reasonable to restore sensation and mobility to amputees, perhaps even those with paralysis, with an intimately connected endoprosthetic limb67. However, the problem of infection must be aggressively researched: is an antler model actually achievable in humans, or would a fingernail, gum-tooth, or muscular sphincter interface be a better concept to adopt?
Perhaps the most exciting developing frontier of osseointegration may not be strictly medical, but instead may reflect changes in regulation and legislation, with greater access to care afforded by a potential influx of supply. Upon FDA trial completion, American institutions with immediately available funding may quickly scale procedures to meet existing domestic demand. With the resultant increased implant production, the unit cost per implant should be reduced, and this would, in turn, permit greater access worldwide. This is especially important for patients who live in areas of the world where amputation is often the solution to relatively routine trauma, or where land mines and war injuries remain a devastating cause of limb loss68,69. Given the value and impact of orthopaedic outreach recently endorsed by the American Academy of Orthopaedic Surgeons (AAOS)70 and the already-proven success providing high-quality single-surgery osseointegration even in hospitals with modest resources such as in postwar environments71, osseointegration seems ready to quickly and dramatically improve the lives of millions of amputees around the world.
Osseointegration for the reconstruction of the amputated limb appears to now be poised to follow a trajectory similar to that demonstrated by total joint arthroplasty, which gained universal acceptance and then underwent widespread adoption globally over the past 50 years. As the concepts and principles guiding surgical techniques and implant technology become further established and more uniform, the surgeons and other clinicians providing care and the patients benefiting most from this procedure can become even more diverse.
1. Ziegler-Graham K, MacKenzie EJ, Ephraim PL, Travison TG, Brookmeyer R. Estimating the prevalence of limb loss in the United States: 2005 to 2050. Arch Phys Med Rehabil. 2008 Mar;89(3):422-9.
2. Moxey PW, Gogalniceanu P, Hinchliffe RJ, Loftus IM, Jones KJ, Thompson MM, Holt PJ. Lower extremity amputations—a review of global variability in incidence. Diabet Med. 2011 Oct;28(10):1144-53.
3. International Diabetes Federation. IDF diabetes atlas. 8th ed. 2017. https://diabetesatlas.org/
. Accessed 2019 Jun 25.
4. Koc E, Tunca M, Akar A, Erbil AH, Demiralp B, Arca E. Skin problems in amputees: a descriptive study. Int J Dermatol. 2008 May;47(5):463-6.
5. Dillingham TR, Pezzin LE, MacKenzie EJ, Burgess AR. Use and satisfaction with prosthetic devices among persons with trauma-related amputations: a long-term outcome study. Am J Phys Med Rehabil. 2001 Aug;80(8):563-71.
6. Sanders JE, Fatone S. Residual limb volume change: systematic review of measurement and management. J Rehabil Res Dev. 2011;48(8):949-86.
7. Nehler MR, Coll JR, Hiatt WR, Regensteiner JG, Schnickel GT, Klenke WA, Strecker PK, Anderson MW, Jones DN, Whitehill TA, Moskowitz S, Krupski WC. Functional outcome in a contemporary series of major lower extremity amputations. J Vasc Surg. 2003 Jul;38(1):7-14.
8. Hagberg K, Brånemark R. Consequences of non-vascular trans-femoral amputation: a survey of quality of life, prosthetic use and problems. Prosthet Orthot Int. 2001 Dec;25(3):186-94.
9. Li Y, Brånemark R. Osseointegrated prostheses for rehabilitation following amputation: the pioneering Swedish model. Unfallchirurg. 2017 Apr;120(4):285-92.
10. Abraham CM. A brief historical perspective on dental implants, their surface coatings and treatments. Open Dent J. 2014 May 16;8:50-5.
11. van Velzen FJJ, Ofec R, Schulten EAJM, Ten Bruggenkate CM. 10-year survival rate and the incidence of peri-implant disease of 374 titanium dental implants with a SLA surface: a prospective cohort study in 177 fully and partially edentulous patients. Clin Oral Implants Res. 2015 Oct;26(10):1121-8. Epub 2014 Nov 5.
12. Head WC, Bauk DJ, Emerson RH Jr. Titanium as the material of choice for cementless femoral components in total hip arthroplasty. Clin Orthop Relat Res. 1995 Feb;311:85-90.
13. Xu W, Crocombe AD, Hughes SC. Finite element analysis of bone stress and strain around a distal osseointegrated implant for prosthetic limb attachment. Proc Inst Mech Eng H. 2000;214(6):595-602.
14. Mooney V, Schwartz SA, Roth AM, Gorniowsky MJ. Percutaneous implant devices. Ann Biomed Eng. 1977 Mar;5(1):34-46.
15. Murphy EF. History and philosophy of attachment of prostheses to the musculo-skeletal system and of passage through the skin with inert materials. J Biomed Mater Res. 1973;7(3):275-95.
16. Jönsson S, Caine-Winterberger K, Brånemark R. Osseointegration amputation prostheses on the upper limbs: methods, prosthetics and rehabilitation. Prosthet Orthot Int. 2011 Jun;35(2):190-200.
17. Integrum. OPRA Implant System. https://integrum.se/opra-implant-system/
. Accessed 2019 Jun 25.
18. Al Muderis M, Khemka A, Lord SJ, Van de Meent H, Frölke JPM. Safety of osseointegrated implants for transfemoral amputees: a two-center prospective cohort study. J Bone Joint Surg Am. 2016 Jun 1;98(11):900-9.
19. U.S. Food and Drug Administration. Humanitarian Device Exemption (HDE). OPRA. 2019 Jun 24. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfhde/hde.cfm?id=H080004
. Accessed 2019 Jun 25.
20. Wegner L, Rhoda A. Common causes of lower limb amputation in a rural community in South Africa [abstract]. In: Proceedings of the 23rd International Academic Conference, Venice; 2016 Apr 27-30. International Institute of Social and Economic Sciences (IISES); 2016. p 515.
21. de Fátima Dornelas L. Uso da prótese e retorno ao trabalho em amputados por acidentes de transporte. Acta Ortop Bras. 2010 Jan;18(4):204-6. Portuguese.
22. Ahmad N, Thomas GN, Gill P, Torella F. The prevalence of major lower limb amputation in the diabetic and non-diabetic population of England 2003-2013. Diab Vasc Dis Res. 2016 Sep;13(5):348-53. Epub 2016 Jun 22.
23. Norman PE, Schoen DE, Gurr JM, Kolybaba ML. High rates of amputation among indigenous people in Western Australia. Med J Aust. 2010 Apr 5;192(7):421.
24. Thesleff A, Brånemark R, Håkansson B, Ortiz-Catalan M. Biomechanical characterisation of bone-anchored implant systems for amputation limb prostheses: a systematic review. Ann Biomed Eng. 2018 Mar;46(3):377-91. Epub 2018 Jan 11.
25. Al Muderis M, Lu W, Li JJ. Osseointegrated Prosthetic Limb for the treatment of lower limb amputations: experience and outcomes. Unfallchirurg. 2017 Apr;120(4):306-11.
26. Holt BM, Bachus KN, Jeyapalina S, Beck JP, Bloebaum R. Percutaneous osseointegrated prosthetic implant system. United States Patent No. US 9,668,889 B2. 2017 Jun 6. https://patentimages.storage.googleapis.com/03/24/50/b33765aeee1279/US9668889.pdf
. Accessed 2019 Jun 25.
27. McGough RL, Goodman MA, Randall RL, Forsberg JA, Potter BK, Lindsey B. The Compress® transcutaneous implant for rehabilitation following limb amputation. Unfallchirurg. 2017 Apr;120(4):300-5.
28. Kramer MJ, Tanner BJ, Horvai AE, O’Donnell RJ. Compressive osseointegration promotes viable bone at the endoprosthetic interface: retrieval study of Compress implants. Int Orthop. 2008 Oct;32(5):567-71. Epub 2007 Jun 19.
29. Fitzpatrick N, Smith TJ, Pendegrass CJ, Yeadon R, Ring M, Goodship AE, Blunn GW. Intraosseous Transcutaneous Amputation Prosthesis (ITAP) for limb salvage in 4 dogs. Vet Surg. 2011 Dec;40(8):909-25. Epub 2011 Nov 4.
30. Li Y, Kulbacka-Ortiz K, Caine-Winterberger K, Brånemark R. Thumb amputations treated with osseointegrated percutaneous prostheses with up to 25 years of follow-up. J Am Acad Orthop Surg Glob Res Rev. 2019 Jan 23;3(1):e097.
31. Hagberg K, Brånemark R. One hundred patients treated with osseointegrated transfemoral amputation prostheses—rehabilitation perspective. J Rehabil Res Dev. 2009;46(3):331-44.
32. Aschoff H. Osseointegrated percutaneous implants for rehabilitation following below-knee amputation. Read at the First International Symposium on Innovations in Amputation Surgery and Prosthetic Technologies; 2016 May 13; Chicago, IL.
33. Al Muderis M, Atallah R, Lu WY, Li JJ, Frolke JPM. Safety of osseointegrated implants for transtibial amputees: a two-center prospective proof-of-concept study. Read at the Annual Meeting of the American Academy of Orthopaedic Surgeons; 2019 Mar 13; Las Vegas, NV. Paper no. 431.
34. Fragomen AT, Rozbruch SR. Lengthening of the femur with a remote-controlled magnetic intramedullary nail: retrograde technique. JBJS Essent Surg Tech. 2016 May 11;6(2):e20.
35. Rozbruch SR, Birch JG, Dahl MT, Herzenberg JE. Motorized intramedullary nail for management of limb-length discrepancy and deformity. J Am Acad Orthop Surg. 2014 Jul;22(7):403-9.
36. Kirane YM, Fragomen AT, Rozbruch SR. Precision of the PRECICE internal bone lengthening nail. Clin Orthop Relat Res. 2014 Dec;472(12):3869-78.
37. Al Muderis M, Tetsworth K, Khemka A, Wilmot S, Bosley B, Lord SJ, Glatt V. The Osseointegration Group of Australia Accelerated Protocol (OGAAP-1) for two-stage osseointegrated reconstruction of amputated limbs. Bone Joint J. 2016 Jul;98-B(7):952-60.
38. Al Muderis M, Lu W, Tetsworth K, Bosley B, Li JJ. Single-stage osseointegrated reconstruction and rehabilitation of lower limb amputees: the Osseointegration Group of Australia Accelerated Protocol-2 (OGAAP-2) for a prospective cohort study. BMJ Open. 2017 Mar 22;7(3):e013508.
39. Sullivan J, Uden M, Robinson KP, Sooriakumaran S. Rehabilitation of the trans-femoral amputee with an osseointegrated prosthesis: the United Kingdom experience. Prosthet Orthot Int. 2003 Aug;27(2):114-20.
40. Atallah R, Li JJ, Lu W, Leijendekkers R, Frölke JP, Al Muderis M. Osseointegrated transtibial implants in patients with peripheral vascular disease: a multicenter case series of 5 patients with 1-year follow-up. J Bone Joint Surg Am. 2017 Sep 20;99(18):1516-23.
41. Khemka A, FarajAllah CI, Lord SJ, Bosley B, Al Muderis M. Osseointegrated total hip replacement connected to a lower limb prosthesis: a proof-of-concept study with three cases. J Orthop Surg Res. 2016 Jan 19;11:13.
42. Khemka A, Frossard L, Lord SJ, Bosley B, Al Muderis M. Osseointegrated total knee replacement connected to a lower limb prosthesis: 4 cases. Acta Orthop. 2015;86(6):740-4. Epub 2015 Aug 27.
43. Leijendekkers RA, van Hinte G, Nijhuis-van der Sanden MW, Staal JB. Gait rehabilitation for a patient with an osseointegrated prosthesis following transfemoral amputation. Physiother Theory Pract. 2017 Feb;33(2):147-61. Epub 2017 Jan 3.
44. Selvaggi G, Branemark R, Elander A, Liden M, Stalfors J. Titanium-bone-anchored penile epithesis: preoperative planning and immediate postoperative results. J Plast Surg Hand Surg. 2015 Feb;49(1):40-4. Epub 2014 Jun 16.
45. Al Muderis M, Lu W, Glatt V, Tetsworth K. Two-stage osseointegrated reconstruction of post-traumatic unilateral transfemoral amputees. Mil Med. 2018 Mar 1;183(suppl_1):496-502.
46. Van de Meent H, Hopman MT, Frölke JP. Walking ability and quality of life in subjects with transfemoral amputation: a comparison of osseointegration with socket prostheses. Arch Phys Med Rehabil. 2013 Nov;94(11):2174-8. Epub 2013 Jun 14.
47. Frossard L, Hagberg K, Häggström E, Gow DL, Brånemark R, Pearcy M. Functional outcome of transfemoral amputees fitted with an osseointegrated fixation: temporal gait characteristics. J Prosthet Orthot. 2010;22(1):11-20.
48. Frossard L, Stevenson N, Sullivan J, Uden M, Pearcy M. Categorization of activities of daily living of lower limb amputees during short-term use of a portable kinetic recording system: a preliminary study. J Prosthet Orthot. 2011;23(1):2-11.
49. Hagberg K, Häggström E, Uden M, Brånemark R. Socket versus bone-anchored trans-femoral prostheses: hip range of motion and sitting comfort. Prosthet Orthot Int. 2005 Aug;29(2):153-63.
50. van Eck CF, McGough RL. Clinical outcome of osseointegrated prostheses for lower extremity amputations: a systematic review of the literature. Curr Orthop Pract. 2015 Jul/Aug;26(4):349-57.
51. Hagberg K, Brånemark R, Gunterberg B, Rydevik B. Osseointegrated trans-femoral amputation prostheses: prospective results of general and condition-specific quality of life in 18 patients at 2-year follow-up. Prosthet Orthot Int. 2008 Mar;32(1):29-41.
52. Lundberg M, Hagberg K, Bullington J. My prosthesis as a part of me: a qualitative analysis of living with an osseointegrated prosthetic limb. Prosthet Orthot Int. 2011 Jun;35(2):207-14.
53. Klineberg I, Calford MB, Dreher B, Henry P, Macefield V, Miles T, Rowe M, Sessle B, Trulsson M. A consensus statement on osseoperception. Clin Exp Pharmacol Physiol. 2005 Jan-Feb;32(1-2):145-6.
54. Bhatnagar VM, Karani JT, Khanna A, Badwaik P, Pai A. Osseoperception: an implant mediated sensory motor control- a review. J Clin Diagn Res. 2015 Sep;9(9):ZE18-20. Epub 2015 Sep 1.
55. Häggström E, Hagberg K, Rydevik B, Brånemark R. Vibrotactile evaluation: osseointegrated versus socket-suspended transfemoral prostheses. J Rehabil Res Dev. 2013;50(10):1423-34.
56. Jacobs R, Brånemark R, Olmarker K, Rydevik B, Van Steenberghe D, Brånemark PI. Evaluation of the psychophysical detection threshold level for vibrotactile and pressure stimulation of prosthetic limbs using bone anchorage or soft tissue support. Prosthet Orthot Int. 2000 Aug;24(2):133-42.
57. Ysander M, Brånemark R, Olmarker K, Myers RR. Intramedullary osseointegration: development of a rodent model and study of histology and neuropeptide changes around titanium implants. J Rehabil Res Dev. 2001 Mar-Apr;38(2):183-90.
58. Tsikandylakis G, Berlin Ö, Brånemark R. Implant survival, adverse events, and bone remodeling of osseointegrated percutaneous implants for transhumeral amputees. Clin Orthop Relat Res. 2014 Oct;472(10):2947-56.
59. Gillespie B. Development of a percutaneous osseointegrated prosthesis for transfemoral amputees. Presented at the State of the Science Symposium: Recent Advances in Osseointegration Rehabilitation; 2019 May 17; Bethesda, MD.
60. Lu W. Comments made during presentation by Gillepsie B. Development of a percutaneous osseointegrated prosthesis for transfemoral amputees. Presented at the State of the Science Symposium: Recent Advances in Osseointegration Rehabilitation; 2019 May 17; Bethesda, MD.
61. Tillander J, Hagberg K, Hagberg L, Brånemark R. Osseointegrated titanium implants for limb prostheses attachments: infectious complications. Clin Orthop Relat Res. 2010 Oct;468(10):2781-8. Epub 2010 May 15.
62. Tillander J, Hagberg K, Berlin Ö, Hagberg L, Brånemark R. Osteomyelitis risk in patients with transfemoral amputations treated with osseointegration prostheses. Clin Orthop Relat Res. 2017 Dec;475(12):3100-8. Epub 2017 Sep 22.
63. Paley D. Problems, obstacles, and complications of limb lengthening by the Ilizarov technique. Clin Orthop Relat Res. 1990 Jan;250:81-104.
64. Schmolders J, Koob S, Schepers P, Pennekamp PH, Gravius S, Wirtz DC, Placzek R, Strauss AC. Lower limb reconstruction in tumor patients using modular silver-coated megaprostheses with regard to perimegaprosthetic joint infection: a case series, including 100 patients and review of the literature. Arch Orthop Trauma Surg. 2017 Feb;137(2):149-53. Epub 2016 Oct 25.
65. Mastinu E, Branemark R, Aszmann O, Ortiz-Catalan M. Myoelectric signals and pattern recognition from implanted electrodes in two TMR subjects with an osseointegrated communication interface. Conf Proc IEEE Eng Med Biol Soc. 2018 Jul;2018:5174-7.
66. Ortiz-Catalan M, Håkansson B, Brånemark R. An osseointegrated human-machine gateway for long-term sensory feedback and motor control of artificial limbs. Sci Transl Med. 2014 Oct 8;6(257):257re6.
67. Pasquina PF, Evangelista M, Carvalho AJ, Lockhart J, Griffin S, Nanos G, McKay P, Hansen M, Ipsen D, Vandersea J, Butkus J, Miller M, Murphy I, Hankin D. First-in-man demonstration of a fully implanted myoelectric sensors system to control an advanced electromechanical prosthetic hand. J Neurosci Methods. 2015 Apr 15;244:85-93. Epub 2014 Aug 4.
68. Ebrahimzadeh MH, Rajabi MT. Long-term outcomes of patients undergoing war-related amputations of the foot and ankle. J Foot Ankle Surg. 2007 Nov-Dec;46(6):429-33.
69. McKinley TO, DʼAlleyrand JC, Valerio I, Schoebel S, Tetsworth K, Elster EA. Management of mangled extremities and orthopaedic war injuries. J Orthop Trauma. 2018 Mar;32(Suppl 1):S37-42.
70. D’Onofrio K. What you give—and gain—through humanitarian outreach. 2019 Jan. https://www.aaos.org/AAOSNow/2019/Jan/Cover/cover01/?ssopc=1
. Accessed 2019 Jun 25.
71. Al Muderis M, Weaver P. Going back: how a former refugee, now an internationally acclaimed surgeon, returned to Iraq to change the lives of injured soldiers and civilians. Allen & Unwin; 2019.