Characteristics of Marrow Fatty Cells in the Ageing of Bone and Joints, Osteoarthritis and Osteoporosis (MEDADIPO)

Characterization of Bone Marrow Adipocytes in Osteoarthritic and Post-menopausal Patients: a Comparative Study With Adipocytes From Subcutaneous Adipose Tissue

Obesity and other associated complications promote the development and the progression of osteoarthritis. The subcutaneous and abdominal fat release several factors that alter bone and the cartilage. The role of the marrow fat in close connection with bone has not been defined yet, whereas cellular and animal models indicate that this fat depot modifies bone and cartilage.

The aim of the study is to define if the marrow fat produces more joint-altering factors by comparison with subcutaneous fat. This fat depot can be characterized from removed pieces during the prosthetic surgery of the knee. Measuring before surgery the body weight, waist and hip circumferences, blood pressure, glucose, insulin and lipids in blood will also allow to determine if obesity and/or type 2 diabetes make this fat more dangerous for the joint. Such research will allow the elaboration of new therapeutic strategies in osteoarthritis.

Study Overview

• Status: Recruiting
• Conditions: Osteoarthritis, Knee; Prosthesis User
• Intervention / Treatment: Procedure: tissue

• Study Type: Observational
• Enrollment (Anticipated): 45

Contacts and Locations

• Study Contact: Name: Gilles Pasquier, MD,PhD; Phone Number: +33 3.20.44.66.06; Email: gilles.pasquier@chru-lille.fr
• Study Contact Backup: Name: Stéphanie LUCAS; Email: Stephanie.lucas@univ-littoral.fr

Study Locations

• France
  • Lille, France, 59037
    • Recruiting
    • Hôpital Roger Salengro, CHU Lille

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Probability Sample

Study Population

Arthritic post-menopausal patients with knee prosthetic replacement

Description

Inclusion Criteria:

• Post-menopausal woman
• with a symptomatic knee osteoarthritis requiring prosthesis
• able to handle general anaesthesia
• having given her consent
• able to understand the constraints associated with the study
• with health insurance
• able to understand the French language

Exclusion Criteria:

• with refusal to participate to the study
• more than 85-year-old
• with bone pathologies other than osteoarthritis or osteoporosis
• with active infection
• with evolving cancer
• with haematopoietic pathologies such as haemoglobin pathologies
• with thyroid pathologies
• with type 1 diabetes
• with anti-osteoporotic treatments (bisphosphonates, strontium ranelate, teriparatide, denosumab) except calcium and vitamin D supplementation or hormone replacement.
• with replacement of prosthesis

• with previous surgery at the surgery site

  --with a current participation to another study

• with guardianship
• with deprived liberty

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Arthritic patients with knee prosthetic replace; Arthritic post-menopausal patients with knee prosthetic replacement Each patient is her own control since the two cell types are compared within the same patient The main criteria is based on a comparison of two cell types from the same patient. The secondary criteria are based on a comparison of cell types according to a grouping of patients according to different metabolic parameters.

Procedure: tissue; Adipocyte isolation from distal femoral epiphysis and subcutaneous adipose tissue at the surgery site; classical piece removal during prosthetic replacement of the knee

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Expression levels in femoral spinal adipocytes of mRNAs of 18 genes compared to those of adipocytes isolated from the subcutaneous adipose tissue in the same patient	at 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the intra patients difference of the expression level of medullary adipocytes mRNA compared to that of subcutaneous adipocytes according to Obesity state (normal vs overweight vs obese) as defined using BMI		at 3 months
the intra patients difference of the expression level of medullary adipocytes mRNA compared to that of subcutaneous adipocytes according to Central obesity (yes or no) as defined using the waist-to-hip ratio		at 3 months
the intra patients difference of the expression level of medullary adipocytes mRNA compared to that of subcutaneous adipocytes according to Presence or absence of systemic insulin-resistance as measured using the HOMA-IR index	the Homeostatic Model Assessment of Insulin Resistance(HOMA-IR index)Healthy Range: 1.0 (0.5-1.4) Less than 1.0 means you are insulin-sensitive which is optimal. Above 1.9 indicates early insulin resistance. Above 2.9 indicates significant insulin resistance.	at 3 months
the intra patients difference of the expression level of medullary adipocytes mRNA compared to that of subcutaneous adipocytesaccording to Presence or absence of chronic uncontrolled hyperglycaemia as measured using HbA1c plasma levels		at 3 months
the intra patients difference of the expression level of medullary adipocytes mRNA compared to that of subcutaneous adipocytes according to presence or absence of metabolic syndrome	metabolic syndrome as defined by the presence of at least three of the following criteria: large waist circumference, decrease in HDL-cholesterol, hypertriglyceridemia, elevated fasting glycaemia, elevated blood pressure.	at 3 months

Collaborators and Investigators

• Sponsor: University Hospital, Lille
• Collaborators: MSDAVENIR Foundation
• Investigators: Principal Investigator: Gilles Pasquier, MD, University Hospital, Lille

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2020
• Primary Completion (Anticipated): August 1, 2023
• Study Completion (Anticipated): August 1, 2023

Study Registration Dates

• First Submitted: September 18, 2018
• First Submitted That Met QC Criteria: September 18, 2018
• First Posted (Actual): September 20, 2018

Study Record Updates

• Last Update Posted (Actual): January 27, 2023
• Last Update Submitted That Met QC Criteria: January 26, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: Osteoarthritis; obesity; type 2 diabetes; prosthetic surgery of the knee; bone marrow fat
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: 2017_59; 2018-A00660-55 (Other Identifier: ID-RCB number, ANSM)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No