This study shows a high prevalence (47%) of low BMD in both femur and lumbar spine in SpA patients with early disease. Low BMD proved to be significantly associated with male gender and the severity of the disease, as shown by high BASMI and BASFI levels. Our study is the first to report on BMD status in an early SpA population, which is in contrast with other studies reporting only on AS. Furthermore, even in most “early AS studies”, AS patients usually have longer disease durations [19–21].
Osteoporosis is a well-known complication of long-standing AS. However, studies about the degree of osteoporosis in a SpA population and its relation with risk factors are limited, particularly in patients with an early disease. Traditional risk factors affecting the BMD state in the general population are female gender, increasing age, low body mass index, menopause, and the presence of chronic inflammatory diseases. No significant differences were found between SpA patients with low and normal BMD in terms of these risk factors in this study. In contrast with the general population, in this study, low BMD values were particularly found in relatively young men instead of women who usually have lower BMD values due to lower peak bone mass and bone loss during menopause, although the number of postmenopausal women in this study was very low. The relatively high prevalence of osteoporosis in male patients could be explained by a higher disease activity in men compared with women, although this could not be demonstrated (with the BASDAI) in our cross-sectional study. Another possibility could be a difference in hormone levels, testosterone, and estrogen in AS patients (compared with the healthy population), although observations in previous studies were not conclusive on this subject [22–25] and could not explain the early onset of osteoporosis in male patients. However, it is possible that premenopausal women are less prone to SpA-related bone loss than male patients due to the protective action of estrogen.
In SpA (especially AS), other potential risk factors for bone loss occur, such as inflammation and mechanical factors: rigidity of the spine resulting in limited mobility and reduced physical activity due to pain and stiffness. Data about these risk factors, high disease activity variables such as ESR, CRP, BASDAI, as well as indicators of low functional capacity such as high BASFI and BASMI scores, are not consistently reported in relation with low BMD levels in different studies [2, 19, 20]. In this study, disease activity parameters, such as increased CRP and high BASFI and BASMI scores, correlated significantly with low bone mass in femoral neck as well as in lumbar spine. Inflammation in SpA and decreased functional capacity turned out to be major contributors to this process.
The role of pro-inflammatory cytokines might be important for the onset of osteoporosis because increased TNF-alpha levels have been found in patients with AS compared with subjects with non-inflammatory back pain, and correlations have been found between disease activity and markers associated with an increased bone metabolism . This supports the hypothesis that increased inflammatory activity in AS will lead to increased bone resorption and decreased bone density.
Mechanical factors, such as rigidity of the spine due to ankylosis, seem to be a less likely explanation for low BMD in our group of patients because they were relatively young and had a short disease duration. The fact that low BMD is encountered in a young population with an early disease is very interesting. In most other studies, “early” often refers to patients who have not yet developed ankylosis or other radiological progression signs, or these studies made use of disease durations as time since diagnosis and then referred to a disease duration of <10 years [19–21]. The issue of defining disease duration has been much debated in the AS literature, and with the knowledge of today, the onset of the first symptoms is considered to be most important . The majority of the early SpA patients included in this study had a short time since diagnosis (median of 6.6 months) and disease duration (median of 6.3 years), counting from the very first symptoms of axial manifestations (i.e., inflammatory back pain or AS specific symptoms), which is shorter than the mean duration of 8–10 years before diagnosis, as mentioned in the literature [28–30].
Low BMD in this early SpA group is equally prevalent in femur and spine, although osteoporosis is slightly more prevalent in the spine (7.7%) compared with the femur (2.3%). This observation is in contrast with long-standing AS in which reduced bone mass is particularly reflected by low BMD in the hips. The lumbar spine often shows misleading high BMD values due to bridging syndesmophytes and ankylosis, which might mask osteoporosis in AS patients with an advanced disease [1, 2, 10, 11]. Although it seems unlikely that many syndesmophytes and ankylosis of the vertebrae have developed already at such an early stage of the disease, we checked the radiographs of the lumbar spine. Only a few patients (nine patients) had a small syndesmophyte which did not influence the presented results of the analyses (data not shown).
Finally, a relatively small group (28%) of our early SpA cohort had diagnoses other than AS, of which 31% turned out to have a low BMD. In the univariate analysis, the diagnosis AS seemed to be significantly related to low BMD, but after correction for other risk factors in the multivariate model, this association was not found. Therefore, patients with spondylarthropathies as a group are prone to have low BMD at an early stage of the disease.
In conclusion, this study demonstrates that half of the early SpA patients already show low BMD. Especially men at a relatively young age with high disease severity (indicated by impaired physical function with high BASMI and BASFI levels) are prone to have low BMD, and there is a strong tendency for an association with the diagnosis AS and high CRP. At early stages of the disease, no differences are found in low BMD between hips and spine.
These findings are clinically relevant since reduced bone mass will increase the risk of vertebral deformities and fractures. Therefore, we would like to emphasize the need for more alertness for osteoporosis and osteopenia in spondylarthropathy patients at an early stage of the disease.