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

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.

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.