Familial Mediterranean Fever is a chronic auto-inflammatory disease. In the context of chronic inflammation, it seems that, among others, it also affects bone density in children. Bone loss may be due to subclinical inflammation that persists even during periods of remission. In addition, inflammatory cytokines also play an important role (mainly during episodes) resulting in an increase in bone degradation and ultimately a reduction in bone mass. Cytokines mainly associated with bone degradation and osteoclast activity are: IL-1R, IL-2, IL-6, IL-8, TNFa.

The purpose of this study is to determine the effect of FMF on bone density and to compare the results with a healthy population. In addition, the difference between the children with FMF will be studied according to the mutation they carry.

For the above purpose, 62 children will participate, 31 healthy and 31 with FMF(confirmed mutation/s in the MEFV (Marenostrin Encoding Fever Gene) ).

They will be separated based on gender (boys, girls) and age: 2 age groups: a) 6-12 years, b) 12 - 20 years, separation into pre-adolescent children and adolescents (according to Tanner) and Body Mass Index ( BMI) (3rd-90th ED). Of the 31 children with FMF, all will be treated with colchicine and the study will not take place during periods of disease attack.

An attack free period is defined as a period of at least 3 weeks without clinical symptoms (fever, abdominal pain, arthritis) and without acute phase indicators (increased CRP, TKE, WBC).

The healthy population will exclude children with a history of disease related to a bone disorder. In addition, the existence of other factors that could affect bone density will be investigated in all 62 children. For this reason, there will be a check of calcium metabolism, vitamin D, kidney function, hormonal check, thyroid function check. Biomarkers of the RANK/RANKL/OPG axis that have a major role in osteoblast/osteoclast activity will be tested. Children's physical activity will be also assessed.

Bone density measurement will be done with a Hologic DISCOVERY QDR DXA (Dual Energy X-ray Absorptiometry) machine, the "gold standard" for spine and hip bone disorder screening worldwide. The program to be implemented will be adapted to childhood.

Then the following will be assessed: Body Mineral Density (BMD), Body Mineral Content (BMC) and z-score for the vertebrae of the OMSS (O1-O4) and Total Body less Head (TBLH).

Inclusion Criteria:

• For patients:

  • Age > 6 years
  • BMI 3rd - 90th percentile
  • Meet the Tel Hashomer criteria (Avi Linhnen 1997)
  • Confirmed diagnosis by finding mutation(s) in the MEFV gene
  • Taking medication (colchicine) for at least 3 months
  • Normal physical activity during the last month, according to the questionnaire that will be distributed
  • Free individual history for bone diseases
  • Normal thyroid function

• For the control group:

  • Age > 6 years
  • BMI 3rd - 90th percentile
  • Free individual history for bone diseases
  • Normal physical activity according to the questionnaire
  • Normal thyroid function

Exclusion Criteria:

• For patients:

  • Age < 6 years
  • BMI < 3rd or > 90th percentile
  • Period of attack period of the disease
  • Those who have not started treatment with colchicine
  • Those who do not adapt well to taking colchicine
  • Decreased physical activity during the last month according to the questionnaire
  • Finding from the history of bone diseases that could affect the results
  • Taking vitamins that could affect the results
  • Existence of a factor that does not allow the performance of Dexa (when for example the safe and appropriate placement of the child cannot be ensured)
  • History of previous surgery which forced the patient to be bedridden for a significant period of time. Possible unreliable result of bone mineral density measurement due to reduced physical activity.

• For the control group:

  • Age < 6 years
  • BMI < 3rd or > 90th percentile
  • Taking vitamins that could affect the results
  • Decreased physical activity during the last month according to the questionnaire
  • History of previous surgery in the last year

Two groups will be used: patients and control group. The results from blood examination and DEXA will be compared in order to check differences in bone mineral density betwwen the two groups.