Clinical study on osteoporosis in ankylosing spondylitis

ABSTRACT Ankylosing spondylitis (AS) is a disease characterized by chronic inflammation and osteoproliferation in the spine, leading to bony fusion (ankylosis) of the sacroiliacal joints, the growth of bony spurs (syndesmophytes) between the vertebras and impairment of back-mobility. Paradoxically AS patients also have an increased risk of osteoporosis and vertebral fractures. In this cross-sectional study on 210 included AS patients (New York criteria) from West Sweden we found that osteoporosis and vertebral fractures were common but often not diagnosed or treated. Osteoporosis (WHO definition) was found in 21 % and osteopenia in 44 % of patients 50 years or older and bone mineral density (BMD) below expected range for age was found in 5% of patients younger than 50 years. Totally 42 vertebral fractures were diagnosed in 24 patients (12%). Osteoporosis was associated with old age, long disease duration, advanced chronic AS related changes in the spine, impairment of back- mobility, history of coxitis, glucocorticoid use, elevated inflammatory parameters, low BMI and menopause. Vertebral fractures were associated with old age, long disease duration, advanced chronic AS related changes in the spine, impairment of back-mobility, poor self-estimated general health, smoking, menopause and low BMD. The osteoproliferation in AS can cause artifactual increase of lumbar BMD when measured in anteroposterior (AP) projection with dual-energy x-ray absorptiometry (DXA). Lumbar BMD can also be measured in the vertebral bodies using lateral projection. Comparing lateral with AP DXA we found that lateral lumbar DXA was more sensitive in detecting low BMD, less affected by the osteoproliferation in AS and more closely associated with vertebral fractures. Combining AP and lateral lumbar DXA also allows for the estimation of volumetric BMD (vBMD). There is a lack of biomarkers for osteoproliferation and osteoporosis in AS. We analysed serum levels of the following biomarkers for bone metabolism in relation to disease activity, back mobility, osteoproliferation and BMD: Wingless proteins (Wnt-3a, Wnt-5a), Dickkopf-1 (Dkk-1), sclerostin, soluble receptor activator for nuclear factor-κΒ ligand (sRANKL) and osteoprotegerin (OPG). We found that the AS patients in comparison with healthy controls had significantly higher serum levels of Wnt-3a, but lower serum levels of sclerostin and sRANKL. Elevated serum levels of Wnt-3a were associated with osteoproliferation and impairment of back-mobility, independent of age, suggesting that Wnt-3a could be a marker for the osteoproliferative process. High CRP was associated with lower levels of the Wnt inhibitors Dkk-1 and sclerostin. BMD of femoral neck was negatively correlated with Wnt3a and OPG and positively correlated with sRANKL in the univariate analyses, but positively associated with sclerostin after adjusting for age in multiple regression. Osteoproliferation and impairment of back mobility and function were in addition associated with smoking. To study peripheral bone microarchitecture in relation to osteoproliferation, fractures and vBMD of the spine 69 male AS patients were randomized to undergo assessment with High Resolution peripheral Quantitative Computed Tomography (HRpQCT) of the ultra-distal radius and tibia and QCT of the lumbar spine. We found strong correlations between trabecular vBMD in lumbar spine and radius and tibia, indicating coupling of trabecular bone loss in axial and peripheral skeleton. Low lumbar vBMD, vertebral fractures and osteoproliferation were in addition associated with deterioration of the bone microarchitecture of the peripheral skeleton. In lumbar spine decreasing trabecular vBMD was associated with increasing cortical vBMD, suggesting that cortical bone is appositioned as part of the osteoproliferative process meanwhile trabecular bone is lost in the vertebral bodies. AS is closely related to inflammatory bowel disease (IBD) and subclinical intestinal inflammation has been detected in many AS patients. We measured fecal calprotectin, a marker for neutrophil inflammation, to indirectly study the prevalence of gut inflammation in AS. We found elevated levels of fecal calprotectin in 68% of the AS patients, without association with gastrointestinal symptoms. Fecal calprotectin was higher in users of non-steroidal anti-inflammatory drugs (NSAIDs) in a dose dependent manner, but lower in patients treated with methotrexate or TNFα-blockers. No association was found between fecal calprotectin and BMD. ISBN: 978-91-628-8618-

Which measuring site in ankylosing spondylitis is best to detect bone loss and what predicts the decline : results from a 5-year prospective study

Background: Studies have shown increased prevalence of osteoporosis and increased risk for vertebral fractures in patients with ankylosing spondylitis (AS). Measurements of bone mineral density (BMD) in the lumbar spine anterior-posterior (AP) projection may be difficult to interpret due to the ligamentous calcifications, and the lateral projection might be a better measuring site. Our objectives were to investigate BMD changes after 5 years at different measuring sites in patients with AS and to evaluate disease-related variables and medications as predictors for BMD changes. Methods: In a longitudinal study, BMD in Swedish AS patients, 50 +/- 13 years old, was measured with dual-energy x-ray absorptiometry (DXA) at the hip, the lumbar spine AP and lateral projections, and the total radius at baseline and after 5 years. Patients were assessed with questionnaires, blood samples, and spinal radiographs for grading of AS-related alterations in the spine with the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) and assessment of vertebral fractures by the Genant score. Multiple linear regression analyses were used to investigate predictors for BMD changes. Results: Of 204 patients included at baseline, 168 (82%) were re-examined after 5 years (92 men and 76 women). BMD decreased significantly at the femoral neck and radius and increased significantly at the lumbar spine, both for AP and lateral projections. Mean C-reactive protein during follow-up predicted a decrease in the femoral neck BMD (change in %, beta = -0.15, p = 0.046). Use of bisphosphonates predicted an increase in BMD at all measuring sites (p < 0.001 to 0.013), except for the total radius. Use of tumor necrosis factor inhibitors (TNFi) predicted an increase in AP spinal BMD (beta = 3.15, p = 0.012). Conclusion: The current study (which has a long follow-up, many measuring sites, and is the first to longitudinally assess the lateral projection of the spine in AS patients) surprisingly showed that lateral projection spinal BMD increased. This study suggests that the best site to assess bone loss in AS patients is the femoral neck and that inflammation has an adverse effect, and the use of bisphosphonates and TNFi has a positive effect, on BMD in AS patients

Subjective cognitive impairment is a predominantly benign condition in memory clinic patients followed for 6 years : the Gothenburg-Oslo MCI study

Background/Aims: In the quest for prevention or treatment, there is a need to find early markers for preclinical dementia. This study observed memory clinic patients with subjective cognitive impairment (SCI) and normal cognitive function at baseline. The primary aim was to address SCI as a potential risk factor for cognitive decline. The secondary aim was to address a potential relation between (1) baseline cerebrospinal fluid biomarkers and (2) a decline in memory performance over the first 2 years of follow-up, with a possible cognitive decline after 6 years. Methods: Eighty-one patients (mean age 61 years) were recruited from university memory clinics and followed up for 6 years. Results: Eighty-six percent of the cohort remained cognitively stable or improved, 9% developed mild cognitive impairment, and only 5% (n = 4) developed dementia. Regression analysis revealed that low levels of Aβ42 at baseline and memory decline during the first 2 years predicted dementia. When combined, these variables were associated with a 50% risk of developing dementia. Conclusions: Cognitive stability for 86% of the cohort suggests that SCI is predominantly a benign condition with regard to neuropathology. The low number of individuals who developed dementia limits the generalizability of the results and discussion of progression factors.