Assessment of mechanical variables best describing bone remodelling responses based on their correlation with bone density.

Density distribution in bones can be estimated using bone remodelling models (BRM) and applying daily normal loads to assess the stress/strain state to which the bone is subjected. These models locally relate a certain mechanical stimulus, derived from the stress/strain state, directly to bone density or to its variation over time. The background of this idea is Frost's Mechanostat Theory, which states that overloading states tend to increase bone density and disuse states tend to decrease it.

Advances in mechanobiological pharmacokinetic-pharmacodynamic models of osteoporosis treatment - Pathways to optimise and exploit existing therapies.

Osteoporosis (OP) is a chronic progressive bone disease which is characterised by reduction of bone matrix volume and changes in the bone matrix properties which can ultimately lead to bone fracture. The two major forms of OP are related to aging and/or menopause. With the worldwide increase of the elderly population, particularly age-related OP poses a serious health issue which puts large pressure on health care systems.

An in silico approach to elucidate the pathways leading to primary osteoporosis: age-related vs. postmenopausal.

Numerical models of bone remodelling have traditionally been used to perform in silico tests of bone loss in postmenopausal women and also to simulate the response to different drug treatments. These models simulate the menopausal oestrogen decline by altering certain signalling pathways. However, they do not consider the simultaneous effect that ageing can have on cell function and bone remodelling, and thus on bone loss.

Spatio-temporal simulations of bone remodelling using a bone cell population model based on cell availability.

Here we developed a spatio-temporal bone remodeling model to simulate the action of Basic Multicelluar Units (BMUs). This model is based on two major extensions of a temporal-only bone cell population model (BCPM). First, the differentiation into mature resorbing osteoclasts and mature forming osteoblasts from their respective precursor cells was modelled as an intermittent process based on precursor cells availability.

Mechanistic PK-PD model of alendronate treatment of postmenopausal osteoporosis predicts bone site-specific response.

Alendronate is the most widely used drug for postmenopausal osteoporosis (PMO). It inhibits bone resorption, affecting osteoclasts. Pharmacokinetics (PK) and pharmacodynamics (PD) of alendronate have been widely studied, but few mathematical models exist to simulate its effect.

Evolution of relaxation properties of callus tissue during bone transport.

Callus tissue exhibits a viscoelastic behavior that has a strong influence on the distribution of stresses and their evolution with time and, thus, it can affect tissue differentiation during distraction procedures. For this reason, a deep knowledge of that viscoelastic behavior can be very useful to improve current protocols of bone distraction and bone transport. Monitoring stress relaxation of the callus during distraction osteogenesis allows characterizing its viscoelastic behavior.

Combined Effects of Exercise and Denosumab Treatment on Local Failure in Post-menopausal Osteoporosis-Insights from Bone Remodelling Simulations Accounting for Mineralisation and Damage.

Denosumab has been shown to increase bone mineral density (BMD) and reduce the fracture risk in patients with post-menopausal osteoporosis (PMO). Increase in BMD is linked with an increase in bone matrix mineralisation due to suppression of bone remodelling. However, denosumab anti-resorptive action also leads to an increase in fatigue microdamage, which may ultimately lead to an increased fracture risk.

A novel algorithm to resolve lack of convergence and checkerboard instability in bone adaptation simulations using non-local averaging.

Checkerboard is a typical instability in finite element (FE) simulations of bone adaptation and topology optimization in general. It consists in a patchwork pattern with elements of alternating stiffness, producing lack of convergence and instabilities in the predicted bone density. Averaging techniques have been proposed to solve this problem.

Are drug holidays a safe option in treatment of osteoporosis? - Insights from an in silico mechanistic PK-PD model of denosumab treatment of postmenopausal osteoporosis.

Recent reviews by the clinical bone research community suggest caution with prescription of drug holidays for patients with postmenopausal osteoporosis (PMO) treated with denosumab for an extended period of time. Main reasons for this suggestion are based on the fact that discontinuation of denosumab treatment leads to a relapse of osteoclastic bone resorption and a loss of bone mineral density (BMD) to pre-treatment levels at only 12-28 months. The question remains what is the best treatment option for cases where it is required to discontinue and/or reduce the drug dose and what are the consequences on BMD and bone turnover markers (BTMs).

Effects of long-term treatment of denosumab on bone mineral density: insights from an in-silico model of bone mineralization.

Denosumab is one of the most commonly prescribed anti-resorptive drugs for the treatment of postmenopausal osteoporosis. The therapeutic effect of denosumab is to inhibit osteoclast differentiation and consequently bone resorption. Gains in bone mineral density (BMD) are achieved based on the ability of the bone matrix to undergo secondary mineralization.

Comparison of the volumetric composition of lamellar bone and the woven bone of calluses.

Woven tissue is mainly present in the bone callus, formed very rapidly either after a fracture or in distraction processes. This high formation speed is probably responsible for its disorganized microstructure and this, in turn, for its low stiffness. Nonetheless, the singular volumetric composition of this tissue may also play a key role in its mechanical properties.

Comparison of different constitutive models to characterize the viscoelastic properties of human abdominal adipose tissue. A pilot study.

Knowing the mechanical properties of human adipose tissue is key to simulate surgeries such as liposuction, mammoplasty and many plastic surgeries in which the subcutaneous fat is present. One of the most important surgeries, for its incidence, is the breast reconstruction surgery that follows a mastectomy. In this case, achieving a deformed shape similar to the healthy breast is crucial.

Effect of freezing storage time on the elastic and viscous properties of the porcine TMJ disc.

The correct characterisation of the articular disc of the temporomandibular joint (TMJ) is key to study the masticatory biomechanics. For the interval from extraction until testing, freezing is the most used preservation technique for biological tissues, but its influence on their behaviour is still unclear. An important error can be committed in the characterisation of such tissues if freezing has any effect on their mechanical properties.

Is cannulated-screw fixation an alternative to plate osteosynthesis in open book fractures? A biomechanical analysis.

Objectives: The current biomechanical work compares the symphyseal and sacroiliac stability obtained with two systems of bone osteosynthesis. The two methods of fixation compared were the 6-hole suprapubic non-locked plate and pubic fixation with two cannulated screws, a novel technique that can be applied percutaneously in the clinical practice. The aim of this study was to examine the validity of the use of two-cannulated-screws osteosynthesis in order to minimize the secondary effects of open fixation, especially in patients in whom an open reduction is contraindicated.

Fluid Structural Analysis of Urine Flow in a Stented Ureter.

Many urologists are currently studying new designs of ureteral stents to improve the quality of their operations and the subsequent recovery of the patient. In order to help during this design process, many computational models have been developed to simulate the behaviour of different biological tissues and provide a realistic computational environment to evaluate the stents. However, due to the high complexity of the involved tissues, they usually introduce simplifications to make these models less computationally demanding.

On the Use of Bone Remodelling Models to Estimate the Density Distribution of Bones. Uniqueness of the Solution.

Bone remodelling models are widely used in a phenomenological manner to estimate numerically the distribution of apparent density in bones from the loads they are daily subjected to. These simulations start from an arbitrary initial distribution, usually homogeneous, and the density changes locally until a bone remodelling equilibrium is achieved. The bone response to mechanical stimulus is traditionally formulated with a mathematical relation that considers the existence of a range of stimulus, called dead or lazy zone, for which no net bone mass change occurs.

A polynomial hyperelastic model for the mixture of fat and glandular tissue in female breast.

In the breast of adult women, glandular and fat tissues are intermingled and cannot be clearly distinguished. This work studies if this mixture can be treated as a homogenized tissue. A mechanical model is proposed for the mixture of tissues as a function of the fat content.

Percutaneous iliosacral fixation in external rotational pelvic fractures. A biomechanical analysis.

Introduction: Although the gold standard in open book pelvic fractures remains the pubic symphysis (PS) plate fixation, the clinical outcomes are not satisfactory, despite the excellent anatomical reduction assessed radiologically. Some authors suggest that residual instability of the posterior pelvic elements may be responsible for the chronic pain and the early osteoarthritic changes in the sacroiliac joint (SIJ).

Objective: To evaluate whether the isolated posterior fixation with one or two iliosacral screws (ISSs) is sufficient to provide adequate stability for the treatment of Burgess Young APC-II (YB APC-II) type of pelvic ring injuries.

Finite element analysis of the human mastication cycle.

The aim of this paper is to propose a biomechanical model that could serve as a tool to overcome some difficulties encountered in experimental studies of the mandible. One of these difficulties is the inaccessibility of the temporomandibular joint (TMJ) and the lateral pterygoid muscle. The focus of this model is to study the stresses in the joint and the influence of the lateral pterygoid muscle on the mandible movement.

A study of the temporomandibular joint during bruxism.

A finite element model of the temporomandibular joint (TMJ) and the human mandible was fabricated to study the effect of abnormal loading, such as awake and asleep bruxism, on the articular disc. A quasilinear viscoelastic model was used to simulate the behaviour of the disc. The viscoelastic nature of this tissue is shown to be an important factor when sustained (awake bruxism) or cyclic loading (sleep bruxism) is simulated.

Effect of non-uniform thickness of samples in stress relaxation tests under unconfined compression of samples of articular discs.

A precise information of the biomechanical properties of soft tissues is required to develop a suitable simulation model, with which the distribution of stress and strain in the complex structures can be estimated. Many soft tissues have been mechanically characterized by stress relaxation tests under unconfined or confined compression. In general, full-thickness samples are extracted to reduce the damage in the tissue as much as possible.

Numerical simulation of a relaxation test designed to fit a quasi-linear viscoelastic model for temporomandibular joint discs.

The main objectives of this work are: (a) to introduce an algorithm for adjusting the quasi-linear viscoelastic model to fit a material using a stress relaxation test and (b) to validate a protocol for performing such tests in temporomandibular joint discs. This algorithm is intended for fitting the Prony series coefficients and the hyperelastic constants of the quasi-linear viscoelastic model by considering that the relaxation test is performed with an initial ramp loading at a certain rate. This algorithm was validated before being applied to achieve the second objective.