Part 2: The Genetics of metabolic bone diseases which influence back pain
Osteoporotic vertebral fractures
Vertebral insufficiency fractures are a major cause of chronic low back pain. In the year 2000, there were approximately 1.4 million people suffering with vertebral fractures secondary to osteoporosis [51]. There are known genetic factors which influence the onset of osteoporosis, mostly related to oestrogen function. Erdogan et al. [52] found that ERα gene polymorphisms correlated with bone density in 126 postmenopausal Turkish females, which concurred with the findings of Gennari et al. [53]. There may be an advantage conferred to the intervertebral discs by having low bone mineral density, according to Wang and colleagues [54]. An MRI (magentic resonance imaging) and DEXA (dual-energy X-ray absorptiometry) study of 359 people’s lumbar spines showed a significant inverse correlation between bone mineral density and lumbar disc degeneration in females, and a positive trend in males, again supporting the hypothesis that osteoporosis has a protective effect on disc integrity [54].
Whereas low bone density increases the risk of painful insufficiency fractures, it appears that high bone mineral density correlates with disc degeneration. A recent cadaveric study showed that when CT scans calculated vertebral body bone mineral density, i.e. excluding the posterior elements and endplates, there was a significant association with increasing bone density, correlating with more severe adjacent disc degeneration, as seen on discography. Unfortunately, being a cadaveric study, there was no available information relating to associated symptoms [55]. Conflicting evidence comes from Adams et al., who performed mechanical studies of cadaveric lumbar spines. The spines were compressed and the load distribution assessed in the three spinal columns (anterior half vertebral body, posterior half vertebral body and neural arch). The neural arch accepted more load according to the degree of disc degeneration, with approximately two-thirds of total compressive load transferred through the facet joints in spines with severe disc degeneration. They found that the bone mineral density of the anterior vertebral body was reduced in those vertebrae that were effectively stress-shielded by the posterior load transfer. The team hypothesised that this may increase the risk of anterior insufficiency fractures in the flexed position [56]. More research is required to conclude whether there is truly an inverse relationship between vertebral body bone mineral density and disc degeneration.
The genetics of vertebral fractures from other metabolic bone diseases
The most common lysosomal storage disease, Gaucher disease, is due to a genetic deficiency in lysosomal glucocerebrosidase. One study found a 15 per cent prevalence of vertebral fractures in 105 patients with Gaucher disease type 1 [57]. Osteogenesis imperfecta (OI) is a group of inherited diseases affecting collagen type 1, which result in osteopenia. Patients with OI have increased incidence of fractures including vertebral fractures. Paget’s disease is the second most prevalent metabolic bone disease after osteoporosis. There are subsets of Paget’s disease which are caused by genetic mutations of the sequestosome gene (SQSTM1); however, not all types of Paget’s disease have been definitively associated with genetic deficiences [58]. Close associations have been found between four genes and the development of Paget’s disease, implying that patients with this disease are likely to have a genetic mutation which predisposes them to developing the illness [59].
The inherited disorders of renal phosphate wasting result in hypophosphataemia and rickets. This group of disorders results in skeletal deformities as well as an increased risk of fractures.
The genetics of rheumatoid arthritis
Rheumatoid arthritis (RA) is a systemic autoimmune condition which manifests itself as a chronic symmetrical polyarthritis due to synovitis in around one per cent of the population. It mainly affects women and genetics are believed to account for around 60 per cent of susceptibility to RA [60] – there is an increased incidence of RA in first-degree relatives of those with the condition, and 15 per cent concordance is seen in monozygotic twins. Rheumatoid factors are present in the majority of patients with RA, and these comprise circulating autoantibodies against the Fc portion of IgG that aggregate into complexes to trigger inflammation via the activation of complement. The disease process in RA affects the lumbar spine causing symptomatic backache of at least three months in one-third of patients [61]. As the facet joints are synovial joints, rheumatoid synovitis can create synovial cysts which can cause both backache and sciatica [62]. Although most literature refers to cervical spine instability as a consequence of RA, there are several reports which explore histopatholog