Clinical trial NCT06703736: Functional and Morphological Characterization of Multiple Osteochondromas Disorder
Official title: Misure di funzionalità e deformità Dell'Apparato Muscolo-scheletrico Come "Biomarkers" Per il Trattamento di Malattie Ortopediche/Accessible Measurements of Mobility and Deformity as Biomarkers for Orthopaedic Treatments
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Hereditary Multiple Osteochondromas
Keywords: Multiple osteochondromas
Functional limitation
Skeletal deformity
Gait analysis
IMU
Anthropometry
3D scanning
Rare skeletal disease
Cartilage
Growth plates
Lead sponsor: Istituto Ortopedico Rizzoli
Sponsor class: OTHER
First posted: 2024-11-25
Enrollment: 60
Sex: ALL
Minimum age (years): 6
Maximum age (years): 40
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The multiple osteochondromas population is selected from patients taken over by CeMaRS (Centre of Rare Skeletal Disorders) of Istituto Ortopedico Rizzoli (IOR), while the healthy population is recruit via social and IOR website, possibly including healthy relatives of recruited patients if the absence of the causative genetic variant of the disease and the absence of its clinical manifestations are proven.

Brief summary: The main purpose of the study is the characterization of functional and morphological alterations due to multiple osteochondromas in a pediatric and adult population through the identification of relevant anthropometric and functional parameters. The morphological and functional data, supplemented with clinical and postural data, will allow the characterization of the disease with an holistic approach that can provide important information to properly assess timing for surgical treatments and to improve the quality of life of these patients. Another goal of the study is the assessment and the validation of novel instruments and tools to measure joint mobility and bone deformity. These instruments should be easy-to-use and designed to be operated locally by the patients themselves and/or in small clinics by operators with little training and no specific high-technical knowledge. The final goal of the study is the assessment of the quality of life and balance perception of patients, using questionnaires.

Detailed description: Hereditary Multiple Osteochondromas (HMO) disease, also known as 'Hereditary Multiple Exostosis', is a rare autosomal dominant musculoskeletal disorder whose prevalence is estimated at 1:50000. It is characterised by benign osteo-cartilaginous tumours called 'osteochondromas' or 'exostoses', cartilage capped bony outgrowths that originate from the perichondrium of long bones and from the surface of flat bones. The development and growth of exostoses occur in parallel with the growth of the subject and then stop at skeletal maturity. HMO is characterized by phenotypic heterogeneity and the most important complication is malignant transformation of osteochondroma towards secondary peripheral chondrosarcoma, which is estimated to occur in 0.5-5%. In most case, the disease is characterized by a broad-spectrum of mutations in the EXT1 and EXT2 genes coding for transmembrane glycoproteins with glycosyl-transferase activity.

Patients with HMO are subject to functional and postural alterations of the musculoskeletal system caused by bone deformities that begin to appear at an early age. The characterization and monitoring of residual mobility is essential to objectively quantify the motor and morphological deficit and to understand the mechanisms of action and evolution of this pathology. To date, there are no studies in the literature on the instrumental characterisation of OM. Furthermore, although skeletal structure deformities are one of the main causes of functional alterations, studies on the description and instrumental characterisation of macroscopic morphological alterations are limited. The expected results are morphological data (shape, position, size and numerosity) of osteochondromas and functional data (range of motion of the joints affected by the pathology). Other expected results are: accuracy and repeatability of the instruments to be used for monitoring pathology; an overall evaluation of the experience by means of an evaluation questionnaire; information on the feasibility of the pilot study for the implementation of a study on a larger cohort; identification of new prevention and treatment strategies in patients with rare diseases clinically similar to OM (e.g. metachondromatosis) or for other skeletal diseases that are not rare but widespread (e.g. osteoarthritis).

Eligibility criteria: Inclusion Criteria:

For multiple osteochondromas cohort inclusion criteria are:

* clinical and/or molecular diagnosis of Multiple Osteochondromas;
* male and female subjects;
* age minors: 6-17 years at enrollment and adult age: 18-40 years at enrollment;
* collection of appropriate informed consent;
* ability to walk a linear path without aids;
* presence of multiple osteochondromas localized at lower limbs;
* ability to undergo all procedures required by the protocol.

For healthy cohort inclusion criteria are:

* absence of neuro-muskuloskeletal or other limb-limiting conditions in the lower limbs;
* male and female subjects;
* age minors: 6-17 years at enrollment and adult age: 18-40 years at enrollment;
* collection of appropriate informed consent;
* ability to undergo all procedures required by the protocol.

Exclusion Criteria:

* Persons who do not fit the inclusion criteria;
* Any reason which, in the opinion of the investigator, would result in the inability of the participant to comply with the protocol.
* BMI equal to or greater than 30.

Primary outcomes:
measure: Functional motor assessment
timeFrame: From subjects enrollment to the end of the assessment. Patients repeat these activities after 12 months from the first evaluation, while healthy subjects carry out the same activities of unhealthy population only once.
measure: Anthropometric parameters assessment
timeFrame: From subjects enrollment to the end of the assessment. Patients repeat these activities after 12 months from the first evaluation, while healthy subjects carry out the same activities of unhealthy population only once.
Secondary outcomes:
measure: Evaluation of experimental protocols using simplified instrumentation
timeFrame: through study completion
measure: Evaluation questionnaire
timeFrame: The questionnaire is administered to the cohort of patients at the first acquisition and at 12-month follow-up.
measure: Assessment of quality of life and balance perception of hereditary multiple osteochondromas patients
timeFrame: through study completion
Other outcomes:
Locations:
city: Bologna
country: Italy
facility: IRCCS Istituto Ortopedico Rizzoli
Study officials:
References: