Purpose: The immature skeleton demonstrates a remarkable capacity for correcting residual deformations after fracture. Classically, a residual angle of less than 25° can be tolerated for distal fractures of the forearm in children. The degree of remodelling depends on the distance between the fracture line and the epiphyseal line, the time remaining before closure of the growth cartilage, the residual angle after reduction, and is orientation in relation to the motion of the adjacent joint. The purpose of the present study was to better define the upper limit for acceptable deformation by age in order to determine when surgical correction is indicated. Material and methods: We reviewed the radiography files of 106 children with one or two fractures of the distal third of the forearm who had required closed reduction and brachio-antebrachial cast immobilisation. We measured the angle of deformity on the AP and lateral views after reduction, at six weeks and at three, six, and twelve months after trauma. The series included 79 boys and 27 girls, mean age 8.5 years (range 2.5 – 15). Twenty-five fractures were epiphyseal fractures and 81 were metaphyseal fractures. Results: Remodelling was nearly complete one year after fracture in most cases, especially in younger children and more distal fractures. Salter I or II fractures remodelled very rapidly, within four to five months of trauma. This remodelling was mainly achieved by apposition-resorption in the metaphyseal area by reorientation of the epiphyseal line. For the metaphyseal fractures, rate of remodelling was inversely proportional to the distance between the fracture line and the growth cartilage. Remodelling was greatly perturbed in case of open fracture requiring surgical reduction and in case of secondary infection. Discussion and conclusion: These data show that posterior inclination can be tolerated up to 30° for children under eight years of age and up to 25° between eight and ten years and up to 20° at prepuberty. Knowledge of these limits for distal fractures of the forearm is important for proper management and can be helpful in reducing the number of primary or secondary reductions under general or locoregional anaesthesia

Metabolic bone diseases, such as osteoporosis and osteopetrosis, result from an imbalanced bone remodeling process. In vitro bone models are often used to investigate either bone formation or resorption independently, while in vivo, these processes are coupled. Combining these processes in a co-culture is challenging as it requires finding the right medium components to stimulate each cell type involved without interfering with the other cell type's differentiation. Furthermore, differentiation stimulating factors often comprise growth factors in supraphysiological concentrations, which can overshadow the cell-mediated crosstalk and coupling.

To address these challenges, we aimed to recreate the physiological bone remodeling process, which follows a specific sequence of events starting with cell activation and bone resorption by osteoclasts, reversal, followed by bone formation by osteoblasts. We used a mineralized silk fibroin scaffold as a bone-mimetic template, inspired by bone's extracellular matrix composition and organization. Our model supported osteoclastic resorption and osteoblastic mineralization in the specific sequence that represents physiological bone remodeling.

We also demonstrated how culture variables, such as different cell ratios, base media, and the use of osteogenic/osteoclast supplements, and the application of mechanical load, can be adjusted to represent either a high bone turnover system or a self-regulating system. The latter system did not require the addition of osteoclastic and osteogenic differentiation factors for remodeling, therefore avoiding growth factor use.

Our in vitro model for bone remodeling has the potential to reduce animal experiments and advance in vitro drug development for bone remodeling pathologies like osteoporosis. By recreating the physiological bone remodeling cycle, we can investigate cell-cell and cell-matrix interactions, which are essential for understanding bone physiology and pathology. Furthermore, by tuning the culture variables, we can investigate bone remodeling under various conditions, potentially providing insights into the mechanisms underlying different bone disorders.

Abstract

Extracellular matrix (ECM) mechanical cues guide healing in tendons. Yet, the molecular mechanisms orchestrating the healing processes remain elusive. Appropriate tissue tension is essential for tendon homeostasis and tissue health. By mapping the attainment of tensional homeostasis, we aim to understand how ECM tension regulates healing. We hypothesize that diseased tendon returns to homeostasis only after the cells reach a mechanically gated exit from wound healing.

We engineered a 3D mechano-culture system to create tendon-like constructs by embedding patient-derived tendon cells into a collagen I hydrogel. Casting the hydrogel between posts anchored in silicone allowed adjusting the post stiffness. Under this static mechanical stimulation, cells remodel the (unorganized) collagen representing wound healing mechanisms. We quantified tissue-level forces using post deflection measurements. Secreted ECM was visualized by metabolic labelling with non-canonical amino acids, click chemistry and confocal microscopy. We blocked cell-mediated actin-myosin contractility using a ROCK inhibitor (Y27632) to explore the involvement of the Rho/ROCK pathway in tension regulation.

Tissue tension forces reached the same homeostatic level at day 21 independent of post compliance (p = 0.9456). While minimal matrix was synthesized in early phases of tissue formation (d3-d5), cell-deposited ECM was present in later stages (d7-d9). More ECM was deposited by tendon constructs cultured on compliant (1Nm) compared to rigid posts (p = 0.0017). Matrix synthesized by constructs cultured on compliant posts was less aligned (greater fiber dispersion, p = 0.0021). ROCK inhibition significantly decreased tissue-level tensional forces (p < 0.0001).

Our results indicate that tendon cells balance matrix remodeling and synthesis during tissue repair to reach an intrinsically defined “mechanostat setpoint” guiding tension-mediated exit from wound healing towards homeostasis. We are identifying specific molecular mechanosensors governing tension-regulated healing in tendon and investigate the Rho/ROCK system as their possible downstream pathway.

Although resurfacing hip replacement (RHR) is associated with a more demanding patient cohort, it has achieved survivorship approaching that of total hip replacement. Occasional failures from femoral neck fracture, or migration and loosening of the femoral head prosthesis have been observed, the causes of which are multifactorial, but predominately biomechanical in nature. Current surgical technique recommends valgus implant orientation and reduction of the femoral offset, reducing joint contact force and the femoral neck fracture risk. Radiographic changes including femoral neck narrowing and ‘pedestal lines’ around the implant stem are present in well performing hips, but more common in failing joints indicating that loosening may involve remodelling. The importance of prosthesis positioning on the biomechanics of the resurfaced joint was investigated using finite element analysis (FEA). Seven FE models were generated from a CT scan of a male patient: the femur in its intact state, and the resurfaced femur with either a 50mm or 52mm prosthesis head in. neutral orientation,. 10° of relative varus or. 10° of relative valgus tilt. The fracture risk during trauma was investigated for stumbling and a sideways fall onto the greater trochanter, by calculating the volume of yielding bone. Remodelling was quantified for normal gait, as the percentage volume of head and neck bone with over 75% post-operative change in strain energy density for an older patient, and 50% for a younger patient. Resurfacing with the smaller, 50mm prosthesis reduced the femoral offset by 3.0mm, 4.3mm and 5.1mm in varus, neutral and valgus orientations. When the 52mm head was used, the natural joint centre could be recreated rrespective of orientation, without notching the femoral neck. The 50mm head reduced the volume of yielding femoral neck bone relative to the intact femur in a linear correlation with femoral offset. When the natural femoral offset was recreated with the 52mm prosthesis, the predicted neck fracture load in stumbling was decreased by 9% and 20% in neutral and varus orientations, but remained in line with the intact bone when implanted with valgus orientation. This agrees with clinical experience and justifies currently recommended techniques. In oblique falling, the neck fracture load was again improved slightly when the femoral offset was reduced, and never fell below 97% of the natural case for the larger implant in all orientations. Predicted patterns of remodelling stimulus were consistent with radiographic clinical evidence. Stress shielding increased slightly from varus to valgus orientation, but was restricted to the superior femoral head in the older patient. Bone densification around the stem was predicted, indicating load transfer. Stress shielding only extended into the femoral neck in the young patient and where the femoral offset was reduced with the 50mm prosthesis. The increase in remodelling correlated with valgus orientation, or reduced femoral offset. The trend would become more marked if this were to reduce the joint contact force, but there was no such correlation for the 52mm prosthesis, when the natural femoral offset was recreated. Only in extreme cases would remodelling alone be sufficient to cause visible femoral neck narrowing, i.e. patients with a high metabolism and considerably reduced femoral offset, implying that other factors including damage from surgery or impingement, inflammatory response or retinacular blood supply interruption may also be involved in femoral neck adaptation. The results of this FEA biomechanical study justify current surgical techniques, indicating improved femoral neck fracture strength in stumbling with valgus position. Fracture risk under oblique falling was less sensitive to resurfacing. Furthermore, the results imply that reduced femoral offset could be linked to narrowing of the femoral neck; however the effects of positioning alone on bone remodelling may be insufficient to account for this. The study suggests that surgical technique should attempt to recreate the natural head centre, but still aim primarily for valgus positioning of the prosthesis, to reduce the femoral neck fracture risk

Knowledge of the premorbid glenoid shape and the morphological changes the bone undergoes in patients with glenohumeral arthritis can improve surgical outcomes in total and reverse shoulder arthroplasty. Several studies have previously used scapular statistical shape models (SSMs) to predict premorbid glenoid shape and evaluate glenoid erosion properties. However, current literature suggests no studies have used scapular SSMs to examine the changes in glenoid surface area in patients with glenohumeral arthritis. Therefore, the purpose of this study was to compare the glenoid articular surface area between pathologic glenoid cavities from patients with glenohumeral arthritis and their predicted premorbid shape using a scapular SSM. Furthermore, this study compared pathologic glenoid surface area with that from virtually eroded glenoid models created without influence from internal bone remodelling activity and osteophyte formation. It was hypothesized that the pathologic glenoid cavities would exhibit the greatest glenoid surface area despite the eroded nature of the glenoid and the medialization, which in a vault shape, should logically result in less surface area.

Computer tomography (CT) scans from 20 patients exhibiting type A2 glenoid erosion according to the Walch classification [Walch et al., 1999] were obtained. A scapular SSM was used to predict the premorbid glenoid shape for each scapula. The scapula and humerus from each patient were automatically segmented and exported as 3D object files along with the scapular SSM from a pre-operative planning software. Each scapula and a copy of its corresponding SSM were aligned using the coracoid, lateral edge of the acromion, inferior glenoid tubercule, scapular notch, and the trigonum spinae. Points were then digitized on both the pathologic humeral and glenoid surfaces and were used in an iterative closest point (ICP) algorithm in MATLAB (MathWorks, Natick, MA, USA) to align the humerus with the glenoid surface. A Boolean subtraction was then performed between the scapular SSM and the humerus to create a virtual erosion in the scapular SSM that matched the erosion orientation of the pathologic glenoid. This led to the development of three distinct glenoid models for each patient: premorbid, pathologic, and virtually eroded (Fig. 1). The glenoid surface area from each model was then determined using 3-Matic (Materialise, Leuven, Belgium).

Figure 1. (A) Premorbid glenoid model, (B) pathologic glenoid model, and (C) virtually eroded glenoid model.

The average glenoid surface area for the pathologic scapular models was 70% greater compared to the premorbid glenoid models (P < 0 .001). Furthermore, the surface area of the virtual glenoid erosions was 6.4% lower on average compared to the premorbid glenoid surface area (P=0.361).

The larger surface area values observed in the pathologic glenoid cavities suggests that sufficient bone remodelling exists at the periphery of the glenoid bone in patients exhibiting A2 type glenohumeral arthritis. This is further supported by the large difference in glenoid surface area between the pathologic and virtually eroded glenoid cavities as the virtually eroded models only considered humeral anatomy when creating the erosion.

For any figures or tables, please contact the authors directly.

The effect of high-fat diet and testosterone replacement therapy upon bone remodelling was investigated in orchiectomised male APOE-/- mice.

Mice were split in to three groups: sham surgery + placebo treatment (control, n=9), orchiectomy plus placebo treatment (n=8) and orchiectomy plus testosterone treatment (n=10). Treatments were administered via intramuscular injection once a fortnight for 17 weeks before sacrifice at 25 weeks of age. Tibiae were scanned ex-vivo using µCT followed by post-analysis histology and immunohistochemistry.

Previously presented µCT data demonstrated orchiectomised, placebo treated mice exhibited significantly reduced trabecular bone volume, number, thickness and BMD compared to control mice despite no significant differences in body weight. Trabecular parameters were rescued back to control levels in orchiectomised mice treated with testosterone. No significant differences were observed in the cortical bone.

Assessment of TRAP stained FFPE sections revealed no significant differences in osteoclast or osteoblast number along the endocortical surface. IHC assessment of osteoprotegerin (OPG) expression in osteoblasts is to be quantified alongside markers of osteoclastogenesis including RANK and RANKL.

Results support morphological analysis of cortical bone where no change in cortical bone volume or density between groups is in line with no significant change in osteoblast or osteoclast number and percentage across all three groups.

Future work will include further IHC assessment of bone remodelling and adiposity, as well as utilisation of mechanical testing to establish the effects of observed morphological differences in bone upon mechanical properties. Additionally, the effects of hormone treatments upon murine-derived bone cells will be investigated to provide mechanistic insights.

Introduction and Objective

Bone remodelling is a continuous process whereby osteocytes regulate the activity of osteoblasts and osteoclasts to repair loading-induced microdamage. While many in vitro studies have established the role of paracrine factors (e.g., RANKL/OPG) and cellular pathways involved in bone homeostasis, these techniques are generally limited to two-dimensional cell culture, which neglects the role of the native extracellular matrix in maintaining the phenotype of osteocyte. Recently, ex vivo models have been used to understand cell physiology and mechanobiology in the presence of the native matrix. Such approaches could be applicable to study the mechanisms of bone repair, whilst also enabling exploration of biomechanical cues. However, to date an ex vivo model of bone remodelling in cortical bone has not been developed. In this study, the objective was to develop an ex vivo model where cortical bone was subjected to cyclic strains to study the remodelling of bone.

Introduction

Chondrocytes are enveloped within the pericellular matrix (PCM), a structurally intricate network primarily demarcated by the presence of collagen type VI microfibrils and perlecan, resembling a protective cocoon. The PCM serves pivotal functions in facilitating cell mechanoprotection and mechanotransduction. The progression of osteoarthritis (OA) is associated with alterations in the spatial arrangement of chondrocytes, transitioning from single strings to double strings, small clusters, and eventually coalescing into large clusters in advanced OA stages. Changes in cellular patters coincide with structural degradation of the PCM and loss of biomechanical properties. Here, we systematically studied matrix metalloproteinases (MMPs), their distribution, activity, and involvement in PCM destruction, utilizing chondrocyte arrangement as an OA biomarker.

Introduction

Bone mineral density (BMD) is correlated with component migration and aseptic loosening after total knee arthroplasty (TKA). Older implant designs have demonstrated BMD loss up to 23% in the first 6 months after TKA, and continued to BMD decline at an average of 5% per year for as long as 2 years after TKA. The impact of component design and fixation method on BMD loss after TKA in modern implant designs has not been fully elucidated. The purpose of this study is to determine the effect of tibial tray thickness and fixation method (cemented versus cementless) on BMD loss patterns of the proximal tibia in two different modern TKA implant systems

Introduction and Objective

Global prevalence of obesity has risen almost three-fold between 1975 and 2016. Alongside the more well-known health implications of obesity such as cardiovascular disease, cancer and type II diabetes, is the effect of male obesity on testosterone depletion and hypogonadism. Hypogonadism is a well-known contributor to the acceleration of bone loss during aging, and obesity is the single biggest risk factor for testosterone deficiency in men. Understanding the micro and macro structural changes to bone in response to testosterone depletion in combination with a high fat ‘Western’ diet, will advance our understanding of the relationship between obesity and bone metabolism. This study investigated the impact of surgically induced testosterone depletion and subsequent testosterone treatment upon bone remodelling in mice fed a high fat diet.

Surgical failure, mainly caused by loosening implants, causes great mental and physical trauma to patients. Improving the physicochemical properties of implants to achieve favourable osseointegration will continue to be the focus of future research. Strontium (Sr), a trace element, is often incorporated into hydroxyapatite (HA) to improve its osteogenic activity. Our previous studies have shown that miR-21 can promote the osteogenic differentiation of mesenchymal stem cells by the PI3K/β-catenin pathway. The aim of this study is to fabricate a SrHA and miR-21 composite coating and it is expected to have a favorable bone healing capability.

Ti discs (20 mm diameter and one mm thickness for the in vitro section) and rods (four mm diameter and seven mm length for the in vivo section) were prepared by machining pure Ti. The Ti cylinders were placed in a Teflon-lined stainless-steel autoclave for treating at 150°C for 24 h to form SrHA layer. The miR-21 was encapsulated in nanocapsules. The miR-21 nanocapsules were mixed with CMCS powder to form a gel-like sample and uniformly coated on the SrHA modifed Ti. Osteoblast-like MG63 cells were cultured on SrHA and miR-21 modified Ti, Cell proliferation activity and osteogenesis-related gene expression were evaluated. A bone defect model was established with mature New Zealand to evaluate the osseointegration. Cylindrical holes (four mm in diameter) were created at the distal femur and tibial plateau. Each rabbit was implanted with four of the aforementioned rods (distal femur and tibial plateau of the hind legs). After implantation for one, two and three months, the rabbits were observed by X-ray and scanned using u-CT. Histological and Immunohistochemical analysis were performed to examine the osteogenic markers. A biomechanical push-in test was used to assess the bone-implant bonding strength.

Both SrHA nanoparticles with good superhydrophilicity and miR-21 nanocapsules with uniform sizes were distributed evenly on the surface of the Ti. In vitro experiments revealed that the composite coating was beneficial to osteoblast proliferation, differentiation and mineralization. In vivo evaluations demonstrated that this coating could not only promote the expression of angiogenic factor CD31 but also enhance the expression of osteoblastic genes to facilitate angio-osteogenesis. In addition, the composite coating also showed a decreased RANKL expression compared with the miR-21 coating. As a result, the SrHA/miR-21 composite coating promoted new bone formation and mineralization and thus enhanced osseointegration and bone-implant bonding strength.

A homogeneous SrHA and miR-21 composite coating was fabricated by generating pure Ti through a hydrothermal process, followed by adhering miR-21 nanocapsules. This coating combined the favorable physicochemical properties of SrHA and miR-21 that synergistically promoted angiogenesis, osteogenesis, osseointegration, bone mineralization and thus bone-implant bonding strength. This study provided a new strategy for surface modification of biomedical implants.

Aims

Hip displacement, common in patients with cerebral palsy (CP), causes pain and hinders adequate care. Hip reconstructive surgery (HRS) is performed to treat hip displacement; however, only a few studies have quantitatively assessed femoral head sphericity after HRS. The aim of this study was to quantitatively assess improvement in hip sphericity after HRS in patients with CP.

INTRODUCTION

Hip resurfacing offers a more bone conserving solution than total hip replacement (THR) but currently has limited clinical indications related to some poor design concepts and metal ion related issues. Other materials are currently being investigated based on their successful clinical history in THR such as Zirconia Toughened Alumina (ZTA, Biolox Delta, CeramTec, Germany) which has shown low wear rates and good biocompatibility but has previously only been used as a bearing surface in THR. A newly developed direct cementless fixation all-ceramic (ZTA) resurfacing cup offers a new solution for resurfacing however ZTA has a Young's modulus approximately 1.6 times greater than CoCr - such may affect the acetabular bone remodelling. This modelling study investigates whether increased stress shielding may occur when compared to a CoCr resurfacing implant with successful known clinical survivorship.

Introduction

Direct skeletal attachment of prosthetic limbs, commonly known as osseointegration (“OI”), is being investigated by our team with the goal of safely introducing this technology into the United States for human use. OI technology allows for anchorage of prosthetic devices directly to bone using an intramedullary stem. For OI to be effective and secure, bone ingrowth and remodeling around the implant must be achieved. Physicians need an effective way to measure bone remodeling in order to make informed decisions on prescribed loading. This work describes methodology that was developed that utilizes computed tomography (CT) imaging as a tool for analyzing bone remodeling around an osseointegrated implant.

Introduction

The purpose of this study was to evaluate the long term changes in bone mineral density (BMD) following implantation of a low-modulus composite femoral component designed to closely match the stiffness of the proximal femur and minimize stress shielding. Specifically, we asked: 1) How does BMD in the proximal femur change with time and with Gruen zone location; 2) Does BMD in the proximal femur stabilize after two years of implantation?

Aim

This study describes the histologic changes seen with a gentamicin-eluting synthetic bone graft substitute (BGS)(1) in managing bone defects after resection of chronic osteomyelitis (cOM).

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.

Background

Children suffering from primary bone cancer necessitating resection of growth plates, may suffer progressive leg length discrepancy, which can be attenuated with extendable prostheses. A serious complication is catastrophic implant failure. Over time, bone will remodel, altering the stress pattern in the implant. By using finite element analysis we can model different bone remodeling conditions to ascertain the effect that this will have on stress distribution and magnitude.

A finite element analysis was performed. Simplified computer generated models were designed of a cemented femoral Stanmore growing massive endoprosthesis. Three scenarios were designed, modelled on post-operative radiographs. Scenario 1 had a gap between the end of the femur and the implant collar, scenario 2 had no gap, but with no bone attachment into the collar, and scenario 3 had growth of the bone over the length of the collar with attachment. Physiological loading conditions were applied. The resultant stress in the implant for each scenario was measured, and compared to the strength of the material. Peak stresses were recorded at the stem-collar junction.

The maximum stress recorded in the implant in scenario 1 was 3104.2Mpa, compared to 1054.4Mpa in scenario 2, and 321.2Mpa in scenario 3.

Objectives

There remains conflicting evidence regarding cortical bone strength following bisphosphonate therapy. As part of a study to assess the effects of bisphosphonate treatment on the healing of rat tibial fractures, the mechanical properties and radiological density of the uninjured contralateral tibia was assessed.