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The Journal of Bone & Joint Surgery British Volume
Vol. 81-B, Issue 6 | Pages 963 - 968
1 Nov 1999
Krettek C Stephan C Schandelmaier P Richter M Pape HC Miclau T

Intramedullary nailing of metaphyseal fractures may be associated with deformity as a result of instability after fixation. Our aim was to evaluate the clinical use of Poller screws (blocking screws) as a supplement to stability after fixation with statically locked intramedullary nails of small diameter.

We studied, prospectively, 21 tibial fractures, 10 in the proximal third and 11 in the distal third in 20 patients after the insertion of Poller screws over a mean period of 18.5 months (12 to 29).

All fractures had united. Healing was evident radiologically at a mean of 5.4 ± 2.1 months (3 to 12) with a mean varus-valgus alignment of −1.0° (−5 to 3) and mean antecurvatum-recurvatum alignment of 1.6° (−6 to 11). The mean loss of reduction between placement of the initial Poller screw and follow-up was 0.5° in the frontal plane and 0.4° in the sagittal plane. There were no complications related to the Poller screw.

The clinical outcome, according to the Karström-Olerud score, was not influenced by previous or concomitant injuries in 18 patients and was judged as excellent in three (17%), good in seven (39%), satisfactory in six (33%), fair in one (6%), and poor in one (6%).


Bone & Joint Open
Vol. 2, Issue 5 | Pages 338 - 343
21 May 2021
Harvey J Varghese BJ Hahn DM

Aims. Displaced distal radius fractures were investigated at a level 1 major trauma centre during the COVID-19 2020 lockdown due to the implementation of temporary changes in practice. The primary aim was to establish if follow-up at one week in place of the 72-hour British Orthopaedic Association Standards for Trauma & Orthopaedics (BOAST) guidance was safe following manipulation under anaesthetic. A parallel adaptation during lockdown was the non-expectation of Bier’s block. The secondary aim was to compare clinical outcomes with respect to block type. Methods. Overall, 90 patients were assessed in a cross-sectional cohort study using a mixed, retrospective-prospective approach. Consecutive sampling of 30 patients pre-lockdown (P1), 30 during lockdown (P2), and 30 during post-lockdown (P3) was applied. Type of block, operative status, follow-up, and complications were extracted. Primary endpoints were early complications (≤ one week). Secondary endpoints were later complications including malunion, delayed union or osteotomy. Results. In P1, 86.6% of patients were seen between days one to three, 26.7% in P2, and 56.7% in P3. There were no documented complications from days one to three. Operative rate was 35.5%, which did not vary significantly (p= 0.712). Primary endpoints occurred between day four to seven, and included one patient each period treated for plaster cast pain. Secondary endpoints in P1 included delayed union (one patient). During P2, this included malunion (one patient), a pressure sore (one patient) and ulnar cutaneous nerve symptoms (two patients). In P3, malunion was identified in one patient. Mean follow-up was six months (4 to 9) with union rate 96%. Change in block practice varied significantly (p =<0.05). The risk ratio of complications using regional block (Bier’s) over haematoma block was 0.65. Conclusion. Follow-up adaptations during lockdown did not adversely affect patient outcomes. Regional anaesthesia is gold standard for manipulation of displaced distal radial fractures. Cite this article: Bone Jt Open 2021;2(5):338–343


Bone & Joint Open
Vol. 2, Issue 7 | Pages 562 - 568
28 Jul 2021
Montgomery ZA Yedulla NR Koolmees D Battista E Parsons III TW Day CS

Aims. COVID-19-related patient care delays have resulted in an unprecedented patient care backlog in the field of orthopaedics. The objective of this study is to examine orthopaedic provider preferences regarding the patient care backlog and financial recovery initiatives in response to the COVID-19 pandemic. Methods. An orthopaedic research consortium at a multi-hospital tertiary care academic medical system developed a three-part survey examining provider perspectives on strategies to expand orthopaedic patient care and financial recovery. Section 1 asked for preferences regarding extending clinic hours, section 2 assessed surgeon opinions on expanding surgical opportunities, and section 3 questioned preferred strategies for departmental financial recovery. The survey was sent to the institution’s surgical and nonoperative orthopaedic providers. Results. In all, 73 of 75 operative (n = 55) and nonoperative (n = 18) providers responded to the survey. A total of 92% of orthopaedic providers (n = 67) were willing to extend clinic hours. Most providers preferred extending clinic schedule until 6pm on weekdays. When asked about extending surgical block hours, 96% of the surgeons (n = 53) were willing to extend operating room (OR) block times. Most surgeons preferred block times to be extended until 7pm (63.6%, n = 35). A majority of surgeons (53%, n = 29) believe that over 50% of their surgical cases could be performed at an ambulatory surgery centre (ASC). Of the strategies to address departmental financial deficits, 85% of providers (n = 72) were willing to work extra hours without a pay cut. Conclusion. Most orthopaedic providers are willing to help with patient care backlogs and revenue recovery by working extended hours instead of having their pay reduced. These findings provide insights that can be incorporated into COVID-19 recovery strategies. Level of Evidence: III. Cite this article: Bone Jt Open 2021;2(7):562–568


The Bone & Joint Journal
Vol. 106-B, Issue 10 | Pages 1100 - 1110
1 Oct 2024
Arenas-Miquelez A Barco R Cabo Cabo FJ Hachem A

Bone defects are frequently observed in anterior shoulder instability. Over the last decade, knowledge of the association of bone loss with increased failure rates of soft-tissue repair has shifted the surgical management of chronic shoulder instability. On the glenoid side, there is no controversy about the critical glenoid bone loss being 20%. However, poor outcomes have been described even with a subcritical glenoid bone defect as low as 13.5%. On the humeral side, the Hill-Sachs lesion should be evaluated concomitantly with the glenoid defect as the two sides of the same bipolar lesion which interact in the instability process, as described by the glenoid track concept. We advocate adding remplissage to every Bankart repair in patients with a Hill-Sachs lesion, regardless of the glenoid bone loss. When critical or subcritical glenoid bone loss occurs in active patients (> 15%) or bipolar off-track lesions, we should consider anterior glenoid bone reconstructions. The techniques have evolved significantly over the last two decades, moving from open procedures to arthroscopic, and from screw fixation to metal-free fixation. The new arthroscopic techniques of glenoid bone reconstruction procedures allow precise positioning of the graft, identification, and treatment of concomitant injuries with low morbidity and faster recovery. Given the problems associated with bone resorption and metal hardware protrusion, the new metal-free techniques for Latarjet or free bone block procedures seem a good solution to avoid these complications, although no long-term data are yet available. Cite this article: Bone Joint J 2024;106-B(10):1100–1110


Bone & Joint 360
Vol. 13, Issue 4 | Pages 40 - 42
2 Aug 2024

The August 2024 Research Roundup. 360. looks at: Effect of vitamin D deficiency on periprosthetic joint infection and complications after primary total joint replacement; Postoperative angiotensin receptor blocker use associated with decreased rates of manipulation under anaesthesia in patients undergoing total knee arthroplasty; Central sensitization: the missing link between psychological distress and poor outcome following primary total knee arthroplasty; Thromboprophylaxis for the trauma and orthopaedic surgeon; Life expectancy after treatment of metastatic bone disease: an international trend analysis


Bone & Joint Research
Vol. 13, Issue 6 | Pages 294 - 305
17 Jun 2024
Yang P He W Yang W Jiang L Lin T Sun W Zhang Q Bai X Sun W Guo D

Aims. In this study, we aimed to visualize the spatial distribution characteristics of femoral head necrosis using a novel measurement method. Methods. We retrospectively collected CT imaging data of 108 hips with non-traumatic osteonecrosis of the femoral head from 76 consecutive patients (mean age 34.3 years (SD 8.1), 56.58% male (n = 43)) in two clinical centres. The femoral head was divided into 288 standard units (based on the orientation of units within the femoral head, designated as N[Superior], S[Inferior], E[Anterior], and W[Posterior]) using a new measurement system called the longitude and latitude division system (LLDS). A computer-aided design (CAD) measurement tool was also developed to visualize the measurement of the spatial location of necrotic lesions in CT images. Two orthopaedic surgeons independently performed measurements, and the results were used to draw 2D and 3D heat maps of spatial distribution of necrotic lesions in the femoral head, and for statistical analysis. Results. The results showed that the LLDS has high inter-rater reliability. As illustrated by the heat map, the distribution of Japanese Investigation Committee (JIC) classification type C necrotic lesions exhibited clustering characteristics, with the lesions being concentrated in the northern and eastern regions, forming a hot zone (90% probability) centred on the N4-N6E2, N3-N6E units of outer ring blocks. Statistical results showed that the distribution difference between type C2 and type C1 was most significant in the E1 and E2 units and, combined with the heat map, indicated that the spatial distribution differences at N3-N6E1 and N1-N3E2 units are crucial in understanding type C1 and C2 necrotic lesions. Conclusion. The LLDS can be used to accurately measure the spatial location of necrotic lesions and display their distribution characteristics. Cite this article: Bone Joint Res 2024;13(6):294–305


Bone & Joint 360
Vol. 12, Issue 5 | Pages 30 - 34
1 Oct 2023

The October 2023 Shoulder & Elbow Roundup. 360. looks at: Arthroscopic capsular shift surgery in patients with atraumatic shoulder joint instability: a randomized, placebo-controlled trial; Superior capsular reconstruction partially restores native glenohumeral loads in a dynamic model; Gene expression in glenoid articular cartilage varies in acute instability, chronic instability, and osteoarthritis; Intra-articular injection versus interscalene brachial plexus block for acute-phase postoperative pain management after arthroscopic shoulder surgery; Level of pain catastrophizing rehab in subacromial impingement: secondary analyses from a pragmatic randomized controlled trial (the SExSI Trial); Anterosuperior versus deltopectoral approach for primary reverse total shoulder arthroplasty: a study of 3,902 cases from the Dutch National Arthroplasty Registry with a minimum follow-up of five years; Assessment of progression and clinical relevance of stress-shielding around press-fit radial head arthroplasty: a comparative study of two implants; A number of modifiable and non-modifiable factors increase the risk for elbow medial ulnar collateral ligament injury in baseball players: a systematic review


Bone & Joint Research
Vol. 13, Issue 4 | Pages 137 - 148
1 Apr 2024
Lu Y Ho T Huang C Yeh S Chen S Tsao Y

Aims. Pigment epithelium-derived factor (PEDF) is known to induce several types of tissue regeneration by activating tissue-specific stem cells. Here, we investigated the therapeutic potential of PEDF 29-mer peptide in the damaged articular cartilage (AC) in rat osteoarthritis (OA). Methods. Mesenchymal stem/stromal cells (MSCs) were isolated from rat bone marrow (BM) and used to evaluate the impact of 29-mer on chondrogenic differentiation of BM-MSCs in culture. Knee OA was induced in rats by a single intra-articular injection of monosodium iodoacetate (MIA) in the right knees (set to day 0). The 29-mer dissolved in 5% hyaluronic acid (HA) was intra-articularly injected into right knees at day 8 and 12 after MIA injection. Subsequently, the therapeutic effect of the 29-mer/HA on OA was evaluated by the Osteoarthritis Research Society International (OARSI) histopathological scoring system and changes in hind paw weight distribution, respectively. The regeneration of chondrocytes in damaged AC was detected by dual-immunostaining of 5-bromo-2'-deoxyuridine (BrdU) and chondrogenic markers. Results. The 29-mer promoted expansion and chondrogenic differentiation of BM-MSCs cultured in different defined media. MIA injection caused chondrocyte death throughout the AC, with cartilage degeneration thereafter. The 29-mer/HA treatment induced extensive chondrocyte regeneration in the damaged AC and suppressed MIA-induced synovitis, accompanied by the recovery of cartilage matrix. Pharmacological inhibitors of PEDF receptor (PEDFR) and signal transducer and activator of transcription 3 (STAT3) signalling substantially blocked the chondrogenic promoting activity of 29-mer on the cultured BM-MSCs and injured AC. Conclusion. The 29-mer/HA formulation effectively induces chondrocyte regeneration and formation of cartilage matrix in the damaged AC. Cite this article: Bone Joint Res 2024;13(4):137–148


Bone & Joint Research
Vol. 9, Issue 7 | Pages 429 - 439
1 Jul 2020
Tahir M Chaudhry EA Zaffar Z Anwar K Mamoon MAH Ahmad M Jamali AR Mehboob G

Aims. We hypothesized that the wide-awake local anaesthesia with no tourniquet (WALANT) technique is cost-effective, easy to use, safe, and reproducible, with a low learning curve towards mastery, having a high patient satisfaction rate. Furthermore, WALANT would be a suitable alternative for the austere and developing nation environments where lack of funds and resources are a common issue. Methods. This was a randomized control trial of 169 patients who required surgery for closed isolated distal radius fractures. The study was performed between March 2016 and April 2019 at a public sector level 1 trauma centre. General anaesthesia was used in 56 patients, Bier’s block in 58 patients, and WALANT in 55 patients. Data were collected on pre-, peri-, and postoperative parameters, clinical outcome, hospital costs, and patient satisfaction. One-way analysis of variance (ANOVA) was used with a p-value of 0.05 being significant. Results. Operations with WALANT proceeded sooner, and patients recovered faster, resulting in mean fewer missed working days (7.8 (SD 1.67)) compared with general anaesthesia (20.1 (SD 7.37)) or Bier’s block (14.1 (SD 7.65)) (p < 0.001). The WALANT patients did not develop complications, while the other patients did (p < 0.04). Clinical outcomes did not differ, nor did surgeon qualification affect clinical outcomes. Mean hospital costs were lower for WALANT ($428.50 (SD 77.71)) than for general anaesthesia ($630.63 (SD 114.77)) or Bier’s block ($734.00 (SD 37.54)) (p < 0.001). Patient satisfaction was also higher (p < 0.001). Conclusion. WALANT for distal radius fractures results in a faster recovery, is more cost-effective, has similar clinical outcomes, and has fewer complications than general anaesthesia or Bier's block. This makes WALANT an attractive technique in any setting, but especially in middle- and low-income countries. Cite this article: Bone Joint Res 2020;9(7):429–439


Bone & Joint Research
Vol. 12, Issue 3 | Pages 202 - 211
7 Mar 2023
Bai Z Shou Z Hu K Yu J Meng H Chen C

Aims. This study was performed to explore the effect of melatonin on pyroptosis in nucleus pulposus cells (NPCs) and the underlying mechanism of that effect. Methods. This experiment included three patients diagnosed with lumbar disc herniation who failed conservative treatment. Nucleus pulposus tissue was isolated from these patients when they underwent surgical intervention, and primary NPCs were isolated and cultured. Western blotting, reverse transcription polymerase chain reaction, fluorescence staining, and other methods were used to detect changes in related signalling pathways and the ability of cells to resist pyroptosis. Results. Western blot analysis confirmed the expression of cleaved CASP-1 and melatonin receptor (MT-1A-R) in NPCs. The cultured NPCs were identified by detecting the expression of CD24, collagen type II, and aggrecan. After treatment with hydrogen peroxide, the pyroptosis-related proteins NLR family pyrin domain containing 3 (NLRP3), cleaved CASP-1, N-terminal fragment of gasdermin D (GSDMD-N), interleukin (IL)-18, and IL-1β in NPCs were upregulated, and the number of propidium iodide (PI)-positive cells was also increased, which was able to be alleviated by pretreatment with melatonin. The protective effect of melatonin on pyroptosis was blunted by both the melatonin receptor antagonist luzindole and the nuclear factor erythroid 2–related factor 2 (Nrf2) inhibitor ML385. In addition, the expression of the transcription factor Nrf2 was up- or downregulated when the melatonin receptor was activated or blocked by melatonin or luzindole, respectively. Conclusion. Melatonin protects NPCs against reactive oxygen species-induced pyroptosis by upregulating the transcription factor Nrf2 via melatonin receptors. Cite this article: Bone Joint Res 2023;12(3):202–211


Bone & Joint Research
Vol. 13, Issue 2 | Pages 52 - 65
1 Feb 2024
Yao C Sun J Luo W Chen H Chen T Chen C Zhang B Zhang Y

Aims. To investigate the effects of senescent osteocytes on bone homeostasis in the progress of age-related osteoporosis and explore the underlying mechanism. Methods. In a series of in vitro experiments, we used tert-Butyl hydroperoxide (TBHP) to induce senescence of MLO-Y4 cells successfully, and collected conditioned medium (CM) and senescent MLO-Y4 cell-derived exosomes, which were then applied to MC3T3-E1 cells, separately, to evaluate their effects on osteogenic differentiation. Furthermore, we identified differentially expressed microRNAs (miRNAs) between exosomes from senescent and normal MLO-Y4 cells by high-throughput RNA sequencing. Based on the key miRNAs that were discovered, the underlying mechanism by which senescent osteocytes regulate osteogenic differentiation was explored. Lastly, in the in vivo experiments, the effects of senescent MLO-Y4 cell-derived exosomes on age-related bone loss were evaluated in male SAMP6 mice, which excluded the effects of oestrogen, and the underlying mechanism was confirmed. Results. The CM and exosomes collected from senescent MLO-Y4 cells inhibited osteogenic differentiation of MC3T3-E1 cells. RNA sequencing detected significantly lower expression of miR-494-3p in senescent MLO-Y4 cell-derived exosomes compared with normal exosomes. The upregulation of exosomal miR-494-3p by miRNA mimics attenuated the effects of senescent MLO-Y4 cell-derived exosomes on osteogenic differentiation. Luciferase reporter assay demonstrated that miR-494-3p targeted phosphatase and tensin homolog (PTEN), which is a negative regulator of the phosphoinositide 3-kinase (PI3K)/AKT pathway. Overexpression of PTEN or inhibition of the PI3K/AKT pathway blocked the functions of exosomal miR-494-3p. In SAMP6 mice, senescent MLO-Y4 cell-derived exosomes accelerated bone loss, which was rescued by upregulation of exosomal miR-494-3p. Conclusion. Reduced expression of miR-494-3p in senescent osteocyte-derived exosomes inhibits osteogenic differentiation and accelerates age-related bone loss via PTEN/PI3K/AKT pathway. Cite this article: Bone Joint Res 2024;13(2):52–65


Bone & Joint Research
Vol. 13, Issue 4 | Pages 169 - 183
15 Apr 2024
Gil-Melgosa L Llombart-Blanco R Extramiana L Lacave I Abizanda G Miranda E Agirre X Prósper F Pineda-Lucena A Pons-Villanueva J Pérez-Ruiz A

Aims. Rotator cuff (RC) injuries are characterized by tendon rupture, muscle atrophy, retraction, and fatty infiltration, which increase injury severity and jeopardize adequate tendon repair. Epigenetic drugs, such as histone deacetylase inhibitors (HDACis), possess the capacity to redefine the molecular signature of cells, and they may have the potential to inhibit the transformation of the fibro-adipogenic progenitors (FAPs) within the skeletal muscle into adipocyte-like cells, concurrently enhancing the myogenic potential of the satellite cells. Methods. HDACis were added to FAPs and satellite cell cultures isolated from mice. The HDACi vorinostat was additionally administered into a RC injury animal model. Histological analysis was carried out on the isolated supra- and infraspinatus muscles to assess vorinostat anti-muscle degeneration potential. Results. Vorinostat, a HDACi compound, blocked the adipogenic transformation of muscle-associated FAPs in culture, promoting myogenic progression of the satellite cells. Furthermore, it protected muscle from degeneration after acute RC in mice in the earlier muscle degenerative stage after tenotomy. Conclusion. The HDACi vorinostat may be a candidate to prevent early muscular degeneration after RC injury. Cite this article: Bone Joint Res 2024;13(4):169–183


Bone & Joint Research
Vol. 12, Issue 4 | Pages 259 - 273
6 Apr 2023
Lu R Wang Y Qu Y Wang S Peng C You H Zhu W Chen A

Aims. Osteoarthritis (OA) is a prevalent joint disorder with inflammatory response and cartilage deterioration as its main features. Dihydrocaffeic acid (DHCA), a bioactive component extracted from natural plant (gynura bicolor), has demonstrated anti-inflammatory properties in various diseases. We aimed to explore the chondroprotective effect of DHCA on OA and its potential mechanism. Methods. In vitro, interleukin-1 beta (IL-1β) was used to establish the mice OA chondrocytes. Cell counting kit-8 evaluated chondrocyte viability. Western blotting analyzed the expression levels of collagen II, aggrecan, SOX9, inducible nitric oxide synthase (iNOS), IL-6, matrix metalloproteinases (MMPs: MMP1, MMP3, and MMP13), and signalling molecules associated with nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. Immunofluorescence analysis assessed the expression of aggrecan, collagen II, MMP13, and p-P65. In vivo, a destabilized medial meniscus (DMM) surgery was used to induce mice OA knee joints. After injection of DHCA or a vehicle into the injured joints, histological staining gauged the severity of cartilage damage. Results. DHCA prevented iNOS and IL-6 from being upregulated by IL-1β. Moreover, the IL-1β-induced upregulation of MMPs could be inhibited by DHCA. Additionally, the administration of DHCA counteracted IL-1β-induced downregulation of aggrecan, collagen II, and SOX9. DHCA protected articular cartilage by blocking the NF-κB and MAPK pathways. Furthermore, DHCA mitigated the destruction of articular cartilage in vivo. Conclusion. We present evidence that DHCA alleviates inflammation and cartilage degradation in OA chondrocytes via suppressing the NF-κB and MAPK pathways, indicating that DHCA may be a potential agent for OA treatment. Cite this article: Bone Joint Res 2023;12(4):259–273


Bone & Joint Research
Vol. 11, Issue 11 | Pages 763 - 776
1 Nov 2022
Zhang Y Jiang B Zhang P Chiu SK Lee MH

Aims. Tissue inhibitors of metalloproteinases (TIMPs) are the endogenous inhibitors of the zinc-dependent matrix metalloproteinases (MMP) and A disintegrin and metalloproteinases (ADAM) involved in extracellular matrix modulation. The present study aims to develop the TIMPs as biologics for osteoclast-related disorders. Methods. We examine the inhibitory effect of a high affinity, glycosyl-phosphatidylinositol-anchored TIMP variant named ‘T1. PrαTACE. ’ on receptor activator of nuclear factor kappa-Β ligand (RANKL)-induced osteoclast differentiation. Results. Osteoclast progenitor cells transduced with T1. PrαTACE. failed to form tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts or exhibit bone-resorbing activity following treatment with RANKL. At the messenger RNA level, T1. PrαTACE. strongly attenuated expression of key osteoclast marker genes that included TRAP, cathepsin K, osteoclast stimulatory transmembrane protein (OC-STAMP), dendritic cell-specific transmembrane protein (DC-STAMP), osteoclast-associated receptor (OSCAR), and ATPase H. +. -transporting V0 subunit d2 (ATP6V0D2) by blocking autoamplification of nuclear factor of activated T cells 1 (NFATc1), the osteoclastogenic transcription factor. T1. PrαTACE. selectively extended p44/42 mitogen-activated protein kinase activation, an action that may have interrupted terminal differentiation of osteoclasts. Inhibition studies with broad-spectrum hydroxamate inhibitors confirmed that the anti-resorptive activity of T1. PrαTACE. was not reliant on its metalloproteinase-inhibitory activity. Conclusion. T1. PrαTACE. disrupts the RANKL-NFATc1 signalling pathway, which leads to osteoclast dysfunction. As a novel candidate in the prevention of osteoclastogenesis, the TIMP could potentially be developed for the treatment of osteoclast-related disorders such as osteoporosis. Cite this article: Bone Joint Res 2022;11(11):763–776


Bone & Joint Open
Vol. 4, Issue 5 | Pages 357 - 362
17 May 2023
Naathan H Ilo K Berber R Matar HE Bloch B

Aims. It is common practice for patients to have postoperative blood tests after total joint replacement (TJR). However, there have been significant improvements in perioperative care with arthroplasty surgery, and a drive to reduce the length of stay (LOS) and move towards day-case TJR. We should reconsider whether this intervention is necessary for all patients. Methods. This retrospective study included all patients who underwent a primary unilateral TJR at a single tertiary arthroplasty centre during a one-year period. Electronic medical records of 1,402 patients were reviewed for patient demographics, LOS, and American Society of Anesthesiologists (ASA) grade. Blood tests were examined to investigate the incidence of postoperative anaemia, electrolyte abnormalities, and incidence of acute kidney injury (AKI). Results. For total knee arthroplasties, preoperative (R = −0.22) and postoperative haemoglobin (R = 0.2) levels were both negatively correlated with LOS (p < 0.001). For all patients who had undergone a TJR, 19 patients (0.014%) required a blood transfusion postoperatively due to symptomatic anaemia. Risk factors identified were age, preoperative anaemia, and long-term aspirin use. Significant abnormal sodium levels were found in123 patients (8.7%). However, only 36 patients (2.6%) required intervening treatment. Risk factors identified were age, preoperative abnormal sodium level, and long-term use of non-steroidal anti-inflammatory drugs, angiotensin receptor blockers, and corticosteroids. Similarly, abnormal potassium levels were evident in 53 patients (3.8%), and only 18 patients (1.3%) required intervening treatment. Risk factors identified were preoperative abnormal potassium level, and long-term use of angiotensin-converting enzyme inhibitors and diuretics. The incidence of AKI was 4.4% (61 patients). Risk factors identified were age, increased ASA grade, preoperative abnormal sodium, and creatinine level. Conclusion. Routine blood tests after primary TJR is unnecessary for most patients. Blood tests should only be performed on those with identifiable risk factors such as preoperative anaemia and electrolyte abnormalities, haematological conditions, long-term aspirin use, and electrolyte-altering medications. Cite this article: Bone Jt Open 2023;4(5):357–362


Bone & Joint Research
Vol. 12, Issue 11 | Pages 677 - 690
1 Nov 2023
Wang X Jiang W Pan K Tao L Zhu Y

Aims. Currently, the effect of drug treatment for osteoporosis is relatively poor, and the side effects are numerous and serious. Melatonin is a potential drug to improve bone mass in postmenopausal women. Unfortunately, the mechanism by which melatonin improves bone metabolism remains unclear. The aim of this study was to further investigate the potential mechanism of melatonin in the treatment of osteoporosis. Methods. The effects of melatonin on mitochondrial apoptosis protein, bmal1 gene, and related pathway proteins of RAW264.7 (mouse mononuclear macrophage leukaemia cells) were analyzed by western blot. Cell Counting Kit-8 was used to evaluate the effect of melatonin on cell viability. Flow cytometry was used to evaluate the effect of melatonin on the apoptosis of RAW264.7 cells and mitochondrial membrane potential. A reactive oxygen species (ROS) detection kit was used to evaluate the level of ROS in osteoclast precursors. We used bmal1-small interfering RNAs (siRNAs) to downregulate the Bmal1 gene. We established a postmenopausal mouse model and verified the effect of melatonin on the bone mass of postmenopausal osteoporosis in mice via micro-CT. Bmal1 lentiviral activation particles were used to establish an in vitro model of overexpression of the bmal1 gene. Results. Melatonin promoted apoptosis of RAW264.7 cells and increased the expression of BMAL1 to inhibit the activation of ROS and phosphorylation of mitogen-activated protein kinase (MAPK)-p38. Silencing the bmal1 gene weakened the above effects of melatonin. After that, we used dehydrocorydaline (DHC) to enhance the activation of MAPK-p38, and the effects of melatonin on reducing ROS levels and promoting apoptosis of RAW264.7 cells were also blocked. Then, we constructed a mouse model of postmenopausal osteoporosis and administered melatonin. The results showed that melatonin improves bone loss in ovariectomized mice. Finally, we established a model of overexpression of the bmal1 gene, and these results suggest that the bmal1 gene can regulate ROS activity and change the level of the MAPK-p38 signalling pathway. Conclusion. Our study confirmed that melatonin promotes the apoptosis of RAW264.7 cells through BMAL1/ROS/MAPK-p38, and revealed the therapeutic effect and mechanism of melatonin in postmenopausal osteoporosis. This finding enriches BMAL1 as a potential target for the treatment of osteoporosis and the pathogenesis of postmenopausal osteoporosis. Cite this article: Bone Joint Res 2023;12(11):677–690


Bone & Joint Research
Vol. 13, Issue 4 | Pages 157 - 168
4 Apr 2024
Lin M Chen G Yu H Hsu P Lee C Cheng C Wu S Pan B Su B

Aims. Osteosarcoma is the most common primary bone malignancy among children and adolescents. We investigated whether benzamil, an amiloride analogue and sodium-calcium exchange blocker, may exhibit therapeutic potential for osteosarcoma in vitro. Methods. MG63 and U2OS cells were treated with benzamil for 24 hours. Cell viability was evaluated with the MTS/PMS assay, colony formation assay, and flow cytometry (forward/side scatter). Chromosome condensation, the terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay, cleavage of poly-ADP ribose polymerase (PARP) and caspase-7, and FITC annexin V/PI double staining were monitored as indicators of apoptosis. Intracellular calcium was detected by flow cytometry with Fluo-4 AM. The phosphorylation and activation of focal adhesion kinase (FAK) and signal transducer and activator of transcription 3 (STAT3) were measured by western blot. The expression levels of X-linked inhibitor of apoptosis protein (XIAP), B-cell lymphoma 2 (Bcl-2), B-cell lymphoma-extra large (Bcl-xL), SOD1, and SOD2 were also assessed by western blot. Mitochondrial status was assessed with tetramethylrhodamine, ethyl ester (TMRE), and intracellular adenosine triphosphate (ATP) was measured with BioTracker ATP-Red Live Cell Dye. Total cellular integrin levels were evaluated by western blot, and the expression of cell surface integrins was assessed using fluorescent-labelled antibodies and flow cytometry. Results. Benzamil suppressed growth of osteosarcoma cells by inducing apoptosis. Benzamil reduced the expression of cell surface integrins α5, αV, and β1 in MG63 cells, while it only reduced the expression of αV in U2OS cells. Benzamil suppressed the phosphorylation and activation of FAK and STAT3. In addition, mitochondrial function and ATP production were compromised by benzamil. The levels of anti-apoptotic proteins XIAP, Bcl-2, and Bcl-xL were reduced by benzamil. Correspondingly, benzamil potentiated cisplatin- and methotrexate-induced apoptosis in osteosarcoma cells. Conclusion. Benzamil exerts anti-osteosarcoma activity by inducing apoptosis. In terms of mechanism, benzamil appears to inhibit integrin/FAK/STAT3 signalling, which triggers mitochondrial dysfunction and ATP depletion. Cite this article: Bone Joint Res 2024;13(4):157–168


Bone & Joint Open
Vol. 1, Issue 9 | Pages 520 - 529
1 Sep 2020
Mackay ND Wilding CP Langley CR Young J

Aims. COVID-19 represents one of the greatest global healthcare challenges in a generation. Orthopaedic departments within the UK have shifted care to manage trauma in ways that minimize exposure to COVID-19. As the incidence of COVID-19 decreases, we explore the impact and risk factors of COVID-19 on patient outcomes within our department. Methods. We retrospectively included all patients who underwent a trauma or urgent orthopaedic procedure from 23 March to 23 April 2020. Electronic records were reviewed for COVID-19 swab results and mortality, and patients were screened by telephone a minimum 14 days postoperatively for symptoms of COVID-19. Results. A total of 214 patients had orthopaedic surgical procedures, with 166 included for analysis. Patients undergoing procedures under general or spinal anaesthesia had a higher risk of contracting perioperative COVID-19 compared to regional/local anaesthesia (p = 0.0058 and p = 0.0007, respectively). In all, 15 patients (9%) had a perioperative diagnosis of COVID-19, 14 of whom had fragility fractures; six died within 30 days of their procedure (40%, 30-day mortality). For proximal femoral fractures, our 30-day mortality was 18.2%, compared to 7% in 2019. Conclusion. Based on our findings, patients undergoing procedures under regional or local anaesthesia have minimal risk of developing COVID-19 perioperatively. Those with multiple comorbidities and fragility fractures have a higher morbidity and mortality if they contract COVID-19 perioperatively; therefore, protective care pathways could go some way to mitigate the risk. Our 30-day mortality of proximal femoral fractures was 18.2% during the COVID-19 pandemic in comparison to the annual national average of 6.1% in 2018 and the University Hospital Coventry average of 7% for the same period in 2019, as reported in the National Hip Fracture Database. Patients undergoing procedures under general or spinal anaesthesia at the peak of the pandemic had a higher risk of contracting perioperative COVID-19 compared to regional block or local anaesthesia. We question whether young patients undergoing day-case procedures under regional block or local anaesthesia with minimal comorbidities require fourteen days self-isolation; instead, we advocate that compliance with personal protective equipment, a negative COVID-19 swab three days prior to surgery, and screening questionnaire may be sufficient. Cite this article: Bone Joint Open 2020;1-9:520–529


The Bone & Joint Journal
Vol. 102-B, Issue 10 | Pages 1354 - 1358
3 Oct 2020
Noureddine H Vejsbjerg K Harrop JE White MJ Chakravarthy J Harrison JWK

Aims. In the UK, fasciectomy for Dupuytren’s contracture is generally performed under general or regional anaesthetic, with an arm tourniquet and in a hospital setting. We have changed our practice to use local anaesthetic with adrenaline, no arm tourniquet, and perform the surgery in a community setting. We present the outcome of a consecutive series of 30 patients. Methods. Prospective data were collected for 30 patients undergoing open fasciectomy on 36 digits (six having two digits affected), over a one-year period and under the care of two surgeons. In total, 10 ml to 20 ml volume of 1% lidocaine with 1:100,000 adrenaline was used. A standard postoperative rehabilitation regime was used. Preoperative health scores, goniometer measurements of metacarpophalangeal (MCP), proximal interphalangeal (PIP) contractures, and Unité Rheumatologique des Affections de la Main (URAM) scores were measured pre- and postoperatively at six and 12 weeks. Results. The mean preoperative contractures were 35.3° (0° to 90°) at the metacarpophalangeal joint (MCPJ), 32.5° (0° to 90°) at proximal interphalangeal joint (PIPJ) (a combined deformity of 67.8°). The mean correction was 33.6° (0° to 90°) for the MCPJ and 18.2° (0° to 70°) for the PIPJ leading to a combined correction of 51.8°. There was a complete deformity correction in 21 fingers (59.5%) and partial correction in 14 digits (37.8%) with no correction in one finger. The mean residual deformities for the partial/uncorrected group were MCP 4.2° (0° to 30°), and PIP 26.1° (0° to 85°). For those achieving a full correction the mean preoperative contracture was less particularly at the PIP joint (15.45° (0° to 60°) vs 55.33° (0° to 90°)). Mean preoperative URAM scores were higher in the fully corrected group (17.4 (4 to 31) vs 14.0 (0 to 28)), but lower at three months post-surgery (0.5 (0 to 3) vs 4.40 (0 to 18)), with both groups showing improvements. Infections occurred in two patients (three digits) and both were successfully treated with oral antibiotics. No other complications were noted. The estimated cost of a fasciectomy under local anaesthetic in the community was £184.82 per patient. The estimated hospital theatre costs for a fasciectomy was £1,146.62 under general anaesthetic (GA), and £1,085.30 under an axillary block. Conclusion. This study suggests that a fasciectomy performed under local anaesthetic with adrenaline and without an arm tourniquet and in a community setting is safe, and results in favourable outcomes regarding the degree of correction of contracture achieved, functional scores, and short-term complications. Local anaesthetic fasciectomy in a community setting achieves a saving of £961.80 for a GA and £900.48 for an axillary block per case. Cite this article: Bone Joint J 2020;102-B(10):1354–1358


Bone & Joint Research
Vol. 10, Issue 10 | Pages 693 - 703
1 Oct 2021
Wang X Wang D Xia P Cheng K Wang Q Wang X Lin Q Song J Chen A Li X

Aims. To evaluate the effect of ultrasound-targeted simvastatin-loaded microbubble destruction (UTMDSV) for alleviation of the progression of osteoarthritis (OA) in rabbits through modulation of the peroxisome proliferator-activated receptor (PPARγ). Methods. In vitro, OA chondrocytes were treated with ultrasound (US), US-targeted microbubble destruction (UTMD), simvastatin (SV), and UTMDSV on alternate days for four weeks. Chondrocytes were also treated with PPARγ inhibitor, PPARγ inhibitor+ UTMDSV, and UTMDSV. The cholesterol efflux rate and triglyceride levels were measured using an assay kit and oil red O staining, respectively. In vivo, the OA rabbits were treated with a single intra-articular injection of UTMD, SV, and UTMDSV every seven days for four weeks. Cartilage histopathology was assessed by safranin-O staining and the Mankin score. Total cholesterol (TC) and high-density lipoprotein-cholesterol (HDL-C) in rabbit knee synovial fluid were detected by enzyme-marker assay. Aggrecan, collagen II, and PPARγ expression levels were analyzed by Western blotting (WB). Results. In vitro, UTMDSV significantly increased the cholesterol efflux rate and aggrecan, collagen II, and PPARγ levels in OA chondrocytes; these effects were blocked by the PPARγ inhibitor. In vivo, UTMD. SV. significantly increased aggrecan, collagen II, PPARγ, and HDL-C levels, while TC levels and Mankin scores were decreased compared with the UTMD, SV, OA, and control groups. Conclusion. UTMDSV promotes cartilage extracellular matrix synthesis by modulating the PPARγ-mediated cholesterol efflux pathway in OA rabbits. Cite this article: Bone Joint Res 2021;10(10):693–703