Eur J Orthop Surg Traumatol DOI 10.1007/s00590-013-1366-z
GENERAL REVIEW
Osteolysis in cemented total hip arthroplasty involving the OptiPlug cement restrictor: more than an incident? N. M. A. I. Hanssen • M. G. M. Schotanus A. D. Verburg
•
Received: 8 August 2013 / Accepted: 8 November 2013 Ó Springer-Verlag France 2013
Abstract The case report of a severe osteolytic reaction surrounding the OptiPlug cement restrictor in a 74-year-old male patient initiated a retrospective case series and closer investigation into the OptiPlug and its active compound, PolyActive. Not only did we find several cases of severe osteolysis in our own study population of 284 patients, several articles have lately described potential harmful side effects of the PolyActive material in humans. Although none of the articles have been based on large databases, we cannot guarantee the safety of this product. More research would help in our understanding of this phenomenon. Until then, we cannot recommend the use of the OptiPlug cement restrictor. Keywords Hip arthroplasty Cement restrictor Osteolysis Resorbable PolyActive OptiPlug
plugs, a wide variety of materials and shapes exists: a factor that definitely contributes to the lack of evidence on the superiority of any of these plugs in achieving an adequate cement mantle [2, 5–9, 12, 17, 18]. Even less is known about the long-term in vivo effects of these plugs [1, 5, 18, 19]. In this case report and subsequent retrospective case series of 284 patients, osteolytic reaction was observed surrounding the OptiPlug (Biomet Inc., Warsaw, Indiana, USA), a cement restrictor consisting of the biodegradable synthetic PEG/PBT copolymer PolyActive (OctoPlus NV, Leiden, the Netherlands) [20, 21]. We present this case report and case series and compare these findings to the current literature on the OptiPlug cement restrictor and its active compound PolyActive.
Introduction
Case report
Worldwide, cemented arthroplasty of the hip is a common treatment for osteoarthritis of this joint. Despite the vast number of total cemented hip arthroplasties that are performed every year, little is known about the in vivo effects of the cement restrictors that are inextricably linked to this procedure. A large number of different cement restrictors is currently available. In both resorbable and nonresorbable
In February 2007, a 74-year-old healthy male suffering from disability and pain due to osteoarthritis underwent a cemented total arthroplasty of the right hip. After insertion of the OptiPlug cement restrictor, the medullar cavity was rinsed (Pulse-Lavage, Stryker Inc., Kalamazoo, Michigan, USA) and the femur was cemented with Gentamicin Palacos (Heraeus Kulzer GmbH., Hanau, Germany). A retrograde cementing technique was applied, using a cement gun, without additional pressurization. An anatomic polished chrome-cobalt stem (ABG-2, Stryker Inc.) was inserted. No irregularities were reported during the procedure. Recovery after surgery was normal and without complications. Radiographs did not reveal any irregularities (Figs. 1, 2). Six months after surgery, the patient had recovered to his preoperative level of mobility. At 1-year follow-up, however, routine radiographs revealed osteolysis distal to the cement with mild cortical thinning (Fig. 3).
N. M. A. I. Hanssen (&) Resident at Maartenskliniek, Van Welderenstraat 13, 6511 MA Nijmegen, The Netherlands e-mail: [email protected] M. G. M. Schotanus A. D. Verburg Orbis Medisch Centrum, Sittard-Geleen, The Netherlands e-mail: [email protected] A. D. Verburg e-mail: [email protected]
123
Eur J Orthop Surg Traumatol
Fig. 1 AP view, post-op Fig. 3 AP view, 1 year post-op
During further follow-up, progression of the osteolysis was observed (Figs. 4, 5, 6). As there were no complaints, no specific action was undertaken. Computer tomography of the affected region showed severe osteolysis, especially of the posterior cortex, with an estimate of about 1/3 of bone loss (Figs. 7, 8). In January 2013, a needle biopsy of the osteolytic lesion was performed. Pathological evaluation showed signs of cement remnants without granulomatous inflammation. Culture was negative. Regular follow-up will be continued.
Case series The dramatic single case as described above sparked our interest and lead to the start of a retrospective radiographic investigation of all total hip arthroplasties involving this cement restrictor, focusing on the year 2005, including all patients operated with the OptiPlug cement restrictor from one and the same batch.
Materials and methods
Fig. 2 AP view, 3 months post-op
123
After approval of the local ethics committee (METC Atrium-Orbis Zuyd, Heerlen, the Netherlands, nr 13N28),
Eur J Orthop Surg Traumatol
Fig. 4 AP view, 3 years post-op
Fig. 6 AP view, 4 years post-op
restrictor, consisting of the PolyActive material. Of these 284, 104 patients were considered ‘at risk’ for osteolytic reaction surrounding the plug and called in for extra X-rays, either because of abnormalities in an existing X-ray or because of the lack of adequate radiographic follow-up. Radiographic follow-up of 3 years or more without visible abnormalities was considered as adequate follow-up. Bone densitometry test were done in order to obtain a more objective estimate of the severity of the bone loss. The femur distal to the prosthesis and cement plug was divided in three areas of interest. Bone density through all three areas was measured, and an average bone density of the entire area was calculated for both the male and female patients (Fig. 9). Statistical analysis was conducted using SPSS (version 17). Outcome variables and their differences were tested with nonparametric techniques (Wilcoxon/Mann–Whitney tests). P values of \ 0.05 were considered statistically significant.
Fig. 5 Lateral view, 4 years post-op
Results
the study was conducted according to the declaration of Helsinki. In 2005, 284 patients underwent a cemented total hip arthroplasty with use of the OptiPlug resorbable cement
A total of 52 patients complied to our appeal for extra radiographs. In 25 out of these 52 patients, marked osteolysis and weakening of the cortex were observed surrounding the plug, including one bilateral case. In another
123
Eur J Orthop Surg Traumatol
Fig. 7 AP view, CT scan 4, 5 years post-op
Fig. 9 Division of the femur in three areas of interest Table 1 Outcomes of bone densitometry testing within each gender and between male and female patients Gender Male Female
N
BMD plug
BMD net
% BMD loss
p value
5
1.7 (1.4–1.9)
1.8 (1.5–2.0)
6.3 % (2.2–8.6)
n.s.
14
1.4 (1.2–1.8)
1.6 (1.2–1.9)
9.2 % (0.6–17.6)
n.s.
n.s.
n.s
n.s.
p value
None of the outcomes were statistically significant (n.s.)
reported. Statistical analysis by means of a Mann–Whitney U test and nonparametric T test did not show any statistical significant difference.
Discussion
Fig. 8 Lateral view, CT scan 4, 5 years post-op
19 cases, a minor osteolytic reaction around the OptiPlug was observed. Of the 25 patients with marked osteolysis, 19 underwent a bone densitometry test. Average follow-up at this point was 7 years (range 6.1–7.6). Bone density through the area of the plug was compared to the average bone density of the entire area (Table 1). Average loss of bone density in men was 6.3 %, compared to 9.2 % in woman. Percentages of up to 17.6 were
123
In this retrospective radiographic investigation of 284 patients, 25 confirmed cases of substantial osteolysis surrounding the OptiPlug were identified. Another 19 cases of less severe osteolysis were observed. Although the attendance rate of the 104 ‘at risk’ patients was less than we had hoped for, we can certainly state that this disturbing discovery confirms our suspicion that osteolysis associated with the OptiPlug cement restrictor is more than an incidental finding. We regret the rather high percentage of patients that did not comply to our request for extra radiographic and clinical follow-up. However, the affected population consists mainly of elderly patients, some of whom already live in a nursing home and/or have limited access to their own means of transportation. The
Eur J Orthop Surg Traumatol
Fig. 10 Chemical composition of the PolyActive polymer [21]
asymptomatic nature of the condition may also contribute to the rather low percentage of attendance. Fortunately, all patients are currently still without symptoms. This includes the ‘original’ elderly male patient, whose dramatic radiographic images initiated the retrospective investigation. The risk of a periprosthetic fracture in the event of a trauma in the more severely affected patients seems realistic however. The PolyActive material is a resorbable PEG/PBT polymer (Fig. 10). The material is widely used in the orthopedic industry and has multiple applications, for instance as implant scaffold or coating. It is also been implemented as a dermal scaffold for skin tissue engineering and in the dental industry [10, 11, 25, 26]. Another utilization of the material is the slow drug delivery technology in microspheres [21]. The older evidence regarding the PolyActive material describes favorable osteoconductive effects [4, 10, 14, 15, 22, 24]. All these studies involved an animal model. The first positive report on the performance of the OptiPlug in a human pilot study was published in 1996. At 2 years follow-up, no local changes were observed in the femur [1]. We are not the first, however, to present more side effects of the PolyActive material. In 2000, Roessler et al. [16] were the first to describe a missing osteoconductive effect of PolyActive in humans. Seven patients underwent anterior spinal interbody fusion surgery, for which two bicortical iliac defects were created. One defect was filled with PolyActive, and the other was left untreated as control. At follow-up at 52 weeks, spiral CT revealed significant less formation of new bone in the treated defects. Another negative report, describing massive osteolysis in live minipigs following the implantation of PolyActive, was published in 2008. In this study, elastomeric stems made of PolyActive were used to anchor polylactate joint scaffolds for the reconstruction of metacarpophalangeal joints [19]. In 2011, a large study group of 100 patients with a 5-year follow-up period was presented by Ockendon et al. [13]. In 87 patients, radiographs showed marked thinning of the cortex. There were 5 severe cases with more than 33 % thinning of the cortex. The authors noted that local changes in the femur did not appear to progress or regress significantly between 1 and 5 years. This in contrast to both the current study and the study presented by Ockendon et al. [13] report visible changes after 1 year. We believe
that radiographic osteolysis appears after several months, and that it progresses through the years. PEG, or polyethylene glycol, (also known as polyethylene oxide (PEO) or polyoxyethylene (POE) depending on its molecular weight) is a polymer of ethylene oxide. This compound has a tremendous amount of applications; several of which can be found in our current medical practice. Some examples include the use of PEG in antibody production, slow drug release formulas or the use of this substance as laxatives. PBT, or polybutylene terephthalate, is a thermoplastic polymer, which is commonly used as an insulator in the electronic industries and car production. It also has applications as the stretching fiber in swim- and sportswear and can be found in the fibers of toothbrushes. At a first glance, one might suspect the PolyActive material to be related to polylactate. A comparison to the tissue reaction following the implantation of polylactate screws or other implants of this material might therefore seem interesting and relevant. The chemical composition of PEG and PBT does not include a lactate acid group though; therefore, they are not related to the lactate group. In short, they are two different chemical entities. The only aspect they have in common is the mere fact that both substances are resorbable. Besides this chemical argument, biomechanical aspects are also suspected to be important in the tissue reaction that follows the implantation of PolyActive, as described by Radder et al. [15]. From research, we further know that the PEG/PEB ratios in the polymer are important in the calcification process within the near surface of the material. Several ratios have been observed in in vitro tests: 70/30, 60/40, 55/45, 40/60 and 30/70 [14, 15]. The higher the PEG/ PBT ratio, the more rapid the calcification [14]. The best result was achieved with the 70/30 ratio; this is the ratio used in PolyActive. Healing response in a osteochondral defect model in rabbits proved also to be superior in the 70/30 ratio when compared to the 55/45 ratio [27]. In all these studies, the percentage PEG proved to be crucial in the calcification process. It is proposed that this is due to the remarkable high affinity of the PEG segment for calcium ions in the environment [26]. Biomechanical properties also appear to influence the tissue reaction in the near surrounding of the implant. PEG is a softer material than PBT and is an hydrophylic component. The swelling behavior of the PEG component results in a high degree of bone contact and calcification [15]. Average BMD loss of 6.3–9.2 % was observed in our patient population. Some cases were more severely affected: e.g., a BMD loss of 17.3 % or up to one-third of the cortical bone. Though we do not exactly know how relevant this is for the particular patient concerned, we can certainly state that any amount of BMD loss in elderly
123
Eur J Orthop Surg Traumatol
patients with osteoporosis poses health risks and is both undesirable and unacceptable. Sadly, our exact knowledge as to why long-term exposure of this polymer to cortical bone sometimes results in osteolysis, is very limited. Most animal studies did not show these reactions. We suspect that the degradation of the material triggers an osteolytic reaction. The relatively short follow-up period in the animal studies may therefore account for the absence of osteolysis surrounding the polymer. In other words, the period of exposure in these studies might simply have been too short to provoke osteolysis. Both the current study and the findings of Ockendon et al. [13] reported visible changes after 1 year. The first serious adverse event due to osteolysis surrounding an OptiPlug cement restrictor as described by Dhawan et al. [3] supports our hypothesis that the osteolytic process probably is a long-term phenomenon. Their paper presents the case of a spontaneous periprosthetic fracture, 5 years after insertion of the plug. Whatever the underlying mechanism, osteolysis around the OptiPlug is not merely an incident and may pose serious health risks. Despite these alarming new insights, new applications for the PolyActive polymer are currently being tested. Among these new applications is the use of PolyActive as a filling agent to prevent post-operative bleeding from the donor site in mosaicplasty in articular lesions [23]. At this point, however, we cannot guarantee the safety of this material in humans since we know so little of the long-term tissue reaction. To conclude, we cannot recommend the OptiPlug cement restrictor in total arthroplasty of the hip and advise caution to all involved in experimental research on this resorbable material. Conflict of interest
None.
References 1. Bulstra SK, Geesink RG, Bakker D, Bulstra TH, Bouwmeester SJ, van der Linden AJ (1996) Femoral canal occlusion in total hip replacement using a resorbable and flexible cement restrictor -. J Bone Joint Surg Br 6:892–898 2. Danter MR, King GJ, Chess DG, Johnson JA, Faber KJ (2000) The effect of cement restrictors on the occlusion of the humeral canal: an in vitro comparative study of 2 devices. J Arthroplasty 1:113–119 3. Dhawan RK, Mangham DC, Graham NM (2012) Periprosthetic femoral fracture due to biodegradable cement restrictor. J Arthroplast 27(8):1581.e13–1581.e15 4. Du C, Meijer GJ, van de Valk C, Haan RE, Bezemer JM, Hesseling SC, Cui FZ, de Groot K, Layrolle P (2002) Bone growth in biomimeticapatite coated porous Polyactive 1000PEGT70PBT30 implants. Biomaterials 23:4649–4656 5. Faraj AA, Rajasekar K (2006) The effect of two different types of cement restrictors on the femoral cement mantle. Acta Orthop Belg 6:702–708
123
6. Freund KG, Herold N, Røck ND, Riegels-Nielsen P (2003) Poo results with the shuttle stop: resorbable versus nonresorbable intramedullar cement restrictor in a prospective and randomized study with a 2-year follow-up. Acta OrthopScand 1:37–41 7. Heisel C, Norman TL, Rupp R, Pritsch M, Ewerbeck V, Breusch SJ (2003) In vitro performance of intramedullary cement restrictors in total hip arthroplasty. J Biomech 6:835–843 8. Heisel C, Norman TL, Rupp R, Mau H, Breusch SJ (2003) Stability and occlusion of six different femoral cement restrictors. Orthopade 6:541–547 9. Kroon M, Visser CP, Mootanah R, Brand R (2006) Performance of 3 gelatine-based resorbable cement plugs: a study on 15 synthetic femurs and a prospective randomized study on 103 patients. Acta Orthop 6:893–898 10. Meijer GJ, Heethaar J, Cune MS, De Putter C, Van Blitterswijk CA (1997) Flexible (Polyactive) versus rigid (hydroxyapatite) dental implants. Int J Oral Maxillo fac Surg 2:135–140 11. Meijer GJ, Radder A, Dalmeijer R, de Putter C, Van Blitterswijk CA (1995) Observations of the bone activity adjacent to unloaded dental implants coated with Polyactive or HA. J OralRehabil 3:167–174 12. Moran M, Heisel C, Rupp R, Simpson AH, Breusch SJ (2007) Cement restrictor function below the femoral isthmus. ClinOrthopRelatRes 458:111–116 13. Ockendon M, Oakley JE, Graham NM (2011) Osteolysis associated with ‘Optiplug’ bioabsorbable cement restrictors. J Bone Joint Surgery 93(Suppl 4):547 14. Radder AM, Davies JE, Leenders H, van Blitterswijk CA (1994) Interfacial behavior of PEO/PBT copolymers (Polyactive) in a calvarial system: an in vitro study. J Biomed Mater Res 2:269–277 15. Radder AM, Leenders H, van Blitterswijk CA (1994) Interface reactions to PEO/PBT copolymers (Polyactive) after implantation in cortical bone. J Biomed Mater Res 2:141–151 16. Roessler M, Wilke A, Griss P, Kienapfel H (2000) Missing osteoconductive effects of a resorbable PEO/PBT copolymer in human bone defects: a clinically relevant pilot study with contrary results to previous animal studies. J Biomed Mater Res 2:167–173 17. Schauss SM, Hinz M, Mayr E, Bach CM, Krismer M, Fischer M (2006) Inferior stability of a biodegradable cement plug. 122 total hip replacements randomized to degradable or non-degradable cement restrictor. ArchOrthop Trauma Surg 5:324–329 18. Smith EL, Wohlrab KP, Matzkin EG, Providence BC (2004) A comparison of distal canal restrictors in primary cemented femoral hip arthroplasty. Orthopedics 8:847–851 19. Waris E, Ashammakhi N, Lehtima¨ki M, Tulamo RM, To¨rma¨la¨ P, Kelloma¨ki M, Konttinen YT (2008) Long-term bone tissue reaction to polyethylene oxide/poly butylene ter phthalate copolymer (Polyactive) in metacarpophalangeal joint reconstruction. Biomaterials 16:2509–2515 20. http://www.biomet.co.uk/medhome-uk/cement/pressurisation/ hip-femoral 21. http://www.octoplus-annualreport.nl/index.php?id=446 22. Bouwmeester SJ, Kuijer R, Sollie-Drees MM, van der Linden AJ, Bulstra SK (1998) Quantitative histological analysis of bony ingrowth within the biomaterial Polyactive implanted in different bone locations: an experimental study in rabbits. Journal Mater Sci Mater Med 4:181–185 23. Albert R, Va´sa´rhelyi G, Bodo´ G, Kenyeres A, Wolf E, Papp T, Terdik T, Mo´dis L, Felszeghy S (2012) A computer-assisted microscopic analysis of bone tissue developed inside a poly active polymer implanted into an equine articular surface. HistolHistopathol 9:1203–1209 24. Wu G, Liu Y, Iizuka T, Hunziker EB (2010) The effect of a slow mode of BMP-2 delivery on the inflammatory response provoked
Eur J Orthop Surg Traumatol by bone-defect-filling polymeric scaffolds -. Biomaterials 29:7485–7493 25. El-Ghalbzouri A, Lamme EN, van Blitterswijk C, Koopman J, Ponec M (2004) The use of PEGT/PBT as a dermal scaffold for skin tissue engineering. Biomaterials 15:2987–2996 26. Li P, Bakker D, van Blitterswijk CA (1997) The bone-bondingpolymerPolyactive 80/20 induces hydroxy carbonate apatite formation in vitro. Journal of Bio Mater Res 1:79–86
27. Jansen EJ, Pieper J, Gijbels MJ, Guldemond NA, Riesle J, Van Rhijn LW, Bulstra SK, Kuijer R (2009) PEOT/PBT based scaffolds with low mechanical properties improve cartilage repair tissue formation in osteochondral defects -. J Biomed Mater Res A 2:444–452
123
GENERAL REVIEW
Osteolysis in cemented total hip arthroplasty involving the OptiPlug cement restrictor: more than an incident? N. M. A. I. Hanssen • M. G. M. Schotanus A. D. Verburg
•
Received: 8 August 2013 / Accepted: 8 November 2013 Ó Springer-Verlag France 2013
Abstract The case report of a severe osteolytic reaction surrounding the OptiPlug cement restrictor in a 74-year-old male patient initiated a retrospective case series and closer investigation into the OptiPlug and its active compound, PolyActive. Not only did we find several cases of severe osteolysis in our own study population of 284 patients, several articles have lately described potential harmful side effects of the PolyActive material in humans. Although none of the articles have been based on large databases, we cannot guarantee the safety of this product. More research would help in our understanding of this phenomenon. Until then, we cannot recommend the use of the OptiPlug cement restrictor. Keywords Hip arthroplasty Cement restrictor Osteolysis Resorbable PolyActive OptiPlug
plugs, a wide variety of materials and shapes exists: a factor that definitely contributes to the lack of evidence on the superiority of any of these plugs in achieving an adequate cement mantle [2, 5–9, 12, 17, 18]. Even less is known about the long-term in vivo effects of these plugs [1, 5, 18, 19]. In this case report and subsequent retrospective case series of 284 patients, osteolytic reaction was observed surrounding the OptiPlug (Biomet Inc., Warsaw, Indiana, USA), a cement restrictor consisting of the biodegradable synthetic PEG/PBT copolymer PolyActive (OctoPlus NV, Leiden, the Netherlands) [20, 21]. We present this case report and case series and compare these findings to the current literature on the OptiPlug cement restrictor and its active compound PolyActive.
Introduction
Case report
Worldwide, cemented arthroplasty of the hip is a common treatment for osteoarthritis of this joint. Despite the vast number of total cemented hip arthroplasties that are performed every year, little is known about the in vivo effects of the cement restrictors that are inextricably linked to this procedure. A large number of different cement restrictors is currently available. In both resorbable and nonresorbable
In February 2007, a 74-year-old healthy male suffering from disability and pain due to osteoarthritis underwent a cemented total arthroplasty of the right hip. After insertion of the OptiPlug cement restrictor, the medullar cavity was rinsed (Pulse-Lavage, Stryker Inc., Kalamazoo, Michigan, USA) and the femur was cemented with Gentamicin Palacos (Heraeus Kulzer GmbH., Hanau, Germany). A retrograde cementing technique was applied, using a cement gun, without additional pressurization. An anatomic polished chrome-cobalt stem (ABG-2, Stryker Inc.) was inserted. No irregularities were reported during the procedure. Recovery after surgery was normal and without complications. Radiographs did not reveal any irregularities (Figs. 1, 2). Six months after surgery, the patient had recovered to his preoperative level of mobility. At 1-year follow-up, however, routine radiographs revealed osteolysis distal to the cement with mild cortical thinning (Fig. 3).
N. M. A. I. Hanssen (&) Resident at Maartenskliniek, Van Welderenstraat 13, 6511 MA Nijmegen, The Netherlands e-mail: [email protected] M. G. M. Schotanus A. D. Verburg Orbis Medisch Centrum, Sittard-Geleen, The Netherlands e-mail: [email protected] A. D. Verburg e-mail: [email protected]
123
Eur J Orthop Surg Traumatol
Fig. 1 AP view, post-op Fig. 3 AP view, 1 year post-op
During further follow-up, progression of the osteolysis was observed (Figs. 4, 5, 6). As there were no complaints, no specific action was undertaken. Computer tomography of the affected region showed severe osteolysis, especially of the posterior cortex, with an estimate of about 1/3 of bone loss (Figs. 7, 8). In January 2013, a needle biopsy of the osteolytic lesion was performed. Pathological evaluation showed signs of cement remnants without granulomatous inflammation. Culture was negative. Regular follow-up will be continued.
Case series The dramatic single case as described above sparked our interest and lead to the start of a retrospective radiographic investigation of all total hip arthroplasties involving this cement restrictor, focusing on the year 2005, including all patients operated with the OptiPlug cement restrictor from one and the same batch.
Materials and methods
Fig. 2 AP view, 3 months post-op
123
After approval of the local ethics committee (METC Atrium-Orbis Zuyd, Heerlen, the Netherlands, nr 13N28),
Eur J Orthop Surg Traumatol
Fig. 4 AP view, 3 years post-op
Fig. 6 AP view, 4 years post-op
restrictor, consisting of the PolyActive material. Of these 284, 104 patients were considered ‘at risk’ for osteolytic reaction surrounding the plug and called in for extra X-rays, either because of abnormalities in an existing X-ray or because of the lack of adequate radiographic follow-up. Radiographic follow-up of 3 years or more without visible abnormalities was considered as adequate follow-up. Bone densitometry test were done in order to obtain a more objective estimate of the severity of the bone loss. The femur distal to the prosthesis and cement plug was divided in three areas of interest. Bone density through all three areas was measured, and an average bone density of the entire area was calculated for both the male and female patients (Fig. 9). Statistical analysis was conducted using SPSS (version 17). Outcome variables and their differences were tested with nonparametric techniques (Wilcoxon/Mann–Whitney tests). P values of \ 0.05 were considered statistically significant.
Fig. 5 Lateral view, 4 years post-op
Results
the study was conducted according to the declaration of Helsinki. In 2005, 284 patients underwent a cemented total hip arthroplasty with use of the OptiPlug resorbable cement
A total of 52 patients complied to our appeal for extra radiographs. In 25 out of these 52 patients, marked osteolysis and weakening of the cortex were observed surrounding the plug, including one bilateral case. In another
123
Eur J Orthop Surg Traumatol
Fig. 7 AP view, CT scan 4, 5 years post-op
Fig. 9 Division of the femur in three areas of interest Table 1 Outcomes of bone densitometry testing within each gender and between male and female patients Gender Male Female
N
BMD plug
BMD net
% BMD loss
p value
5
1.7 (1.4–1.9)
1.8 (1.5–2.0)
6.3 % (2.2–8.6)
n.s.
14
1.4 (1.2–1.8)
1.6 (1.2–1.9)
9.2 % (0.6–17.6)
n.s.
n.s.
n.s
n.s.
p value
None of the outcomes were statistically significant (n.s.)
reported. Statistical analysis by means of a Mann–Whitney U test and nonparametric T test did not show any statistical significant difference.
Discussion
Fig. 8 Lateral view, CT scan 4, 5 years post-op
19 cases, a minor osteolytic reaction around the OptiPlug was observed. Of the 25 patients with marked osteolysis, 19 underwent a bone densitometry test. Average follow-up at this point was 7 years (range 6.1–7.6). Bone density through the area of the plug was compared to the average bone density of the entire area (Table 1). Average loss of bone density in men was 6.3 %, compared to 9.2 % in woman. Percentages of up to 17.6 were
123
In this retrospective radiographic investigation of 284 patients, 25 confirmed cases of substantial osteolysis surrounding the OptiPlug were identified. Another 19 cases of less severe osteolysis were observed. Although the attendance rate of the 104 ‘at risk’ patients was less than we had hoped for, we can certainly state that this disturbing discovery confirms our suspicion that osteolysis associated with the OptiPlug cement restrictor is more than an incidental finding. We regret the rather high percentage of patients that did not comply to our request for extra radiographic and clinical follow-up. However, the affected population consists mainly of elderly patients, some of whom already live in a nursing home and/or have limited access to their own means of transportation. The
Eur J Orthop Surg Traumatol
Fig. 10 Chemical composition of the PolyActive polymer [21]
asymptomatic nature of the condition may also contribute to the rather low percentage of attendance. Fortunately, all patients are currently still without symptoms. This includes the ‘original’ elderly male patient, whose dramatic radiographic images initiated the retrospective investigation. The risk of a periprosthetic fracture in the event of a trauma in the more severely affected patients seems realistic however. The PolyActive material is a resorbable PEG/PBT polymer (Fig. 10). The material is widely used in the orthopedic industry and has multiple applications, for instance as implant scaffold or coating. It is also been implemented as a dermal scaffold for skin tissue engineering and in the dental industry [10, 11, 25, 26]. Another utilization of the material is the slow drug delivery technology in microspheres [21]. The older evidence regarding the PolyActive material describes favorable osteoconductive effects [4, 10, 14, 15, 22, 24]. All these studies involved an animal model. The first positive report on the performance of the OptiPlug in a human pilot study was published in 1996. At 2 years follow-up, no local changes were observed in the femur [1]. We are not the first, however, to present more side effects of the PolyActive material. In 2000, Roessler et al. [16] were the first to describe a missing osteoconductive effect of PolyActive in humans. Seven patients underwent anterior spinal interbody fusion surgery, for which two bicortical iliac defects were created. One defect was filled with PolyActive, and the other was left untreated as control. At follow-up at 52 weeks, spiral CT revealed significant less formation of new bone in the treated defects. Another negative report, describing massive osteolysis in live minipigs following the implantation of PolyActive, was published in 2008. In this study, elastomeric stems made of PolyActive were used to anchor polylactate joint scaffolds for the reconstruction of metacarpophalangeal joints [19]. In 2011, a large study group of 100 patients with a 5-year follow-up period was presented by Ockendon et al. [13]. In 87 patients, radiographs showed marked thinning of the cortex. There were 5 severe cases with more than 33 % thinning of the cortex. The authors noted that local changes in the femur did not appear to progress or regress significantly between 1 and 5 years. This in contrast to both the current study and the study presented by Ockendon et al. [13] report visible changes after 1 year. We believe
that radiographic osteolysis appears after several months, and that it progresses through the years. PEG, or polyethylene glycol, (also known as polyethylene oxide (PEO) or polyoxyethylene (POE) depending on its molecular weight) is a polymer of ethylene oxide. This compound has a tremendous amount of applications; several of which can be found in our current medical practice. Some examples include the use of PEG in antibody production, slow drug release formulas or the use of this substance as laxatives. PBT, or polybutylene terephthalate, is a thermoplastic polymer, which is commonly used as an insulator in the electronic industries and car production. It also has applications as the stretching fiber in swim- and sportswear and can be found in the fibers of toothbrushes. At a first glance, one might suspect the PolyActive material to be related to polylactate. A comparison to the tissue reaction following the implantation of polylactate screws or other implants of this material might therefore seem interesting and relevant. The chemical composition of PEG and PBT does not include a lactate acid group though; therefore, they are not related to the lactate group. In short, they are two different chemical entities. The only aspect they have in common is the mere fact that both substances are resorbable. Besides this chemical argument, biomechanical aspects are also suspected to be important in the tissue reaction that follows the implantation of PolyActive, as described by Radder et al. [15]. From research, we further know that the PEG/PEB ratios in the polymer are important in the calcification process within the near surface of the material. Several ratios have been observed in in vitro tests: 70/30, 60/40, 55/45, 40/60 and 30/70 [14, 15]. The higher the PEG/ PBT ratio, the more rapid the calcification [14]. The best result was achieved with the 70/30 ratio; this is the ratio used in PolyActive. Healing response in a osteochondral defect model in rabbits proved also to be superior in the 70/30 ratio when compared to the 55/45 ratio [27]. In all these studies, the percentage PEG proved to be crucial in the calcification process. It is proposed that this is due to the remarkable high affinity of the PEG segment for calcium ions in the environment [26]. Biomechanical properties also appear to influence the tissue reaction in the near surrounding of the implant. PEG is a softer material than PBT and is an hydrophylic component. The swelling behavior of the PEG component results in a high degree of bone contact and calcification [15]. Average BMD loss of 6.3–9.2 % was observed in our patient population. Some cases were more severely affected: e.g., a BMD loss of 17.3 % or up to one-third of the cortical bone. Though we do not exactly know how relevant this is for the particular patient concerned, we can certainly state that any amount of BMD loss in elderly
123
Eur J Orthop Surg Traumatol
patients with osteoporosis poses health risks and is both undesirable and unacceptable. Sadly, our exact knowledge as to why long-term exposure of this polymer to cortical bone sometimes results in osteolysis, is very limited. Most animal studies did not show these reactions. We suspect that the degradation of the material triggers an osteolytic reaction. The relatively short follow-up period in the animal studies may therefore account for the absence of osteolysis surrounding the polymer. In other words, the period of exposure in these studies might simply have been too short to provoke osteolysis. Both the current study and the findings of Ockendon et al. [13] reported visible changes after 1 year. The first serious adverse event due to osteolysis surrounding an OptiPlug cement restrictor as described by Dhawan et al. [3] supports our hypothesis that the osteolytic process probably is a long-term phenomenon. Their paper presents the case of a spontaneous periprosthetic fracture, 5 years after insertion of the plug. Whatever the underlying mechanism, osteolysis around the OptiPlug is not merely an incident and may pose serious health risks. Despite these alarming new insights, new applications for the PolyActive polymer are currently being tested. Among these new applications is the use of PolyActive as a filling agent to prevent post-operative bleeding from the donor site in mosaicplasty in articular lesions [23]. At this point, however, we cannot guarantee the safety of this material in humans since we know so little of the long-term tissue reaction. To conclude, we cannot recommend the OptiPlug cement restrictor in total arthroplasty of the hip and advise caution to all involved in experimental research on this resorbable material. Conflict of interest
None.
References 1. Bulstra SK, Geesink RG, Bakker D, Bulstra TH, Bouwmeester SJ, van der Linden AJ (1996) Femoral canal occlusion in total hip replacement using a resorbable and flexible cement restrictor -. J Bone Joint Surg Br 6:892–898 2. Danter MR, King GJ, Chess DG, Johnson JA, Faber KJ (2000) The effect of cement restrictors on the occlusion of the humeral canal: an in vitro comparative study of 2 devices. J Arthroplasty 1:113–119 3. Dhawan RK, Mangham DC, Graham NM (2012) Periprosthetic femoral fracture due to biodegradable cement restrictor. J Arthroplast 27(8):1581.e13–1581.e15 4. Du C, Meijer GJ, van de Valk C, Haan RE, Bezemer JM, Hesseling SC, Cui FZ, de Groot K, Layrolle P (2002) Bone growth in biomimeticapatite coated porous Polyactive 1000PEGT70PBT30 implants. Biomaterials 23:4649–4656 5. Faraj AA, Rajasekar K (2006) The effect of two different types of cement restrictors on the femoral cement mantle. Acta Orthop Belg 6:702–708
123
6. Freund KG, Herold N, Røck ND, Riegels-Nielsen P (2003) Poo results with the shuttle stop: resorbable versus nonresorbable intramedullar cement restrictor in a prospective and randomized study with a 2-year follow-up. Acta OrthopScand 1:37–41 7. Heisel C, Norman TL, Rupp R, Pritsch M, Ewerbeck V, Breusch SJ (2003) In vitro performance of intramedullary cement restrictors in total hip arthroplasty. J Biomech 6:835–843 8. Heisel C, Norman TL, Rupp R, Mau H, Breusch SJ (2003) Stability and occlusion of six different femoral cement restrictors. Orthopade 6:541–547 9. Kroon M, Visser CP, Mootanah R, Brand R (2006) Performance of 3 gelatine-based resorbable cement plugs: a study on 15 synthetic femurs and a prospective randomized study on 103 patients. Acta Orthop 6:893–898 10. Meijer GJ, Heethaar J, Cune MS, De Putter C, Van Blitterswijk CA (1997) Flexible (Polyactive) versus rigid (hydroxyapatite) dental implants. Int J Oral Maxillo fac Surg 2:135–140 11. Meijer GJ, Radder A, Dalmeijer R, de Putter C, Van Blitterswijk CA (1995) Observations of the bone activity adjacent to unloaded dental implants coated with Polyactive or HA. J OralRehabil 3:167–174 12. Moran M, Heisel C, Rupp R, Simpson AH, Breusch SJ (2007) Cement restrictor function below the femoral isthmus. ClinOrthopRelatRes 458:111–116 13. Ockendon M, Oakley JE, Graham NM (2011) Osteolysis associated with ‘Optiplug’ bioabsorbable cement restrictors. J Bone Joint Surgery 93(Suppl 4):547 14. Radder AM, Davies JE, Leenders H, van Blitterswijk CA (1994) Interfacial behavior of PEO/PBT copolymers (Polyactive) in a calvarial system: an in vitro study. J Biomed Mater Res 2:269–277 15. Radder AM, Leenders H, van Blitterswijk CA (1994) Interface reactions to PEO/PBT copolymers (Polyactive) after implantation in cortical bone. J Biomed Mater Res 2:141–151 16. Roessler M, Wilke A, Griss P, Kienapfel H (2000) Missing osteoconductive effects of a resorbable PEO/PBT copolymer in human bone defects: a clinically relevant pilot study with contrary results to previous animal studies. J Biomed Mater Res 2:167–173 17. Schauss SM, Hinz M, Mayr E, Bach CM, Krismer M, Fischer M (2006) Inferior stability of a biodegradable cement plug. 122 total hip replacements randomized to degradable or non-degradable cement restrictor. ArchOrthop Trauma Surg 5:324–329 18. Smith EL, Wohlrab KP, Matzkin EG, Providence BC (2004) A comparison of distal canal restrictors in primary cemented femoral hip arthroplasty. Orthopedics 8:847–851 19. Waris E, Ashammakhi N, Lehtima¨ki M, Tulamo RM, To¨rma¨la¨ P, Kelloma¨ki M, Konttinen YT (2008) Long-term bone tissue reaction to polyethylene oxide/poly butylene ter phthalate copolymer (Polyactive) in metacarpophalangeal joint reconstruction. Biomaterials 16:2509–2515 20. http://www.biomet.co.uk/medhome-uk/cement/pressurisation/ hip-femoral 21. http://www.octoplus-annualreport.nl/index.php?id=446 22. Bouwmeester SJ, Kuijer R, Sollie-Drees MM, van der Linden AJ, Bulstra SK (1998) Quantitative histological analysis of bony ingrowth within the biomaterial Polyactive implanted in different bone locations: an experimental study in rabbits. Journal Mater Sci Mater Med 4:181–185 23. Albert R, Va´sa´rhelyi G, Bodo´ G, Kenyeres A, Wolf E, Papp T, Terdik T, Mo´dis L, Felszeghy S (2012) A computer-assisted microscopic analysis of bone tissue developed inside a poly active polymer implanted into an equine articular surface. HistolHistopathol 9:1203–1209 24. Wu G, Liu Y, Iizuka T, Hunziker EB (2010) The effect of a slow mode of BMP-2 delivery on the inflammatory response provoked
Eur J Orthop Surg Traumatol by bone-defect-filling polymeric scaffolds -. Biomaterials 29:7485–7493 25. El-Ghalbzouri A, Lamme EN, van Blitterswijk C, Koopman J, Ponec M (2004) The use of PEGT/PBT as a dermal scaffold for skin tissue engineering. Biomaterials 15:2987–2996 26. Li P, Bakker D, van Blitterswijk CA (1997) The bone-bondingpolymerPolyactive 80/20 induces hydroxy carbonate apatite formation in vitro. Journal of Bio Mater Res 1:79–86
27. Jansen EJ, Pieper J, Gijbels MJ, Guldemond NA, Riesle J, Van Rhijn LW, Bulstra SK, Kuijer R (2009) PEOT/PBT based scaffolds with low mechanical properties improve cartilage repair tissue formation in osteochondral defects -. J Biomed Mater Res A 2:444–452
123
