Familial, structural, and environmental correlates of MRI-defined bone marrow lesions: a sibpair study

Graeme Jones,Flavia Cicuttini,Changhai Ding,James Stankovich,Guangju Zhai

doi:10.1186/ar2027

Abstract

The aim of this study was to estimate the heritability and describe the correlates of bone marrow lesions in knee subchondral bone. A sibpair design was used. T2- and T1-weighted MRI scans were performed on the right knee to assess bone marrow lesions at lateral tibia and femora and medial tibia and femora, as well as chondral defects. A radiograph was taken on the same knee and scored for individual features of osteoarthritis (radiographic osteoarthritis; ROA) and alignment. Other variables measured included height, weight, knee pain, and lower-limb muscle strength. Heritability was estimated with the program SOLAR (Sequential Oligogenetic Linkage Analysis Routines). A total of 115 siblings (60 females and 55 males) from 48 families, representing 95 sib pairs, took part. The adjusted heritability estimates were 53 ± 28% (mean ± SEM; p = 0.03) and 65 ± 32% (p = 0.03) for severity of bone marrow lesions at lateral and medial compartments, respectively. The estimates were reduced by 8 to 9% after adjustment for chondral defects and ROA (but not alignment). The adjusted heritability estimate was 99% for prevalent bone marrow lesions at both lateral and medial compartments. Both lateral and medial bone marrow lesions were significantly correlated with age, chondral defects, and ROA of the knee (all p < 0.05). Medial bone marrow lesions were also more common in males and were correlated with body mass index (BMI). Thus, bone marrow lesions have a significant genetic component. They commonly coexist with chondral defects and ROA but only share common genetic mechanisms to a limited degree. They are also more common with increasing age, male sex, and increasing BMI.

Highlights

Osteoarthritis (OA) is the most common form of arthritis, especially of the knee, and is a leading cause of musculoskeletal disability in most developed countries [1]
Bone marrow lesions have a significant genetic component. They commonly coexist with chondral defects and Radiographic osteoarthritis (ROA) but only share common genetic mechanisms to a limited degree
With the use of the same sibpair cohort measured at follow-up, the aim of the present study was to estimate the heritability of bone marrow lesions and to assess whether the heritability is independent of other factors including chondral defects and knee alignment

Summary

Introduction

Osteoarthritis (OA) is the most common form of arthritis, especially of the knee, and is a leading cause of musculoskeletal disability in most developed countries [1]. Knee alignment is one of the key determinants of load distribution [5], and knee medial bone marrow lesions are more likely in OA patients with varus knee alignment, whereas lateral bone marrow lesions are more common in those with valgus alignment [6]. Chondral defects and bone marrow lesions commonly coexist in patients with either OA or chondral injuries, and bone marrow lesions are mostly located beneath chondral defects [7,8,9]. We recently found in a large sample that chondral defects and bone marrow lesions were independently associated with knee pain [10], suggesting other pathways between bone marrow lesions and pain

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