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

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.

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.

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

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

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.

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 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.

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.

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).

Despite the generally inferior clinical performance of acetabular prostheses as compared to the femoral implants, the causes of acetabular component loosening and the extent to which mechanical factors play a role in the failure mechanism are not clearly understood yet. The study was aimed at investigating the load transfer and bone remodelling around the uncemented acetabular prosthesis.

The 3-D FE model of a natural right hemi-pelvis was developed using CT-scan data. The same bone was implanted with two uncemented hemispherical acetabular components, one metallic (CoCrMo alloy) and the other ceramic (Biolox delta), with 54 mm outer diameter and 48 mm bearing diameter. The FE models of the implanted pelvis (containing ∼116000 quadratic tetrahedrals) were generated using a submodelling approach, which were based on an overall full model of implanted pelvis (containing ∼217600 quadratic tetrahedrals) acted upon by hip joint force and twenty one muscle forces. The apparent density (ρ in g cm⁻³) of each cancellous bone element was calculated using linear calibration of CT numbers of bone, from which the Young's modulus (E in MPa) was determined using the relationship, E = 2017.3 ρ^2.46 [1]. Implant-bone interface conditions, fully bonded and debonded with friction coefficient μ = 0.5, were simulated using contact elements. Applied loading conditions consist of two load cases during a gait cycle, corresponding to 13% and 52% of the walking cycle. Fixed constraints were prescribed at the pubis and at the sacroiliac joint. The bone remodelling algorithm was based on strain energy based site-specific formulation [2]. The FE analysis, in combination with the bone remodelling simulation, was performed using ANSYS FE software.

The predicted changes in peri-prosthetic bone density were similar for the metallic and the ceramic implant. For debonded implant-bone interface, stress shielding led to ∼20% reductions in bone density at supero-anterior, infero-anterior and posterior part of the acetabulum (Fig. 1). However, bone apposition was observed at the supero-posterior part of the acetabulum, where implantation led to ∼60% increase in bone density (Fig. 1). The effect of bone resorption was higher for the fully bonded implant-bone interface, wherein bone density reductions of 20–50% were observed in the cancellous bone underlying the implant (Fig. 1), which is indicative of implant loosening over time. However, implantation led to an increase in bone density around the acetabular rim for both the interface conditions (Fig. 1). These results are well corroborated by the earlier studies [3, 4]. Implantation with a ceramic component resulted in 2–7% increase in bone density at supero-posterior part of the acetabulum as compared to the metallic component, for the debonded interface condition. Considering better wear resistant properties and absence of metal ion release, results of this study suggest that the ceramic component might be a viable alternative to the metallic prosthesis.

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?

Purpose

The study aim was to assess how the periprosthetic bone density of the MiniHip™ changed in the course of the first year. Is there a correlation between the decrease in bone density with CCD angle or stem size? Are there other variables influencing the changes in bone density?

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.

Hip Resurfacing (HR) is nowadays widely used as an alternative to Total Hip Replacement (THR), especially for the young and active patients. Because of the more physiological distribution of the load in the femur, this technique is particularly known to reduce bone loss due to stress shielding behaviour, a major problem encountered with THA. Different computational studies have analysed the performance of HR prostheses. Therefore, the purpose of this study is to apply a computational approach, in fact a bone remodelling analysis, in order to investigate its application to evaluate the bone structure changes postoperatively.

A Finite Element model was developed of a femur with HR prosthesis. The model was reconstructed starting with the femur medical images, and then the prosthesis was positioned in the clinical implantation angle (5° valgus). A cement mantle thickness of 1mm was included. Then a Finite Element Analysis in combination with a bone remodelling model (bone material properties) was performed. The results obtained predict as there is a certain bone loss in the superolateral and inferior medial zone. Additional bone material apposition is locally found with the aim of fixing the implant stem on the medial side, but also a remarkable distal ingrowth around the stem tip. All these findings are in good qualitative agreement with clinical observations.

We conclude that the numerical simulation used in this study is a useful tool in predicting bone remodelling inside a cemented HR prosthesis. This kind of methodologies will help on the design of devices, surgical techniques, etc.

Most of researches related to osteoporosis emphasized on trabecular bone loss. However, cortical bone has a prominent role on bone strength determined by bone quality, such as 2D or 3D geometry and microstructure of bone, not only density.[1] The focal thinning of cortical bone associated with aging in post-menopausal osteoporotic bone in the proximal femur may predispose a hip to fracture.[2, 3] As the trabecular bone is lost with progression of osteoporosis, the remaining cortical bone take more predominant role on bone strength.[4] To date, no effective osteoporotic agent was demonstrated to enhance both cortical geometric change and bone strength. Herein, we investigate the effect of Teriparatide (rhPTH(1–34)) on cortical bone at femoral diaphysis in OVX rat model.

Twenty 12-week-old, female Sprague Dawley rats were used in this study. Bilateral ovariectomies were performed in 16 animals and randomly divided to three groups as control (N=6), OVX (N=6) and treatment group after OVX (OVX+F) by teriparatide (N=8). After twelve weeks of intervention, all rats were euthanized and right femurs and L5 vertebrae were extracted for further tests. All bone specimens were subjected to dual-energy X-ray absorptiometer (DXA) to evaluate areal bone mineral density (aBMD) of L5 vertebrae and femurs, micro-computed tomography (micro-CT) to analyze cortical bone parameters of femoral diaphysis, including cortical cross section area (CSA), cortical thickness and cross-sectional moment of inertia (CSMI). A three-point bending test was applied to determine fracture load of each femurs.

Compare to OVX group, increase of aBMD by 14.6 % at L5 vertebrae and 13.3% at femoral diahpysis in treatment group. The cortical parameters of femoral diaphysis, CSA and cortical thickness, analyzed by micro-CT were significantly increased but the increasing tendency of CSMI did not have significant changes statistically after teriparatide intervention for 3 months duration. The increase of cortical bone strength (OVX vs OVX+F group, 120.72±2.72 vs 137.93±5.02, p < 0.05) at femoral diaphysis after treatment were also noticed.

This study has point out a deeper look at geometric change of cortical bone after teriparatide treatment. This finding imply teirparatide has the ability to change the geometry of cortical bone and increase bone strength at femoral diaphysis.

Introduction: Conservative hip replacements are advantageous because resection of bone in the proximal femur is minimised. This study investigated a new design of conservative hip in the goat model where the femoral head was resected and two hydroxyapatite coated ‘pegs’ were introduced into the femoral neck. The hypothesis was that the ‘pegs’ would provide a direct method of transmitting forces within the femoral neck thus resulting in less adverse bone remodelling and reduced loosening. Bone stock is also preserved should subsequent revision be required.

Methods: Eight unilateral implants were inserted into the right femur of adult female goats for 1 year. Retrieved specimens were analysed radiographically and histologically. Image analysis was used to quantify bone attachment and total bone area adjacent to the implant. Tetracycline bone markers quantified bone turnover. Operated hips were compared with non-operated hips. The students t-test was used for comparative statistical analysis where p< 0.05 were classified as significant.

Results: Radiographic analysis demonstrated bone loss beneath the cup with increased bone density at the distal end of the pins (fig.1). Light microscopy revealed areas of new and mature bone adjacent to the implant. Osseointegration to the HA coating was observed. Bone markers established significantly decreased bone formation rates (p< 0.05) in bone adjacent to the implant in the operated versus control hips.

Image analysis results demonstrated an average bone attachment of 30.94% to the implant surface (fig 2). Greatest bone attachment occurred at the end of the pins (78.99%) contributing 22% of overall attachment to the implant. Least attachment occurred beneath the prosthetic cup (13.82%) and in the medial aspect adjacent to the central pin. Greater total bone area was measured in control hips and no significant correlation between bone attachment to the ‘pegs’ and bone area beneath the prosthetic cup was identified.

Discussion: From this study we have concluded that despite the resorption of bone beneath the prosthetic cup, the conservatve hip design investigated remained well fixed in the femur during the 1 year in vivo period. It appears that an implant design that resurfaces the femoral head with two pins used to transmit forces into the femoral neck is a useful approach in conservative hip design.

Introduction

Fixation patterns of cementless stem were known as proximal or distal part. Distal fixation was seen in fully porous coated stem and stress shielding of the proximal femur was indicative. These phenomena did not lower the clinical results, but technical difficulties were more and more in revision surgery because of infection or dislocation. There was lot of reports that alendronate was effective for treatment of osteoporosis by induction of apoptosis in osteoclasts. We can expect alendronate to modify the bone quality around the stem after cementless THA.