Bone Density
Conditions
Keywords
Myokines
Brief summary
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
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.
Interventions
DIAGNOSTIC_TESTBlood 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)
DIAGNOSTIC_TESTSaliva sample
5 ml of saliva will be taken.
OTHERMicroFET2® 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
DIAGNOSTIC_TESTGrip 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.
OTHERMaximum 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.
OTHERThe SPPB (Short Physical Performance Battery)
Battery of tests comprising a balance test, a walking speed test and a chair-lift test
OTHERThe 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.
OTHERSegmental 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.
OTHERIndirect 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.
OTHERFardellone's questionnaire
Completion of a questionnaires on calcium intake (Fardellone)
OTHERONAPS questionnaire
The ONAPS questionnaire contains questions on physical activity and sedentariness
OTHERDietary 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.
Sponsors
Centre Hospitalier Universitaire de Nīmes
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
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.
Eligibility
Sex/Gender
FEMALE
Age
20 Years to 89 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Lean body mass | Baseline | Impedencemetry, measured in Kg |
| Irisin | Baseline | Plasma concentration of irisin will be measured in pg/ml by Enzyme-Linked Immuno Sorbent Assay |
| Bone Mineral Density | Baseline | Bone densitometry using X-ray absorptiometry (DXA) measured in g/cm² |
| Myostatin | Baseline | Plasma concentration of myostatin will be measured in pg/ml by Enzyme-Linked Immuno Sorbent Assay |
| Follistatin | Baseline | Plasma concentration of follistatin will be measured in pg/ml by Enzyme-Linked Immuno Sorbent Assay |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adiponecotin | Baseline | Plasma concentration of adiponecotin will be measured in pg/ml by Enzyme-Linked Immuno Sorbent Assay |
| Bone mineral density: impedencemetry | Baseline | Bone densitometry will be measured by impedencemetry in g/cm² |
| Grip test | Baseline | Measured by a digital dynamometer (MicroFET2) |
| Isometric force | Baseline | bench test |
| Walking test | Baseline | 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 |
| Short Physical Performance Battery : Balance test | Baseline | The person's ability to stand for 10 sec with feet in 3 different positions (together side-by-side, semi-tandem, and tandem) is tested and scored as follows : 1. Side-by-side stance scored from 0-1 2. Semi-tandem stance scored from 0-1 3. Tandem stance scored from 0-2 |
| Short Physical Performance Battery : Walking speed test | Baseline | Two timed trials of a 3-meter or 4-meter walk (fastest recorded in seconds) |
| Short Physical Performance Battery : Chair lift test | Baseline | The time taken to raise a chair 5 times is recorded in seconds. |
| Plasma concentration of osteocalcin, a bone remodelling marker. | Baseline | Measured in ng/ml |
| Plasma concentration of serum cross-linked C-telopeptide of type I collagen (CTX), a bone remodelling marker. | Baseline | Measured in pmol/l |
| Calcium intake | Baseline | Calcium intake (mg/day) will be measured using the Fardellone Dietary intake questionnaire (protein (gr), carbohydrate (gr), fat (gr)) will be assessed using the dietary habits questionnaire. |
| Level of physical activity | Baseline | Level of physical activity (hours/week) will be assessed using the Physical Activity and Sedentariness Questionnaire (Observatoire National de l'Activité Physique et se Sédantarité = National Observatory on Physical Activity and Sedentariness). |
| Muscle mass : DXA | Baseline | Muscle mass will be measured by DXA in kg |
| Muscle mass : impedancemetry | Baseline | Muscle mass will be measured by impedancemetry in kg |
| Bone mineral density | Baseline | Bone mineral density will be measured by DXA in g/cm² |
| Resting energy metabolism | Baseline | Resting energy metabolism will be measured by indirect calorimetry in Kcal/day |
| Leptin | Baseline | Plasma concentration of leptin will be measured in pg/ml by Enzyme-Linked Immuno Sorbent Assay |
| Fat mass | Baseline | Impedencemetry, measured in Kg |
Other
| Measure | Time frame | Description |
|---|---|---|
| Creation of a blood bank | Baseline | Blood samples will be stored at the biological resource centers of Nîmes and Montpellier University Hospitals. As soon as the samples have been taken, the tubes are left at room temperature for about 5 minutes to coagulate (only dry tubes will coagulate). They are then centrifuged at 3800 rpm for 20 minutes at 4°C, aliquoted into cryotubes (volume 600 µl) and frozen as quickly as possible at -80°C. |
| Creation of a saliva bank | Baseline | The saliva sample is taken at least 60 minutes after brushing the teeth or taking medication and at least 10 minutes after drinking (water). The subject must place the cotton swab in the mouth without touching it and leave it in the mouth for at least 3 minutes until he or she can no longer avoid swallowing the saliva produced. The subject then returns the inhibited saliva swab to the suspended container and seals the tube with the stopper. The tube was then centrifuged at 3800 rpm for 20 minutes at 4°C. The clear saliva (without residue) thus extracted is aliquoted into cryotubes (volume 600 µl) and frozen as quickly as possible at -80°C. Saliva samples will be stored at the biological resource centers of Nîmes and Montpellier University Hospitals. |
Countries
France
Contacts
Primary ContactVincent BOUDOUSQ, Dr
Backup ContactAnissa MEGZARI
Outcome results
None listed