Plasma levels of platelet-derived growth factor BB and transforming growth factor in patients with failed hip prostheses

Background The role of growth factors in prosthesis loosening is unclear. We evaluated the levels of plate-let-derived growth factor BB (PDGF-BB), transforming growth factors β1 (TGF-β1) and β2 (TGF-β2), both before and after activation, in patients with aseptic loosening of their hip prosthesis.

Patients and methods 26 patients with loosened hip implants were compared with 21 patients who had stable hip prostheses, and 28 patients undergoing primary hip replacement. The plasma levels of the growth factors were analyzed by enzyme immunoassay. TGF-β1 and TGF-β2 were determined both before and after activation.

Results Patients with aseptic loosening had significantly lower PDGF-BB levels than patients undergoing primary hip replacement, and significantly lower TGF-β2 levels than patients with a stable implant. Patients with stable prostheses had significantly higher TGF-β1 and TGF-β2 levels than patients undergoing primary hip replacement.

Interpretation It is possible that the prosthetic implant itself causes a local increase in PDGF-BB, TGF-β1 and TGF-β2, released by osteoblasts and other cells in the microenvironment. The plasma PDGF-BB measured does not correspond to local release, which is probably due to local consumption or degradation. The consumption of PDGF-BB is low in stable implants, and TGF-β1 and TGF-β2 levels increase during bone formation. In loosening, PDGF-BB consumption is higher and causes a significant reduction in plasma levels as compared to presurgery. The formation of poor-quality bone may be related to the scarce increase in TGF-β1 and TGF-β2. In conclusion, compared with patients with a stable implant, a reduction in bone-forming growth factors appears to occur in individuals with aseptic loosening.     

Postoperative analgesia in total hip arthroplasty: a randomized double-blinded, placebo-controlled study on peroperative and postoperative ropivacaine, ketorolac, and adrenaline wound infiltration

Background Comfort and lack of pain are important for optimal mobilization after hip replacement. We investigated the efficacy of double wound infiltration.

Patients and methods 40 consecutive patients undergoing total hip replacement were randomized into two groups in this double-blinded study. They received wound infiltration at the end of surgery and through an intraarticular catheter 24 h postoperatively. The catheter was placed at the end of surgery. One group received solutions of ropivacaine, ketorolac, and adrenaline. Patients in the control group were injected with saline instead. The observation period was 6 weeks.

Results The patients who received the analgesic solution had less pain up to 2 weeks postoperatively. They reached an earlier and lower pain minimum during the first days postoperatively, had lower use of analgesia up to day 4 postoperatively, and were more satisfied. Use of analgesic solution resulted in less joint stiffness and better function 1 week postoperatively.

Interpretation Operative and postoperative wound infiltration with multimodal drugs reduces pain and the requirement for analgesics after hip replacement, leading to faster postoperative mobilization.     

Serum total acid phosphatase for monitoring the clinical course of giant cell tumors of bone--26 patients with 5 local recurrences

Background Giant cell tumor of bone (GCT) is a bone-destroying tumor that sometimes recurs locally after treatment. A recent study showed increased levels of serum total acid phosphatase (TACP).

Methods We assessed TACP in the serum of 26 patients with primary GCT, and in 5 of them who developed a local recurrence.

Results We found a correlation between TACP level in serum and tumor size. TACP levels that were elevated preoperatively in patients with GCT became normalized after surgery, but increased in 3 of the 5 patients with local recurrence.

Interpretation TACP could be used as a tumor marker for monitoring response to treatment of GCT.     

Socket wall addition device in the treatment of recurrent hip prosthesis dislocation: good outcome in 12 patients followed for 4.5 (1-9) years

Background Recurrent dislocation in total hip replacement is difficult to treat and causes severe morbidity.

Patients and methods 12 patients suffering dislocations were reoperated with a socket wall addition device (anti-luxation ring) for the Lubinus SPII prosthesis, and were followed up after a mean of 4.5 (1-9) years with regard to redislocation, function and radiographic loos-ening.

Results 1 of the patients suffered a redislocation after almost 7 years of use. There was no loosening during the follow-up time. A Harris hip score of 87 (60-100), a health-related quality of life (EQ-5D) index of 0.8 (0.6-1.0) and total range of motion of 145° (125-165) indicate that the patients had a level of function comparable to that of age-matched hip surgery patients with no com-plications.

Interpretation The anti-luxation ring shows promising mid-term results and seems to provide an alternative to more extensive revision surgery for selected patients. ▪     

The effect of recombinant human bone morphogenetic protein-2 on the osteogenic potential of rat mesenchymal stem cells after several passages

Background Since the osteogenic potential of bone marrow derived mesenchymal stem cells (BMSCs) becomes reduced with passage, establishment of culture condition that permit the rapid expansion of BMSCs while retaining their potential for differentiation is needed for clinical application. Bone morphogenetic proteins stimulate osteogenic differentiation in mesenchymal progenitor cells as well as increase stem cell numbers. Thus, we analyzed the effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) on the osteogenic potential of rat BMSCs over several passages.

Material and methods Osteogenic differentiation in vitro was evaluated in terms of the alkaline phosphatase (ALP) activity and the osteocalcin (OC) concentration in the supernatants, and the expression of ALP and OC mRNA in the cultured cells. For in-vivo osteogenesis, BMSCs cultured with and without rhBMP-2 through all passages were implanted into athymic mice.

Results  The levels of osteogenic markers were significantly higher in the cells of the BMP(+) group than in the cells of the BMP(-) group, although they decreased with passage irrespective of whether or not rhBMP-2 was added. Similar to the in-vitro experiments, there was a greater degree of bone and cartilage tissue formation in the BMP(+) group over all passages.

Interpretation  From our results, osteogenic potential can be maintained even in BMSCs that have been passaged several times in the presence of rhBMP-2. These cells are capable of inducing and participating in bone formation and can be used for clinical applications.     

Inflammatory response in 85 patients with loosened hip prostheses: a prospective study comparing inflammatory markers in patients with aseptic and septic prosthetic loosening

Background The most common complications of prosthetic hip joints are aseptic mechanical failure and infection. Delayed low-grade infections are seen most often, and they are also most difficult to distinguish from aseptic mechanical failures.

Methods We conducted a prospective study to compare inflammatory markers in patients diagnosed with aseptic or septic prosthetic loosening. The diagnostic criteria were based on the decisions of experienced orthopedic surgeons and microbiological analysis of periprosthetic tissue samples taken perioperatively.

Results Coagulase-negative staphylococci were the commonest pathogens in the infected patients. Pre- or perioperative elevation of C-reactive protein and erythrocyte sedimentation rate were significantly greater in the infection group, as were white blood cell count and levels of cytokines in synovial fluid. The patterns of infiltration of inflammatory cells in periprosthetic tissue were also significantly different between the groups.

Interpretation A combination of clinical judgment and multiple tissue samples constitutes a good platform for distinguishing between septic and aseptic loosening of prostheses. Moreover, the combined use of several laboratory and histopathological markers of inflammation, especially infiltration of polymorphonuclear cells, further helps the diagnosis.     

Surface-bound bisphosphonates enhance screw fixation in rats--increasing effect up to 8 weeks after insertion

Background A bisphosphonate coating improves screw fixation 2 weeks after implantation in cancellous bone. This study on rats examined further development of fixation over time for screws inserted in cancellous and cortical bone.

Methods SS screws were coated with a multiple layer of fibrinogen. Half of the screws were coated further with bisphosphonates, which were linked to the fibrinogen. The screws were inserted in cancellous and cortical bone in rats. The rats were killed after 5 h, 4 days, 1, 2, 4, 8, and 24 weeks, and fixation was evaluated by pullout test.

Results There was a gradual increase in pull-out force over time in both cancellous and cortical bone. The bisphosphonate coating improved fixation. Moreover, the difference between the bisphosphonate and control groups increased with time. The pull-out force was almost twice that of the controls for screws inserted in cancellous bone at 8 weeks. Energy uptake was increased more than 3-fold.

Discussion The energy uptake and pull-out force of a screw depends on the bone engaged with the threads. Thus, the presence of bisphosphonates increased the amount or quality of this bone by affecting the resorp-tion/formation in a positive way. The increased effect of the bisphosphonates with time thus suggests that bisphosphonate is retained within the remodeling bone, with a positive effect on its gradual adaptation to the implant.     

Tissue concentrations of vancomycin and Moxifloxacin in periprosthetic infection in rats

Background A one-step exchange of an endoprosthesis with periprosthetic infection requires effective antibiotics at high concentrations around the endoprosthesis. We evaluated the tissue distribution of vancomycin and Moxifloxacin in a standardized in vivo model of periprosthetic infection.

Methods 36 male rats with periprosthetic infection of the left hind leg, induced by a standardized procedure, received either antibiotic treatment with vancomycin or Moxifloxacin twice daily for 2 weeks, or a sham treatment. After the last administration, different tissues from each animal were evaluated for concentrations of antibiotic.

Results Compared to plasma, the tissue concentrations of Moxifloxacin were higher in all tissues investigated (lung, muscle, fat, bone) and the tissue-plasma ratio of Moxifloxacin was considerably higher than that of vancomycin. The concentrations of Moxifloxacin were equally high in the infected and the uninfected hind leg, whereas the vancomycin concentrations were significantly higher in the infected leg.

Interpretation The standardized model of periprosthetic infection described here can be extrapolated to different bacterial and mycotic pathogens, and also to different antibiotics or therapeutic regimes. It provides a way of correlating tissue concentrations with clinical outcome in future studies.     

Structural allografts for bone stock reconstruction in two-stage revision for infected total hip arthroplasty: good outcome in 16 of 18 patients followed for 5-14 years

Background The use of massive bone allografts in cases of revision of failed total hip arthroplasties (THAs) due to infection is controversial.

Patients and methods 18 patients presented with infection at the site of a THA and were treated with a two-stage protocol. In the first stage, the prosthesis was removed together with all necrotic tissues and cement material if present. A custom-made mold of Palacos R cement containing 1 g of gentamicin was then inserted in 17 of the 18 patients. Systemic antibiotics were used during the interval period. In the second stage, the patients had either acetabular or femoral reconstruction using bulk allograft bone.

Results Mean follow-up was 9 (5-14) years. 1 patient presented with recurrent infection and underwent a Girdlestone resection arthroplasty as definitive treatment. Another patient had a mechanical failure of the acetabular component, which was revised 10 years after the second stage of the reconstruction. The mean Harris Hip Score improved from 34 points preoperatively to 71 points at the last review. By our definition, 16/18 of the patients had a successful outcome.

Interpretation Our results support the use of massive allografts in staged reconstructions of infected THAs complicated by considerable bone loss. ▪     

Introduction of total hip arthroplasty in Lithuania: results from the first 10 years

Background Hip replacement as a routine procedure was introduced in Lithuania in 1991. At Klaipeda Hospital, one of the 2 hospitals at which this was begun, the arthroplasties were followed prospectively from the start. This study concerns the 10-year results from a country with no previous experience of hip replacement. The results are compared with those from a hospital with considerable experience of total hip replacement.

Methods We compared the revision rate for the first 658 primary ScanHip arthroplasties inserted at Klaipeda to that for the first 939 ScanHip primary arthroplasties inserted at Lund University Hospital, Sweden. Only patients with osteoarthritis were included, and the endpoint was revision for aseptic loosening with exchange of one or both components.

Results We found that patients operated at Klaipeda Hospital had a significantly higher risk of revision (12%) than those operated in Lund (6%).

Interpretation Although we could not identify any specific reason for the Swedish results being better than the Lithuanian results, it is probable that previous surgical inexperience of hip replacement in Lithuania played a role. We believe that the findings will stimulate surgeons in Lithuania to analyze their failures and improve the results.     

Selective COX-2 inhibitor versus indomethacin for the prevention of heterotopic ossification after hip replacement: a double-blind randomized trial of 100 patients with 1-year follow-up

Introduction Recent reports have suggested that selective COX-2 inhibition may be sufficient for the prevention of heterotopic ossification.

Methods We performed a randomized controlled study to evaluate the effect of the selective COX-2 inhibitor rofecoxib compared to that of indomethacin on the incidence and extent of heterotopic ossification in patients who had undergone hip replacement surgery. 50 patients received a daily dose of 25 mg rofecoxib and 50 patients received a daily dose of 100 mg indomethacin (25, 25, and 50 mg).

Results No ossifications were found in 48 patients. Grade-II ossifications were seen in 5/46 patients in the rofecoxib group and in 6/50 patients in the indomethacin group. Grade-III and grade-IV ossifications were seen in 3/46 patients in the rofecoxib group only. The differences were not statistically significant. The study medication had to be discontinued in 2 patients in the indomethacin group, due to dyspepsia.

Interpretation After short-term administration, the selective COX-2 inhibitor rofecoxib was effective in preventing heterotopic ossification after total hip arthroplasty.     

Continuous bone loss around a tapered uncemented femoral stem: a long-term evaluation with DEXA

Background Periprosthetic bone loss is a well-docu-mented phenomenon after uncemented total hip arthroplasty (THA); however, little is known about how bone mineral density (BMD) changes after 2 years.

Patients and methods 14 patients with hip arthrosis (group A) were operated with a proximally porous- and hydroxyapatite-coated stem and followed for 10 years with DEXA, radiographs and Harris hip score (HHS). Another group of 14 patients (group B) was evaluated at 6 and 14 years using the same prosthesis and protocol.

Results No stem was revised and all stems were well-Fixed. At final follow-up, HHS was 97 points in group A after 10 years and 94 points in group B after 14 years. Bone mineral changes in group A were greatest in Gruen zones 1 and 7, where the losses were 31% and 26%, respectively, after 2 years on the operated side. The decrease in BMD continued after 2 years and in Gruen zone 7 it was faster than the rate of bone loss on the control side. In group B, the annual change in BMD on the operated side was not significantly different from the bone loss in group A.

Interpretation Up to 14 years after implantation of a tapered uncemented stem, the BMD in the calcar region continues to decrease faster than would be expected from normal ageing.     

Long-standing increased bone turnover at the fixation points after anterior cruciate ligament reconstruction: a positron emission tomography (PET) study of 8 patients

Background A secure incorporation of the graft in a bone tunnel is a prerequisite for successful anterior cruciate ligament reconstruction. In this cross-sectional pilot study, we studied the healing process with positron emission tomography (PET) scanning.

Patients and methods 8 young patients underwent an anterior cruciate ligament reconstruction with a bonepatellar tendon-bone graft (BTB, n = 4) or a quadruple semitendinosus and gracilis graft (ST/G, n = 4). Regional bone turnover was quantified with an 18F-fluoride PET scan in each patient 1 day, 3 weeks, 7 months, or 22 months after surgery.

Results The highest activity level was found 3 weeks after surgery, but the activity at the femoral fixation points was markedly increased even after 7 months. The bone turnover was almost normalized 22 months after the operation.

Interpretation It would take at least 7 months until an anterior cruciate ligament graft, fixed with an interference screw, is completely incorporated. This finding is important for postoperative rehabilitation. Furthermore, PET is a feasible tool when studying new ways of fixing soft tissue to bone.     

Gas chromatography-mass spectroscopy analysis of emissions from cement when using ultrasonically driven tools

Background Ultrasonically driven tools have been used to reduce the incidence of complications during cement removal at revision hip replacement operations. These have been shown to be safe and effective in various ways, but produce fumes.

Methods Using gas chromatography-mass spectroscopy, we analyzed the fumes produced during the use of these ultrasonic tools for the removal of bone cement, both in the laboratory and during actual surgery.

Results Benzene, styrene, methylmethacrylate, xylene, toluene, isopropyl alcohol and dichlorobenzene were some of the substances isolated from the fumes in the laboratory. Styrene and methylmethacrylate were the main components. Concentrations of all the above components taken from the breathing zone of the operating staff during actual surgery were well below the safety limits.

Interpretation The use of ultrasonic tools for cement removal appears to be safe.     

The Swedish Ankle Arthroplasty Register: An analysis of 531 arthroplasties between 1993 and 2005

Background Whether or not ankles can be replaced with reasonable safety has been the subject of debate. We present the results of a nationwide series of total ankle arthroplasties.

Patients and methods All Swedish hospitals that implant or have implanted modern three-component ankle prostheses reported demographic data and date of index and revision surgery to a central register. After the data had been introduced into a database, prosthetic survival rates with exchange or permanent extraction of components as endpoint were calculated.

Results Of the 531 prostheses implanted, 101 had been revised by June 15, 2006. The overall survival rate at 5 years was 0.78 (95%CI: 0.74-0.82). For the three surgeons who had inserted the majority of the STAR ankles, the survival rates became significantly higher after the first 30 cases had been performed and was estimated to be 0.86 (0.80-0.93) at 5 years. Lower age at index surgery implied increased risk of revision whereas diagnosis or gender did not.

Interpretation Ankle replacement is a valuable alternative to arthrodesis. However, replacing an ankle is a demanding procedure and the survival is not comparable to that after hip or knee replacement. It is obvious that with increasing experience, the results—including prosthetic survival—will improve.     

No positive effects of OP-1 device on the incorporation of impacted graft materials after 8 weeks: a bone chamber study in goats

Background Bone morphogenetic proteins (BMPs) have the potential to improve clinical outcome after hip revision surgery by improving graft incorporation and implant fixation. However, impaction of cancellous bone grafts and TCP/HA bone substitute mixed with OP-1 device in a bone chamber in goats in a previous study led to reduced fibrous tissue ingrowth after 4 weeks. New bone formation was not promoted by OP-1. In the current study we examined whether this reduction represented a final loss of ingrowth or was just a delay, and whether the reduction can be overcome and ultimately results in a better late ingrowth.

Methods Bone chambers with impacted allografts and impacted TCP/HA granules mixed with 2 doses of OP-1 device were implanted in proximal medial goat tibias. Impacted allografts and TCP/HA not treated with OP-1 served as controls. After 8 weeks, the incorporation was evaluated using histology and histomorphometry.

Results Histology revealed evidence of bone graft incorporation, which proceeded in a similar way in both allografts and TCP/HA, with and without the addition of OP-1. After 8 weeks, no difference in bone ingrowth was found between the OP-1 groups and their controls. It was only in the allografts that the addition of OP-1 resulted in more fibrous tissue ingrowth.

Interpretation We conclude that the previously observed delay in fibrous tissue ingrowth can be only partially overcome.     

One fracture is enough! Experience with a prospective and consecutive osteoporosis screening program with 239 fracture patients

Background Fracture and low bone mineral density both have strong predictive value for future fractures. The risk of future fractures can be reduced by medi-cal treatment if patients with osteoporosis are identified, for example by screening fracture patients for low bone mineral density. We suggest that these screening rou-tines be organized at orthopedics departments and we report our experience with such a screening system.

Patients and methods We screened all patients between 50-75 years of age with a wrist, vertebral, prox-imal humerus, or hip fracture visiting our orthopedics department by measuring bone mineral density (BMD) using DEXA scans. After diagnosis, the patients were referred to their primary care physician for treatment.

Results Between November 1, 2002, and October 31, 2003, 239 patients were investigated and only 13% had normal BMD values. 45% of the patients were diagnosed with osteopenia and 42% with osteoporosis.

Interpretation Screening of fracture patients who visit an orthopedics department appears to be an effec-tive way of identifying individuals with low bone min-eral density. The screening routines can be organized as an osteoporosis team consisting of a doctor, a nurse and a secretary at each department. Today, these patients are largely undetected and untreated—at least in our region. In our series, only 13 patients had been DEXA-scanned and were treated by antiresorptive drugs at the time of fracture. ▪     

Risk factors associated with acute hip prosthetic joint infections and outcome of treatment with a rifampinbased regimen

Background and purpose Acute prosthetic infection is a serious problem. We report factors related to the incidence of acute infection and results of combined joint debridement and prolonged rifampicin-based antibiotic therapy.

Patients and methods Between 1998 and 2004, 14 acute infections occurred after 819 primary hip arthroplasties. The association between patient-related and surgical factors and the risk of infection were analyzed. Infections were treated with multiple joint lavage, debridement, 2 weeks of antibiotic therapy, and then oral antibiotics for a minimum of 6 months.

Results There was a correlation between having a body mass index (BMI) of ≥ 30, and also more than 2 co-morbidities, and an increased risk of infection. Diabetes was a potential risk factor. Following our regime of treatment, 11 of 14 patients retained their prosthesis. 2 of 3 who required resection arthroplasty underwent successful staged revision, while the third patient had no further surgery because of being deemed unfit.

Interpretation Primary joint replacement was salvaged in 11 of 14 patients. When successful re-implanta-tion was included, 13 of 14 patients had a mobile prosthetic joint without further infection.     

Cement is recommended in intralesional surgery of giant cell tumors: a Scandinavian Sarcoma Group study of 294 patients followed for a median time of 5 years

Background Giant cell tumors of bone rarely metasta-size but often recur locally after surgery. There is limited knowledge about the risk of recurrence related to different types of treatment.

Patients and methods We analyzed factors affecting the local recurrence rate in 294 patients with giant cell tumors of the extremities using prospectively collected material from 13 centers. The median follow-up time was 5 (0.2-18) years.

Results A local recurrence was diagnosed in 57 of 294 patients (19%). The overall 5-year local recurrence rate was 0.22. Univariate analysis identified young age and intralesional surgery to be associated with a higher risk of recurrence. Based on multivariate analysis, the relative risk was 2.4-fold for intralesional surgery compared to more extensive operative methods. There was no correlation between tumor size, tumor extension, sex of the patient, tumor location, or fracture at diagnosis and outcome. In the subgroup of 200 patients treated with intralesional surgery, the method of filling (cement or bone) was known for 194 patients and was statistically highly significant in favor of the use of cement.

Interpretation Intralesional surgery should be the first choice in most giant cell tumors, even in the presence of a pathological fracture. After thorough evacuation, the cavity should be filled with cement.