Introduction: Activated peri-prosthetic macrophages release pro-inflammatory cytokines, including interleukin-6 (IL-6), that stimulate osteoclast activation and aseptic loosening. Natural sequence variations (polymorphisms) within the IL-6 gene promoter region are associated with diseases characterised by increased osteoclast activity, including osteoporosis, and affect IL-6 production in-vitro. We tested whether polymorphisms in the IL-6 gene promoter influence the risk of aseptic loosening after total hip arthroplasty (THA).

Methods: 614 Caucasians, 292 men and 322 women, mean age 75.8 years who had undergone primary cemented THA for idiopathic osteoarthritis a mean of 13.4 years previously were recruited. Peripheral blood was taken and DNA extracted using standard techniques. Subjects were genotyped for the IL-6 -174, -572, and -597 promoter single nucleotide polymorphisms using the Taqman 5′ nuclease method.

Results: The allele frequencies and carriage rates for both alleles at promoter positions −174, −572, and −597 were similar between controls and aseptic loosening subjects (Table, χ² P> 0.05 all comparisons).

Discussion: Although Il-6 has been implicated in the pathogenesis of aseptic loosening and the −174, −572, and −597 polymorphisms are associated with bone loosing pathologies, they do not appear to play a major role in aseptic loosening after THA.

Dual energy X-ray absorptiometry (DXA) is a precise tool for measuring bone mineral density (BMD) around total joint prostheses. The Hologic ‘metal-removal hip’ analysis package (Hologic Inc, Waltham, Massachusetts) is a DOS-based analysis platform that has been previously validated for measurement of pelvic and proximal BMD after total hip arthroplasty (THA). This software has undergone a change in the operating platform to a Windows-based system that has also incorporated changes to DXA image manipulation on-screen. These changes may affect the magnitude of random error (precision) and systematic error (bias) when compared with measurements made using the previously validated DOS-based system. These factors could influence interpretation of longitudinal studies commenced using the DOS system and later completed using the Windows system. The aims of this study were to compare the precision and bias of pelvic and femoral periprosthetic BMD measurements made using the Windows versus the DOS analysis platform of the Hologic ‘metal-removal hip’ software. A total of 29 subjects (17 men and 12 women) with a mean age of 51years (SD±10), who had undergone hybrid THA using a cemented stem and uncemented cup. Subjects underwent duplicate DXA scans of the hemipelvis and proximal femur taken on the same day after a period for repositioning.. Scans were obtained with the patient lying supine in the scanner with the legs in extension and the foot in a neutral position. Scans were carried out using the same Hologic QDR 4500-A fan-beam densitometer in ‘metal-removal hip’ scanning mode. The DXA scan acquisitions were analysed using both the DOS and the Windows versions of the analysis software. The same observer made all analyses (NRS). Pelvic scans were analysed using a four region of interest model and femoral scans were analysed using a seven region of interest model. Precision was expressed as coefficient of variation (CV%) and compared between methods using the F-test. Systematic bias was examined using the Bland and Altman method and paired t-test. The CV% for the pelvic regions of interest (n=4) varied from 3.92 to 8.54 and from 2.36 to 5.96 for the Windows and DOS systems, respectively. The CV% for the net pelvic region was 3.04 and 2.36 for Windows versus DOS, respectively (F- test, p> 0.05). The CV% for the femoral regions of interest (n=7) varied from 1.58 to 4.14 and from 1.84 to 4.65 for the Windows and DOS systems, respectively. The CV% for the net femoral region was 1.75 and 1.51 for Windows versus DOS, respectively (F- test, p> 0.05). Absolute BMD values for the net pelvic region were similar (Bland-Altman, Windows minus DOS value mean = -1.0%, 95% CI −7.5 to 5.6; t-test p.0.05). Absolute BMD values for the net femoral region were also similar (Bland-Altman, Windows minus DOS value mean = 1.3%, 95% CI −8.3 to 10.8; t-test p.0.05). In summary precision of the measurements using the 2 operating systems was similar and there was no systematic bias between methods. These data suggest that scans analysed using each platform may be used interchangeably within the same study subjects, without the need of a calibration correction.

Peri-prosthetic bone loss may contribute to aseptic loosening after THA. The aims of this randomised controlled trial extension study were to study the effect of pamidronate therapy on Peri-prosthetic bone mineral density (BMD) and Peri-prosthetic osteolysis over 5 years after primary THA.

50 patients were enrolled in the study in 1998. All received a hybrid THA (Ultima-TPS stem, Plasmacup) for osteoarthritis. Subjects were randomised to receive either 90mg of pamidronate or placebo by intravenous infusion on the 5^th post-operative day. At 5 years 36 patients (41 Hips: placebo n=21, pamidronate n=20) returned for measurement of BMD and clinical and plain radiographic assessment. Five patients had died and nine had withdrawn from the study.

The effect of pamidronate in maintaining femoral bone mass in the region of the calcar previously reported at 2 years was maintained at 5 years (Gruen zone 6 pamidronate versus placebo ANOVA P=0.038; Gruen zone 7 ANOVA P=0.048). No differences in pelvic BMD were found between treatment groups at 5 years. Harris hip scores used to evaluate clinical outcome did not show any significant difference between the 2 groups over the 5-year period. (Mann Whitney p> 0.05). Isolated expansile osteolytic lesions were identified on AP radiographs of the hip at 5 years in 4 patients (2 placebo, 2 pamidronate; P> 0.05). One patient had a 5x9mm lytic lesion in the region of the femoral calcar, and 3 patients had pelvic lytic lesions in the region of the acetabular dome (largest measuring 20x10mm).

Single-dose peri-operative pamidronate therapy preserves femoral calcar bone mass over a 5 year period after THA. However, although the number of subjects with osteolysis is small, we have seen no difference in the rate of osteolytic lesions between treatment groups. Long term study of this patient group is required to examine the rate of aseptic loosening between the treatment groups.

The Exeter (Howmedica Ltd) and Ultima-TPS (Depuy Ltd) implants are both collarless, polished, double-tapered, cemented femoral implants. The Exeter is manufactured in stainless steel and has an excellent long-term survivorship. The Ultima-TPS is manufactured in cobalt-chrome and has been recently introduced. The aim of this study was to compare the early performance of these implants in a 2-year randomised clinical trial.

65 patients with unilateral hip osteoarthritis were randomised to receive either the Exeter or TPS stem. All received a Charnley Cup. Outcome measures included the Oxford Hip Questionnaire, proximal femoral bone mineral density (BMD) measured by dual energy x-ray absorptiometry, and implant subsidence measured using EBRA. At 2 years 43 patients (66%) were reviewed. 22 patients (mean age 70 years, 16 female, BMI 27.9Kg/m²) received the TPS implant, and 21 patients (mean age 70 years, 15 female, BMI 28.9Kg/m²) received the Exeter implant. 19 patients withdrew for reasons unrelated to the study, 2 died, and 1 was withdrawn after deep wound infection.

Complete Oxford hip scores were available pre-operatively and at 2 years in 37 patients (n=20 TPS). Median (IQR) pre-operative hip scores were 51 (43 to 54) and 48 (36 to 53) for the TPS and Exeter implants, respectively. At 2 years the hip scores improved to 24 (18 to 31) and 22 (16 to 31), respectively. There were no differences in scores between groups at each time-point. There were no differences in BMD between groups at pre-operative baseline, 3 months, 1 and 2 years (Gruen zones 1–7, all time-points; n=19 TPS, n=13 Exeter implants: P> 0.05). Maximum bone loss was seen in Gruen zone 7 at 2 years for bone implants (TPS-11%, Exeter -14%, P> 0.05). Measurement of subsidence over 2 years using EBRA was possible in 20 patients (n=7 TPS, n=13 Exeter). Mean subsidence at 2 years was 1.62mm for the TPS implant and 1.60mm for the Exeter implant (P> 0.05). There was no plain radiographic evidence of osteolysis in either group.

These data suggest that the early performance of the two implants studied is similar. However, long-term survivorship data is required to confirm their equivalency.

In-vitro evidence suggests that wear debris can alter osteoblast function resulting in decreased bone matrix production and negative remodelling balance. FRZB encodes for Secreted Frizzled-Related Protein 3 which may play a role in bone formation and osteoarthritis. This study was undertaken to investigate whether the recently described single nucleotide polymorphisms (SNPs) at positions [+6] and [+109] of the FRZB gene are associated with osteolysis after THA.

Genomic DNA was extracted from 481 North European Caucasians at a mean of 12 years following cemented THA for idiopathic osteoarthritis. The control group consisted of 267 subjects and the osteolysis group 214 subjects. The [+6] and [+109] FRZB SNPs were genotyped using standard techniques.

For the FRZB [+6] SNP, the rare T allele was significantly over-represented in control versus the osteolysis group (χ² test for trend, p=0.02,). The odds ratio for osteolysis associated with carriage of the [+6] T-allele versus the [+6] C-allele was 0.58 (95%CI 0.36 to 0.94), p=0.03. The odds ratio for osteolysis associated with carriage of the [+109] G-allele versus the [+109] C-allele was 0.66 (0.38 to 1.12), p=0.15. A number of covariates have previously been described in this cohort and after adjustment for the effects of these covariates, the odds ratio for osteolysis with carriage of the [+6] T-allele was 0.69 (0.42–1.16).

We found that the FRZB [+6] T-allele is less common in subjects with osteolysis after THA versus controls, suggesting that allelic variants of genes associated with bone formation pathways may have a role in modulating the risk of osteolysis. However its loss of significance after correction for other factors suggests an interaction between this allele and other risk factors in osteolysis.

Phagocytosis of wear particles by perimplant macrophages results in cytokine release and osteoclast activation and osteolysis. Some investigators have proposed that this response may be mediated by adherent endotoxin. The aim of this study was to determine the role of endotoxin in modulating pro-inflammatory cytokine mRNA expression of macrophages when stimulated with titanium particles using relative quantitative real-time polymerase chain reaction (rqRT-PCR)

Human peripheral blood mononuclear cells were isolated from healthy subjects and plated in chamber slides. Three types of titanium particles were prepared; commercially pure titanium particles (cpTi), endotoxin stripped particles and endotoxin stripped particles with endotoxin (LPS) added back. Endotoxin levels of 450, 0 and 140 Eu/ml respectively were confirmed by high sensitivity Limulus Amebocyte Lysate assay. Macrophages were stimulated with particle concentrations of 0, 8.3, 83 and 830 particles per cell at time points 0 and 3 hours. LPS (200ng/ml) was used as a positive control. rqRT-PCR was performed using standard techniques.

Stimulation of human macrophages with cpTi demonstrated a significant dose dependent increase in TNFα, IL-1A, IL-1B and, IL-6. (Kruskal-Wallis p=0.01, p=0.017, p=0.001 and p=0.013 respectively). IL-18 mRNA levels were not increased (P> 0.05). The expression of mRNA following stimulation with the highest dose of titanium particles was similar to that following LPS stimulation. Endotoxin-free cpTi particles did not elicit any increase in mRNA expression above base line levels (P > 0.05, all cytokines). This lack of response was rescued in endotoxin-stripped particles with LPS added back. Particle dose dependent increases in cytokine mRNA levels were observed for TNFα, IL-1A, IL-1B and, IL-6 mRNA but not IL-18 (p=0.01, p=0.01, p=0.01, p=0.05 and p=0.> 0.05 respectively).

Our results show that adherent endotoxin plays a role in modulating particle induced pro-inflammatory cytokine mRNA expression in-vitro. Further study is required in evaluating the role of adherent endotoxin in vivo

Cytokine mediated activation of osteoclasts can lead to peri-implant osteolysis and aseptic loosening. The aim of this study was to determine the IL-1β and TNFα mRNA cytokine expression profile of human macrophages when stimulated with polyethylene particles using relative quantitative real-time polymerase chain reaction (rqRT-PCR).

Human peripheral blood monocytes or human monocytes from the cell line THP-1 were used in this study. rqRT-PCR conditions were optimized by stimulating human macrophages with 200ng/ml lipopolysaccharide (LPS). The median CV% value for duplicate measures was 12.6 (range 4.5–54). Stimulation assays were performed using unfractionated endotoxin-free commercial polyethylene particles (median size 7μm); or fractionated particles (size range 0.1–1.2μm). Human macrophages were stimulated with high dose unfractionated polyethylene particles at 0, 3500 or 10500 mm³/cell or with fractionated polyethylene particles at 0 and 100mm³/cell at time points 0 and 3 hours. Low dose unfractionated polyethylene stimulation was performed on THP-1 cells at 0, 50, 100, 1000 and 10000 mm³/cell. In all experiments LPS stimulation was used as a positive control. RNA was extracted and rqRT-PCR was performed using standard techniques

High dose unfractionated polyethylene stimulation did not result in a significant difference in cytokine mRNA levels between groups. Using fractionated polyethylene, a small increase in IL-1β mRNA was identified (21% versus maximal stimulation using LPS). Low dose unfractionated polyethylene stimulation of THP-1 cells demonstrated dose dependent decreases in TNFα and IL-1β mRNA expression that was not due to inhibition of RNA extraction or a decrease of cell viability.

Endotoxin-free polyethylene particles do not appear to be a major stimulus for IL-1β and TNFα mRNA production as measured by rqRT-PCR. We did observe a small positive effect on IL-1β mRNA expression using a fractionated polyethylene stimulus. However it remains unclear whether this effect is due to fractionation of particles into the submicron range or is due to introduction of endotoxin during the filtration process.

Aim To assess whether prosthetic femoral stem centralisers have a detrimental effect on the maroporosity of the cement mantle, and if so, whether this is independent of their design and the rate of implantation.

Methods 30 identical moulded prosthetic femora were divided into 3 groups. Group 1; no centraliser (control), Group 2; centraliser A, Group 3 centraliser B. Using third generation cementation techniques and pressure monitoring, Charnley C-stems +/− the appropriate centraliser were implanted to a constant depth. Half in each group were implanted as rapidly as possible and the other half over 90 seconds. The stems were removed and the cement mantle then underwent a preliminary arthroscopic examination prior to being sectioned transversely at 3 constant levels. Each level was then photographed and digitally enlarged to a known scale to allow examination and determination of any cement voids (macropores) surface area.

Results There were no significant pressure fluctuations between the groups. Preliminary arthroscopic examination revealed that cement voids appeared more common when a centraliser was used. This difference was statistically confirmed (p=0.002) following sectioning of the specimens with cement voids found in 85% of femora when a centraliser was used and only 20% in the control group. Centraliser B performed worst with cement voids of a larger volume and more frequent occurrence (p=0.002). The macroporosity of the cement mantle was independent of the rate of implantation (p=0.39).

Conclusion The use of femoral stem centralisers is helpful in preventing malposition of the implant but results in increased macroporosity of the cement mantle. This may have implications regarding the longevity of an implant in terms of early loosening and therefore their design and use must always be carefully considered.

Background: Perioperative red cell salvage may be of use in cases where significant blood loss is likely. The purpose of this investigation was to see if its use in revision hip surgery led to a reduction in homologous blood transfusion requirement.

Methods: 48 patients were identified who had undergone revision hip surgery with the use of a Cell Saver device for perioperative autologous transfusion. Patients were individually matched to control patients who had undergone revision hip surgery without the Cell Saver. Patients were matched for age, sex and eight operative variables, which were chosen to indicate the type of revision surgery and possible level of blood loss, to ensure that the groups were comparable. Total homologous transfusion requirement in both groups was recorded as well as pre and post-operative haemoglobin levels.

Results: The groups were well matched for age, sex and operative variables. The total homologous transfusion requirement was significantly lower in the Cell Saver group than the control group (mean 2.6 v 6.4 units of packed cells respectively, p 0.0006). There was no difference in pre-operative haemoglobin between the groups but it was lower in the Cell Saver group post-operatively (Cell Saver 10.1g/dl v Control 10.6g/dl, p 0.06). There was no difference in length of operation.

Conclusions: Use of perioperative red cell salvage was associated with significantly lower homologous transfusion requirement. This is the first study looking at the use of perioperative red cell salvage in revision hip surgery with matching of patients on the basis of operative variables. A cost analysis shows that use of the Cell Saver has significant financial advantage in these patients.

The aim of this study was to determine whether there is evidence to support the [often quoted] concept of a threshold effect of implant wear rate on osteolysis risk after total hip arthroplasty (THA). The study design was a case control study of 115 subjects with osteolysis after Charnley THA for idiopathic osteoarthritis (mean age at primary surgery 61.1 years; M:F =49:66; osteolysis-free survival 10.9 years) compared with 115 individually case-matched subjects following Charnley THA for idiopathic osteoarthritis with no current radiographic evidence of osteolysis (mean age 61.3 years; M:F = 49:66; osteolysis-free survival 11.0 years).

Calculated median (interquartile range) annual linear wear rate (measured using the EBRA method) was 0.12mm (0.08 to 0.18) and 0.07mm (0.05 to 0.10) in the osteolysis and control groups, respectively (Wilcoxon, P< 0.001). Subjects were divided into wear quintiles based on wear rate (n=46 subjects per quintile). The proportions of osteolysis subjects in each successive wear quintile groups were 0.22, 0.39, 0.48, 0.61, and 0.80 (χ² P< 0.001). The proportion of subjects with osteolysis thus increased in a uniform manner with no evidence of a disproportionate increase between groups. The odds-ratio for osteolysis for each incremental increase in annual linear wear above the median wear rate in the control subjects was 2.4 (logistic regression analysis, 95% CI 1.7 to 3.3, P< 0.001).

In summary, the proportion of subjects with osteolysis increases steadily by wear quintile. Our data suggest a continuous gradient of risk for osteolysis associated with increasing annual wear rate in the Charnley prosthesis. We found no evidence to support the concept of a defined threshold above which the risk of osteolysis is disproportionately increased. The implication of this finding is that the goal of advances in bearing surface technologies should be aimed at the elimination of wear, rather than simply it’s reduction to below an arbitrarily-defined level

Information on the complication rates of revision THA is well documented. However, there is little data on functional outcome of revision THA. We aimed to determine the functional outcome of revision THA (n=72 subjects) versus individually matched THA controls. All subjects underwent THA for idiopathic osteoarthritis, and the same investigator made all clinical assessments. The mean ages (±SD) at primary THA were 61.3±7.2 years (THA revisions) and 61.1±7.4 years (THA controls). The male: female ratio was 36:36 in both groups. The groups were also individually matched for primary THA year (median 1984), presence of bilateral THA (43 subjects per group), and total follow up time (mean 14±4 years). Revision-free survival in the THA revision group was 9.8±3.9 years, and post revision follow up was 4.5±3.0 years.

Sixteen subjects had revision of 1 implant component and 56 had both revised. Allograft was required in 25 and 17 of the cup and stem revisions, respectively. The median (Interquartile range) Oxford and Harris Hip Scores in the revision and control groups were 28 (21 to 39) and 72 (60 to 86) versus 21 (16 to 32) and 89 (79 to 97), respectively (Wilcoxon, P< 0.001 both comparisons). The largest difference in Harris Hip Score was found in the function domain; revision THA median score 24 (17 to 36) versus 38 (28 to 44) in the controls (P< 0.001). Male subjects had slightly better outcomes versus females in both groups (P< 0.05). Revision of both versus 1 component, bilateral THA, age at revision, and use of allograft did not affect outcome (P> 0.05 all comparisons).

The clinical outcome of revision hip arthroplasty for aseptic loosening is worse than that of primary arthroplasty, principally in terms of function. However, use of allograft, number of components revised, and age at revision are not strongly associated with clinical outcome of revision surgery.

Background: Perioperative red cell salvage may be of use in cases where significant blood loss is likely. The purpose of this investigation was to see if its use in revision hip surgery led to a reduction in homologous blood transfusion requirement.

Methods: 48 patients were identified who had undergone revision hip surgery with the use of a Cell Saver device for perioperative autologous transfusion. Patients were individually matched to control patients who had undergone revision hip surgery without the Cell Saver. Patients were matched for age, sex and eight operative variables ,which were chosen to indicate the type of revision surgery and possible level of blood loss, to ensure that the groups were comparable. Total homologous transfusion requirement in both groups was recorded as well as pre and post-operative haemoglobin levels.

Results: The groups were well matched for age, sex and operative variables. The total homologous transfusion requirement was significantly lower in the Cell Saver group than the control group (mean 2.6 v 6.4 units of packed cells respectively, p 0.0006). There was no difference in pre-operative haemoglobin between the groups but it was lower in the Cell Saver group post-operatively (Cell Saver 10.1g/dl v Control 10.6g/dl, p 0.06). There was no difference in length of operation.

Conclusions: Use of perioperative red cell salvage was associated with significantly lower homologous transfusion requirement. This is the first study looking at the use of perioperative red cell salvage in revision hip surgery with matching of patients on the basis of operative variables. A cost analysis shows that use of the Cell Saver has significant financial advantage in these patients.

One of the major surgical challenges at revision arthroplasty is the management of bone stock loss in the acetabulum.

There are several options available for reconstruction; cemented sockets within thick cement mantles, custom sockets jumbo uncemented sockets, support rings and bone grafting. Slooff and others have shown good results with impaction grafting.(JBJS 80B 1998)

If one is to use bone graft, does the preparation of the graft have any effect on the graft itself? There are a number of ways bone can be presented, freeze dried, fresh frozen or frozen irradiated. Concerns have been raised that irradiated bone has an altered and weakened structure. There is a paucity of clinical results on this subject. In this study we present a series of patients using gamma irradiated bone for reconstruction.23% of the cases reconstructions secondary to failure due to sepsis.

Between 1987 and 2000 192 revision arthroplasties in 165 patients were performed with irradiated morcellised bone allograft for acetabular reconstruction. Only those patients with a minimum follow up of 24 months were reviewed. Clinical and radiological follow up was achieved in 130 hips in 115 patients. 9 patients had died at a range of 1 to 66 months after surgery. There were 23 (17%) re-revisions of the acetabular component. Of these 13 were for deep sepsis, 5 for persistent early dislocation and 4 for aseptic loosening. Of those hips revised for infection there was a 13% re-revision rate for reinfection. There was only one catastrophic failure of the graft and only three re-revisions for aseptic loosening to date.

We feel that impaction grafting of the acetabulum is a useful technique for reconstruction even when the index arthroplasty failed for sepsis. We have found no evidence to show that gamma irradiated bone performs any worse than other types of allograft bone.

The Charnley total hip replacement has had favourable long-term survival results. On the strength of these results orthopaedic companies have introduced “Charnley Copies” incorporating identical design parameters.

The objective of the study was to determine whether the acetabular cups provided as DePuy Charnley copies by different manufacturers are identical with regards to their geometry. To analyze how any differences present may affect the motion characteristics of the arthroplasty.

A jig was designed which allowed the measurements of: i) range of movement free from impingement, ii) the arc of movement during which the femoral neck is impinging on the cup, iii) point of subluxation and dislocation of the femoral head from the cup. The cups obtained for analysis where the Standard and Long Posterior Wall models of the DePuy Charnley, Aesculap ALFA, Corin Cenator and Avatar LFA. The Aesculap Plasma Symmetrical and Asymmetrical were analyzed for comparison.

The Alfa has a greater free range of movement compared to the Charnley cup and the other copies. The Charnley cup, the Cenator and the LFA differed in their pattern of impingement. The Alfa had the earliest point of dislocation. Long Posterior Wall: The Avatar had the greatest free ROM. The Charnley and the Alfa dislocated in an anterior direction latest. The Avatar and Cenator dislocated latest in the posterior direction. Plasma Cup: Compared to the Charnley and its copies its free range of movement was greater, it had only one point of impingement and impinged through the smallest arc before dislocating. It did, however, dislocate easiest.

Charnley copies are not identical. Differences in geometry exist and these alter important motion characteristics. Long term outcome may be affected. Surgeons should be aware of these differences when choosing implants.

An acute phase of periprosthetic bone loss occurs following total hip arthroplasty (THA). Periprosthetic bone loss undermines implant support, may contribute to its failure, and complicates revision surgery as allograft may be required to replace lost bone. We assessed the effect of a single 90mg dose of the bisphosphonate pamidronate on early periprosthetic bone mineral density (BMD), biochemical markers of bone turnover, and clinical outcome in 47 men and women undergoing hybrid THA in a randomised, double-blinded, placebo-controlled trial.

The mean (± 95% CI) differences in BMD (area under BMD change.time curve) between those receiving pamidronate and those receiving placebo was 0.91(± 0.51) g.weeks/cm² for the proximal femur (P=0.002), and 0.80 (±0.60) g.weeks/cm² for the pelvis (P=0.009). Patients in the pamidronate group had suppression of all biochemical markers of bone turnover compared to placebo (P< 0.05), except for urinary free deoxypyridinoline. Both treatment groups experienced similar improvement in Harris hip and SF-36 UK outcome scores. The frequency of adverse events was similar in each treatment group (placebo 7/24, pamidronate 8/23, P> 0.05).

Acute periprosthetic bone loss following THA is due to a transient increase in bone turnover. A single dose infusion of pamidronate in the early post-operative period significantly reduces this bone loss, and is well tolerated.