Mediating Role of Myokines in the Dialogue Between Muscle and Bone Tissue in a Population of Healthy Women Aged 20-89 Years

NCT ID: NCT06683222

Last Updated: 2024-11-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

280 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-11-06

Study Completion Date

2029-09-30

Brief Summary

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The main hypothesis is that muscle acts on bone tissue via the secretion of myokines (myostatin, follistatin, irisin). This is based on previous results showing that muscle mass in different patient populations with very different body mass indexes (anorexic or obese patients) is significantly and independently associated with bone mineral density.

Detailed Description

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Bone densitometry using X-ray absorptiometry (DXA) is the reference technique for measuring Bone Mineral Density (BMD). According to the International Osteoporosis Foundation (IOF), if a single site is to be preferred, it should be the total hip or femoral neck, using a single NHANES III reference curve. It should be stressed, however, that this curve was obtained from a North American population with anthropometric parameters, notably body mass index (BMI), that differ from those of the European population, particularly the Caucasian population. Apparently, only one reference curve has been obtained in France, from the OFELY study in 1993. Given the age of this cohort and the possibility of BMI changes over time in the Caucasian population, but even more so, the impossibility of transposing this curve onto new DXAs of different brands, new reference curves need to be developed. DMS IMAGING is therefore financing the MONIKA study, with the CHU de Nîmes as sponsor.

As part of this study, some 425 healthy female volunteers aged between 20 and 89 will be recruited from three centers (Nîmes, Montpellier, Lyon). A DXA examination at various bone sites (femur, rachis, radius and whole body) will provide up-to-date normalcy curves for BMD, but also for body composition (fat and lean mass), which are currently lacking. Access to this population could also enable us to better understand bone physiology and the links that may exist between bone tissue and muscle and fat tissue.For example, the serum concentration of leptin, a hormone secreted by adipose tissue, is associated with bone mass in non-obese women.More recent data show that skeletal muscle also has a secretory activity, characterized by the production of myokines.In humans, there are various arguments in favour of myostatin's action on bone tissue.However, clinical studies in humans are very limited.Through two clinical studies, myokine levels were assessed in two populations with very different BMIs. Female patients suffering from anorexia nervosa, for example, showed decreased myostatin levels, increased follistatin levels and comparable irisin levels, in parallel with very low BMD, compared with a population of young, non-malignant women.

In obese women with high BMD, it was also shown that myostatin and follistatin levels were high, whereas irisin levels were lower than in a control population. Furthermore, the effect of lean body mass on BMD was partially mediated by irisin. These results are still preliminary, having been obtained on a small group of subjects, and merit further investigation on a representative population scale. However, there are apparently no age-dependent reference values for these myokines.

In addition to the involvement of these myokines in the muscle-bone complex, these factors could also be involved in the muscle-fat complex, since new functions are now being attributed to them, such as lipolysis, which could affect the concentrations of certain adipokines, such as leptin, which in turn could have an impact on bone formation and resorption. The main hypothesis is that muscle acts on bone tissue via the secretion of myokines (myostatin, follistatin, irisin). This is based on previous results showing that muscle mass in different patient populations with very different BMIs (anorexic or obese patients) is significantly and independently associated with BMD.

Conditions

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Bone Density

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

The cohort will be a sub-group derived from the 425 healthy female volunteers who will be recruited for the MONIKA study. For the MONIKA study, we expect around 350 to be recruited at the Nîmes and Montpellier sites. Among these women recruited at the Nîmes and Montpellier sites, 280 participants will be invited to take part in the MyOs study.
Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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Sub-group of 280 patients derived from the MONIKA study

Group Type OTHER

Blood sample

Intervention Type DIAGNOSTIC_TEST

36 ml of blood in 3 x 7 ml dry tubes, 1 x 5 ml EDTA tube, 1 x 5 ml heparinized tube, 1 x 5 ml anti-protease tube)

Saliva sample

Intervention Type DIAGNOSTIC_TEST

5 ml of saliva will be taken.

Grip test

Intervention Type DIAGNOSTIC_TEST

The grip strength of the dominant arm will be measured with the participant in a standing position, with the arm close to the body and the elbow at 90◦ flexion, while the non-dominant arm will be positioned alongside the body. Three measurements will be taken for the dominant hand, and the mean value will be calculated and used for analysis. One minute is allowed between each repetition, to avoid muscle fatigue. Dynamometer quality control is ensured by regularly checking known resistance values.

MicroFET2® maximum isometric force test

Intervention Type OTHER

The microFET2 device is used to test isometric force. The microFET2 dynamometer is battery-powered and ergonomically designed to fit in the palm of the hand. The system is microprocessor-controlled to provide accurate, repeatable muscle force readings. The microFET Clinical software automatically performs calculations and validity tests, and allows graphs to be generated from the data, enabling reports of different patient tests to be compared

Maximum isometric knee extension bench test.

Intervention Type OTHER

The maximal isometric knee extension strength test on a specially-adapted strength bench consists in performing 3 maximal contractions with 1 minute's rest between each test.

The SPPB (Short Physical Performance Battery)

Intervention Type OTHER

Battery of tests comprising a balance test, a walking speed test and a chair-lift test

The 6-minute walking test.

Intervention Type OTHER

Muscular function will be determined by the 6-minute walk test to assess aerobic endurance. Participants will be asked to walk for 6 min as fast as possible on a shuttle track. The distance (m) covered in 6 min will be measured. Walking speed (m/s) will be calculated as the distance (m) covered in 6 min. A walking speed \<0.8 m/s has been defined as a low value.

Segmental impedancemetry examination.

Intervention Type OTHER

Segmental impedancemetry involves measuring body composition using the body's resistance to the passage of a low-intensity electric current. This test is harmless to the body.

Indirect calorimetry test.

Intervention Type OTHER

An Indirect calorimetry is the standard method for measuring energy expenditure at rest. It is based on the principle that the human body burns nutrients using O2 and producing CO2.

Fardellone's questionnaire

Intervention Type OTHER

Completion of a questionnaires on calcium intake (Fardellone)

ONAPS questionnaire

Intervention Type OTHER

The ONAPS questionnaire contains questions on physical activity and sedentariness

Dietary intake.questionnaire

Intervention Type OTHER

The dietary intake questionnaire contains questions regarding the person's eating habits - how many meals a day, where they eat, whether they eat alone, what foods they eat/drink and whether they are following a particular diet and, if so, the reasons why.

Interventions

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Blood sample

36 ml of blood in 3 x 7 ml dry tubes, 1 x 5 ml EDTA tube, 1 x 5 ml heparinized tube, 1 x 5 ml anti-protease tube)

Intervention Type DIAGNOSTIC_TEST

Saliva sample

5 ml of saliva will be taken.

Intervention Type DIAGNOSTIC_TEST

Grip test

The grip strength of the dominant arm will be measured with the participant in a standing position, with the arm close to the body and the elbow at 90◦ flexion, while the non-dominant arm will be positioned alongside the body. Three measurements will be taken for the dominant hand, and the mean value will be calculated and used for analysis. One minute is allowed between each repetition, to avoid muscle fatigue. Dynamometer quality control is ensured by regularly checking known resistance values.

Intervention Type DIAGNOSTIC_TEST

MicroFET2® maximum isometric force test

The microFET2 device is used to test isometric force. The microFET2 dynamometer is battery-powered and ergonomically designed to fit in the palm of the hand. The system is microprocessor-controlled to provide accurate, repeatable muscle force readings. The microFET Clinical software automatically performs calculations and validity tests, and allows graphs to be generated from the data, enabling reports of different patient tests to be compared

Intervention Type OTHER

Maximum isometric knee extension bench test.

The maximal isometric knee extension strength test on a specially-adapted strength bench consists in performing 3 maximal contractions with 1 minute's rest between each test.

Intervention Type OTHER

The SPPB (Short Physical Performance Battery)

Battery of tests comprising a balance test, a walking speed test and a chair-lift test

Intervention Type OTHER

The 6-minute walking test.

Muscular function will be determined by the 6-minute walk test to assess aerobic endurance. Participants will be asked to walk for 6 min as fast as possible on a shuttle track. The distance (m) covered in 6 min will be measured. Walking speed (m/s) will be calculated as the distance (m) covered in 6 min. A walking speed \<0.8 m/s has been defined as a low value.

Intervention Type OTHER

Segmental impedancemetry examination.

Segmental impedancemetry involves measuring body composition using the body's resistance to the passage of a low-intensity electric current. This test is harmless to the body.

Intervention Type OTHER

Indirect calorimetry test.

An Indirect calorimetry is the standard method for measuring energy expenditure at rest. It is based on the principle that the human body burns nutrients using O2 and producing CO2.

Intervention Type OTHER

Fardellone's questionnaire

Completion of a questionnaires on calcium intake (Fardellone)

Intervention Type OTHER

ONAPS questionnaire

The ONAPS questionnaire contains questions on physical activity and sedentariness

Intervention Type OTHER

Dietary intake.questionnaire

The dietary intake questionnaire contains questions regarding the person's eating habits - how many meals a day, where they eat, whether they eat alone, what foods they eat/drink and whether they are following a particular diet and, if so, the reasons why.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* Self-reported Caucasian ethnicity (Europe, Middle East, North Africa) only as there is a difference in BMD by ethnicity.
* Person affiliated with or benefiting from a social security scheme.
* Free, informed consent signed by the participant and the investigator (at the latest on the day of inclusion and before any examination required by the research).

Exclusion Criteria

* Fragility fracture defined as a spontaneous or low-kinetic fracture (≤ one fall from height).
* Early menopause (\< 40 years), hysterectomy (complete \< 40 years), primary amenorrhea (absence of menstruation before 15 years), current amenorrhea of more than 3 months without contraceptive if the patient is less than 40 years old.
* Patients on treatments: prolonged corticosteroid therapy \> 3 months or \> 1 g (cumulative dose).
* Immobilization of more than 3 months, less than 12 months old.
* Hip fracture in a first-degree relative.

Patients with any of the following pathologies affecting bone, muscle or adipose tissue:

* Inflammatory bowel disease (IBD: Crohn's disease, ulcerative colitis) and untreated celiac disease.
* Renal insufficiency on dialysis or patients with nephrology follow-up.
* Known hypercalciuria.
* Osteomalacia, rickets, osteogenesis imperfecta.
* Osteopathy (Paget's disease, osteopetrosis, etc.).
* Chronic inflammatory rheumatism.
* Hemopathy, neoplasia.
* Hepatic insufficiency or chronic hepatitis.
* Endocrinopathy: diabetes, dysthyroidism, hypogonadism, hypercorticism, untreated acromegaly.
* Anorexia nervosa.
* Hyperparathyroidism (even controlled).
* History of digestive surgery (bariatric, gastrectomy, digestive resection other than appendectomy, etc.).
* History of organ transplantation.
* Chronic infectious disease (HIV, etc.).
* Weight loss of more than 10 kg within 6 months.
* Paresis, marked lameness or unloading of a limb, or prolonged immobilization of more than one month in the last 12 months.
* Patients on treatments that may affect bone mass or body composition:
* Biphosphonates (Alendronate (Fosamax® and generics), Risedronate (Actonel® and generics), Zoledronate (Aclasta® and generics).
* Teriparatide (Forsteo®).
* Denosumab (Prolia®)
* Selective estrogen receptor modulators (Clomifene, Tamoxifene, Toremifene, Raloxifene).
* Anabolic steroids.
* Strontium ranelate.
* Carbamazepine.
* Phenobarbital.
* Immunosuppressants.
* Patients on anti-epileptics.
* Patients with any of the following abnormalities in the measurement area:
* Major deformities of the wrist, hip or vertebrae.
* Compression of vertebral bodies, cementoplasty.
* Prosthesis, implant (breast, buttock, etc.), foreign body.
* Hip paraosteoarthropathy.
* Injection of radiological contrast medium, barium enema, nuclear medicine examination within 10 days.
* Intensive sport (more than 10 h/week).
* Extreme BMI (BMI \< 18, BMI \> 35 kg/m²).
* Loss of autonomy.
* People with neurodegenerative disorders affecting their ability to give consent.
* Pregnant, parturient or breast-feeding women.
* Participation in an interventional study involving a drug or medical device or a category 1 RIPH within 3 months prior to inclusion.
Minimum Eligible Age

20 Years

Maximum Eligible Age

89 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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Centre Hospitalier Universitaire de Nīmes

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Thibault MURA, Prof.

Role: STUDY_DIRECTOR

Centre Hospitalier Universitaire de Nīmes

Locations

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C.H.R.U. Lapeyronie

Montpellier, , France

Site Status RECRUITING

Chu Nimes

Nîmes, , France

Site Status RECRUITING

Countries

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France

Central Contacts

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Vincent BOUDOUSQ, Dr

Role: CONTACT

+334.66.68.32.66

Anissa MEGZARI

Role: CONTACT

0466684236

Facility Contacts

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Denis Mariano Goulart, Pr

Role: primary

+334 64 33 85 98

Vincent BOUDOUSQ, Dr

Role: primary

+334.66.68.32.66

Other Identifiers

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AO12022/2023/VB-01

Identifier Type: -

Identifier Source: org_study_id