4/10/15
by Wayne Kuznar
Contributing Writer
In patients with axial spondyloarthritis (SpA), increased serum alkaline phosphatase (ALP) levels not only reflect high disease activity but also low bone mineral density (BMD) and structural damage, according to a cross-sectional study by South Korean researchers.
The need for biomarkers that reflect both disease activity and bone metabolism in SpA is clear. “At present, few laboratory markers provide a reliable indication of disease activity, low BMD, or new bone formation in these patients,” the authors, led by Kwi Young Kang at the Catholic University of Korea, Seoul, South Korea, wrote in Seminars in Arthritis and Rheumatism.
They sought to determine the relationship between ALP and disease activity, as measured by the Ankylosing Spondylitis Disease Activity Score (ASDAS), and to evaluate the association between serum ALP levels and BMD and radiological damage in 115 patients (mean age, 35 years) with ankylosing spondylitis (AS). All women were premenopausal and younger than 50 years; all men were younger than 60. Mean symptom duration was 8.5 years and the time after axial SpA diagnosis was 4.9 years.
In addition to the ASDAS, disease activity was measured using patient global assessment (PGA) and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). The Bath Ankylosing Spondylitis Functional Index (BASFI) was also recorded. BMD at the lumbar spine, and femoral neck was evaluated in 70 of the 115 patients.
Radiographs of the cervical spine, lumbar spine, and pelvis were obtained and used as a measure of disease activity. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were also measured; in 40 patients, these markers, in addition to serum ALP, were also measured at 3 months.
The mean serum ALP level was 77±26 U/l. Fourteen (13%) of the 115 patients had an increase in serum ALP levels. ASDAS-ESR and ASDAS-CRP scores were significantly higher in patients with increased ALP levels than in those with normal ALP levels (P=0.009 and P=0.019, respectively).
Mean ESR and CRP levels were also significantly higher in patients with increased versus normal ALP (P=0.004 and P=0.001, respectively).
The levels of two bone resorption markers, bone-specific alkaline phosphatase (BALP) and cross-linked telopeptide of type-I collagen (sCTX), were significantly different between patients with normal ALP and those with increased ALP levels (P= 0.001 and P=0.001, respectively).
“Regardless of the differences in ALP levels between individual patients, the ASDAS showed that serum ALP levels were higher in AS patients with more active disease,” the authors wrote.
After adjustment for age and sex (P=0.004), serum ALP levels increased with disease activity. ALP showed a significant correlation with BASDAI (r=0.20, P=0.042), BASFI (r=0.27, P=0.006), and the PGA score (r=0.27, P=0.006). ALP was also correlated with ASDAS-ESR (r=0.32, P=0.001) and ASDAS-CRP (r=0.40, P< 0.001).
ESR and CRP were also correlated with ALP levels (r=0.22 and r=0.80, P=0.024 and P< 0.001, respectively). Bone BALP and sCTX did not correlate with disease activity variables.
A significant correlation was found between ALP and the sacroiliitis grade (r=0.36 and P<0.001) and between serum ALP levels and the modified Stoke AS Spinal Score (r=0.30, P=0.002).
There was a negative correlation between ALP levels and BMD in the lumbar spine and femoral neck, and also between ALP and BMD, T score and Z score in the lumbar spine and femoral neck, and between ALP and the hip Z score.
On multivariate analysis, serum ALP and ESR were independently associated with the ASDAS-CRP score (ß=0.217, P=0.012 and ß=0.530, P< 0.001, respectively).
Differences in ALP levels at baseline and 3 months correlated well with differences in CRP levels (r=0.401, P=0.014).
The investigators claim that serum ALP levels may be useful for monitoring disease activity in patients with SpA. “Further prospective studies that include larger numbers of patients are needed to confirm the association between ALP levels and disease activity,” they conclude.
The cross-sectional design represents one limitation of the study. In addition, only the BALP isoform of ALP was measured, limiting the ability to determine the source of excess ALP in patients.
The authors have no competing interests to declare.
The study was supported by a grant from the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology.
Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco