| Rheumatoid arthritis |
BMD data of patients with low to moderately active RA demonstrated an association between high radiological RA damage and low BMD at the hip, which suggests an association between the severity of RA and the risk of generalised bone loss, which also occurred in corticosteroid naive patients [27]. There is a significant negative relationship between femoral neck BMD and disease duration in RA. The value of OR increases proportionately with lengthening of disease duration which can be reduced significantly by methotrexate therapy [28]. |
[27–28] |
| TGF-beta signaling pathway |
TGF-beta is the possible Link between loss of bone mineral density and chronic inflammation [29]. TGF-β/BMPs have widely recognized roles in bone formation during mammalian development and exhibit versatile regulatory functions in the body [30]. |
[29–30] |
| Focal adhesion |
Proline-rich tyrosine kinase 2 (PYK2), a member of the focal adhesion kinase family, plays a key role in the regulation of bone formation, and so inhibitors of this kinase might represent potential bone-building therapies for osteoporotic disease [31]. The focal adhesion, the actin cytoskeleton and cell-cycle are connected pathways and their genes are implicated in the pathogenesis of low BMD [32]. |
[31–32] |
| Type I diabetes mellitus |
The lower BMD in type 1 versus type 2 diabetic patients and control subjects probably results from more rapid bone loss after the onset of type 1 diabetes [33]. patients with type 1 diabetes have a 6.9-fold increased incidence of hip fracture compared to controls [34]. |
[33–34] |
| Regulation of actin cytoskeleton |
The focal adhesion, the actin cytoskeleton and cell-cycle are connected pathways [32]. Genes in these three pathways are implicated in the pathogenesis of low BMD [32]. Genome-wide linkage studies have highlighted the chromosomal region 3p14-p22 as a quantitative trait locus for BMD [35]. The FLNB gene, which is thought to have a role in cytoskeletal actin dynamics, is located within this chromosomal region and presents as a strong candidate for BMD regulation [35]. Mullin et al. identified significant associations between SNPs in the FLNB gene and BMD in Caucasian women [35]. |
[32, 35] |
