Aims. This study aimed to examine the effects of tumour necrosis factor-alpha (TNF-α) on osteoblasts in metal wear-induced bone loss. Methods. TNF-α immunoexpression was examined in periprosthetic tissues of patients with failed metal-on-metal hip arthroplasties and also in myeloid MM6 cells after treatment with cobalt ions. Viability and function of human osteoblast-like SaOs-2 cells treated with recombinant TNF-α were studied by immunofluorescence, terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) assay, western blotting, and enzyme-linked immunosorbent assay (ELISA). Results. Macrophages, lymphocytes, and endothelial cells displayed strong TNF-α immunoexpression in periprosthetic tissues containing metal wear debris. Colocalization of TNF-α with the macrophage marker CD68 and the pan-T cell marker CD3 confirmed TNF-α expression in these cells. Cobalt-treated MM6 cells secreted more TNF-α than control cells, reflecting the role of metal wear products in activating the TNF-α pathway in the myeloid cells. While TNF-α did not alter the immunoexpression of the TNF-receptor 1 (TNF-R1) in SaOs-2 cells, it increased the release of the soluble TNF-receptor 1 (sTNF-R1). There was also evidence for TNF-α-induced apoptosis. TNF-α further elicited the expression of the endoplasmic reticulum stress markers inositol-requiring enzyme (IRE)-1α, binding-immunoglobulin protein (BiP), and endoplasmic oxidoreductin1 (Ero1)-Lα. In addition, TNF-α decreased pro-collagen I α 1 secretion without diminishing its synthesis. TNF-α also induced an inflammatory response in SaOs-2 cells, as evidenced by the release of reactive oxygen and nitrogen species and the proinflammatory cytokine vascular endothelial growth factor. Conclusion. The results suggest a novel osteoblastic mechanism, which could be mediated by TNF-α and may be involved in metal wear debris-induced periprosthetic bone loss. Cite this article: Bone Joint Res 2020;9(11):827–839

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/cm. 2. for the proximal femur (P=0.002), and 0.80 (±0.60) g.weeks/cm. 2. 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

Introduction and Aims: Periprosthetic bone loss is responsible for the majority of cases of implant failure after total joint arthroplasty. Bisphosphonates are effective in reducing bone loss in many conditions associated with accelerated bone turnover. Our aim was to determine the effect of bisphosphonates on periprosthetic bone mineral density (BMD, g/cm2) after total joint arthroplasty. Method: We conducted computerised searches for randomised controlled trials, evaluating the effects of bisphosphonates on periprosthetic bone mineral density in patients undergoing primary total joint arthroplasty. We searched MEDLINE, EMBASE, CINAHL, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews and the United Kingdom National Research Register Web-site to November 2003. Computerised searches of the archives of AAOS Annual Meetings 1989–2003 were also conducted. Additional strategies to identify articles included a hand search of the bibliographies of relevant articles and direct contact with the authors. Results: Of 386 citations initially identified, nine citations met our eligibility criteria. The total number of randomised controlled trials was six (five published and one abstract). Four trials evaluated total hip arthroplasty and two examined total knee arthroplasty. Five trials used alendronate and one used pamidronate. Quality scores ranged from 65 to 75. The pooled sample size was 290 patients. Less periprosthetic bone loss occurred in the intervention group compared to the control group at the following follow-up intervals: three months (n=128, Weighted Mean Difference (WMD): 3.3%, 95% Confidence Interval (CI): 1.9–4.7, p< 0.01); six months (n=224, WMD: 4.5%, CI: 1.6–7.4, p< 0.001); and 12 months (n=173, WMD: 4.2%, CI: 1.5–6.9, p=0.03). Tests of heterogeneity revealed greater maintenance of BMD in cemented arthroplasty than in uncemented arthroplasty (WMD: 7.5%, CI: 4.3–10.7 versus WMD: 2.1%, CI: 0.61–3.6, respectively, p< 0.001) at 12 months follow-up. Conclusion: Bisphosphonates have a beneficial effect on maintaining periprosthetic bone stock compared to control after total joint arthroplasty. The effect seems greater in cemented arthroplasty and total knee arthroplasty. Whether this increase in BMD results in improved fixation and longevity of prosthetic components remains unanswered. Larger trials evaluating the effect of bisphosphonates on rates of implant loosening and functional outcomes are needed

Periprosthetic bone loss is identified after inserting a hip prosthesis and is many times a result of stress shielding or altered loading of the proximal femur. Depending on the severity, the bone loss may threaten the prosthesis survival. The current study investigated the effect of cyclic etidronate therapy on periprosthetic and contralateral bone mineral density (BMD) in an one-year, prospective, randomized, double-blind study on 46 patients after cemented hip arthroplasty. Etidronate was administered orally in a regimen repeated every 14 weeks and periprosthetic BMD was measured with dual energy X-ray absorptiometry (DXA) in the total periprosthetic area and in the seven Gruen Zones at 1 week (baseline), 6 weeks, 3 months, 6 months, and 12 months postoperatively. In the etidronate group there were significant temporal BMD decreases measured in Gruen Zones 2, 3, 6, and 7 as well as in the entire proximal femur; the greatest decrease was 11.1% and was measured in Zone 2 at 12 months. Also in the etidronate group, there was a significant 3.4% increase in BMD of the spine at 12 months. In the placebo group there were significant temporal BMD decreases measured in Gruen Zones 1, 2, 3, 4, 6, and 7 as well as in the entire proximal; the greatest decrease was 16.4% and was measured in Zone 7 at 12 months. There were no significant differences between the mean BMD measurements of the etidronate and placebo groups with the exception of the mean percent change in the spine at 6 months and 12 months, and in Gruen Zone 3 at 6 months; in all three cases the etidronate group had significantly greater mean values. These findings suggest that cyclic etidronate therapy has no significant effect in surpressing the periprosthetic bone loss following cemented hip arthroplasty

Aim of the study: The aim of the study was to register and þnd out the longterm femoral bone response after insertion of femoral stem with or with-out cement. Materials and methods: Seventeen patients (7 men, 10 women) underwent cemented and 22 patients (14 men, 8 women) uncemented total hip arthroplasty (THA). The mean age in the cemented group was 69 (58–74) years and in the uncemented group 58 (46–68) years. Femoral bone mineral density (BMD) was measured using Lunar DPX or Lunar DPX-IQ densitometry according to zones by Gruen (ROI 1–7). BMD measurements were made preoperatively, and postoperatively over four to 14 days, and at 3, 6, 12, 24, and 36 months after THA. Postoperative BMD changes were calculated using the immediate postoperative BMD value as a reference, the change being expressed as a percent. Results: Peri-prosthetic BMD decreased signiþcantly almost in all ROIs during the þrst three months after both cemented (5–18%) and uncemented (3–14%) THA (p-values < 0.05 to p< 0.001). At the end of the þrst year the most remarkable decrease in BMD was found in the calcar (zone 7) in both groups (cemented 25%; uncemented 23%). Low preoperative bone loss predicted higher periprosthetic bone loss in both groups. From one to three year only small changes in periprosthetic BMD were detected after THA. Conclusions: The present study suggests that postoperative bone loss is equal after uncemented and cemented THA. The bone loss is most pronounced during the þrst six months after THA and mainly associated in proximal femoral bone. After the phase of acute bone loss, further loss is minimal after uncomplicated THA, reßecting merely the normal aging of bone. Patients with poor bone quality at baseline are at higher risk to lose bone around the prosthesis after THA

Aims

This study was designed to develop a model for predicting bone mineral density (BMD) loss of the femur after total hip arthroplasty (THA) using artificial intelligence (AI), and to identify factors that influence the prediction. Additionally, we virtually examined the efficacy of administration of bisphosphonate for cases with severe BMD loss based on the predictive model.

The purpose of this study: is to test the hypothesis that there is little or no stress shielding afforded by a carbon composite femoral hip prosthesis when implanted in the human subject, and to investigate the possibility that a hydroxyapatite coating would prevent loosening.

The need for this development: is that loosening remains a problem for young patients who need a long term, reliable fixation of hip replacements, and it appears that if a solution exists to this problem then it probably lies away from the traditional cemented metal varieties.

One of the causes of loosening is stress shielding caused by rigid metal implants and a carbon composite femoral stem has been developed to overcome this. Paradoxically, flexible stems result in increased micro-motion at the prosthetic-bone interface and as a result they tend to loosen more frequently than metal ones. To overcome this, the carbon stem has been coated on its proximal third with hydroxyapatite, in order to get a secure fixation to the upper femur, but left bare distally to minimise weight transfer within the lower shaft.

The Study: 50 patients have entered the trial to date, and the detailed results of the first 35, which have been followed up for an average of 4 years will be presented. Stress shielding by the prosthesis was assessed, clinically, radiologically, and by dexa-scanning (usinga Hologic scanner with metal exclusion software). Two dexa-scan studies were carried out on each patient, at 1 and 2 years post operatively, and the bone mineral density of the implanted bone was compared with that of the normal contralateral side, using the Gruen zones as the basis of comparison. These results were compared with published figures for metal stems, and also with a small series of our own metal stems.

Results: 13 males and 22 females entered the trial, with an average age of 61.

Bone density around the carbon composite hip was found to increase by an average of 2% between the measurements carried out at 1 and 2 years post-op.

Conclusion: it appears that this prosthesis is fulfilling the predictions made for it, and although there is a spread of responses to it, the average patient is showing a steady increase in periprosthetic bone mineral density and is

Clinically asymptomatic. Progress to a wider trial can now be recommended.

Aims: An argument against the use of canal-þlling, customized femoral stems has been that such implants have a large cross-sectional area and therefore are stiffer than standard, uncemented implants and thus induce more stress shielding and bone loss in the proximal femur. The purpose of this study was to evaluate the association between the volume of an uncemented, customized femoral stem and the postoperative changes in peri-prosthetic bone mineral density (BMD) measured with DEXA.

Material and methods: Forty-eight patients with a mean age of 46 years had a THR using a customized femoral stem (Unique, SCP, Norway). BMD was measured in the 7 Gruen zones postoperatively and after then 3, 6, 12 and 24 months. Based on the 3-D computer model of the implant the volume of the intrafemoral part of the stem was computed. The association between the relative change in BMD at the 2 years follow-up and the volume of the stem was assessed using Pearsonñs correlation test.

Results: A statistically signiþcant correlation between the volume of the intrafemoral part of the stem and change in BMD was found in Gruen zones 2, 4, 5 and for the overall BMD in all zones. No such correlation could be found for the most proximal zones (1, 6 and 7).

Conclusions: No consistent or strong association between the volume of the femoral stem and the periprosthetic stress shielding at 2 years postoperatively was found in this study. In particular, the bone remodelling in the most proximal part of the femur was not correlated to the size of the stem. Contrary to other studies, our þndings imply that stem size or stiffness is not a major determinant for proximal femoral stress shielding following total hip replacement.

For amputated patients, direct attachment of upper leg prosthesis to the skeletal system by a percutaneous implant is an alternative solution to the traditional socket fixation. Currently available implants, the OPRA system (Integrum AB, Göteborg, Sweden) and the ISP Endo/Exo prosthesis (ESKA Implants AG, Lübeck, Germany) [1-2] allow overcoming common soft tissue problems of conventional socket fixation and provide better control of the prosthetic limb [3], higher mobility and comfort [2, 4]. However, restraining issues such as soft-tissue infections, peri-prosthetic bone fractures [3, 5–8] and considerable bone loss around the stem [9], which might lead to implant's loosening, are present. Finally, a long a residual limb is required for implant fitting.

In order to overcome the limiting biomechanical issues of the current designs, a new concept of the direct intramedullary fixation was developed. The aim was to restore the natural load transfer in the femur and allow implantations in short femur remnants (Figure 1). We hypothesize that the new design will reduce the peri-prosthetic bone failure risk and adverse bone remodeling.

Generic CT-based finite element models of an intact femoral bone and amputated bones implanted with 3 analyzed implants were created for the study. Models were loaded with two loading cases from a normal walking obtained from the experimental measurements with the OPRA device [10-11]. Periprosthetic bone failure risk was evaluated by considering the von Mises stress criterion [12-14]. Subsequently the strain adaptive bone remodeling theory was used to predict long-term changes in bone mineral density (BMD) around the implants. The bone mineral content (BMC) change was measured around implants and the results were visualized in the form of DXA scans.

The OPRA and the ISP implants induced the high stress concentration in the proximal region decreasing in the distal direction to values below physiological levels as compared with the intact bone. The stresses around the new design were more uniformly distributed along the cortex and resembled better the intact case. Consequently, the bone failure risk was reduced as compared to the OPRA and the ISP implants. The adaptive bone remodeling simulations showed high bone resorption around distal parts of the OPRA and the ISP implants in the distal end of the femur (on average −75% ISP to −78% OPRA after 60 months). The bone remodeling simulation did not reveal any bone loss around the new design, but more bone densification was seen (Figure 2). In terms of total bone mineral content (BMC) the OPRA and the ISP implants induced only a short-term bone densification in contrast to the new design, which provoked a steady increase in the BMC over the whole analyzed period (Figure 3).

In conclusion, we have seen that the new design offers much better bone maintenance and lower failure probability than the current osseointegrated trans-femoral prostheses. This positive outcome should encourage further developments of the presented concept, which in our opinion has a potential to considerably improve safety of the rehabilitation with the direct fixation implants and allow treatment of patients with short stumps.

Introduction: The management of periprosthetic osteolysis is a challenging problem in revision hip arthroplasty. Filling acetabular bone defects with structural allografts resulted in early failure due to resorption of the graft. The application in combination with reinforcement rings should promote bone incorporation as a result of reduced mechanical stresses. This study evaluates the long-term results in the treatment of acetabular deficiencies using bulk allografts supported with a Burch-Schneider Anti-Protrusio Cage (APC).

Materials and Methods: From January 1992 to December 1995, 69 consecutive patients underwent revision surgery following periprosthetic osteolysis and aseptic loosening of the cup. Acetabular bone loss included IIIA and IIIB types according to Paproski classification. 12 patients died for unrelated causes with a well-functioning total hip arthroplasty in situ. 3 cases were lost at follow-up. The study group consisted of 56 hips in 54 patients. There were 11 males and 43 females, aged from 33 to 84 years (medium 65). Average follow-up was 11.7 years, ranging from 10 to 14.4. Surgical procedure included filling acetabular bone defects with bulk allografts supported with a Burch-Schneider APC which was fixed with screws to the iliac bone. A poly-ethylene cup was finally cemented into the metal cage. Deambulation was allowed one week after surgery, but weightbearing was delayed two months. Clinical evaluation was determined using Harris hip score (HHS). The stability of the acetabular implant was assessed according to Gill criteria. The progression of the bone graft was evaluated using Gross grading.

Results: 2 patients developed deep infection that was treated by resection-arthroplasty. Aseptic loosening of acetabular cage following an extensive resorption of bone graft was observed in 6 cases and 3 of them underwent rerevision. X-ray signs of graft incorporation occurred in 48 hips. Average HHS values of 30 (range, 11 to 81) and 75 (range, 28 to 100) points were assessed respectively in the preoperative time and at follow-up.

Discussion and Conclusions: In severe acetabular bone deficiencies the application of reinforcement rings in combination with massive allografts has been advocated in order to prevent bone graft resorption and cup loosening. Burch-Schneider Anti-Protrusio Cage is able to protect the graft spanning bone defects and promoting augmentation of periprosthetic bone stock. With an aseptic failure rate of 8.9% and a total survival rate of 85.7% at an average of 11.7 years, the use of APC and structural allograft proved out to be an effective procedure in the long-term reconstructive treatment of extensive loss of acetabular bone stock.

Osteolysis and periprosthetic bone loss have been a concern since Charnley’s original reports of metal on Teflon. Willart and Semlitch were the first investigators to propose a biologic mechanism for osteolysis associated with particulate wear debris. Harris in 1976 and Goldring 1983 describe the presence of macrophages and giant cells in the synovial membrane at the bone cement interface in loose THR. Initially it was associated with cement and it was called cement disease. Reports of resorption around cementless implants led to the realization that PE alone was good enough to create bone loss. Aetiology: Submicron wear particles are phagocytosed by macrophages resulting in release of various cellular mediators from these activated cells. Cellular mediators playing significant role in osteolysis are IL-1, IL-6, TNF-a, PGE2. These mediators lead to stimulation and differentiation of osteoclasts and inhibition of osteoblasts. These factors together assist in the dissolution of bone at the interface allowing for micromotion of the prosthesis that leads to further generation of wear debris. On top of the above there is release of collagenase, stromelysin, gelatinase which further destroy the bone. Another active area of research involves roles at Rank, Rank and osteoprotegerin. Recently there is extensive work done as far as it concerns the role of endotoxin in osteolysis and periprosthetic bone loss. It still remains a controversial issue. Other researchers have studied the effects of elevated periarticular hydrostatic pressure and fluid access in the development of osteolysis (effective joint space). Particles bioreactivity: It has been shown that the major determinants of particle bioreactivity are particle size, composition, shape, and concentration. Particles of submicron size are more stimulatory and there is a dose dependent response. Concerning the composition it has been found that UHMWPE, CoCr and stainless steel particles induce more severe reactions than Titanium and alumina ceramic. It also has been found that Al2O3 particles were more easily phagocytosed than UHMWPE at the same size and concentration but TNF-a release was higher with than UHMWPE with Al2O3. Concerning the metal to metal particles it has been found that the volumetric wear is less than M/P with smaller particles and less intensive tissue reaction but Shanbhag reported that bioreactivity of metal wear debris is a function of the total surface area and not the volume of wear debris and casts doubts at the theory that metal to metal wear particles produce a less intense biological response. Concerning the highly crosslinked PE it has been found that wear debris from gamma crossed –linked remelted PE contains very few fibrils after a dose of 5 Mrads and virtually none after 9.5 Mrads. Clinical Manifestations: The majority of patients with osteolysis are asymptomatic. Pain is caused mainly from a fracture.Ultimately periprosthetic bone loss results in aseptic loosening. Furthermore if the component becomes loose bone loss often progress more rapidly resulting in large bone defects that can lead to catastrophic failure or fracture. Radiographic manifestations: Characteristic radiographic patterns of osteolysis have been described on both the femoral and acetabular side with cemented and cementless components. Recent studies have suggested that plain radiographs often underestimate the extent of osteolysis and CT or MRI may be necessary to assess the true extent of the bone loss

Aseptic loosening arises when periprosthetic bone loss results in mechanical failure at the host-implant interface, and is the main factor limiting implant survival after total hip arthroplasty (THA). The aims of this study were to determine whether genetic variation is a risk factor for loosening, explore the metabolic mechanisms of periprosthetic bone loss, and determine whether bisphosphonates may prevent bone loss and enhance implant mechanical stability after THA. In a genetic association study (. J Bone Mineral Res. 2003. ; . 18. :. 1995. –2001. ) we found that carriage of the −238A allele within the promoter region of the TNF gene was an independent risk factor for aseptic loosening. A subsequent reporter gene assay showed differential TNF gene responsiveness between the –238A and –238G alleles to polyethylene particule stimulation (Calcified Tissue Int 2003; 72: 251-273). In a cross-sectional study (J Orthop Res 2003; 214: 691–696) we found that subjects with aseptic loosening had lower bone mineral density (BMD) in the region of the femoral calcar and higher urinary excretion of cross-linked collagen breakdown products than their counterparts with fixed femoral implants. In a randomised controlled trial we found that a single dose infusion of a bisphosphonate (pamidronate) reduced femoral bone loss over 2 years after THA, but did not affect pelvic bone loss or implant migration (. J Bone Miner Res. 2002. ; . 17. : . 1328. ). Transient increases in bone turnover markers occurred after surgery and were highly predictive of later femoral BMD change. The main predictor of early implant migration was patient age, but not periprosthetic BMD change. In summary, genetic as well as environmental factors affect implant survival after THA. Aseptic loosening is associated with regional changes in bone mass and turnover as well as focal osteolytic lesions. Bisphosphonate therapy is well tolerated after THA and has a clear biological effect. However, the impact of preventing early bone loss on late aseptic loosening remains unclear and awaits long term study. [Winner, Robert Jones Gold Medal and Association Prize, 2003]

Factors that allow the generation or ingression of wear particles at the implant-host interface after total hip arthroplasty (THA) may include early migration and periprosthetic bone loss. We have previously shown that a single 90mg dose of the bisphosphonate pamidronate prevents bone loss over 6 months after THA. In this 2 year randomised trial extension study we assessed the longer term effects of this intervention on bone loss and implant migration. Twenty-two patients received 90mg of pamidronate and 22 received placebo at randomisation 5 days after surgery. Femoral and pelvic bone mineral density (BMD) was measured by dual energy x-ray absorptiometry (DXA) and implant migration was measured using the EBRA-Digital method over a 104 week period. In the placebo group rapid periprosthetic bone loss occurred over the first 6 months. After this period a partial recovery in bone mass occurred in most regions. Patients in the pamidronate group had significantly less femoral, but not pelvic, bone loss than those give placebo (ANOVA P=0.02). Pamidronate was most effective in preventing bone loss in Gruen zones 6 and 7 (ANOVA P=0.004, and P=0.014, respectively). At week 104 the mean total stem migration was 1.77mm±0.27 and 1.62mm±0.37 for the placebo and pamidronate groups, respectively (P> 0.05). Total cup migration was 0.75mm±0.26 and 0.76mm±0.14, respectively (P> 0.05). Age at surgery accounted for 26% (linear regression r=−0.65, P=0.02) and 38% (r=−0.51, P=0.007) of the variability in stem and cup migration at week 104, with younger subjects experiencing greater migration. Stem migration at week 104 was also inversely related to the Barrack cement mantle grade (r=−0.66, r. 2. 41%, P=0.0003). Implant migration was not significantly related to changes in periprosthetic bone mass. Pamidronate therapy has a significant effect on bone mass, but not implant stability, after THA.Our findings suggest that the major determinants of early migration after THA are young patient age and poor cementing technique

Introduction Periprosthetic bone loss is a major cause of concern in patients undergoing total hip arthroplasty (THA). In this study we monitored the periprosthetic bone loss around two different types of femoral implant to evaluate their design and investigate the relationship with the preoperative bone mineral density (BMD). Materials and Methods Sixty patients (35 female, 25 male, mean age 63 (range, 46–75) years) undergoing THA were randomised to either the ABG or Mallory Head femoral stem. Preoperative DEXA scans were acquired of the posteroanterior (PA) and lateral lumbar spine, the contra-lateral hip and the non-dominant forearm. Postoperative DEXA scans were performed at 10 days (treated as baseline), six weeks, and 3, 6, 12, 24 and 36 months after THA. Results A total of 50 patients (24 ABG, 26 MH) completed the study. Three months after THA there was a statistically significant BMD decrease in every Gruen zone that varied between 5.6% and 13.8% for the ABG pros-thesis and between 3.8% and 8.7% for the MH prosthesis. Subsequently, in most zones BMD reached a plateau or showed a small recovery. However, BMD continued to fall in Gruen zones 1 and 7 in ABG patients and Gruen zone 1 in MH patients. Bone loss was less in every Gruen zone in MH patients compared with ABG with the largest difference (10%, P = 0.018) in Gruen zone 7. After adjustment for multiple comparisons the relationship between peri-prosthetic bone loss and preoperative BMD was highly statistically significant for spine, hip and radius BMD. Discussion The present study showed that statistically significant bone loss occurred with both stems during the first three months following implantation, and confirmed that prosthesis design influences peri-prosthetic bone loss. Although the greater bone loss in patients with lower spine, hip or forearm BMD may not adversely affect the outcome for patients in the short and mid-term, preservation of femoral bone stock may be important in the longer term because a low femoral BMD can adversely affect the results of a subsequent revision. Greater femoral bone stock may be particularly advantageous in younger patients in whom a future revision is more likely

Wear induces osteolysis leading to periprosthetic bone loss and TJA loosening. Inflammatory immune cells can form an aggressive interface membrane activating osteoclasts. The current study shows the effect of metal particles and ions triggering cellular responses. Blood samples from primary and revision TJA were analysed for systemic inflammation. PBMCs were cultured on different implant materials. Cellular response was monitored by qRT-PCR. Furthermore, cells were exposed to increasing concentrations of metal particles (10-7 and 10–8 particles/ml) and CoCl2 (50 µM and 100 µM). Cellular response was measured using WST-1 reduction, MitoSox-fluorescence and TUNEL-staining. Cobalt ion influx into osteoblasts was measured using FURA2-staining, cellular effects for HIF-1alpha and qRT-PCR. No inflammatory parameters were detected in patients' blood from primary and revision TJA. Short inflammatory reaction of their PBMCs was observed in in vitro culture on ceramic implants, whereas there was no such reaction to other tested implant martials. In MM6 and Jurkat cells only metal ions induced oxidative stress but did not significantly reduce cell viability. An increase in HIF1-alpha was observed in tissue containing large amounts of metal wear in comparison to plastic wear containing tissues and OA synovial tissue without wear particles. Cobalt ions were stored by osteoblasts via a calcium channel inducing hypoxia. This effect could be blocked using a TRPM blocking agent. Ceramic induces a short inflammatory response that may induce periprosthetic inflammation. Ionic Cobalt induces oxidative stress and hypoxia. Ionic metal exerts a more intense reaction on cells than particles

Aims

Osteoporosis is common in total hip arthroplasty (THA) patients. It plays a substantial factor in the surgery’s outcome, and previous studies have revealed that pharmacological treatment for osteoporosis influences implant survival rate. The purpose of this study was to examine the prevalence of and treatment rates for osteoporosis prior to THA, and to explore differences in osteoporosis-related biomarkers between patients treated and untreated for osteoporosis.

Aims

The management of periprosthetic joint infection (PJI) remains a major challenge in orthopaedic surgery. In this study, we aimed to characterize the local bone microstructure and metabolism in a clinical cohort of patients with chronic PJI.

Aims

This study intended to investigate the effect of vericiguat (VIT) on titanium rod osseointegration in aged rats with iron overload, and also explore the role of VIT in osteoblast and osteoclast differentiation.

The Osteoprotegerin/RANK/RANKL system has been implicated in the biological cascade of events initiated by particulate wear debris and bacterial infection resulting in periprosthetic bone loss around loosened total hip arthroplasties (THA). Individual responses to such stimuli may be dictated by genetic variation and we have studied the effect of single nucleotide polymorphisms (SNPs) within these genes. We performed a case control study of the Osteoprotegerin, RANK and RANKL genes for possible association with deep sepsis or aseptic loosening. All patients included in the study were Caucasian and had had a cemented Charnley THA and polyethylene acetabular cup. Cases consisted of 91 patients with early aseptic loosening and 71 patients with microbiological evidence at surgery of deep infection. Controls consisted of 150 THAs that were clinically asymptomatic for over 10 years and demonstrated no radiographic features of aseptic loosening. DNA samples from all individuals were genotyped using Taqman allelic discrimination. The A allele (p<0.001) and homozygous genotype A/A (p<0.001) for the OPG-163 SNP were highly associated with aseptic failure. Additionally, the RANK-575 (C/T SNP) T allele (p=0.004) and T/T genotype (p=0.008) frequencies were associated with aseptic failure. No statistically significant relationship was found between aseptic loosening and the OPG- 245 or OPG-1181 SNPs. When the septic group was compared to controls, the frequency of the A allele (p<0.001) and homozygous genotype A/A (p<0.001) for the OPG-163 SNP were statistically significant. No statistically significant relationship was found between septic failure and the OPG- 245, OPG-1181 or RANK-575 SNPs. Aseptic loosening and possibly deep infection of THA may be under genetic influence to candidate susceptibility genes. SNP markers may serve as predictors of implant survival and aid pharmacogenomic prevention of THA failure

Introduction: Dual-energy x-ray absorptiometry (DEXA) measurement is a valuable and accurate method of assessing periprosthetic bone loss around femoral stems. Method: The cohort was 21 patients who underwent total hip arthroplasties with double-threaded, cone-shaped, modular, femoral stems and who already had a prosthetic contralateral hip. The contralateral hip arthroplasties were Autophur fully porous coated, Exeter cemented and Charnley cemented stems. DEXA measurements were performed in the anteroposterior femoral plane using a Lunar DPXL densitometer and analysed using the Lunar Orthopaedic Software Package, Version 1.7, designed for periprosthetic measurements. The initial measurement was performed between two and four weeks after the surgery as a baseline and then repeated after three, six, 12 and 24 months. The DEXA scan results were analysed comparing the bone density of the double-threaded cone-shaped modular femoral stem side with the contralateral side in a longitudinal study. Results: The contralateral hip bone quality remained fairly constant in keeping with the maturity of the hip arthroplasties. The insertion of the double-threaded cone-shaped modular femoral stem caused the expected initial bone loss in Gruen zones one and seven due to proximal stress-shielding. Only minor bone loss occurred distally, reflecting good fixation and load transfer of the prosthesis