Ankylosing spondylitis and bone mineral density—what is the ideal tool for measurement?
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- Lange, U., Kluge, A., Strunk, J. et al. Rheumatol Int (2005) 26: 115. doi:10.1007/s00296-004-0515-4
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Ankylosing spondylitis (AS) is characterised by chronic inflammation and partial ossification, yet vertebral fractures due to osteoporosis, although common, are frequently unrecognised. The aim of this study was to (1) show the frequency of changes in the progress of osteopenia/osteoporosis in AS depending on duration and stage of the disease and (2) assess the ranking of two different methods of bone density measurement in this clinical pattern. We measured bone density in 84 male and female patients with both dual X-ray absorptiometry (DXA) and single energy quantitative computed tomography (SE-QCT). In the initial and advanced stages of the disease, a high decrease in axial bone density could be verified (DXA: osteopenia in 5% and osteoporosis in 9.2%; SE-QCT: osteopenia in 11.8% and osteoporosis in 30.3%). Peripheral bone density decrease as in osteopenia could be proven in 17.6% by DXA measurement. With SE-QCT, a decrease in vertebral trabecular bone density could already be observed in the initial stage and continued steadily during the course of the disease; cortical bone displayed the same trend up to stages of ankylosis. With DXA, valid conclusions are more likely to be expected in less marked ankylosing stages of AS. In stages of advanced ankyloses in the vertebral region (substantial syndesmophytes), priority should be given to SE-QCT, due to the selective measurement of trabecular and cortical bone. The DXA method often yields values that are too high, and the replacement of vertebral trabecular bone by fatty bone marrow is not usually recorded as standard. There may already be an increased risk of bone fracture in AS in osteopenia on DXA along with an osteoporosis already established on SE-QCT.
KeywordsAnkylosing spondylitisBone mineral densityOsteopeniaOsteoporosis
In the past few decades, the pathogenesis of new bone formation and ossification of the ligamentous apparatus was of primary concern in the characterisation of ankylosing spondylitis (AS). Despite the development of syndesmophytes, patients with AS are not protected against fractures, and osteoporosis can be diagnosed in a large percentage of cases [1, 2, 3, 4, 5]. In contrast to rheumatoid arthritis, in AS the anatomical distribution, clinical significance, and point of the occurrence of osteoporosis are for the most part still not clear.
Current problems in bone density measurement
1. Different methods (dual photon absorptiometry, quantitative ultrasonometry, computed tomography)
2. Different topographic measurement (lumbar, radius, hip [forward triangle, trochanter, total hip], heel)
3. Poor comparison of the place of measurement
4. Different norm area (different definition, different standard: mean±2 SD)
5. False interpretation (low bone mineral density equivalent to osteoporosis)
Problems of integral bone mineral density measurement methods
1. False high BMD because of degenerative manifestations (i.e. spondylophytes, osteochondrosis, scoliosis, inflammation, ossification, or calcifying/sclerotic manifestations (i.e. aorta, lymph nodes, ligaments)
2. X-ray of the spine is necessary for valid interpretation
3. Strong lumbar lordosis reduces the demarcation of the vertebrae and reduces reproduction
4. No possible statement about morphogenetics
5. No separate measurement of cortical and trabecular bone
Problems of computed tomographic measurement
1. Only measurement of the middle layer of the vertebrae (result is not valid for the entire vertebra)
2. High fat error (i.e. SE=10–30%). (Discrepancy between model and reality is the reason for the systematic error)
3. Different selection of the region of interest (ROI)
4. Different norm areas
5. Fractures of the vertebrae must be excluded
6. Higher radiation load (i.e. SE-QCT<100 μS)
Demographic and disease-specific data. NSAIDs nonsteroidal anti-inflammatory drugs, DMARDs disease-modifying antirheumatic drugs, HLA human leukocyte antigen
Group I (n=27)
Group II (n=22)
Group III (n=15)
Group IV (n=20)
Age at time of diagnosis (years)
Duration of disease (years)
NSAIDs in the previous 12 months
DMARDsin the previous 12 months
Glucocorticoids in the previous 12 months
All data are presented as means±SD and evaluated using the version 10.0.7 statistical software package for PC (SPSS, Chicago, Ill., USA). Data were compared using the t-test. P<0.05 was taken as significant.
Osteopenia/osteoporosis by DXA and SE-QCT
DXA total hip
Vertebral fractures by thoracolumbar X-ray
Secondary osteoporosis in inflammatory rheumatic conditions is by no means rare and represents a problematic and pathogenetic heterogenous complication [14, 15, 16, 17]. With its attendant increased fracture risk, osteoporosis is a common complication in AS [4, 17, 18]. Even early descriptions of the clinical picture arrived at by means of pathological studies contain corresponding findings [19, 20].
Only in the past few years have there been publications of international studies dealing with axial osteoporosis in AS [2, 3, 4, 21, 22, 23, 24]. The aetiopathogenesis of secondary osteoporosis in AS is still unclear. According to Schilling [21, 22, 25], it is possible to differentiate between two forms of osteoporosis: a so-called early type, associated with the spondylarthritis type in young people (onset before age 20), and a late type (syndesmophytic development) in adults. The categories presented by Schilling have been corroborated by recent studies which were able to verify decreased bone density already in early forms of AS [1, 2, 3, 4, 23, 24, 26]. Whereas segment inactivity resulting from ensuing ankylosis is assumed as a pathogenetic factor in the late type of osteoporosis, inactivity atrophy in the early type of osteoporosis is quite unlikely a cause [21, 22, 25].
Longitudinal studies in early AS have shown that spine and hip bone mineral density decreased predominantly in patients with active AS [24, 27, 28] who maintained normal spinal mobility and were physically fit and active. Recently, a prospective study showed a clear relationship between loss of bone mass and inflammatory activity in early AS measured according to biological parameters, with no association between reduction in bone mass, vertebral mobility, and daily physical activity . Our study group linked high disease activity in AS with altered vitamin D metabolism and increased bone resorption [30, 31] and reported a correlation between plasma tumor necrosis factor alpha, insulin-like growth factor 1, biochemical markers of bone metabolism with markers of inflammation and disease activity and clinical manifestations in AS .
To summarise: various factors such as treatment, hormone disorders, and decreased mobility or physical activity may contribute to the development of osteopenia/osteoporosis in AS. Lately it was shown that the vitamin D receptor gene may be involved in bone mineral density differences, bone metabolism, and inflammatory processes in AS .
Hitherto, examinations of bone density in AS were carried out mainly with projective methods (single and dual photon absorptiometry). Consequently, a decrease in bone density was observed up to the occurrence of ankylosations, with increased bone density in pronounced ankylosing stages [3, 23, 26]. One of the disadvantages of these methods is that there is no separate measurement of spongiosa and cortical bone. Since osteoporosis is accompanied initially by spongiosa and only later involves cortical bone loss, selective measurement of spongiosa and cortical bone was taken with SE-QCT along with the DXA determination of bone density in this particular study.
A considerable decrease in bone density could be verified in the initial and advanced stages of AS. Correspondingly, in SE-QCT during the initial stage of sacroiliitis, there was evidence of decreased mineral salt content of spongiosa with a further constant decrease in advanced stages of the disease. With projective methods, erroneously high values are often obtained following degenerative changes, scoliosis, anulus ossification, and calcification/sclerosis outside the bone [9, 34]. Thus, at present the most reliable means of verifying beginning and manifest spongiosa loss is the SE-QCT method.
In the studies conducted here, reduction of cortical bone was evident parallel to spongiosa loss and then, in advanced stages, there was a tendency for it to increase. Since cortical bone and spongiosa decrease in parallel up to stages of ankylosation, osteoporosis can not be seen solely as a result of static relief due to the thickening of the cortical bone. Possible immobilisation, especially in the initial phase, is also not an explanation for osteoporosis. This is a possible indication of the involvement of humoral factors in the occurrence of osteoporosis.
Are vertebral-body fractures more common in the syndesmophytic type of AS? (According to Kessler-Leonhardt and Droste , over 80% of the patients with vertebral body deformations had syndesmophytes, and osteoporosis was observed in 70–90%; but vertebral fractures were also present in cases of mild osteopenia.)
Does the so-called mixed form possibly protect against osteoporotic fractures?
Is there the likelihood of a so-called fracture threshold?
Are neurological complications more likely to be found in advanced stages of AS?
In summary, it is interesting that the study presented here verifies a bone density decrease already in the initial stage of AS and continuing in advanced stages as well, not only in the region of the spine but also on the femoral neck. Histological examinations point to an osteoclast/osteoblast imbalance [3, 35], which would indicate the prescription of antiresorptive therapy with a biphosphonate. An initial study has shown its positive effects on bone density . New data suggest that the benefit of anti-tumour-necrosis-factor alpha therapy on bone mineral density in patients with spondylarthropathy may be due to an uncoupling effect on bone cells .