Clodronate prevents prosthetic migration: A randomized radiostereometric study of 50 total knee patients

In a double-blind study, we randomized 50 patients to receive peroral clodronate medication or placebo from 3 weeks before until 6 months after a total knee replacement with a cemented NexGen implant. Migration of the tibial components was measured by radiostereometry at 1 year. Clodronate reduced prosthetic migration, as measured by maximum total point motion, from 0.40 mm to 0.29 mm (p = 0.01). This confirms that the early postoperative migration is related to bone resorption and thus the biology of the bone bed. Since early migration is related to late loosening, 6 months of clodronate medication might reduce the risk of loosening.     

Clodronate prevents prosthetic migration: a randomized radiostereometric study of 50 total knee patients

In a double-blind study, we randomized 50 patients to receive peroral clodronate medication or placebo from 3 weeks before until 6 months after a total knee replacement with a cemented NexGen implant. Migration of the tibial components was measured by radiostereometry at 1 year. Clodronate reduced prosthetic migration, as measured by maximum total point motion, from 0.40 mm to 0.29 mm (p = 0.01). This confirms that the early postoperative migration is related to bone resorption and thus the biology of the bone bed. Since early migration is related to late loosening, 6 months of clodronate medication might reduce the risk of loosening.     

Postoperative clodronate decreases prosthetic migration: 4-year follow-up of a randomized radiostereometric study of 50 total knee patients

Background We have previously reported that 6 months of oral treatment with clodronate reduced the migration of the NexGen total knee prosthesis during the first postoperative year, as measured by radiostereometry (RSA). We now report the 4-year results.

Methods This was a double-blind randomized study, using RSA with maximal total point motion (MTPM).

Results With analysis according to the “intention to treat” principle, the only remaining difference between the groups at 4 years was reduced rotation around the transverse axis (a secondary variable) in the clodronate group. However, 3 patients (all clodronate) did not take any tablet after surgery. If they are excluded, there was an almost statistically significant difference between the groups at 4 years regarding MTPM from baseline, with the clodronate group showing 25% less migration. From 1 to 4 years, there was no difference in migration rate by MTPM, but there was a continuous increase in rotation around the transverse axis in the controls, which differed from the clodronate group. There were no cases of aseptic loosening. 2 patients had migration of more than 1.3 mm from baseline to 4 years; neither of them had taken clodronate. The others had migration of less than 0.9 mm.

Interpretation Because migration was clearly reduced by clodronate during the first postoperative year, and there was still a difference at 4 years when analyzed per protocol, it appears likely that this treatment can diminish the risk of loosening. The difference in the number of outliers also points in this direction, and may be more relevant than mean migration values.     

Local peroperative treatment with a bisphosphonate improves the fixation of total knee prostheses: A randomized,double-blind radiostereometric study of 50 patients

Background?Postoperative migration of a joint prosthesis is related to the risk of late loosening. We have previously reported that oral treatment with clodronate reduced migration of the cemented NexGen total knee prosthesis during the first postoperative year, as measured by radiostereometry (RSA). Oral bisphosphonate treatment is sometimes unpleasant, and local treatment will enable higher local concentrations. We now report the results of local peroperative treatment with another bisphosphonate, ibandronate, with the same prosthesis.

Methods?This is a double-blind, randomized study of 50 patients using RSA with maximal total point motion (MTPM) as primary effect variable. 1 mg ibandronate (1 mL) or 1 mL saline was applied to the tibial bone surface 1 min before cementation. RSA examination was done on the first postoperative day, and at 6, 12, and 24 months.

Results?One ibandronate-treated patient died of unrelated causes, and 1 control patient refused to come for follow-up, leaving 24 patients in each group for analysis. There were no cases of aseptic loosening. By repeated measures ANOVA, migration (MTPM) was reduced by local application of ibandronate (p = 0.006). The effect was most pronounced at 6 months, with a reduction from 0.45 to 0.32 mm (95% CI for reduction: 0.04–0.21 mm). At 12 months, the migration from the postoperative examination was reduced from 0.47 to 0.36 mm (95% CI for reduction: 0.02–0.20 mm). At 24 months, the reduction was from 0.47 to 0.40 mm (95% CI: -0.01–0.16 mm).

Interpretation?This is the first study to show improvement of prosthesis fixation by local pharmacological treatment in humans. The treatment appears to be safe, cheap, and easy to perform. However, the improvement in postoperative stability was not greater than with systemic clodronate treatment.     

Local peroperative treatment with a bisphosphonate improves the fixation of total knee prostheses: a randomized, double-blind radiostereometric study of 50 patients

Background Postoperative migration of a joint prosthesis is related to the risk of late loosening. We have previously reported that oral treatment with clodronate reduced migration of the cemented NexGen total knee prosthesis during the first postoperative year, as measured by radiostereometry (RSA). Oral bisphosphonate treatment is sometimes unpleasant, and local treatment will enable higher local concentrations. We now report the results of local peroperative treatment with another bisphosphonate, ibandronate, with the same prosthesis.

Methods This is a double-blind, randomized study of 50 patients using RSA with maximal total point motion (MTPM) as primary effect variable. 1 mg ibandronate (1 mL) or 1 mL saline was applied to the tibial bone surface 1 min before cementation. RSA examination was done on the first postoperative day, and at 6, 12, and 24 months.

Results One ibandronate-treated patient died of unrelated causes, and 1 control patient refused to come for follow-up, leaving 24 patients in each group for analysis. There were no cases of aseptic loosening. By repeated measures ANOVA, migration (MTPM) was reduced by local application of ibandronate (p = 0.006). The effect was most pronounced at 6 months, with a reduction from 0.45 to 0.32 mm (95% CI for reduction: 0.04-0.21 mm). At 12 months, the migration from the postoperative examination was reduced from 0.47 to 0.36 mm (95% CI for reduction: 0.02-0.20 mm). At 24 months, the reduction was from 0.47 to 0.40 mm (95% CI: -0.01-0.16 mm).

Interpretation This is the first study to show improvement of prosthesis fixation by local pharmacological treatment in humans. The treatment appears to be safe, cheap, and easy to perform. However, the improvement in postoperative stability was not greater than with systemic clodronate treatment.     

Denosumab reduces early migration in total knee replacement

Background and purpose — Aseptic loosening is a main cause of late revision in total knee replacement (TKR). Migration of implants as measured by radiostereometric analysis (RSA) can predict future loosening. This migration is associated with bone resorption. Denosumab is a human monoclonal antibody that binds to receptors on osteoclast precursors and osteoclasts. This prevents osteoclast formation, resulting in less bone resorption in cortical and trabecular bone. We investigated whether denosumab can reduce migration of TKR, as measured with RSA.

Patients and methods — In this 2-center, randomized, double-blind placebo-controlled trial, 50 patients with osteoarthritis of the knee were treated with an injection of either denosumab (60?mg) or placebo 1?day after knee replacement surgery and again after 6 months. RSA was performed postoperatively and after 6, 12, and 24 months. The primary effect variable was RSA maximal total point motion (MTPM) after 12 months. We also measured other RSA variables and the knee osteoarthritis outcome score (KOOS).

Results — The primary effect variable, MTPM after 12 months, showed that migration in the denosumab group was statistically significantly less than in the controls. Denosumab MTPM 12 months was reduced by one-third (denosumab: median 0.24?mm, 10% and 90% percentiles: 0.15 and 0.41; placebo: median 0.36?mm, 10% and 90% percentiles: 0.20 and 0.62). The secondary MTPM variables (6 and 24 months) also showed a statistically significant reduction in migration. There was no significant difference in MTPM for the period 12–24 months. KOOS sub-variables were similiar between denosumab and placebo after 12 and 24 months.

Interpretation — Denosumab reduces early migration in total knee replacement, as in previous trials using bisphosphonates. As migration is related to the risk of late loosening, denosumab may be beneficial for long-term results.     

Decreased migration with locally administered bisphosphonate in cemented cup revisions using impaction bone grafting technique

Background and purpose — Impaction bone grafting (IBG) in revision hip surgery is an established method in restoring bone stock deficiencies. We hypothesized that local treatment of the morsellized allograft with a bisphosphonate in cemented revision would, in addition to increased bone density, also reduce the early migration of the cup as measured by radiostereometry (RSA).

Patients and methods — 20 patients with aseptic cup loosening underwent revision using the IBG technique. The patients were randomized to either clodronate (10 patients) or saline (10 patients, control group) as local adjunct to the morsellized bone. The outcome was evaluated by dual-energy X-ray absorptiometry (DXA) during the first year regarding periacetabular bone density and with radiostereometric analysis (RSA) for the first 2 years regarding cup migration.

Results — 2 patients were lost to follow-up: 9 patients remained in the clodronate and 9 in the control group. Less proximal migration was found in the clodronate group compared with the controls, measured both over time (mixed-models analysis, p = 0.02) as well as at the specified time points up to 2 years (0.22?mm and 0.59?mm respectively, p = 0.02). Both groups seemed to have stabilized at 1 year. We found similar bone mineral density measured by DXA, and similar RSA migration in the other directions. No cups were re-revised.

Interpretation — Local treatment of the allograft bone with clodronate reduced early proximal migration of the revised cup but without any measurable difference in periacetabular bone density.     

Migration of the Acetabular Socket After Total hip Replacement Determined by Roentgen Stereophotogrammetry

In order to evaluate the feasibility of a roentgen stereophotogrammetric method for the analysis of the migration pattern of joint prostheses, tantalum balls were implanted into the acetabular socket and the pelvic bone during total hip replacement in four patients with rheumatoid arthritis. During the postoperative period, the migration of the acetabular socket was determined. the observation period varied from 5–24 months.

No clinical or radiographic signs of mechanical loosening or infection were noted.

All the investigated patients showed a gradual migration of the acetabular socket. the cranial migration measured up to 1.8 mm in 2 years. the migration along the transverse and sagittal axes was less but not constantly directed. the rotatory movements about the three axes varied and measured up to 5.5° in 2 years. the translation and rotation were greatest during the first few months.

The results indicate a gradual migration of the acetabular socket in hip arthroplasty in the osteopenic skeleton in rheumatoid arthritis.

In conclusion: roentgen stereophotogrammetry may prove to be a valuable means of analysing the migration of implanted prostheses and detecting prosthetic loosening, thereby increasing the possibility of early and correct diagnosis and therapy.     

Modes of failure of a threaded acetabular cup

A radiographic study of a singular type of threaded cup, revised due to aseptic loosening, was performed with Einzel-Bild-Roentgen-Analyse (EBRA) to detect eventual risk factors and patterns of loosening. Fifty-three cups of 50 patients were revised. Forty-two cups could be measured with EBRA. No cup had obvious osteolysis, 33 cups demonstrated early migration, and all cups had migrated at the time of revision. Twenty-eight of the cups had a change of inclination and 21 of anteversion, respectively. The mean migration was 1.9 mm in the medial and 7.9 mm in the cranial direction; the mean wear rate was 0.2 mm/year. Cups with early migration had a higher migration rate. All male patients had early migration; medially placed cups had less migration than the other cups. Wear was not significantly affected by the migration of the implant. No cup had a complete radiolucent line, and the only radiographic sign for loosening was the change of position of the cup. Medial placement showed less migration in case of loosening. Regular radiographic follow-up is recommended for the examined implant, and the cup should not be used in the future.     

Monoblock versus modular polyethylene insert in uncemented total knee arthroplasty

Background and purpose — Backside wear of the polyethylene insert in total knee arthroplasty (TKA) can produce clinically significant levels of polyethylene debris, which can lead to loosening of the tibial component. Loosening due to polyethylene debris could theoretically be reduced in tibial components of monoblock polyethylene design, as there is no backside wear. We investigated the effect of 2 different tibial component designs, monoblock and modular polyethylene, on migration of the tibial component in uncemented TKA.

Patients and methods — In this randomized study, 53 patients (mean age 61 years), 32 in the monoblock group and 33 in the modular group, were followed for 2 years. Radiostereometric analysis (RSA) was done postoperatively after weight bearing and after 3, 6, 12, and 24 months. The primary endpoint of the study was comparison of the tibial component migration (expressed as maximum total point motion (MTPM)) of the 2 different implant designs.

Results — We did not find any statistically significant difference in MTPM between the groups at 3 months (p = 0.2) or at 6 months (p = 0.1), but at 12 and 24 months of follow-up there was a significant difference in MTPM of 0.36?mm (p = 0.02) and 0.42?mm (p = 0.02) between groups, with the highest amount of migration (1.0?mm) in the modular group. The difference in continuous migration (MTPM from 12 and 24 months) between the groups was 0.096?mm (p = 0.5), and when comparing MTPM from 3–24 months, the difference between the groups was 0.23?mm (p = 0.07).

Interpretation — In both study groups, we found the early migration pattern expected, with a relatively high initial amount of migration from operation to 3 months of follow-up, followed by stabilization of the implant with little migration thereafter. However, the modular implants had a statistically significantly higher degree of migration compared to the monoblock. We believe that the greater stiffness of the modular implants was the main reason for the difference in migration, but an initial creep in the polyethylene metal-back locking mechanism of the modular group could also be a possible explanation for the observed difference in migration between the 2 study groups.     

The prediction of failure of the stem in THR by measurement of early migration using EBRA-FCA. Einzel-Bild-Roentgen-Analyse-femoral component analysis

We report the ten-year results for three designs of stem in 240 total hip replacements, for which subsidence had been measured on plain radiographs at regular intervals. Accurate migration patterns could be determined by the method of Einzel-Bild-Roentgen-Analyse-femoral component analysis (EBRA-FCA) for 158 hips (66%). Of these, 108 stems (68%) remained stable throughout, and five (3%) started to migrate after a median of 54 months. Initial migration of at least 1 mm was seen in 45 stems (29%) during the first two years, but these then became stable. We revised 17 stems for aseptic loosening, and 12 for other reasons. Revision for aseptic loosening could be predicted by EBRA-FCA with a sensitivity of 69%, a specificity of 80%, and an accuracy of 79% by the use of a threshold of subsidence of 1.5 mm during the first two years. Similar observations over a five-year period allowed the long-term outcome to be predicted with an accuracy of 91%. We discuss the importance of four different patterns of subsidence and confirm that the early measurement of migration by a reasonably accurate method can help to predict long-term outcome. Such methods should be used to evaluate new and modified designs of prosthesis.     

Experiences with the Plasmacup--early stability, wear, remodelling, and outcome

Whilst advances in cementing technique have led to improvement in the survival of cemented femoral stems in total hip arthroplasty (THA), cup failure due to aseptic loosening remains a major clinical problem. These observations have led to a move away from cemented cup designs, particularly in young patients, towards uncemented implants. The Plasmacup is a hemispherical, press-fit, cementless, titanium-shelled, acetabular component with a polyethylene liner. In this article we review our experience of its pattern of early migration, wear, bone remodelling, and mid-term survival. In 18 cups followed for 2 years in subjects with a mean age at operation of 58 years, the mean total vectorial cup migration was 0.75 mm, and cup orientation remained stable (EBRA method). The mean polyethylene linear wear rate over this period was 0.21 mm/year. In 27 cups followed for 6 months using dual-energy X-ray absorptiometry (DXA), average bone loss was -5%, and the pelvic bone-remodelling pattern was consistent with the rim-loading principle of the cup design. In a clinical review of the outcome of 128 cups in 104 patients with a mean age at operation of 51 years and follow-up of 59 months, we found that 82% of patients had a good or very good Merle D'Aubigne score, and cup survival rate was 98% (Kaplan-Meier). Four cups had small radiographic areas of focal osteolysis and three had been revised (two for recurrent dislocation and one for deep sepsis; none were revised for aseptic loosening). The mean linear wear rate in this series was 0.14 mm/year. In conclusion, the Plasmacup shows satisfactory early stability, a wear rate similar to other uncemented cups, and favourable mid-term clinical function and survival rates.     

EBRA-FCA for measurement of migration of the femoral component in surface arthroplasty of the hip

Studies on the migration of an implant may be the only way of monitoring the early performance of metal-on-metal prostheses. The Ein Bild Roentgen Analyse--femoral component analysis (EBRA-FCA) method was adapted to measure migration of the femoral component in a metal-on-metal surface arthroplasty of the hip using standard antero-posterior radiographs. In order to determine the accuracy and precision of this method a prosthesis was implanted into cadaver bones. Eleven series of radiographs were used to perform a zero-migration study. After adjustment of the femoral component to simulate migration of 3 mm the radiographs were repeated. All were measured independently by three different observers. The accuracy of the method was found to be +/- 1.6 mm for the x-direction and +/- 2 mm for the y-direction (95% percentile). The method was validated using 28 hips with a minimum follow-up of 3.5 years after arthroplasty. Seventeen were sound, but 11 had failed because of loosening of the femoral component. The normal (control) group had a different pattern of migration compared with that of the loose group. At 29.2 months, the control group showed a mean migration of 1.62 mm and 1.05 mm compared with 4.39 mm and 4.05 mm in the failed group, for the centre of the head and the tip of the stem, respectively (p = 0.001). In the failed group, the mean time to migration greater than 2 mm was earlier than the onset of clinical symptoms or radiological evidence of failure, 19.1 versus 32.2 months (p = 0.001) and 24.8 months (p = 0.012), respectively. EBRA-FCA is a reliable and valid tool for measuring migration of the femoral component after surface arthroplasty and can be used to predict early failure of the implant. It may be of value in determining the long-term performance of surface arthroplasty.     

Mechanical loosening of total hip prostheses. A radiographic and roentgen stereophotogrammetric study

Twenty patients were examined by standard radiography and roentgen stereophotogrammetric analysis (RSA) during a two-year period after total hip arthroplasty. Eleven of the acetabular components migrated cranially and three femoral components migrated distally. This migration was most rapid during the first four months after operation. Our findings support the possibility that mechanical loosening is initiated by thermal injury during polymerisation of the cement; the less frequent migration of the metallic femoral component compared with the polyethylene acetabular component may be because the metal acts as a heat sink. Standard radiographs were inadequate for assessment of early mechanical loosening, whereas RSA could reveal migration within four months of the arthroplasty.     

The effect of early weight bearing on migration pattern of the uncemented CLS stem in total hip arthroplasty

Forty-two patients (younger than 65 years) with osteoarthritis were operated on with an uncemented CLS stem and randomized to early unrestricted weight bearing combined with intensive physiotherapy or to partial weight bearing combined with self-training. Radiostereometric analysis showed 1.2 (+0.11 to -6.76) mm subsidence of the stem at 24 months in both groups. There was no significant difference in the migration pattern between the unrestricted and partial weight bearing groups. Actual loading on the operated leg, measured with the F-scan system, did not influence the migration of the stem. There was a strong correlation between the average subsidence at 3 and 24 months (r = 0.96). Early full weight bearing and active rehabilitation can be used for the uncemented CLS stem without increased risk of early loosening.     

Analysis of migration of press-fit porous-coated acetabular components with medial lucencies using Ein-Bild-Roentegen-Analyse

A total of 136 patients who underwent total hip arthroplasty (154 hips) with press-fit acetabular components were evaluated for the presence of medial radiographic lucencies. Thirty patients (22.1%) demonstrated radiolucencies greater than 1 mm in zone 2 on initial postoperative films. Ein-Bild-Roentegen-Analyse (EBRA) was used to evaluate component migration over a 5-year follow-up period. Migration, measured by EBRA, was not observed during the first 6 months when the radiolucencies were noted to disappear. After 2 years, the mean total migration was 0.8 mm, and at 5 years, it was 1.6 mm. Our results indicate that disappearance of a medial radiolucency seen on early postoperative radiographs is not associated with component migration, which supports the concept that the medial radiolucency fills in with bone or represents bony remodeling around a stable implant.     

Migration of the Duraloc cup at two years

We carried out 71 primary total hip arthroplasties using porous-coated, hemispherical press-fit Duraloc '100 Series' cups in 68 consecutive patients; 61 were combined with the cementless Spotorno stem and ten with the cemented Lubinus SP II stem. Under-reaming of 2 mm achieved a press-fit. Of the 71 hips, 69 (97.1%) were followed up after a mean of 2.4 years. Migration analysis was performed by the Ein Bild Rontgen Analyse method, with an accuracy of 1 mm. The mean total migration after 24 months was 1.13 mm. Using the definition of loosening as a total migration of 1 mm, it follows that 30 out of 63 cups (48%) were loose at 24 months.     

Early weight bearing after uncemented total hip prostheses--an analysis of acetabulum cup migration]

PURPOSE: The postoperative mobilisation after cementless total hip arthroplasty is usually non-weight bearing within the first six weeks to achieve bony ingrowth for the implant. Since 1995 weight bearing mobilisation is performed at our clinic even after cementless implantation of the Alloclassic (Zweymüller-Sulzer) system. The aim of the presented study was the detection of any negative influence of weight bearing mobilisation on the stability of this cementless implant. METHOD: The horizontal and vertical cup migration of 42 cementless acetabular cups (Alloclassic Zweymüller-Sulzer) in 40 patients after weight bearing mobilisation and a minimum follow up of 24 months were analysed by a digital migration analysis. The results were compared to a normative migration profile of the same that was recently established. RESULTS: The migration analysis did not exceed the level of accuracy of 1.3 mm in any patient. The mean horizontal cup migration was 0.3 mm in both groups after 24 months, the mean vertical migration was 0.4 mm in both groups. No significant difference of the acetabular stability was detectable. None of the implants showed radiological signs of loosening or migration. CONCLUSION: The presented data justify an early postoperative weight bearing mobilisation using the cementless Alloclassic threated cup, provided that primary stability of the implant can be achieved.     

Early head penetration into cemented Hylamer Ogee socket

The authors reviewed 18 consecutive cemented total hip arthroplasties with the Hylamer Ogee socket. The average follow-up period was 47 months. All Hylamer Ogee sockets were sterilized by gamma irradiation in air, and the average period from production to surgery was 12 months. Two-dimensional penetration of the femoral head into the Hylamer Ogee socket was determined from anteroposterior radiographs of the pelvis using a digitizer. The average head penetration rate of the present series was 0.36 mm/y. Osteolysis around both components was found in 6 cases (30%). Of 4 cases defined as aseptic loosening, 2 were revised during the follow-up period. To detect component loosening because of catastrophic high wear of the cemented Hylamer Ogee socket as early as possible, precise radiographic follow-up is essential.     

Early migration of tibial components is associated with late revision

Purpose We performed two parallel systematic reviews and meta-analyses to determine the association between early migration of tibial components and late aseptic revision.

Methods One review comprised early migration data from radiostereometric analysis (RSA) studies, while the other focused on revision rates for aseptic loosening from long-term survival studies. Thresholds for acceptable and unacceptable migration were determined according to that of several national joint registries: < 5% revision at 10 years.

Results Following an elaborate literature search, 50 studies (involving 847 total knee prostheses (TKPs)) were included in the RSA review and 56 studies (20,599 TKPs) were included in the survival review. The results showed that for every mm increase in migration there was an 8% increase in revision rate, which remained after correction for age, sex, diagnosis, hospital type, continent, and study quality. Consequently, migration up to 0.5 mm was considered acceptable during the first postoperative year, while migration of 1.6 mm or more was unacceptable. TKPs with migration of between 0.5 and 1.6 mm were considered to be at risk of having revision rates higher than 5% at 10 years.

Interpretation There was a clinically relevant association between early migration of TKPs and late revision for loosening. The proposed migration thresholds can be implemented in a phased, evidence-based introduction of new types of knee prostheses, since they allow early detection of high-risk TKPs while exposing only a small number of patients.