Decreased plasma fibronectin levels are associated with increased fracture rates in men – a pilot study on Canadian Multicentre Osteoporosis Study (CaMos) participants
Mahdokht Mahmoodi1, Claudie Berger2, Lucie Canaff2, Suzanne Morin2, David Goltzman2,3,Mari T. Kaartinen1,3
1Faculty of Dental Medicine and Oral Health Sciences, McGill University, Montreal, Canada 2Faculty of Medicine and Health Sciences, RI of the MUHC, Montreal, Canada 3Centre for Bone and Periodontal Research, McGill University, Montreal, Canada
Osteoporosis is a polygenic bone metabolic disorder characterized by an increased prevalence of fractures. A major osteoporosis fracture) (MOF) is considered to be a fracture of the hip, spine,
wrist or humerus. While osteoporosis is most common in postmenopausal females, osteoporosis can affect both sexes. At the cellular level, osteoporosis results from imbalanced bone remodeling
leading to a net loss of bone mass. Bone remodeling is orchestrated by bone multicellular units (BMU) which can be regulated by extracellular matrix (ECM) components of bone and bone
marrow. The liver is an important regulator of bone health, and bone disease is a major complication in patients with chronic liver disease. Liver-derived plasma fibronectin (pFN) accumulates in bone and marrow from the blood and contributes to BMU cell activities and bone strength by contributing to ECM formation, however, its role in osteoporosis has not been fully explored. Here we investigated the potential association of pFN levels with human fracture rates using blood samples and data from the Canadian Multicenter Osteoporosis Study (CaMos) biobank. pFN levels were analyzed with ELISA in serum samples of CaMos participants aged 50 years old or older, with and without osteoporosis. CaMos participants with at least one of the following conditions were considered as osteoporosis cases: 1) having a bone mineral density(BMD) T-score at the femoral neck, total hip or lumbar spine(L1-L4) of <-2.5 or 2) having a 10-year probability of sustaining a MOF>20% or a hip fracture >3% using the fracture risk assessment tool, FRAX, or 3) having a history of a MOF aber age 50. The control group included CaMos participants with all of the following conditions: 1) having all 3 T-scores (femoral neck, total hip and L1-L4) >-1, 2) having a FRAX MOF risk<20% and a FRAX hip fracture risk <3%, 3) not having sustained a MOF, and 4) not having reported any osteoporosis therapy (bisphosphonate)
use. Patients with diabetes and those with known renal disease(eGFR<60) or liver disease were excluded from the study. Cases and controls were matched by sex, age (+/- 5 years) and year of
blood draw. pFN levels were significantly higher (p<0.0001) in normal male sera compared to female sera and significantly decreased in male osteoporotic cases compared to their controls
(p<0.0001). pFN levels correlated significantly with vitamin D status (p= 0.0136), T-score of L1-L4 (p=0.0088) and T-score of the total hip (p=0.0066) in men, but not in women. Our pilot study
suggests that pFN may be involved in male osteoporosis.