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Bone & Joint Research
Vol. 7, Issue 1 | Pages 85 - 93
1 Jan 2018
Saleh A George J Faour M Klika AK Higuera CA

Objectives. The diagnosis of periprosthetic joint infection (PJI) is difficult and requires a battery of tests and clinical findings. The purpose of this review is to summarize all current evidence for common and new serum biomarkers utilized in the diagnosis of PJI. Methods. We searched two literature databases, using terms that encompass all hip and knee arthroplasty procedures, as well as PJI and statistical terms reflecting diagnostic parameters. The findings are summarized as a narrative review. Results. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were the two most commonly published serum biomarkers. Most evidence did not identify other serum biomarkers that are clearly superior to ESR and CRP. Other serum biomarkers have not demonstrated superior sensitivity and have failed to replace CRP and ESR as first-line screening tests. D-dimer appears to be a promising biomarker, but more research is necessary. Factors that influence serum biomarkers include temporal trends, stage of revision, and implant-related factors (metallosis). Conclusion. Our review helped to identify factors that can influence serum biomarkers’ level changes; the recognition of such factors can help improve their diagnostic utility. As such, we cannot rely on ESR and CRP alone for the diagnosis of PJI prior to second-stage reimplantation, or in metal-on-metal or corrosion cases. The future of serum biomarkers will likely shift towards using genomics and proteomics to identify proteins transcribed via messenger RNA in response to infection and sepsis. Cite this article: A. Saleh, J. George, M. Faour, A. K. Klika, C. A. Higuera. Serum biomarkers in periprosthetic joint infections. Bone Joint Res 2018;7:85–93. DOI: 10.1302/2046-3758.71.BJR-2017-0323


Bone & Joint Research
Vol. 8, Issue 3 | Pages 146 - 155
1 Mar 2019
Langton DJ Natu S Harrington CF Bowsher JG Nargol AVF

Objectives. We investigated the reliability of the cobalt-chromium (CoCr) synovial joint fluid ratio (JFR) in identifying the presence of a severe aseptic lymphocyte-dominated vasculitis-associated lesion (ALVAL) response and/or suboptimal taper performance (SOTP) following metal-on-metal (MoM) hip arthroplasty. We then examined the possibility that the CoCr JFR may influence the serum partitioning of Co and Cr. Methods. For part A, we included all revision surgeries carried out at our unit with the relevant data, including volumetric wear analysis, joint fluid (JF) Co and Cr concentrations, and ALVAL grade (n = 315). Receiver operating characteristic curves were constructed to assess the reliability of the CoCr JFR in identifying severe ALVAL and/or SOTP. For part B, we included only patients with unilateral prostheses who had given matched serum and whole blood samples for Co and Cr analysis (n = 155). Multiple regression was used to examine the influence of JF concentrations on the serum partitioning of Co and Cr in the blood. Results. A CoCr JFR > 1 showed a specificity of 83% (77% to 88%) and sensitivity of 63% (55% to 70%) for the detection of severe ALVAL and/or SOTP. In patients with CoCr JFRs > 1, the median blood Cr to serum Cr ratio was 0.99, compared with 0.71 in patients with CoCr JFRs < 1 (p < 0.001). Regression analysis demonstrated that the blood Cr to serum Cr value was positively associated with the JF Co concentration (p = 0.011) and inversely related to the JF Cr concentration (p < 0.001). Conclusion. Elevations in CoCr JFRs are associated with adverse biological (severe ALVAL) or tribocorrosive processes (SOTP). Comparison of serum Cr with blood Cr concentrations may be a useful additional clinical tool to help to identify these conditions. Cite this article: D. J. Langton, S. Natu, C. F. Harrington, J. G. Bowsher, A. V. F. Nargol. Is the synovial fluid cobalt-to-chromium ratio related to the serum partitioning of metal debris following metal-on-metal hip arthroplasty? Bone Joint Res 2019;8:146–155. DOI: 10.1302/2046-3758.83.BJR-2018-0049.R1


Bone & Joint Open
Vol. 5, Issue 6 | Pages 514 - 523
24 Jun 2024
Fishley W Nandra R Carluke I Partington PF Reed MR Kramer DJ Wilson MJ Hubble MJW Howell JR Whitehouse SL Petheram TG Kassam AM

Aims. In metal-on-metal (MoM) hip arthroplasties and resurfacings, mechanically induced corrosion can lead to elevated serum metal ions, a local inflammatory response, and formation of pseudotumours, ultimately requiring revision. The size and diametral clearance of anatomical (ADM) and modular (MDM) dual-mobility polyethylene bearings match those of Birmingham hip MoM components. If the acetabular component is satisfactorily positioned, well integrated into the bone, and has no surface damage, this presents the opportunity for revision with exchange of the metal head for ADM/MDM polyethylene bearings without removal of the acetabular component. Methods. Between 2012 and 2020, across two centres, 94 patients underwent revision of Birmingham MoM hip arthroplasties or resurfacings. Mean age was 65.5 years (33 to 87). In 53 patients (56.4%), the acetabular component was retained and dual-mobility bearings were used (DM); in 41 (43.6%) the acetabulum was revised (AR). Patients underwent follow-up of minimum two-years (mean 4.6 (2.1 to 8.5) years). Results. In the DM group, two (3.8%) patients underwent further surgery: one (1.9%) for dislocation and one (1.9%) for infection. In the AR group, four (9.8%) underwent further procedures: two (4.9%) for loosening of the acetabular component and two (4.9%) following dislocations. There were no other dislocations in either group. In the DM group, operating time (68.4 vs 101.5 mins, p < 0.001), postoperative drop in haemoglobin (16.6 vs 27.8 g/L, p < 0.001), and length of stay (1.8 vs 2.4 days, p < 0.001) were significantly lower. There was a significant reduction in serum metal ions postoperatively in both groups (p < 0.001), although there was no difference between groups for this reduction (p = 0.674 (cobalt); p = 0.186 (chromium)). Conclusion. In selected patients with Birmingham MoM hips, where the acetabular component is well-fixed and in a satisfactory position with no surface damage, the metal head can be exchanged for polyethylene ADM/MDM bearings with retention of the acetabular prosthesis. This presents significant benefits, with a shorter procedure and a lower risk of complications. Cite this article: Bone Jt Open 2024;5(6):514–523


Bone & Joint Research
Vol. 2, Issue 5 | Pages 84 - 95
1 May 2013
Sidaginamale RP Joyce TJ Lord JK Jefferson R Blain PG Nargol AVF Langton DJ

Objectives. The aims of this piece of work were to: 1) record the background concentrations of blood chromium (Cr) and cobalt (Co) concentrations in a large group of subjects; 2) to compare blood/serum Cr and Co concentrations with retrieved metal-on-metal (MoM) hip resurfacings; 3) to examine the distribution of Co and Cr in the serum and whole blood of patients with MoM hip arthroplasties; and 4) to further understand the partitioning of metal ions between the serum and whole blood fractions. Methods. A total of 3042 blood samples donated to the local transfusion centre were analysed to record Co and Cr concentrations. Also, 91 hip resurfacing devices from patients who had given pre-revision blood/serum samples for metal ion analysis underwent volumetric wear assessment using a coordinate measuring machine. Linear regression analysis was carried out and receiver operating characteristic curves were constructed to assess the reliability of metal ions to identify abnormally wearing implants. The relationship between serum and whole blood concentrations of Cr and Co in 1048 patients was analysed using Bland-Altman charts. This relationship was further investigated in an in vitro study during which human blood was spiked with trivalent and hexavalent Cr, the serum then separated and the fractions analysed. Results. Only one patient in the transfusion group was found to have a blood Co > 2 µg/l. Blood/Serum Cr and Co concentrations were reliable indicators of abnormal wear. Blood Co appeared to be the most useful clinical test, with a concentration of 4.5 µg/l showing sensitivity and specificity for the detection of abnormal wear of 94% and 95%, respectively. Generated metal ions tended to fill the serum compartment preferentially in vivo and this was replicated in the in vitro study when blood was spiked with trivalent Cr and bivalent Co. Conclusions. Blood/serum metal ion concentrations are reliable indicators of abnormal wear processes. Important differences exist however between elements and the blood fraction under study. Future guidelines must take these differences into account


Bone & Joint Research
Vol. 5, Issue 9 | Pages 370 - 378
1 Sep 2016
Munir S Oliver RA Zicat B Walter WL Walter WK Walsh WR

Objectives. This study aimed to characterise and qualitatively grade the severity of the corrosion particles released into the hip joint following taper corrosion. Methods. The 26 cases examined were CoC/ABG Modular (n = 13) and ASR/SROM (n = 13). Blood serum metal ion levels were collected before and after revision surgery. The haematoxylin and eosin tissue sections were graded on the presence of fibrin exudates, necrosis, inflammatory cells and corrosion products. The corrosion products were identified based on visible observation and graded on abundance. Two independent observers blinded to the clinical patient findings scored all cases. Elemental analysis was performed on corrosion products within tissue sections. X-Ray diffraction was used to identify crystalline structures present in taper debris. Results. The CoC/ABG Modular patients had a mean age of 64.6 years (49.4 to 76.5) and ASR/SROM patients had a mean age of 58.2 years (33.3 to 85.6). The mean time in situ for CoC/ABG was 4.9 years (2 to 6.4) and ASR/SROM was 6.1 years (2.5 to 8.1). The blood serum metal ion concentrations reduced following revision surgery with the exception of Cr levels within CoC/ABG. The grading of tissue sections showed that the macrophage response and metal debris were significantly higher for the ASR/SROM patients (p < 0.001). The brown/red particles were significantly higher for ASR/SROM (p < 0.001). The taper debris contained traces of titanium oxide, chromium oxide and aluminium nitride. Conclusion. This study characterised and qualitatively graded the severity of the corrosion particles released into the hip joint from tapers that had corrosion damage. Cite this article: S. Munir, R. A. Oliver, B. Zicat, W. L. Walter, W. K. Walter, W. R. Walsh. The histological and elemental characterisation of corrosion particles from taper junctions. Bone Joint Res 2016;5:370–378. DOI: 10.1302/2046-3758.59.2000507


Bone & Joint Open
Vol. 5, Issue 6 | Pages 479 - 488
6 Jun 2024
Paksoy A Meller S Schwotzer F Moroder P Trampuz A Imiolczyk J Perka C Hackl M Plachel F Akgün D

Aims

Current diagnostic tools are not always able to effectively identify periprosthetic joint infections (PJIs). Recent studies suggest that circulating microRNAs (miRNAs) undergo changes under pathological conditions such as infection. The aim of this study was to analyze miRNA expression in hip arthroplasty PJI patients.

Methods

This was a prospective pilot study, including 24 patients divided into three groups, with eight patients each undergoing revision of their hip arthroplasty due to aseptic reasons, and low- and high-grade PJI, respectively. The number of intraoperative samples and the incidence of positive cultures were recorded for each patient. Additionally, venous blood samples and periarticular tissue samples were collected from each patient to determine miRNA expressions between the groups. MiRNA screening was performed by small RNA-sequencing using the miRNA next generation sequencing (NGS) discovery (miND) pipeline.


Bone & Joint Research
Vol. 11, Issue 12 | Pages 873 - 880
1 Dec 2022
Watanabe N Miyatake K Takada R Ogawa T Amano Y Jinno T Koga H Yoshii T Okawa A

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.

Methods

This single-centre retrospective study included 398 hip joints of patients who underwent THA. Using medical records, we examined preoperative bone mineral density measures of the hip and lumbar spine using dual energy X-ray absorptiometry (DXA) scans and the medications used to treat osteoporosis at the time of admission. We also assessed the following osteoporosis-related biomarkers: tartrate-resistant acid phosphatase 5b (TRACP-5b); total procollagen type 1 amino-terminal propeptide (total P1NP); intact parathyroid hormone; and homocysteine.


Bone & Joint Open
Vol. 3, Issue 12 | Pages 991 - 997
23 Dec 2022
McPherson EJ Stavrakis AI Chowdhry M Curtin NL Dipane MV Crawford BM

Aims

Large acetabular bone defects encountered in revision total hip arthroplasty (THA) are challenging to restore. Metal constructs for structural support are combined with bone graft materials for restoration. Autograft is restricted due to limited volume, and allogenic grafts have downsides including cost, availability, and operative processing. Bone graft substitutes (BGS) are an attractive alternative if they can demonstrate positive remodelling. One potential product is a biphasic injectable mixture (Cerament) that combines a fast-resorbing material (calcium sulphate) with the highly osteoconductive material hydroxyapatite. This study reviews the application of this biomaterial in large acetabular defects.

Methods

We performed a retrospective review at a single institution of patients undergoing revision THA by a single surgeon. We identified 49 consecutive patients with large acetabular defects where the biphasic BGS was applied, with no other products added to the BGS. After placement of metallic acetabular implants, the BGS was injected into the remaining bone defects surrounding the new implants. Patients were followed and monitored for functional outcome scores, implant fixation, radiological graft site remodelling, and revision failures.


Bone & Joint Open
Vol. 3, Issue 12 | Pages 924 - 932
23 Dec 2022
Bourget-Murray J Horton I Morris J Bureau A Garceau S Abdelbary H Grammatopoulos G

Aims

The aims of this study were to determine the incidence and factors for developing periprosthetic joint infection (PJI) following hemiarthroplasty (HA) for hip fracture, and to evaluate treatment outcome and identify factors associated with treatment outcome.

Methods

A retrospective review was performed of consecutive patients treated for HA PJI at a tertiary referral centre with a mean 4.5 years’ follow-up (1.6 weeks to 12.9 years). Surgeries performed included debridement, antibiotics, and implant retention (DAIR) and single-stage revision. The effect of different factors on developing infection and treatment outcome was determined.


Bone & Joint Open
Vol. 3, Issue 4 | Pages 340 - 347
22 Apr 2022
Winkler T Costa ML Ofir R Parolini O Geissler S Volk H Eder C

Aims

The aim of the HIPGEN consortium is to develop the first cell therapy product for hip fracture patients using PLacental-eXpanded (PLX-PAD) stromal cells.

Methods

HIPGEN is a multicentre, multinational, randomized, double-blind, placebo-controlled trial. A total of 240 patients aged 60 to 90 years with low-energy femoral neck fractures (FNF) will be allocated to two arms and receive an intramuscular injection of either 150 × 106 PLX-PAD cells or placebo into the medial gluteal muscle after direct lateral implantation of total or hemi hip arthroplasty. Patients will be followed for two years. The primary endpoint is the Short Physical Performance Battery (SPPB) at week 26. Secondary and exploratory endpoints include morphological parameters (lean body mass), functional parameters (abduction and handgrip strength, symmetry in gait, weightbearing), all-cause mortality rate and patient-reported outcome measures (Lower Limb Measure, EuroQol five-dimension questionnaire). Immunological biomarker and in vitro studies will be performed to analyze the PLX-PAD mechanism of action. A sample size of 240 subjects was calculated providing 88% power for the detection of a 1 SPPB point treatment effect for a two-sided test with an α level of 5%.


Bone & Joint Research
Vol. 1, Issue 3 | Pages 25 - 30
1 Mar 2012
Wroblewski BM Siney PD Fleming PA

Objectives. Metal-on-metal (MoM) hip resurfacing was introduced into clinical practice because it was perceived to be a better alternative to conventional total hip replacement for young and active patients. However, an increasing number of reports of complications have arisen focusing on design and orientation of the components, the generation of metallic wear particles and serum levels of metallic ions. The procedure introduced a combination of two elements: large-dimension components and hard abrasive particles of metal wear. The objective of our study was to investigate the theory that microseparation of the articular surfaces draws in a high volume of bursal fluid and its contents into the articulation, and at relocation under load would generate high pressures of fluid ejection, resulting in an abrasive water jet. Methods. This theoretical concept using MoM resurfacing components (head diameter 55 mm) was modelled mathematically and confirmed experimentally using a material-testing machine that pushed the head into the cup at a rate of 1000 mm/min until fully engaged. Results. The mathematical model showed the pattern but not the force of fluid ejection, the highest pressures were expected when the separation of the components was only a fraction of one millimetre. The experimental work confirmed the results; with the mean peak ejection pressure of 43 763 N/m. 2. equivalent to 306 mmHg or 5 psi. Conclusions. The mechanical effect of the high-pressure abrasive water jet is the likely cause of the spectrum of complications reported with metal-on-metal resurfacing. Investigating serum levels of metallic elements may not be the best method for assessing the local mechanical effects of the abrasive water jet


Bone & Joint Open
Vol. 2, Issue 10 | Pages 858 - 864
18 Oct 2021
Guntin J Plummer D Della Valle C DeBenedetti A Nam D

Aims

Prior studies have identified that malseating of a modular dual mobility liner can occur, with previous reported incidences between 5.8% and 16.4%. The aim of this study was to determine the incidence of malseating in dual mobility implants at our institution, assess for risk factors for liner malseating, and investigate whether liner malseating has any impact on clinical outcomes after surgery.

Methods

We retrospectively reviewed the radiographs of 239 primary and revision total hip arthroplasties with a modular dual mobility liner. Two independent reviewers assessed radiographs for each patient twice for evidence of malseating, with a third observer acting as a tiebreaker. Univariate analysis was conducted to determine risk factors for malseating with Youden’s index used to identify cut-off points. Cohen’s kappa test was used to measure interobserver and intraobserver reliability.


Bone & Joint Open
Vol. 3, Issue 1 | Pages 77 - 84
24 Jan 2022
Onishi E Ota S Fujita S Tsukamoto Y Yamashita S Hashimura T Matsunaga K Yasuda T

Aims

This study aimed to evaluate sagittal spinopelvic alignment (SSPA) in the early stage of rapidly destructive coxopathy (RDC) compared with hip osteoarthritis (HOA), and to identify risk factors of SSPA for destruction of the femoral head within 12 months after the disease onset.

Methods

This study enrolled 34 RDC patients with joint space narrowing > 2 mm within 12 months after the onset of hip pain and 25 HOA patients showing femoral head destruction. Sharp angle was measured for acetabular coverage evaluation. Femoral head collapse ratio was calculated for assessment of the extent of femoral head collapse by RDC. The following parameters of SSPA were evaluated using the whole spinopelvic radiograph: pelvic tilt (PT), sacral slope (SS), pelvic incidence (PI), sagittal vertical axis (SVA), thoracic kyphosis angle (TK), lumbar lordosis angle (LL), and PI-LL.


Bone & Joint Research
Vol. 10, Issue 9 | Pages 558 - 570
1 Sep 2021
Li C Peng Z Zhou Y Su Y Bu P Meng X Li B Xu Y

Aims

Developmental dysplasia of the hip (DDH) is a complex musculoskeletal disease that occurs mostly in children. This study aimed to investigate the molecular changes in the hip joint capsule of patients with DDH.

Methods

High-throughput sequencing was used to identify genes that were differentially expressed in hip joint capsules between healthy controls and DDH patients. Biological assays including cell cycle, viability, apoptosis, immunofluorescence, reverse transcription polymerase chain reaction (RT-PCR), and western blotting were performed to determine the roles of the differentially expressed genes in DDH pathology.


Bone & Joint Research
Vol. 10, Issue 8 | Pages 498 - 513
3 Aug 2021
Liu Z Lu C Shen P Chou S Shih C Chen J Tien YC

Aims

Interleukin (IL)-1β is one of the major pathogenic regulators during the pathological development of intervertebral disc degeneration (IDD). However, effective treatment options for IDD are limited. Suramin is used to treat African sleeping sickness. This study aimed to investigate the pharmacological effects of suramin on mitigating IDD and to characterize the underlying mechanism.

Methods

Porcine nucleus pulposus (NP) cells were treated with vehicle, 10 ng/ml IL-1β, 10 μM suramin, or 10 μM suramin plus IL-1β. The expression levels of catabolic and anabolic proteins, proinflammatory cytokines, mitogen-activated protein kinase (MAPK), and nuclear factor (NF)-κB-related signalling molecules were assessed by Western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), and immunofluorescence analysis. Flow cytometry was applied to detect apoptotic cells. The ex vivo effects of suramin were examined using IDD organ culture and differentiation was analyzed by Safranin O-Fast green and Alcian blue staining.


Bone & Joint Research
Vol. 10, Issue 6 | Pages 354 - 362
1 Jun 2021
Luo Y Zhao X Yang Z Yeersheng R Kang P

Aims

The purpose of this study was to examine the efficacy and safety of carbazochrome sodium sulfonate (CSS) combined with tranexamic acid (TXA) on blood loss and inflammatory responses after primary total hip arthroplasty (THA), and to investigate the influence of different administration methods of CSS on perioperative blood loss during THA.

Methods

This study is a randomized controlled trial involving 200 patients undergoing primary unilateral THA. A total of 200 patients treated with intravenous TXA were randomly assigned to group A (combined intravenous and topical CSS), group B (topical CSS), group C (intravenous CSS), or group D (placebo).


Bone & Joint Open
Vol. 2, Issue 6 | Pages 443 - 456
28 Jun 2021
Thompson JW Corbett J Bye D Jones A Tissingh EK Nolan J

Aims

The Exeter V40 cemented polished tapered stem system has demonstrated excellent long-term outcomes. This paper presents a systematic review of the existing literature and reports on a large case series comparing implant fractures between the Exeter V40 series; 125 mm and conventional length stem systems.

Methods

A systematic literature search was performed adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. In parallel, we performed a retrospective single centre study of Exeter V40 femoral stem prosthetic fractures between April 2003 and June 2020.


The Bone & Joint Journal
Vol. 101-B, Issue 4 | Pages 365 - 371
1 Apr 2019
Nam D Salih R Nahhas CR Barrack RL Nunley RM

Aims

Modular dual mobility (DM) prostheses in which a cobalt-chromium liner is inserted into a titanium acetabular shell (vs a monoblock acetabular component) have the advantage of allowing supplementary screw fixation, but the potential for corrosion between the liner and acetabulum has raised concerns. While DM prostheses have shown improved stability in patients deemed ‘high-risk’ for dislocation undergoing total hip arthroplasty (THA), their performance in young, active patients has not been reported. This study’s purpose was to assess clinical outcomes, metal ion levels, and periprosthetic femoral bone mineral density (BMD) in young, active patients receiving a modular DM acetabulum and recently introduced titanium, proximally coated, tapered femoral stem design.

Patients and Methods

This was a prospective study of patients between 18 and 65 years of age, with a body mass index (BMI) < 35 kg/m2 and University of California at Los Angeles (UCLA) activity score > 6, who received a modular cobalt-chromium acetabular liner, highly crosslinked polyethylene mobile bearing, and cementless titanium femoral stem for their primary THA. Patients with a history of renal disease and metal hardware elsewhere in the body were excluded. A total of 43 patients (30 male, 13 female; mean age 52.6 years (sd 6.5)) were enrolled. All patients had a minimum of two years’ clinical follow-up. Patient-reported outcome measures, whole blood metal ion levels (ug/l), and periprosthetic femoral BMD were measured at baseline, as well as at one and two years postoperatively. Power analysis indicated 40 patients necessary to demonstrate a five-fold increase in cobalt levels from baseline (alpha = 0.05, beta = 0.80). A mixed model with repeated measures was used for statistical analysis.


Bone & Joint Research
Vol. 5, Issue 9 | Pages 379 - 386
1 Sep 2016
Pahuta M Smolders JM van Susante JL Peck J Kim PR Beaule PE

Objectives

Alarm over the reported high failure rates for metal-on-metal (MoM) hip implants as well as their potential for locally aggressive Adverse Reactions to Metal Debris (ARMDs) has prompted government agencies, internationally, to recommend the monitoring of patients with MoM hip implants. Some have advised that a blood ion level >7 µg/L indicates potential for ARMDs. We report a systematic review and meta-analysis of the performance of metal ion testing for ARMDs.

Methods

We searched MEDLINE and EMBASE to identify articles from which it was possible to reconstruct a 2 × 2 table. Two readers independently reviewed all articles and extracted data using explicit criteria. We computed a summary receiver operating curve using a Bayesian random-effects hierarchical model.


Bone & Joint Research
Vol. 5, Issue 9 | Pages 393 - 402
1 Sep 2016
Yang Z Liu H Li D Xie X Qin T Ma J Kang P

Objectives

The primary purpose of this meta-analysis was to determine whether statin usage could reduce the risk of glucocorticoid-related osteonecrosis in animal models.

Methods

A systematic literature search up to May 2015 was carried out using the PubMed, Ovid, EBM reviews, ISI Web of Science, EBSCO, CBM, CNKI databases with the term and boolean operators: statins and osteonecrosis in all fields. Risk ratio (RR), as the risk estimate of specific outcome, was calculated along with 95% confidence intervals (CI). The methodological quality of individual studies was assessed using a quantitative tool based on the updated Stroke Therapy Academic Industry Roundtable (STAIR) recommendations.