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

Bone marrow stem cells (BMSCs) represent a collection of different cell types exhibiting stem cell characteristics but with notable heterogeneity. Among these, Skeletal Stem Cells (SSCs) represent a distinct matrix subgroup within BMSC and demonstrate a specialized capacity to facilitate bone formation, recruit chondrocytes, and contribute to hematopoiesis. SSCs play a pivotal role in orchestrating the functions of skeletal organs. Local ischemia has a significant impact on cell survival and function. We hypothesize that bone ischemia induces alterations in the differentiation potential of SSCs, consequently influencing changes in bone structure. We mechanically dissected tissue from the necrotic segment in the femoral head and more normal appearing areas from the femoral neck of specimens from 5 patients diagnosed with osteonecrosis of the femoral head (ONFH). These tissues were enzymatically broken down into individual cell suspensions. Utilizing fluorescence-activated cell sorting (FACS) based on specific surface markers indicative of human skeletal stem cells (hSSC), namely CD45- CD235a- CD31- TIE2- Podoplanin (PDPN)+ CD146- CD73+ CD164+, we isolated a distinct cell population. Subsequent in vitro evaluations, focusing on clonogenicity, osteogenesis, and chondrogenesis were conducted to assess the functional prowess of these SSCs. Moreover, we introduced BMP2 at a concentration of 50ng/ml to SSCs extracted from necrotic regions to potentially reinstate their osteogenic capabilities. We effectively isolated SSCs from both Necrotic and Non-necrotic Zones. We observed an augmented clonal formation capacity and chondrogenesis ability of SSCs isolated from the necrotic region, accompanied by a significant decline in osteogenic ability (P＜0.01), an effect not reversible even with the addition of BMP2. Ischemia adversely affects the proliferation and function of SSCs, resulting in a diminished osteogenic capacity and an insensitivity to BMP2, ultimately leading to structural alterations in bone tissue

Introduction. Ultra-high molecular weight polyethylene (UHMWPE) can provide local sustained delivery of therapeutics. 1,2. For example, it can deliver analgesics to address post-arthroplasty pain. 2. Given that several analgesics, such as bupivacaine (anesthetic) and tolfenamic acid (NSAID), were shown to possess antibacterial activity against Staphylococci, we hypothesize that analgesic-loaded UHMWPE can also yield antimicrobial effects, preventing the development of periprosthetic joint infections. Methods. Bupivacaine and tolfenamic acid were incorporated into UHMWPE via phase-separated compression molding. Drug release from the prepared samples was measured using high-performance liquid chromatography. Antibacterial studies of the obtained materials were conducted against methicillin-sensitive, and methicillin-resistant S. aureus, as well as S. epidermidis. Time-kill curves were obtained to characterize antimicrobial activity against planktonic bacteria. The dynamics of bacterial adhesion were assessed to characterize antibiofilm activity. Scanning electron microscopy (SEM) was used to visualize adherent bacteria. Anticolonizing activity of the tested materials was characterized using the “daughter cell” method as outlined elsewhere. 3. Cytotoxicity profile of drug-loaded UHMWPEs was evaluated using MG-63 osteoblast cell line. Results. The bupivacaine release rate generally increased with increasing drug loading (e.g. a model knee implant loaded with bupivacaine would release ca. 15–500 mg over 24 hours). While also proportional, drug release from UHMWPE loaded with tolfenamic acid was much lower. The bacterial viability curves showed that bupivacaine-loaded UHMWPE possessed moderate antibacterial activity against planktonic MSSA, MRSA, and S. epidermidis, slowing bacteria proliferation by up to 70%. Bupivacaine-loaded UHMWPE also mitigated biofilm formation and development during the initial culture period. SEM images confirmed the observed antibiofilm effect (Fig. 1). Tolfenamic acid-loaded UHMWPE allowed proliferation of planktonic bacteria. At the same time, these materials showed pronounced dose-dependent anticolonizing activity against tested strains, providing 3-log reduction of “daughter” cells. Bupivacaine- and tolfenamic acid-loaded UHMWPEs showed little-to-no cytotoxicity against osteoblasts. Discussion & Conclusions. We demonstrated for the first time that bupivacaine-loaded UHMWPE possesses dose-dependent antibacterial properties against planktonic and adherent MSSA, MRSA, and S. epidermidis – pathogens commonly associated with periprosthetic joint infections. Pronounced anticolonizing activity was evident for tolfenamic acid-loaded UHMWPE. Due to the low solubility of tolfenamic acid, the material's antibacterial effect against planktonic bacteria was lower. These results demonstrate that analgesic-loaded UHMWPE, used as a tool in multimodal pain management, can also yield antibacterial effects, opening an entirely new avenue for providing post-arthroplasty antibacterial prophylaxis. This pioneering approach has a potential to reduce patients' morbidity and mortality after arthroplasty. For any tables or figures, please contact the authors directly

Aims

Cemented hemiarthroplasty is an effective form of treatment for most patients with an intracapsular fracture of the hip. However, it remains unclear whether there are subgroups of patients who may benefit from the alternative operation of a modern uncemented hemiarthroplasty – the aim of this study was to investigate this issue. Knowledge about the heterogeneity of treatment effects is important for surgeons in order to target operations towards specific subgroups who would benefit the most.

Aims

The Birmingham Hip Resurfacing (BHR) was introduced in 1997 to address the needs of young active patients using a historically proven large-diameter metal-on-metal (MoM) bearing. A single designer surgeon’s consecutive series of 130 patients (144 hips) was previously reported at five and ten years, reporting three and ten failures, respectively. The aim of this study was to extend the follow-up of this original cohort at 25 years.

We studied nine patients who had had a transtrochanteric anterior rotational osteotomy, as developed by Sugioka, for osteonecrosis of the femoral head. At a mean of 2.5 years after the initial operation we carried out a histological study of the previously necrotic femoral head which had not shown collapse of the new primary weight-bearing site. In seven joints, there was proliferation of fibrous tissue in the dead trabeculae with vascular ingrowth. New bone covering dead trabeculae created the characteristic appearance of ‘creeping substitution’. However, these changes were limited and did not extend over the entire necrotic area. Dead bone remained in all the cases. In the other two heads we did not observe proliferation of fibrous tissue or vascular ingrowth, only dead trabeculae and dead bone marrow

Aims

To evaluate the effect of ultrasound-targeted simvastatin-loaded microbubble destruction (UTMD_SV) for alleviation of the progression of osteoarthritis (OA) in rabbits through modulation of the peroxisome proliferator-activated receptor (PPARγ).

Aims

The main advantage of 3D-printed, off-the-shelf acetabular implants is the potential to promote enhanced bony fixation due to their controllable porous structure. In this study we investigated the extent of osseointegration in retrieved 3D-printed acetabular implants.

Aims

Aseptic loosening is a leading cause of uncemented arthroplasty failure, often accompanied by fibrotic tissue at the bone-implant interface. A biological target, neutrophil extracellular traps (NETs), was investigated as a crucial connection between the innate immune system’s response to injury, fibrotic tissue development, and proper bone healing. Prevalence of NETs in peri-implant fibrotic tissue from aseptic loosening patients was assessed. A murine model of osseointegration failure was used to test the hypothesis that inhibition (through Pad4^-/- mice that display defects in peptidyl arginine deiminase 4 (PAD4), an essential protein required for NETs) or resolution (via DNase 1 treatment, an enzyme that degrades the cytotoxic DNA matrix) of NETs can prevent osseointegration failure and formation of peri-implant fibrotic tissue.

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.

Aims

The aim of this study was to evaluate blood metal ion levels, leucocyte profiles, and serum cytokines in patients with a total hip arthroplasty (THA) involving modular dual-mobility components.

Objectives

The injured anterior cruciate ligament (ACL) is thought to exhibit an impaired healing response, and attempts at surgical repair have not been successful. Connective tissue growth factor (CTGF) is reported to be associated with wound healing, probably through transforming growth factor beta 1 (TGF-β1).

Aims

Total hip arthroplasty (THA) has well known subjective benefits, but little is known objectively about the recovery of mobility in the early post-operative period.

Objectives

T-cells are considered to play an important role in the inflammatory response causing arthroplasty failure. The study objectives were to investigate the composition and distribution of CD4+ T-cell phenotypes in the peripheral blood (PB) and synovial fluid (SF) of patients undergoing revision surgery for failed metal-on-metal (MoM) and metal-on-polyethylene (MoP) hip arthroplasties, and in patients awaiting total hip arthroplasty.

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.

We present a series of 35 patients (19 men and 16 women) with a mean age of 64 years (36.7 to 75.9), who underwent total hip replacement using the ESKA dual-modular short stem with metal on-polyethylene bearing surfaces. This implant has a modular neck section in addition to the modular head. Of these patients, three presented with increasing post-operative pain due to pseudotumour formation that resulted from corrosion at the modular neck-stem junction. These patients underwent further surgery and aseptic lymphocytic vaculitis associated lesions were demonstrated on histological analysis.

Retrieval analysis of two modular necks showed corrosion at the neck-stem taper. Blood cobalt and chromium levels were measured at a mean of nine months (3 to 28) following surgery. These were compared with the levels in seven control patients (three men and four women) with a mean age of 53.4 years (32.1 to 64.1), who had an identical prosthesis and articulation but with a prosthesis that had no modularity at neck-stem junction. The mean blood levels of cobalt in the study group were raised at 50.75 nmol/l (5 to 145) compared with 5.6 nmol/l (2 to 13) in control patients.

Corrosion at neck-stem tapers has been identified as an important source of metal ion release and pseudotumour formation requiring revision surgery. Finite element modelling of the dual modular stem demonstrated high stresses at the modular stem-neck junction. Dual modular cobalt-chrome hip prostheses should be used with caution due to these concerns.

Four uncemented Symax hip stems were extracted at three weeks and nine, 13 and 32 months, respectively, for reasons other than loosening. The reasons for implant removal were infection in two cases, recurrent dislocation in one and acetabular fracture in one. They were analysed to assess the effect and behaviour of an electrochemically deposited, completely resorbable biomimetic BONIT-hydroxyapatite (HA) coating (proximal part) and a DOTIZE surface treatment (distal part) using qualitative histology, quantitative histomorphometry and scanning electron microscopy (SEM). Early and direct bone-implant bonding with signs of active remodelling of bone and the HA coating were demonstrated by histology and SEM. No loose BONIT-HA particles or delamination of the coating were observed, and there was no inflammation or fibrous interposition at the interface.

Histomorphometry showed bone-implant contact varying between 26.5% at three weeks and 83.5% at 13 months at the HA-coated implant surface. The bone density in the area of investigation was between 24.6% at three weeks and 41.1% at 32 months. The DOTIZE surface treatment of the distal part of the stem completely prevented tissue and bone apposition in all cases, thereby optimising proximal stress transfer.

The overall features of this implant, in terms of geometry and surface texture, suggest a mechanically stable design with a highly active biomimetic coating, resulting in rapid and extensive osseo-integration, exclusively in the metaphyseal part of the stem. Early remodelling of the HA coating does not seem to have a detrimental effect on short-term bone-implant coupling. There were no adverse effects identified from either the BONIT-HA coating or the DOTIZE surface treatment.

This preliminary study evaluates a combination of bone morphogenetic protein (BMP)-7 and non-vascularised autologous fibular grafting (AFG) for the treatment of osteonecrosis of the femoral head.

BMP-7/AFG combination was applied in seven pre-collapse femoral heads (five Steinberg stage II, two stage III) in six patients. Pre- and post-operative evaluation included clinical (Harris hip score (HHS), visual analogue scale (VAS) for pain) and radiological assessment (radiographs, quantitative CT) at a mean follow-up of 4 years (2 to 5.5).

A marked improvement of function (mean HHS increase of 49.2) and decrease of pain level (mean VAS decrease of 5) as well as retention of the sphericity of the femoral head was noted in five hips at the latest follow-up, while signs of consolidation were apparent from the third post-operative month. One patient (two hips) required bilateral total hip replacement at one year post-operatively. In the series as a whole, quantitative-CT evaluation revealed similar densities between affected and normal bone. Heterotopic ossification was observed in four hips, without compromise of the clinical outcome.

In this limited series AFG/BMP-7 combination proved a safe and effective method for the treatment of femoral head osteonecrosis, leading to early consolidation of the AFG and preventing collapse in five of seven hips, while the operative time and post-operative rehabilitation period were much shorter compared with free vascularised fibular grafts.

Cite this article: Bone Joint J 2014;96-B:31–5.

It has recently been reported that the transverse acetabular ligament (TAL) is helpful in determining the position of the acetabular component in total hip replacement (THR). In this study we used a computer-assisted navigation system to determine whether the TAL is useful as a landmark in THR. The study was carried out in 121 consecutive patients undergoing primary THR (134 hips), including 67 dysplastic hips (50%). There were 26 men (29 hips) and 95 women (105 hips) with a mean age of 60.2 years (17 to 82) at the time of operation. After identification of the TAL, its anteversion was measured intra-operatively by aligning the inferomedial rim of the trial acetabular component with the TAL using computer-assisted navigation. The TAL was identified in 112 hips (83.6%). Intra-observer reproducibility in the measurement of anteversion of the TAL was high, but inter-observer reproducibility was moderate.

Each surgeon was able to align the trial component according to the target value of the angle of anteversion of the TAL, but it was clear that methods may differ among surgeons. Of the measurements of the angle of anteversion of the TAL, 5.4% (6 of 112 hips) were outliers from the safe zone.

In summary, we found that the TAL is useful as a landmark when implanting the acetabular component within the safe zone in almost all hips, and to prevent it being implanted in retroversion in all hips, including dysplastic hips. However, as anteversion of the TAL may be excessive in a few hips, it is advisable to pay attention to individual variations, particularly in those with severe posterior pelvic tilt.

Cite this article: Bone Joint J 2014;96-B:306–11.

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.