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Bone & Joint Research
Vol. 5, Issue 11 | Pages 586 - 593
1 Nov 2016
Rakhra KS Bonura AA Nairn R Schweitzer ME Kolanko NM Beaule PE

Objectives. The purpose of this study was to compare the thickness of the hip capsule in patients with surgical hip disease, either with cam-femoroacetabular impingement (FAI) or non-FAI hip pathology, with that of asymptomatic control hips. Methods. A total of 56 hips in 55 patients underwent a 3Tesla MRI of the hip. These included 40 patients with 41 hips with arthroscopically proven hip disease (16 with cam-FAI; nine men, seven women; mean age 39 years, 22 to 58) and 25 with non-FAI chondrolabral pathology (four men, 21 women; mean age 40 years, 18 to 63) as well as 15 asymptomatic volunteers, whose hips served as controls (ten men, five women; mean age 62 years, 33 to 77). The maximal capsule thickness was measured anteriorly and superiorly, and compared within and between the three groups with a gender subanalysis using student’s t-test. The correlation between alpha angle and capsule thickness was determined using Pearson’s correlation coefficient. Results. Superiorly, the hip capsule was significantly greater in cam- (p = 0.028) and non-FAI (p = 0.048) surgical groups compared with the asymptomatic group. Within groups, the superior capsule thickness was significantly greater than the anterior in cam- (p < 0.001) and non-FAI (p < 0.001) surgical groups, but not in the control group. There was no significant correlation between the alpha angle and capsule thickness. There were no gender differences identified in the thickness of the hip capsule. Conclusion. The thickness of the capsule does not differ between cam- and non-FAI diseased hips, and thus may not be specific for a particular aetiology of hip disease. The capsule is, however, thicker in diseased surgical hips compared with asymptomatic control hips. Cite this article: K. S. Rakhra, A. A. Bonura, R. Nairn, M. E. Schweitzer, N. M. Kolanko, P. E. Beaule. Is the hip capsule thicker in diseased hips? Bone Joint Res 2016;5:586–593. DOI: 10.1302/2046-3758.511.2000495


The Bone & Joint Journal
Vol. 101-B, Issue 4 | Pages 426 - 434
1 Apr 2019
Logishetty K van Arkel RJ Ng KCG Muirhead-Allwood SK Cobb JP Jeffers JRT

Aims. The hip’s capsular ligaments passively restrain extreme range of movement (ROM) by wrapping around the native femoral head/neck. We determined the effect of hip resurfacing arthroplasty (HRA), dual-mobility total hip arthroplasty (DM-THA), conventional THA, and surgical approach on ligament function. Materials and Methods. Eight paired cadaveric hip joints were skeletonized but retained the hip capsule. Capsular ROM restraint during controlled internal rotation (IR) and external rotation (ER) was measured before and after HRA, DM-THA, and conventional THA, with a posterior (right hips) and anterior capsulotomy (left hips). Results. Hip resurfacing provided a near-native ROM with between 5° to 17° increase in IR/ER ROM compared with the native hip for the different positions tested, which was a 9% to 33% increase. DM-THA generated a 9° to 61° (18% to 121%) increase in ROM. Conventional THA generated a 52° to 100° (94% to 199%) increase in ROM. Thus, for conventional THA, the capsule function that exerts a limit on ROM is lost. It is restored to some extent by DM-THA, and almost fully restored by hip resurfacing. In positions of low flexion/extension, the posterior capsulotomy provided more normal function than the anterior, possibly because the capsule was shortened during posterior repair. However, in deep flexion positions, the anterior capsulotomy functioned better. Conclusion. Native head-size and capsular repair preserves capsular function after arthroplasty. The anterior and posterior approach differentially affect postoperative biomechanical function of the capsular ligaments. Cite this article: Bone Joint J 2019;101-B:426–434


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. Results. More than 1,000 genes were differentially expressed in hip joint capsules between healthy controls and DDH. Both gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that extracellular matrix (ECM) modifications, muscle system processes, and cell proliferation were markedly influenced by the differentially expressed genes. Expression of Collagen Type I Alpha 1 Chain (COL1A1), COL3A1, matrix metalloproteinase-1 (MMP1), MMP3, MMP9, and MMP13 was downregulated in DDH, with the loss of collagen fibres in the joint capsule. Expression of transforming growth factor beta 1 (TGF-β1) was downregulated, while that of TGF-β2, Mothers against decapentaplegic homolog 3 (SMAD3), and WNT11 were upregulated in DDH, and alpha smooth muscle actin (αSMA), a key myofibroblast marker, showed marginal increase. In vitro studies showed that fibroblast proliferation was suppressed in DDH, which was associated with cell cycle arrest in G0/G1 and G2/M phases. Cell cycle regulators including Cyclin B1 (CCNB1), Cyclin E2 (CCNE2), Cyclin A2 (CCNA2), Cyclin-dependent kinase 1 (CDK1), E2F1, cell division cycle 6 (CDC6), and CDC7 were downregulated in DDH. Conclusion. DDH is associated with the loss of collagen fibres and fibroblasts, which may cause loose joint capsule formation. However, the degree of differentiation of fibroblasts to myofibroblasts needs further study. Cite this article: Bone Joint Res 2021;10(9):558–570


The Bone & Joint Journal
Vol. 95-B, Issue 6 | Pages 770 - 776
1 Jun 2013
Haversath M Hanke J Landgraeber S Herten M Zilkens C Krauspe R Jäger M

Our understanding of the origin of hip pain in degenerative disorders of the hip, including primary osteoarthritis, avascular necrosis and femoroacetabular impingement (FAI), is limited. We undertook a histological investigation of the nociceptive innervation of the acetabular labrum, ligamentum teres and capsule of the hip, in order to prove pain- and proprioceptive-associated marker expression. These structures were isolated from 57 patients who had undergone elective hip surgery (44 labral samples, 33 ligamentum teres specimens, 34 capsular samples; in 19 patients all three structures were harvested). A total of 15 000 histological sections were prepared that were investigated immunohistochemically for the presence of protein S-100, 68 kDa neurofilament, neuropeptide Y, nociceptin and substance P. The tissues were evaluated in six representative areas. Within the labrum, pain-associated free nerve ending expression was located predominantly at its base, decreasing in the periphery. In contrast, the distribution within the ligamentum teres showed a high local concentration in the centre. The hip capsule had an almost homogeneous marker expression in all investigated areas. This study showed characteristic distribution profiles of nociceptive and pain-related nerve fibres, which may help in understanding the origin of hip pain. Cite this article: Bone Joint J 2013;95-B:770–6


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 9 | Pages 1201 - 1209
1 Sep 2011
Peng K Hsu W Shih H Hsieh C Huang T Hsu RW Chang P

In this study of 41 patients, we used proteomic, Western blot and immunohistochemical analyses to show that several reactive oxygen species scavenging enzymes are expressed differentially in patients with primary osteoarthritis and those with non-loosening and aseptic loosening after total hip replacement (THR). The patients were grouped as A (n = 16, primary THR), B (n = 10, fixed THR but requiring revision for polyethylene wear) and C (n = 15, requiring revision due to aseptic loosening) to verify the involvement of the identified targets in aseptic loosening. When compared with Groups A and B, Group C patients exhibited significant up-regulation of transthyretin and superoxide dismutase 3, but down-regulation of glutathione peroxidase 2 in their hip synovial fluids. Also, higher levels of superoxide dismutase 2 and peroxiredoxin 2, but not superoxide dismutase 1, catalase and glutathione perioxidase 1, were consistently detected in the hip capsules of Group C patients. We propose that dysregulated reactive oxygen species-related enzymes may play an important role in the pathogenesis and progression of aseptic loosening after THR


Bone & Joint Research
Vol. 10, Issue 9 | Pages 594 - 601
24 Sep 2021
Karunaseelan KJ Dandridge O Muirhead-Allwood SK van Arkel RJ Jeffers JRT

Aims

In the native hip, the hip capsular ligaments tighten at the limits of range of hip motion and may provide a passive stabilizing force to protect the hip against edge loading. In this study we quantified the stabilizing force vectors generated by capsular ligaments at extreme range of motion (ROM), and examined their ability to prevent edge loading.

Methods

Torque-rotation curves were obtained from nine cadaveric hips to define the rotational restraint contributions of the capsular ligaments in 36 positions. A ligament model was developed to determine the line-of-action and effective moment arms of the medial/lateral iliofemoral, ischiofemoral, and pubofemoral ligaments in all positions. The functioning ligament forces and stiffness were determined at 5 Nm rotational restraint. In each position, the contribution of engaged capsular ligaments to the joint reaction force was used to evaluate the net force vector generated by the capsule.


Bone & Joint Open
Vol. 3, Issue 4 | Pages 291 - 301
4 Apr 2022
Holleyman RJ Lyman S Bankes MJK Board TN Conroy JL McBryde CW Andrade AJ Malviya A Khanduja V

Aims

This study uses prospective registry data to compare early patient outcomes following arthroscopic repair or debridement of the acetabular labrum.

Methods

Data on adult patients who underwent arthroscopic labral debridement or repair between 1 January 2012 and 31 July 2019 were extracted from the UK Non-Arthroplasty Hip Registry. Patients who underwent microfracture, osteophyte excision, or a concurrent extra-articular procedure were excluded. The EuroQol five-dimension (EQ-5D) and International Hip Outcome Tool 12 (iHOT-12) questionnaires were collected preoperatively and at six and 12 months post-operatively. Due to concerns over differential questionnaire non-response between the two groups, a combination of random sampling, propensity score matching, and pooled multivariable linear regression models were employed to compare iHOT-12 improvement.


The Bone & Joint Journal
Vol. 103-B, Issue 7 Supple B | Pages 53 - 58
1 Jul 2021
Lawrie CM Bechtold D Schwabe M Clohisy JC

Aims

The direct anterior approach (DAA) for total hip arthroplasty (THA) has potential advantages over other approaches and is most commonly performed with the patient in the supine position. We describe a technique for DAA THA with the patient in the lateral decubitus position and report the early clinical and radiological outcomes, the characteristics of the learning curve, and perioperative complications.

Methods

All primary DAA THAs performed in the lateral position by a single surgeon over a four-year period from the surgeon’s first case using the technique were identified from a prospectively collected database. Modified Harris Hip Scores (mHHS) were collected to assess clinical outcome, and routine radiological analysis was performed. Retrospective review of the medical records identified perioperative complications, the characteristics of the learning curve, and revisions.


The Bone & Joint Journal
Vol. 103-B, Issue 2 | Pages 321 - 328
1 Feb 2021
Vandeputte F Vanbiervliet J Sarac C Driesen R Corten K

Aims

Optimal exposure through the direct anterior approach (DAA) for total hip arthroplasty (THA) conducted on a regular operating theatre table is achieved with a standardized capsular releasing sequence in which the anterior capsule can be preserved or resected. We hypothesized that clinical outcomes and implant positioning would not be different in case a capsular sparing (CS) technique would be compared to capsular resection (CR).

Methods

In this prospective trial, 219 hips in 190 patients were randomized to either the CS (n = 104) or CR (n = 115) cohort. In the CS cohort, a medial based anterior flap was created and sutured back in place at the end of the procedure. The anterior capsule was resected in the CR cohort. Primary outcome was defined as the difference in patient-reported outcome measures (PROMs) after one year. PROMs (Harris Hip Score (HHS), Hip disability and Osteoarthritis Outcome Score (HOOS), and Short Form 36 Item Health Survey (SF-36)) were collected preoperatively and one year postoperatively. Radiological parameters were analyzed to assess implant positioning and implant ingrowth. Adverse events were monitored.


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 1 | Pages 32 - 35
1 Jan 2005
Diab M Clark JM Weis MA Eyre DR

In developmental dysplasia of the hip, a deficient acetabulum may be augmented by placing local autogenous iliac osseous graft, or the ilium itself, over the head of the femur with the expectation that the added bone will function as a bearing surface. We analysed this bone obtained en bloc during subsequent surgery which was performed for degenerative osteoarthritis in three patients at 6, 25 and 30 years after the initial augmentation procedure. In each patient, the augmentation comprised of red cancellous bone covered on its articulating surface by a distinct layer of white tissue. Microscopy of this tissue showed parallel rows of spindle-shaped cells lying between linearly arranged collagen bundles typical of joint capsule. Biochemical analysis showed type I collagen, the principal collagen of joint capsule and bone, with no significant quantity of type II collagen, the principal collagen of cartilage. While the added bone produced by acetabular augmentation was durable, histological and biochemical analyses suggested that it had not undergone cartilage metaplasia. The augmented acetabulum articulates with the head of the femur by means of an interposed hip joint capsule


The Bone & Joint Journal
Vol. 100-B, Issue 8 | Pages 1010 - 1017
1 Aug 2018
Jain S Magra M Dube B Veysi VT Whitwell GS Aderinto JB Emerton ME Stone MH Pandit HG

Aims

This study aimed to evaluate implant survival of reverse hybrid total hip arthroplasty (THA) at medium-term follow-up.

Patients and Methods

A consecutive series of 1082 THAs in 982 patients with mean follow-up of 7.9 years (5 to 11.3) is presented. Mean age was 69.2 years (21 to 94). Of these, 194 (17.9%) were in patients under 60 years, 663 (61.3%) in female patients and 348 (32.2%) performed by a trainee. Head size was 28 mm in 953 hips (88.1%) or 32 mm in 129 hips (11.9%). Survival analysis was performed and subgroups compared using log rank tests.


The Bone & Joint Journal
Vol. 99-B, Issue 1 | Pages 22 - 28
1 Jan 2017
Khan OH Malviya A Subramanian P Agolley D Witt JD

Aims

Periacetabular osteotomy is an effective way of treating symptomatic hip dysplasia. We describe a new minimally invasive technique using a modification of the Smith-Peterson approach.

We performed a prospective, longitudinal cohort study to assess for any compromise in acetabular correction when using this approach, and to see if the procedure would have a higher complication rate than that quoted in the literature for other approaches. We also assessed for any improvement in functional outcome.

Patients and Methods

From 168 consecutive patients (189 hips) who underwent acetabular correction between March 2010 and March 2013 we excluded those who had undergone previous pelvic surgery for DDH and those being treated for acetabular retroversion. The remaining 151 patients (15 men, 136 women) (166 hips) had a mean age of 32 years (15 to 56) and the mean duration of follow-up was 2.8 years (1.2 to 4.5). In all 90% of cases were Tönnis grade 0 or 1. Functional outcomes were assessed using the Non Arthritic Hip Score (NAHS), University of California, Los Angeles (UCLA) and Tegner activity scores.


The Bone & Joint Journal
Vol. 98-B, Issue 12 | Pages 1582 - 1588
1 Dec 2016
Dewar DC Lazaro LE Klinger CE Sculco PK Dyke JP Ni AY Helfet DL Lorich DG

Aims

We aimed to quantify the relative contributions of the medial femoral circumflex artery (MFCA) and lateral femoral circumflex artery (LFCA) to the arterial supply of the head and neck of the femur.

Materials and Methods

We acquired ten cadaveric pelvises. In each of these, one hip was randomly assigned as experimental and the other as a matched control. The MFCA and LFCA were cannulated bilaterally. The hips were designated LFCA-experimental or MFCA-experimental and underwent quantitative MRI using a 2 mm slice thickness before and after injection of MRI-contrast diluted 3:1 with saline (15 ml Gd-DTPA) into either the LFCA or MFCA. The contralateral control hips had 15 ml of contrast solution injected into the root of each artery. Next, the MFCA and LFCA were injected with a mixture of polyurethane and barium sulfate (33%) and their extra-and intra-arterial course identified by CT imaging and dissection.


The Bone & Joint Journal
Vol. 98-B, Issue 6 | Pages 730 - 735
1 Jun 2016
Bsat S Frei H Beaulé PE

The acetabular labrum is a soft-tissue structure which lines the acetabular rim of the hip joint. Its role in hip joint biomechanics and joint health has been of particular interest over the past decade. In normal hip joint biomechanics, the labrum is crucial in retaining a layer of pressurised intra-articular fluid for joint lubrication and load support/distribution. Its seal around the femoral head is further regarded as a contributing to hip stability through its suction effect. The labrum itself is also important in increasing contact area thereby reducing contact stress. Given the labrum’s role in normal hip joint biomechanics, surgical techniques for managing labral damage are continuously evolving as our understanding of its anatomy and function continue to progress. The current paper aims to review the anatomy and biomechanical function of the labrum and how they are affected by differing surgical techniques.

Take home message: The acetabular labrum plays a critical role in hip function and maintaining and restoring its function during surgical intervention remain an essential goal.

Cite this article: Bone Joint J 2016;98-B:730–5.


The Bone & Joint Journal
Vol. 97-B, Issue 4 | Pages 484 - 491
1 Apr 2015
van Arkel RJ Amis AA Cobb JP Jeffers JRT

In this in vitro study of the hip joint we examined which soft tissues act as primary and secondary passive rotational restraints when the hip joint is functionally loaded. A total of nine cadaveric left hips were mounted in a testing rig that allowed the application of forces, torques and rotations in all six degrees of freedom. The hip was rotated throughout a complete range of movement (ROM) and the contributions of the iliofemoral (medial and lateral arms), pubofemoral and ischiofemoral ligaments and the ligamentum teres to rotational restraint was determined by resecting a ligament and measuring the reduced torque required to achieve the same angular position as before resection. The contribution from the acetabular labrum was also measured. Each of the capsular ligaments acted as the primary hip rotation restraint somewhere within the complete ROM, and the ligamentum teres acted as a secondary restraint in high flexion, adduction and external rotation. The iliofemoral lateral arm and the ischiofemoral ligaments were primary restraints in two-thirds of the positions tested. Appreciation of the importance of these structures in preventing excessive hip rotation and subsequent impingement/instability may be relevant for surgeons undertaking both hip joint preserving surgery and hip arthroplasty.

Cite this article: Bone Joint J 2015; 97-B:484–91.


The Bone & Joint Journal
Vol. 97-B, Issue 8 | Pages 1056 - 1062
1 Aug 2015
Kanawati AJ Narulla RS Lorentzos P Facchetti G Smith A Stewart F

The aim of this cadaver study was to identify the change in position of the sciatic nerve during arthroplasty using the posterior surgical approach to the hip. We investigated the position of the nerve during this procedure by dissecting 11 formalin-treated cadavers (22 hips: 12 male, ten female). The distance between the sciatic nerve and the femoral neck was measured before and after dislocation of the hip, and in positions used during the preparation of the femur. The nerve moves closer to the femoral neck when the hip is flexed to > 30° and internally rotated to 90° (90° IR). The mean distance between the nerve and femoral neck was 43.1 mm (standard deviation (sd) 8.7) with the hip at 0° of flexion and 90° IR; this significantly decreased to a mean of 36.1 mm (sd 9.5), 28.8 mm (sd 9.8) and 19.1 mm (sd 9.7) at 30°, 60° and 90° of hip flexion respectively (p < 0.001). In two hips the nerve was in contact with the femoral neck when the hip was flexed to 90°.

This study demonstrates that the sciatic nerve becomes closer to the operative field during hip arthroplasty using the posterior approach with progressive flexion of the hip.

Cite this article: Bone Joint J 2015;97-B:1056–62.


The Bone & Joint Journal
Vol. 97-B, Issue 7 | Pages 899 - 904
1 Jul 2015
Arduini M Mancini F Farsetti P Piperno A Ippolito E

In this paper we propose a new classification of neurogenic peri-articular heterotopic ossification (HO) of the hip based on three-dimensional (3D) CT, with the aim of improving pre-operative planning for its excision.

A total of 55 patients (73 hips) with clinically significant HO after either traumatic brain or spinal cord injury were assessed by 3D-CT scanning, and the results compared with the intra-operative findings.

At operation, the gross pathological anatomy of the HO as identified by 3D-CT imaging was confirmed as affecting the peri-articular hip muscles to a greater or lesser extent. We identified seven patterns of involvement: four basic (anterior, medial, posterior and lateral) and three mixed (anteromedial, posterolateral and circumferential). Excellent intra- and inter-observer agreement, with kappa values > 0.8, confirmed the reproducibility of the classification system.

We describe the different surgical approaches used to excise the HO which were guided by the 3D-CT findings. Resection was always successful.

3D-CT imaging, complemented in some cases by angiography, allows the surgeon to define the 3D anatomy of the HO accurately and to plan its surgical excision with precision.

Cite this article: Bone Joint J 2015; 97-B:899–904.


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 10 | Pages 1298 - 1303
1 Oct 2008
Grose AW Gardner MJ Sussmann PS Helfet DL Lorich DG

The inferior gluteal artery is described in standard anatomy textbooks as contributing to the blood supply of the hip through an anastomosis with the medial femoral circumflex artery. The site(s) of the anastomosis has not been described previously. We undertook an injection study to define the anastomotic connections between these two arteries and to determine whether the inferior gluteal artery could supply the lateral epiphyseal arteries alone. From eight fresh-frozen cadaver pelvic specimens we were able to inject the vessels in 14 hips with latex moulding compound through either the medial femoral circumflex artery or the inferior gluteal artery. Injected vessels around the hip were then carefully exposed and documented photographically.

In seven of the eight specimens a clear anastomosis was shown between the two arteries adjacent to the tendon of obturator externus. The terminal vessel arising from this anastomosis was noted to pass directly beneath the posterior capsule of the hip before ascending the superior aspect of the femoral neck and terminating in the lateral epiphyseal vessels. At no point was the terminal vessel found between the capsule and the conjoined tendon. The medial femoral circumflex artery receives a direct supply from the inferior gluteal artery immediately before passing beneath the capsule of the hip.

Detailed knowledge of this anatomy may help to explain the development of avascular necrosis after hip trauma, as well as to allow additional safe surgical exposure of the femoral neck and head.


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.


The Bone & Joint Journal
Vol. 97-B, Issue 6 | Pages 734 - 740
1 Jun 2015
den Hartog YM Mathijssen NMC van Dasselaar NT Langendijk PNJ Vehmeijer SBW

Only limited data are available regarding the infiltration of local anaesthetic for total hip arthroplasty (THA), and no studies were performed for THA using the anterior approach.

In this prospective, randomised placebo-controlled study we investigated the effect of both standard and reverse infiltration of local anaesthetic in combination with the anterior approach for THA. The primary endpoint was the mean numeric rating score for pain four hours post-operatively. In addition, we recorded the length of hospital stay, the operating time, the destination of the patient at discharge, the use of pain medication, the occurrence of side effects and pain scores at various times post-operatively.

Between November 2012 and January 2014, 75 patients were included in the study. They were randomised into three groups: standard infiltration of local anaesthetic, reversed infiltration of local anaesthetic, and placebo. There was no difference in mean numeric rating score for pain four hours post-operatively (p = 0.87). There were significantly more side effects at one and eight hours post-operatively in the placebo group (p = 0.02; p = 0.03), but this did not influence the mobilisation of the patients. There were no differences in all other outcomes between the groups.

We found no clinically relevant effect when the infiltration of local anaesthetic with ropivacaine and epinephrine was used in a multimodal pain protocol for THA using the anterior approach.

Cite this article: Bone Joint J 2015; 97-B:734–40.