Higher bone turnover is related to spinal radiographic damage and low bone mineral density in ankylosing spondylitis patients with active disease: a cross-sectional analysis.

Hendrika Bootsma,Martha K Leijsma,Eveline Van Der Veer,Suzanne Arends,Monique Efde,Elisabeth Brouwer,Anneke Spoorenberg,Nic J G M Veeger,Reinhard Bos

doi:10.1371/journal.pone.0099685

Hendrika Bootsma, Martha K Leijsma + Show 7 more

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https://doi.org/10.1371/journal.pone.0099685

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Abstract

IntroductionAnkylosing spondylitis (AS) is characterized by excessive bone formation and bone loss. Our aim was to investigate the association of bone turnover markers (BTM) with spinal radiographic damage and bone mineral density (BMD) in AS patients with active disease.Methods201 consecutive AS outpatients of the Groningen Leeuwarden AS (GLAS) cohort were included. Serum markers of bone resorption (C-telopeptides of type-I collagen, sCTX) and bone formation (procollagen type-I N-terminal peptide, PINP; bone-specific alkaline phosphatase, BALP) were measured. Z-scores were used to correct for the normal influence that age and gender have on bone turnover. Radiographs were scored by two independent readers according to modified Stoke AS Spinal Score (mSASSS). The presence of complete bridging (ankylosis of at least two vertebrae) was considered as measure of more advanced radiographic damage. Low BMD was defined as lumbar spine and/or hip BMD Z-score ≤ −1.ResultsOf the 151 patients with complete data, 52 (34%) had ≥1 complete bridge, 49 (33%) had ≥1 syndesmophyte (non-bridging), and 50 (33%) had no syndesmophytes. 66 (44%) had low BMD. Patients with bridging had significantly higher sCTX and PINP Z-scores than patients without bridging (0.43 vs. −0.55 and 0.55 vs. 0.04, respectively). Patients with low BMD had significantly higher sCTX Z-score than patients with normal BMD (−0.08 vs. −0.61). After correcting for gender, symptom duration, and CRP, sCTX Z-score remained significantly related to the presence of low BMD alone (OR: 1.60), bridging alone (OR: 1.82), and bridging in combination with low BMD (OR: 2.26).ConclusionsThis cross-sectional study in AS patients with active and relatively long-standing disease demonstrated that higher serum levels of sCTX, and to a lesser extent PINP, are associated with the presence of complete bridging. sCTX was also associated with low BMD. Longitudinal studies are needed to confirm that serum levels of sCTX can serve as objective marker for bone-related outcome in AS.

Highlights

Ankylosing spondylitis (AS) is characterized by excessive bone formation and bone loss
Severe vertebral bone loss may lead to vertebral fractures with increased spinal deformity. [8,9] The presence of inflammation, low serum vitamin D levels, medication use, and decreased mobility related to pain, stiffness, and radiographic damage may contribute to bone loss in AS patients.[10,11,12,13]
A relation was found between a biochemical marker of type II collagen degradation and increased radiographic damage or 2-year progression. [17,18] These studies showed a relation between a biochemical marker of type I collagen degradation and lower bone mineral density (BMD) at the hip. [17,18] In one of our previous studies, we demonstrated that higher serum levels of CTX-I are associated with bone loss in AS patients with active disease. [11]

Summary

Introduction

Ankylosing spondylitis (AS) is characterized by excessive bone formation and bone loss. Our aim was to investigate the association of bone turnover markers (BTM) with spinal radiographic damage and bone mineral density (BMD) in AS patients with active disease. Spinal radiographic outcome related to excessive bone formation, so called osteoproliferation, comprises the formation of syndesmophytes with as final outcome complete bridging (ankylosis of two vertebrae). Excessive bone loss can lead to osteopenia and osteoporosis, assessed by bone mineral density (BMD), which can already be observed at early stages of the disease. [8,9] The presence of inflammation, low serum vitamin D levels, medication use, and decreased mobility related to pain, stiffness, and radiographic damage may contribute to bone loss in AS patients.[10,11,12,13] Severe vertebral bone loss may lead to vertebral fractures with increased spinal deformity. [8,9] The presence of inflammation, low serum vitamin D levels, medication use, and decreased mobility related to pain, stiffness, and radiographic damage may contribute to bone loss in AS patients.[10,11,12,13]

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