The optimal treatment strategy for post-traumatic long bone non-unions is subject of an ongoing discussion. At the Maastricht University Medical Center (MUMC+) the induced membrane technique is used to treat post-traumatic long bone non-unions. This technique uses a multimodal treatment algorithm involving bone marrow aspirate concentrate (BMAC), the reamer-irrigator-aspirator (RIA) and P-15 bioactive peptide (iFactor, Cerapedics). Bioactive glass (S53P4 BAG, Bonalive) is added when infection is suspected. This study aims to objectify the effect of this treatment algorithm on the health-related quality of life (HRQoL) of patients with post-traumatic long bone non-unions. We hypothesized that HRQoL would improve after treatment.

From January 2020 to March 2023, consecutive patients who were referred to a multidisciplinary (trauma, orthopaedic and plastic surgery) non-union clinic at the MUMC+, The Netherlands, were evaluated using the Non-Union Scoring System (NUSS). The EQ-5D-5L questionnaire and the Lower Extremity Functional Scale (LEFS) were employed to obtain HRQoL outcomes both prior to and subsequent to surgery, with a follow-up at 6, 18 and 35 weeks.

Seventy-six patients were assessed at baseline (T0), with a mean NUSS of 40 (± 13 SD). Thirty-eight patients had their first follow-up, six weeks after surgery (T1). Thirty-one patients had a second follow-up at 18 weeks (T2), and twenty patients had the third follow-up at 35 weeks (T3). The EQ-5D index mean at baseline was 0.480, followed by an index of 0.618 at T1, 0.636 at T2, and 0.702 at T3. A significant difference was found in the HRQoL score between T0 and T1, as well as T2 and T3 (p<0.001; p=0.011). The mean LEFS significantly increased from 26 before intervention to 34, 39, and 43 after treatment (p<0.001; p=0.033; p=0.016).

This study demonstrated a significant improvement in the health-related quality of life of patients with post-traumatic long bone non-unions after the standardized treatment algorithm following the induced membrane technique.

Recent clinical studies on targeting nerve growth factor (NGF) in chronic low back pain and knee osteoarthritis have demonstrated efficient pain reduction in a short-term treatment regimen. However, the increased risk for the development of rapid progressive osteoarthritis at the required high drug dose remains a serious concern and prompts thorough analysis of the tissue distribution and role of NGF in degenerative musculoskeletal disorders. Here, we sought to investigate tissue distribution of NGF, its high affinity receptor TrkA and CD68-positive macrophages in human facet joint osteoarthritis of the lumbar spine.

Facet joint specimens (n=10) were harvested by facetectomy from patients undergoing elective lumbar intervertebral spine fusion. Facet joint osteoarthritis and presence of synovitis was graded using preoperative magnetic resonance imaging. Tissue distribution of NGF, TrkA and CD68 was determined using immunohistochemistry. Tissue degradation was graded on safranin-O-stained tissue sections. Association between imaging parameters and tissue distribution was determined using Pearson correlation analysis.

Synovitis was present in 6 cases and facet joints displayed moderate to severe radiological osteoarthritis (median Weishaupt grade; 2 [1.5–3]). NGF was expressed in 8 of 10 specimens. NGF was expressed in connective tissue, articular and fibrocartilage, but not bone tissue. Cartilaginous NGF expression was predominantly found in the extracellular matrix of superficial cartilage tissue with complete loss of proteoglycans, chondrocyte death and structural damage (fissures). Loss of cartilage proteoglycan staining alone did not display NGF immunoreactivitiy. NGF expression was not correlated with radiological osteoarthritis severity or presence of synovitis. NGF high affinity receptor TrkA was exclusively expressed in bone marrow tissues. Differential grades of bone marrow infiltration by CD68-positive macrophages were observed, yet these were not associated with NGF expression.

Targeting NGF in chronic low back pain and/or facet joint osteoarthritis might affect pathomechanisms in cartilaginous tissues and NGF signalling in the bone marrow compartment.

Mitochondrial dysfunction has been demonstrated in aging and osteoarthritic tissues. We investigated knee joints of prematurely aging mitochondrial DNA mutator mice (PolgD275A) to evaluate a relationship between mitochondrial dysfunction and osteoarthritis.

Cartilage damage was evaluated using OARSI histopathology grading and osteoclast numbers were quantified by tartrate-resistant acid phosphatase staining in wild type, heterozygous and homozygous PolgD275A mice. Subchondral cortical plate and epiphyseal trabecular bone structures were determined by micro-computed tomography. Apoptosis in cartilage and subchondral bone tissues was studied using an indirect TUNEL method.

Homozygous mutants displayed osteopenia of the epiphyseal trabecular bone and subchondral cortical plate in comparison to wild type and heterozygous mutants. Subchondral osteopenia was associated with a strong increase of osteoclast numbers (0.88±0.30/mm bone perimeter) compared to heterozygous (0.25±0.03/mm) and wild type mice (0.12±0.04/mm). Wild type mice as well as hetero- and homozygous mutants displayed low-grade cartilage degeneration due to loss of cartilage proteoglycans. In contrast, chondrocyte hypertrophy was more abundant in the homozygous mice. There were no differences in chondrocyte apoptosis rates between groups.

Prematurely ageing mtDNA mutator mice with or without further mechanic or metabolic stimuli might serve as a valuable model for further experimental studies on aging-induced osteoporotic OA phenotype.

Introduction

Histology remains the gold standard in morphometric and pathological analyses of osteochondral tissues in human and experimental bone and joint disease. However, histological tissue processing is laborious, destructive and only provides a two-dimensional image in a single anatomical plane. Micro computed tomography (μCT) enables non-destructive three-dimensional visualization and morphometry of mineralized tissues and, with the aid of contrast agents, soft tissues. In this study, we evaluated phosphotungstic acid-enhanced (PTA) μCT to visualize joint pathology in spine osteoarthritis.

Introduction

Elevated remodelling of subchondral bone and marrow tissues has been firmly established as diagnostic and prognostic radiological imaging marker for human osteoarthritis. While these tissues are considered as promising targets for disease-modifying OA drugs, the development of novel treatment approaches is complicated by the lack of knowledge whether similar tissue changes occur in rodent OA models and poor understanding of joint-specific molecular and cellular pathomechanisms in human OA. Here, we describe the establishment of a human OA explant model to address this crucial niche in translational preclinical OA research.

Introduction

Facet joint osteoarthritis (FJOA) is a prominent clinical hallmark of degenerative spine disorders. During disease progression, cartilage and subchondral bone tissues undergo increased turnover and remodeling. The structural changes to the subchondral tissue of FJOA have not been studied thus far. In this study, we performed a micro computed tomography (µCT) study of the subchondral cortical plate (SCP) and trabecular bone (STB) in FJOA and determined osteoarthritis-specific alterations.

Introduction

Augmentation of spinal fusion using bone grafts is largely mediated by the osteoinductive potential of mesenchymal stem cells (MSC) that reside in cancellous bone. Iliac crest (IC) is a common autograft, but its use presents an increased risk for donor-site pain, morbidity and infection. Degenerative facet joints (FJ) harvested during facetectomy might servce as alternative local grafts. In this study, we conducted an intra-individual comparison of the osteogenic potential of MSC from both sources.

Background

Bio-Active Glass (BAG) is a promising bone graft substitute for large bone defect reconstruction because of its favourable osteoconductive, antibacterial and angiogenic properties. Potentially, it could also mechanically reinforce the defect, thus making it suitable for load-bearing defects. However, the mechanical properties of the reconstructive layer consisting of BAG/bone allograft mixtures are unknown. The goals of this study therefore were, first, to measure the mechanical properties of different BAG/bone graft mixtures and, second, to investigate to what extent such mixtures could reinforce distal tibial defects using micro-FE analysis and high-resolution CT scans.

Background

Implant stability and is an important factor for adequate bone remodelling and both are crucial in the long-term clinical survival of total hip arthroplasty (THA). Assessment of early bone remodelling on X-rays during the first 2 years post-operatively is mandatory when stepwise introduction of a new implant is performed. Regardless of fixation type (cemented or cementless), early acetabular component migration is usually the weakest link in THA, eventually leading to loosening. Over the past years, a shift towards uncemented cup designs has occurred. Besides the established hydroxyapatite (HA) coated uncemented cups which provide ongrowth of bone, new uncemented implant designs stimulating ingrowth of bone have increased in popularity. These cups initiate ingrowth of bone into the implant by their open metallic structure with peripheral pores, to obtain a mechanical interlock with the surrounding bone, thereby stabilising the prosthesis in an early stage after implantation. This retrospective study assessed bone remodelling, osseointegration and occurrence of radiolucency around a new ingrowth philosophy acetabular implant.

Chronic osteomyelitis is historically treated in a two stage fashion with antibiotic-loaded polymethylmethacrylate (PMMA) as local antibacterial therapy. However, two-stage surgeries are associated with high morbidity, long hospitalization and high treatment costs. In recent years new biomaterials were developed that allow to change this treatment algorithm. S53P4 bioactive glass is such a novel biodegradable antibacterial bone graft substitute that enables a one-stage surgery in local treatment of chronic osteomyelitis. This study aimed to explore the eradication of infection and bone healing capacities of S53P4 bioactive glass in clinical practice.

In this prospective longitudinal outcome study, clinical applicability of S53P4 bioactive glass in treatment of patients with chronic osteomyelitis was assessed. All patients with clinically, haematologically and radiologically evident chronic osteomyelitis were included. All patients were treated with an extensive debridement surgery, S53P4 bioactive glass implantation and systemic antibiotic administration. Primary endpoint of this study is eradication of infection. During follow-up eradication was analysed based on clinical outcomes, blood samples (inflammatory parameters) and radiological outcomes. The secondary endpoint, bone healing, is assessed using conventional radiographic images of the treated region.

Between 2011 and 2016, 25 patients were included in this study, with a mean follow-up of 23 months (range 4 – 57). Hospital stay was short with a mean of 18 days (range 4 – 40) and patients required an average of 1,4 surgeries (range 1 – 4). The inflammatory parameter C-reactive protein (CRP) showed a normalization after a mean duration of 46 days (range 0 – 211). At the end of follow-up haematological and clinical outcomes showed eradication of infection in 24 (96%) of all patients. Radiologically none of all patients showed persisting signs of infection and bone healing was observed in 22 (88%) patients based on changes on conventional radiographic images. One patient had a persistent infection without any bone healing, this patient had an infected non-union prior to surgery. There were two other patients with an initial infected non-union fracture which was not consolidated at last follow-up, although they had successful infection treatment. Another patient had a femoral fracture after surgery that needed additional surgery which did not interfere with eradication of infection. Four (16%) of all patients had initial wound healing problems related to compromised skin and/or soft tissue prior to surgery.

Based on the results of our clinical experience, S53P4 bioactive glass can successfully be used in a one-stage procedure for treatment of chronic osteomyelitis. Eradication of infection was successful in almost all patients and so far no patients required a second surgery due to infection recurrence. Bone healing (incorporation of the bioactive glass) was seen in all patients except for the patients with an initial infected non-union fracture. As a consequence of these results, we changed our institutional protocol for treatment of chronic osteomyelitis to a one-stage approach instead of a two-step approach.

Summary Statement

Cross-talk between cells from immune and bone system might play a role in molecular regulation of subchondral bone sclerosis in osteoarthritis. Macrophages, B-lymphocytes and tartrate-resistant acid phosphatase activity are specifically increased in sclerotic subchondral bone of patients with knee osteoarthritis.