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Bone & Joint Research
Vol. 13, Issue 12 | Pages 779 - 789
16 Dec 2024
Zou H Hu F Wu X Xu B Shang G An D Qin D Zhang X Yang A

Aims

The involvement of long non-coding RNA (lncRNA) in bone marrow mesenchymal stem cell (MSC) osteogenic differentiation during osteoporosis (OP) development has attracted much attention. In this study, we aimed to disclose how LINC01089 functions in human mesenchymal stem cell (hMSC) osteogenic differentiation, and to study the mechanism by which LINC01089 regulates MSC osteogenesis.

Methods

Quantitative reverse transcription polymerase chain reaction (RT-qPCR) and western blotting were performed to analyze LINC01089, miR-1287-5p, and heat shock protein family A (HSP70) member 4 (HSPA4) expression. The osteogenic differentiation of MSCs was assessed through alkaline phosphatase (ALP) activity, alizarin red S (ARS) staining, and by measuring the levels of osteogenic gene marker expressions using commercial kits and RT-qPCR analysis. Cell proliferative capacity was evaluated via the Cell Counting Kit-8 (CCK-8) assay. The binding of miR-1287-5p with LINC01089 and HSPA4 was verified by performing dual-luciferase reporter and RNA immunoprecipitation (RIP) experiments.


Bone & Joint Research
Vol. 13, Issue 12 | Pages 750 - 763
11 Dec 2024
Xie C Gong J Zheng C Zhang J Gao J Tian C Guo X Dai S Gao T

Aims

This meta-analysis and systematic review aimed to comprehensively investigate the effects of vitamin K supplementation on bone mineral density (BMD) at various sites and bone metabolism in middle-aged and older adults.

Methods

The databases of PubMed, Web of Science, and Cochrane Library were thoroughly searched from inception to July 2023.


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_18 | Pages 49 - 49
14 Nov 2024
Chen YS Lian WS Lin Y Wang F
Full Access

Introduction

Promoting bone mass homeostasis keeps skeleton away from osteoporosis. a-Ketoglutarate (a-KG) is an indispensable intermediate of tricarboxylic acid cycle (TCA) process for cellular energy production. a-KG mitigates cellular senescence, tissue degeneration, and oxidative stress. We investigated whether a-KG affected osteoblast activity or osteoporosis development.

Method

Serum and bone specimens were biopsied from 26 patients with osteoporosis or 24 patients without osteoporosis who required spinal surgery. Ovariectomized or aged mice were fed 0.25% or 0.75% a-KG in drinking water for 8 – 12 weeks ad libitum. Bone mineral density, trabecular/cortical bone microarchitecture, mechanical strength, bone formation, and osteoclastic erosion were investigated using mCT, material testing device, in vivo calcein labelling, and TRAP histochemical staining. Serum a-KG, osteocalcin, and TRAP5b levels were quantified using ELISA kits. Bone-marrow mesenchymal cells and macrophages were incubated osteogenic and osteoclastogenic media. Histone H3K27me3 levels and enrichment were investigated using immunoblotting and chromatin precipitation-PCR.


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_18 | Pages 124 - 124
14 Nov 2024
Lin Y Lian W Chen Y Wang F
Full Access

Introduction. Osteoporosis accounts for a major risk factor of fracture-associated disability or premature death in the elderly. Enhancement of bone anabolism for slowing osteoporosis is highly demanding. Exerkine fibronectin type III domain containing 5 (FNDC5) regulates energy metabolism, inflammation, and aging. This study was aimed to investigate whether Fndc5 signaling in osteoblasts changed estrogen deficiency-mediated bone loss or microarchitecture deterioration. Method. Female osteoblast-specific Fndc5 transgenic mice (Fndc5Tg), which overexpressed Fndc5 under the control of key osteoblast marker osteocalcin promoter, were given bilateral ovariectomy to induce estrogen deficiency-mediated osteoporosis. Bone mass, microstructures, and biomechanical properties were quantified using μCT imaging and material testing. Dynamic bone formation was traced using fluorescence calcein. Osteogenic differentiation and adipocyte formation of bone-marrow mesenchymal cells were investigated using von Kossa staining and Nile red staining, respectively. Serum osteocalcin, CTX-1 and TRAP5b levels were quantified using designated ELISA kits. Mitochondrial respiration was investigated using Seahorse Extracellular Flux Analyzer. Result. Fndc5Tg mice developed relatively higher bone mass and microarchitecture than wild-type mice. Fndc5 overexpression attenuated the losses of bone mineral density and trabecular network, including trabecular volume, thickness, and trabecular number, and improved cortical thickness and porosity in ovariectomized mice. Gain of Fndc5 function preserved biomechanical characteristics (maximum load, breaking force, and energy), serum bone formation marker osteocalcin levels, and bone formation rate, whereas it reduced serum bone resorption makers CTX-1 and TRAP5b levels, osteoclast overburden, and marrow adiposis. In vitro, Fndc5 reversed the estrogen deficiency-mediated mineralized matrix underproduction and adipocyte formation of bone-marrow mesenchymal cells, and inhibited osteoclast formation in osteoporotic bone. Mechanistically, Fndc5 activated AMPK signaling, promoting mitochondrial respiration and ATP production to enhance osteoblastic activity. Conclusion. Fndc5 signaling exerted bone-protective actions delaying estrogen deficiency-mediated osteoporosis. This study highlighted a new molecular remedial option for osteoporosis development by manipulating Fndc5 functions


The Bone & Joint Journal
Vol. 106-B, Issue 11 | Pages 1342 - 1347
1 Nov 2024
Onafowokan OO Jankowski PP Das A Lafage R Smith JS Shaffrey CI Lafage V Passias PG

Aims

The aim of this study was to investigate the impact of the level of upper instrumented vertebra (UIV) in frail patients undergoing surgery for adult spine deformity (ASD).

Methods

Patients with adult spinal deformity who had undergone T9-to-pelvis fusion were stratified using the ASD-Modified Frailty Index into not frail, frail, and severely frail categories. ASD was defined as at least one of: scoliosis ≥ 20°, sagittal vertical axis (SVA) ≥ 5 cm, or pelvic tilt ≥ 25°. Means comparisons tests were used to assess differences between both groups. Logistic regression analyses were used to analyze associations between frailty categories, UIV, and outcomes.


The Bone & Joint Journal
Vol. 106-B, Issue 11 | Pages 1257 - 1262
1 Nov 2024
Nowak LL Moktar J Henry P Dejong T McKee MD Schemitsch EH

Aims

We aimed to compare reoperations following distal radial fractures (DRFs) managed with early fixation versus delayed fixation following initial closed reduction (CR).

Methods

We used administrative databases in Ontario, Canada, to identify DRF patients aged 18 years or older from 2003 to 2016. We used procedural and fee codes within 30 days to determine which patients underwent early fixation (≤ seven days) or delayed fixation following CR. We grouped patients in the delayed group by their time to definitive fixation (eight to 14 days, 15 to 21 days, and 22 to 30 days). We used intervention and diagnostic codes to identify reoperations within two years. We used multivariable regression to compare the association between early versus delayed fixation and reoperation for all patients and stratified by age (18 to 60 years and > 60 years).


Aims

This study examined the relationship between obesity (OB) and osteoporosis (OP), aiming to identify shared genetic markers and molecular mechanisms to facilitate the development of therapies that target both conditions simultaneously.

Methods

Using weighted gene co-expression network analysis (WGCNA), we analyzed datasets from the Gene Expression Omnibus (GEO) database to identify co-expressed gene modules in OB and OP. These modules underwent Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and protein-protein interaction analysis to discover Hub genes. Machine learning refined the gene selection, with further validation using additional datasets. Single-cell analysis emphasized specific cell subpopulations, and enzyme-linked immunosorbent assay (ELISA), protein blotting, and cellular staining were used to investigate key genes.


The Bone & Joint Journal
Vol. 106-B, Issue 9 | Pages 957 - 963
1 Sep 2024
Baek CH Kim JG Kim BT

Aims

Favourable short-term outcomes have been reported following latissimus dorsi tendon transfer for patients with an irreparable subscapularis (SSC) tendon tear. The aim of this study was to investigate the long-term outcomes of this transfer in these patients.

Methods

This was a retrospective study involving 30 patients with an irreparable SSC tear and those with a SSC tear combined with a reparable supraspinatus tear, who underwent a latissimus dorsi tendon transfer. Clinical scores and active range of motion (aROM), SSC-specific physical examination and the rate of return to work were assessed. Radiological assessment included recording the acromiohumeral distance (AHD), the Hamada grade of cuff tear arthropathy and the integrity of the transferred tendon. Statistical analysis compared preoperative, short-term (two years), and final follow-up at a mean of 8.7 years (7 to 10).


Aims

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

Methods

In this study, 60 rats were included in a titanium rod implantation model and underwent subsequent guanylate cyclase treatment. Imaging, histology, and biomechanics were used to evaluate the osseointegration of rats in each group. First, the impact of VIT on bone integration in aged rats with iron overload was investigated. Subsequently, VIT was employed to modulate the differentiation of MC3T3-E1 cells and RAW264.7 cells under conditions of iron overload.


Bone & Joint Research
Vol. 13, Issue 8 | Pages 411 - 426
28 Aug 2024
Liu D Wang K Wang J Cao F Tao L

Aims

This study explored the shared genetic traits and molecular interactions between postmenopausal osteoporosis (POMP) and sarcopenia, both of which substantially degrade elderly health and quality of life. We hypothesized that these motor system diseases overlap in pathophysiology and regulatory mechanisms.

Methods

We analyzed microarray data from the Gene Expression Omnibus (GEO) database using weighted gene co-expression network analysis (WGCNA), machine learning, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to identify common genetic factors between POMP and sarcopenia. Further validation was done via differential gene expression in a new cohort. Single-cell analysis identified high expression cell subsets, with mononuclear macrophages in osteoporosis and muscle stem cells in sarcopenia, among others. A competitive endogenous RNA network suggested regulatory elements for these genes.


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_15 | Pages 44 - 44
7 Aug 2024
Raghu A Kapilan M Ibrahim M Mushtaq S Sherief T
Full Access

Introduction. Most common osteoporotic fracture. 20-30% of patients with OVFs are presented to hospital while 2.2 million remain undiagnosed, as diagnosis is usually opportunistic. 66,000 OVFs occur annually in the UK with increase by 18,000 cases a year until 2025. 20% chance of another OVF in next 12 months and 3 times risk of hip fracture. Acute painful OVFs poorly tolerated by infirm elderly patients, leading to significant morbidity and 8 times increase in age-adjusted mortality. Materials and Methods. Classify fracture severity and patents with ovfs in 12-month period. To assess follow-up status and if kyphoplasty was offered within 6 weeks as per NICE guidelines. To introduce Royal Osteoporosis Society and GIRFT guidelines on management of symptomatic osteoporotic vertebral fractures. Results. Total no. of patients- 62. Initial pain assessment=40. Pain assessed at ≤6 weeks- 21. Duration from decision to operate to kyphoplasty 8.7 weeks. 11% had kyphoplasty of which 50% noted improvement in pain. 11 deaths. Nearly similar findings to NoSH study. Conclusion. To improve pain assessment on admission of patients with acute osteoporotic vertebral fractures. To follow GIRFT guidelines for early assessment and intervention in patients with acute osteoporotic vertebral fractures to improve pain, mobility and early discharge from hospital. Conflicts of interest. None. Sources of funding. None


Bone & Joint 360
Vol. 13, Issue 4 | Pages 29 - 31
2 Aug 2024

The August 2024 Spine Roundup360 looks at: Laminectomy adjacent to instrumented fusion increases adjacent segment disease; Influence of the timing of surgery for cervical spinal cord injury without bone injury in the elderly: a retrospective multicentre study; Lumbar vertebral body tethering: single-centre outcomes and reoperations in a consecutive series of 106 patients; Machine-learning algorithms for predicting Cobb angle beyond 25° in female adolescent idiopathic scoliosis patients; Pain in adolescent idiopathic scoliosis; Teriparatide prevents surgery for osteoporotic vertebral compression fracture.


The Bone & Joint Journal
Vol. 106-B, Issue 7 | Pages 696 - 704
1 Jul 2024
Barvelink B Reijman M Smidt S Miranda Afonso P Verhaar JAN Colaris JW

Aims

It is not clear which type of casting provides the best initial treatment in adults with a distal radial fracture. Given that between 32% and 64% of adequately reduced fractures redisplace during immobilization in a cast, preventing redisplacement and a disabling malunion or secondary surgery is an aim of treatment. In this study, we investigated whether circumferential casting leads to fewer fracture redisplacements and better one-year outcomes compared to plaster splinting.

Methods

In a pragmatic, open-label, multicentre, two-period cluster-randomized superiority trial, we compared these two types of casting. Recruitment took place in ten hospitals. Eligible patients aged ≥ 18 years with a displaced distal radial fracture, which was acceptably aligned after closed reduction, were included. The primary outcome measure was the rate of redisplacement within five weeks of immobilization. Secondary outcomes were the rate of complaints relating to the cast, clinical outcomes at three months, patient-reported outcome measures (PROMs) (using the numerical rating scale (NRS), the abbreviated version of the Disabilities of the Arm, Shoulder and Hand (QuickDASH), and Patient-Rated Wrist/Hand Evaluation (PRWHE) scores), and adverse events such as the development of compartment syndrome during one year of follow-up. We used multivariable mixed-effects logistic regression for the analysis of the primary outcome measure.


Bone & Joint Research
Vol. 13, Issue 7 | Pages 315 - 320
1 Jul 2024
Choi YH Kwon TH Choi JH Han HS Lee KM

Aims

Achilles tendon re-rupture (ATRR) poses a significant risk of postoperative complication, even after a successful initial surgical repair. This study aimed to identify risk factors associated with Achilles tendon re-rupture following operative fixation.

Methods

This retrospective cohort study analyzed a total of 43,287 patients from national health claims data spanning 2008 to 2018, focusing on patients who underwent surgical treatment for primary Achilles tendon rupture. Short-term ATRR was defined as cases that required revision surgery occurring between six weeks and one year after the initial surgical repair, while omitting cases with simultaneous infection or skin necrosis. Variables such as age, sex, the presence of Achilles tendinopathy, and comorbidities were systematically collected for the analysis. We employed multivariate stepwise logistic regression to identify potential risk factors associated with short-term ATRR.


Bone & Joint Open
Vol. 5, Issue 6 | Pages 489 - 498
12 Jun 2024
Kriechling P Bowley ALW Ross LA Moran M Scott CEH

Aims

The purpose of this study was to compare reoperation and revision rates of double plating (DP), single plating using a lateral locking plate (SP), or distal femoral arthroplasty (DFA) for the treatment of periprosthetic distal femur fractures (PDFFs).

Methods

All patients with PDFF primarily treated with DP, SP, or DFA between 2008 and 2022 at a university teaching hospital were included in this retrospective cohort study. The primary outcome was revision surgery for failure following DP, SP, or DFA. Secondary outcome measures included any reoperation, length of hospital stay, and mortality. All basic demographic and relevant implant and injury details were collected. Radiological analysis included fracture classification and evaluation of metaphyseal and medial comminution.


Bone & Joint 360
Vol. 13, Issue 3 | Pages 35 - 36
3 Jun 2024

The June 2024 Spine Roundup360 looks at: Intraoperative navigation increases the projected lifetime cancer risk in patients undergoing surgery for adolescent idiopathic scoliosis; Intrawound vancomycin powder reduces delayed deep surgical site infections following posterior spinal fusion for adolescent idiopathic scoliosis; Characterizing negative online reviews of spine surgeons; Proximal junctional failure after surgical instrumentation in adult spinal deformity: biomechanical assessment of proximal instrumentation stiffness; Nutritional supplementation and wound healing: a randomized controlled trial.


Bone & Joint Open
Vol. 5, Issue 6 | Pages 457 - 463
2 Jun 2024
Coviello M Abate A Maccagnano G Ippolito F Nappi V Abbaticchio AM Caiaffa E Caiaffa V

Aims

Proximal femur fractures treatment can involve anterograde nailing with a single or double cephalic screw. An undesirable failure for this fixation is screw cut-out. In a single-screw nail, a tip-apex distance (TAD) greater than 25 mm has been associated with an increased risk of cut-out. The aim of the study was to examine the role of TAD as a risk factor in a cephalic double-screw nail.

Methods

A retrospective study was conducted on 112 patients treated for intertrochanteric femur fracture with a double proximal screw nail (Endovis BA2; EBA2) from January to September 2021. The analyzed variables were age, sex, BMI, comorbidities, fracture type, side, time of surgery, quality of reduction, pre-existing therapy with bisphosphonate for osteoporosis, screw placement in two different views, and TAD. The last follow-up was at 12 months. Logistic regression was used to study the potential factors of screw cut-out, and receiver operating characteristic curve to identify the threshold value.


Full Access

Osteoporosis can cause significant disability and cost to health services globally. We aim to compare risk fractures for both osteoporosis and fractures at the L1-L4 vertebrae (LV) and the neck of femurs (NOFs) in patients referred for DEXA scan in the North-West of England. Data was obtained from 31546 patients referred for DEXA scan in the North-West of England between 2004 and 2011. Demographic data was retrospectively analysed using STATA, utilising chi-squared and t-tests. Logistical models were used to report odds ratios for risk factors included in the FRAX tool looking for differences between osteoporosis and fracture risk at the LV and NOFs. In a study involving 2530 cases of LV fractures and 1363 of NOF fractures, age was significantly linked to fractures and osteoporosis at both sites, with a higher risk of osteoporosis at NOFs compared to LV. Height provided protection against fractures and osteoporosis at both sites, with a more pronounced protective effect against osteoporosis at NOFs. Weight was more protective for NOF fractures, while smoking increased osteoporosis risk with no site-specific difference. Steroids were unexpectedly protective for fractures at both sites, with no significant difference, while alcohol consumption was protective against osteoporosis at both sites and associated with increased LV fracture risk. Rheumatoid arthritis increased osteoporosis risk in NOFs and implied a higher fracture risk, though not statistically significant compared to LV. Results summarised in Table 1. Our study reveals that established osteoporosis and fracture risk factors impact distinct bony sites differently. Age and rheumatoid arthritis increase osteoporosis risk more at NOFs than LV, while height and steroids provide greater protection at NOFs. Height significantly protects LV fractures, with alcohol predicting them. Further research is needed to explore risk factors’ impact on additional bony sites and understand the observed differences’ pathophysiology. For any figures or tables, please contact the authors directly


The Bone & Joint Journal
Vol. 106-B, Issue 4 | Pages 365 - 371
1 Apr 2024
Ledford CK Shirley MB Spangehl MJ Berry DJ Abdel MP

Aims

Breast cancer survivors have known risk factors that might influence the results of total hip arthroplasty (THA) or total knee arthroplasty (TKA). This study evaluated clinical outcomes of patients with breast cancer history after primary THA and TKA.

Methods

Our total joint registry identified patients with breast cancer history undergoing primary THA (n = 423) and TKA (n = 540). Patients were matched 1:1 based upon age, sex, BMI, procedure (hip or knee), and surgical year to non-breast cancer controls. Mortality, implant survival, and complications were assessed via Kaplan-Meier methods. Clinical outcomes were evaluated via Harris Hip Scores (HHSs) or Knee Society Scores (KSSs). Mean follow-up was six years (2 to 15).


The Bone & Joint Journal
Vol. 106-B, Issue 4 | Pages 412 - 418
1 Apr 2024
Alqarni AG Nightingale J Norrish A Gladman JRF Ollivere B

Aims

Frailty greatly increases the risk of adverse outcome of trauma in older people. Frailty detection tools appear to be unsuitable for use in traumatically injured older patients. We therefore aimed to develop a method for detecting frailty in older people sustaining trauma using routinely collected clinical data.

Methods

We analyzed prospectively collected registry data from 2,108 patients aged ≥ 65 years who were admitted to a single major trauma centre over five years (1 October 2015 to 31 July 2020). We divided the sample equally into two, creating derivation and validation samples. In the derivation sample, we performed univariate analyses followed by multivariate regression, starting with 27 clinical variables in the registry to predict Clinical Frailty Scale (CFS; range 1 to 9) scores. Bland-Altman analyses were performed in the validation cohort to evaluate any biases between the Nottingham Trauma Frailty Index (NTFI) and the CFS.