Image-guided Computational and Experimental Analyses of Fractured Patient's Bone (GAP)

NCT ID: NCT04787679

Last Updated: 2025-08-11

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 52 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2020-11-09
• Study Completion Date: 2028-08-09

Brief Summary

Due to the increase in the average age of the population, the projections on the number of age-dependent bone fractures appear to be constantly increasing.

They are mainly due to bone pathologies, including osteoporosis. The latter leads to a reduction in bone mineral density and deterioration of the micro-architecture, with a consequent increase in bone fragility. However, the mechanisms of damage at the micro-scale have not yet been elucidated and there is no universally recognized damage criterion. Recent research has evaluated the importance of implementing computational models to study the influence of bone gaps, canaliculi and microporosities on the propagation of damage. These models need to be validated through experimental tests, still lacking, in particular on human bones, in the current scientific landscape. Once the experimental validation of computational models has been developed, it will be possible to introduce new fracture indices at the micro-scale, useful for a preventive diagnosis of osteoporosis.

Detailed Description

The study of the mechanisms of bone damage, which occur at the multiscale, is of fundamental importance for the understanding of fracture processes. In particular, age-related fractures are continuously increasing due to the increase in average age and widespread diseases such as osteoporosis. They result in high economic burdens, morbidity (including psychological, e.g., frailty), and increased mortality. In order to reduce the impact of bone fractures on health and economy, early diagnosis is the key. In this context, one must consider that bone is characterized by a complex hierarchical structure. Both the cortical and trabecular sections consist of micrometric lamellae, composed of collagen fibrils, within which osteocytes are found. They reside in sub-micrometer cavities called lacunae, which are connected by a dense network of canaliculi. At the nanoscale, the fibrils consist primarily of collagen and hydroxyapatite crystals. This complex architecture is reflected in fracture patterns: damage, in fact, occurs at the multiscale. However, fracture patterns and their associated physical phenomena are still not understood, especially at the microscale.

Recently, microscale imaging techniques have been combined with subject-specific numerical models, which are able to calculate local values of bone stress and strain. Preliminary studies have focused on evaluating a possible interaction between micro-cracks and microstructural porosity. This particular research focuses on the lacunar network, which is presumed to significantly affect bone resistance to fracture although the actual role of the lacunar network is not yet elucidated. First, lacunae are areas of stress concentration, which apparently lead to weakening of the bone structure. However, in most cases, the lacunae make a positive contribution to toughness by deflecting the crack front. The connection between the lacunae, determined by the network of canaliculi, is also reduced in osteoporotic subjects, preventing the slowing of damage. In this sense, bone can be considered a damage tolerant material. Donaldson et al developed computational models and estimated a threshold for microdamage initiation and propagation. They used computerized micro-tomography of murine femurs and evaluated the influence of different algorithms on the propagation of in-silico damage. Further results showed that the damage always occurs on the surfaces of blood vessels or porosities and does not instead start from the lacunae. However, further simulations and models would be needed to verify the effectiveness of the damage models.

Computational damage models also require experimental validation. Preliminary studies have been conducted in two main directions: in-vivo imaging and image-guided failure assessment (IGFA) techniques. The first approach allows nondestructive monitoring of bone damage in living animals. The second approach, implemented by A. Levchuk et al. (8), shows enormous potential by allowing the study of microcrack initiation and propagation with sub-micrometer resolution, but only on small animals.

The current research for the first time wants to perform tests on human bone samples applying IGFA techniques.

Despite several studies on the characterization of damage models at the micro-scale, a validation of computational models of fracture on human subjects is still lacking. In addition, the role of morphological features at the micro-scale in samples is still unknown.

These micro-scale studies could improve clinical understanding of bone fracture and prediction of fracture risk. Currently, clinicians use bone mineral density, which is a macro-scale parameter, as the most common predictor of bone fracture. However, recent studies demonstrate the importance of a thorough characterization of the geometric and morphologic characteristics of the microarchitecture.

OBJECTIVES

General Objective The study aims at the experimental validation of computational models of bone damage at the micro-scale. The general objective is pursued by controlled damage in a micro-compression machine on human bone samples from femoral head. The machinery is placed inside a synchrotron.

Primary Objective The primary objective of the present study is to evaluate the difference in the attraction of bone damage with respect to gaps in the two groups considered (osteoporotic and non-osteoporotic) following micro-compression testing.

The discriminating parameter chosen turns out to be the number of bone gaps encountered by micro-damage. We expect to observe an effect size of 0.4 between the two groups with respect to the chosen parameter.

Secondary Objectives

• Determination of the role of gaps, canaliculi and other bone microstructures in damage. Human bone samples are scanned by micro-tomograph for the definition of microstructural morphological parameters and the realization and analysis of numerical models.
• Validation of these numerical models of damage by micro-compression tests carried out in situ in a synchrotron of adequate resolution
• Quantification of damage in human bone samples affected by osteoporosis
• Definition of micro-scale fracture indices, useful for the early diagnosis of osteoporosis

Conditions

Osteoporosis; Fragility Fracture

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

Osteoporotic patients

Osteoporotic patients, age \> 18 years old

Hip replacement surgery

Intervention Type: PROCEDURE

After hip replacement surgery the sponsor obtains femoral head samples for the study

Non osteoporotic patients

Non osteoporotic patients, age \> 18 years old

Hip replacement surgery

Intervention Type: PROCEDURE

After hip replacement surgery the sponsor obtains femoral head samples for the study

Interventions

Hip replacement surgery

After hip replacement surgery the sponsor obtains femoral head samples for the study

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Age: >=18 years
• primary hip replacement
• Signature of informed consent
• Patients who have a routine preoperative CT scan

• Bone disease (non-osteoporotic) such as to invalidate sample analysis, including but not limited to genetic disorders and bone tumors
• Patients with contralateral hip replacement and/or other synthetic means in the contralateral hip
• Patients with synthesis devices in the hip of interest

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ospedale San Donato

OTHER

Sponsor Role: collaborator

Laura Maria Vergani

OTHER

Sponsor Role: lead

Responsible Party

Laura Maria Vergani

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Luigi Zagra

Role: PRINCIPAL_INVESTIGATOR

IRCCS Istituto Ortopedico Galeazzi

Locations

IRCCS Istituto Ortopedico Galeazzi

Miano, Milano, Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Laura M Vergani

Role: CONTACT

luigi.zagra@fastwebnet.it

+393393758630

Federica Buccino

Role: CONTACT

federica.buccino@polimi.it

Facility Contacts

Elena M Cittera

Role: primary

elena.cittera@grupposandonato.it

0266214057

Sara Zacchetti

Role: backup

sara.zacchetti@grupposandonato.it

0266214048

Other Identifiers

Polimi_Galeazzi_GAP

Identifier Type: -

Identifier Source: org_study_id