Clinica Chimica Acta 289 (1999) 99–110

www.elsevier.com / locate / clinchim

Biochemical markers of bone remodeling and bone

sialoprotein in ankylosing spondylitis

Carlos Acebes a , *, Concepcion

´ de la Piedra b , Maria Luisa Traba b ,
Markus J. Seibel c , Carlos Garcıa ´ d , Jacome Armas e ,
´ Martın
Gabriel Herrero-Beaumont a
a
Rheumatology Department, Bone and Mineral Metabolism, Fundacion ´ Jimenez
´ ´ ,
Dıaz
Avda. Reyes Catolicos 2, 28040 Madrid, Spain
b
Biochemistry Laboratory, Bone and Mineral Metabolism, Fundacion ´ Jimenez
´ ´ , Madrid, Spain
Dıaz
c
Department of Medicine, Endocrine and Osteodiagnostic Laboratories, University of Heidelberg,
Heidelberg, Germany
d
BIO-RAD Laboratories, Alcobendas, Madrid, Spain
e
Hospital Angra de Heroismo, Açores, Portugal

Received 5 May 1999; received in revised form 23 August 1999; accepted 25 August 1999

Abstract

The aim of this work was to determine bone mineral density (BMD) in a group of patients with
ankylosing spondylitis (AS) and to study alterations in bone remodeling in these patients. Eighteen
patients (16 males and two females) with AS, mean age 44.7, range 21–75, and 18 age- and
sex-matched healthy controls were studied. BMD was evaluated by dual energy X-ray absor-
ptiometry. The following biochemical markers of bone remodeling were studied: formation –
serum amino and carboxyterminal propeptides of procollagen I (PINP and PICP); resorption –
urinary total and free deoxypyridinoline and pyridinoline (TDpyr, FDpyr, TPyr and FPyr),
crosslinked aminoterminal telopeptides of collagen I (NTX), carboxyterminal telopeptide of
collagen I (CTX) and serum bone sialoprotein (BSP). Receiver operating characteristic (ROC)
curves of markers were also performed. We found a decrease of bone mass and an increase in
TPyr, FPyr, TDpyr, FDpyr, NTX and BSP in AS, but no significant differences were found in
PICP, PINP and CTX. FDpyr, FPyr and TPyr showed the highest discrimination between patients
and controls according to the results of the ROC curves. TPyr / TDpyr was higher in AS than in
controls. We found osteopenia, with a normal formation and a significant increase in bone
resorption in AS. FDpyr, FPyr and TPyr seem to present the best sensitivity for the study of
alterations of bone resorption in this pathology, although NTX, TDpyr and BSP also show

*Corresponding author. Fax: 1 34-91-549-4764.

0009-8981 / 99 / $ – see front matter  1999 Elsevier Science B.V. All rights reserved.
PII: S0009-8981( 99 )00170-9
100 C. Acebes et al. / Clinica Chimica Acta 289 (1999) 99 – 110

significant differences. The elevation in the ratio TPyr / TDpyr in AS compared to controls
indicates that in AS there is a type I-collagen degradation in tissues different from bone.  1999
Elsevier Science B.V. All rights reserved.

Keywords: Ankylosing spondylitis; Osteopenia; Procollagen I propeptides; Pyridinolines; Telopep-

tides; Bone sialoprotein

1. Introduction

Ankylosing spondylitis (AS) is a chronic inflammatory disease of unknown

cause that affects mainly the axial and less frequently the appendicular skeleton
[1]. The disease occurs principally in cartilaginous and synovial joints and in
sites of tendon and ligament attachment to bone (enthesis) [2].Vertebral os-
teopenia has been observed in patients with AS even in early disease [3,4] and it
has been confirmed by densitometric methods and histomorphometric studies
which demonstrate osteopenia and defects of mineralization [5].
The cause of osteopenia in AS remains controversial. A decrease in bone
formation [3,4,6], increase in bone resorption [7], or a normal bone remodeling
[8], have been reported. In spite of the fact that the field of biochemical markers
of bone turnover has experienced a great improvement in the last years [9], there
are few works in the literature that use the new available markers in the study of
bone remodeling in AS. If we exclude the bone isoenzyme of alkaline
phosphatase and osteocalcin, the most recent available bone remodeling markers
are related to collagen metabolism. Thus, amino and carboxyterminal prop-
eptides of procollagen I (PINP, PICP) are employed as bone formation markers
[10,11]. Although recent studies have demonstrated that PINP presents a high
sensitivity in the study of bone remodeling [10], we have not found any previous
report in which this marker has been used to evaluate bone formation in AS.
With respect to biochemical markers of bone resorption derived from collagen
breakdown, there is a series of new available compounds with a better specificity
and sensitivity than the classical hydroxyproline. Determinations of pyridinoline
(Pyr) and deoxypyridinoline (Dpyr) [12], the carboxyterminal telopeptide of
collagen type I (CTX) [13], and the pyridinoline cross-linked aminoterminal
telopeptides of type I collagen (NTX) [14] have shown a very good sensitivity
and specificity in the study of bone disorders such as postmenopausal os-
teoporosis [15]. However, we have not found in the literature any previous
report about their use in the study of AS, unless in the case of urinary Pyr and
Dpyr [7,8].
On the other hand, there is an increased interest about the study of bone
sialoprotein (BSP), a glycoprotein found only in tissues that eventually
 C. Acebes et al. / Clinica Chimica Acta 289 (1999) 99 – 110 101

mineralise. BSP facilitates the adhesion of several cell types through its integrin
binding (RGD) tripeptide sequence [16]. According to recent works, in most
clinical conditions, circulating BSP can be considered a marker of bone
resorption [17,18].
It is possible that measure of bone formation and resorption levels through the
determination of these new bone markers of high specificity and sensitivity
could constitute an important help in the understanding of the status of AS bone
turnover.
The aim of this work was: (1) to determine bone mineral density in a group of
patients with AS compared with a control population; (2) to study alterations in
bone remodeling in these patients through the determinations of a very complete
series of biochemical markers of bone turnover, derived from collagen metabo-
lism, most of them of recent availability; (3) levels of BSP were also studied.

2. Materials and methods

Eighteen patients diagnosed with AS as defined by the New York criteria

[19,20] were recruited from one of our rheumatology outpatient clinics during
six consecutive months. The study group consisted of 16 males (mean age 44.7,
range 21–75) and two females (mean age 44, range 28–60). Thirteen patients
presented a disease duration of more than 3 years (13.464.8, range 6–22) and
five patients of less than 3 years (2.360.8, range 1.3–3) and all of them showed
positive HLA B27. X-Ray of lumbar spine and hips were evaluated in all the
patients. They were receiving different analgesics and nonsteroidal-antiinflam-
matory drugs. Corticosteroids were not administered. The control group was
formed by eighteen healthy volunteers without any evidence of skeletal
abnormalities, matched in age and sex with AS patients.
Patients with radiological evidence of syndesmophytes or extensive os-
teophytes around the femoral neck were excluded from the bone mineral density
(BMD) study. From these premises, the lumbar BMD (L2–L4) of the two
females and ten males and the femoral neck BMD of the two females and 13
males were measured by dual-energy X-ray absorptiometry (DXA, Hologic
QDR 1000). We have used as diagnostic criteria for osteoporosis the definition
of WHO [21]. Although this definition is applied to females, we have extended
it to male population. We took as maximum peak of bone mass in males
0.92760.124 g / cm 2 for the femoral neck and 1.03960.119 g / cm 2 for lumbar
spine measured by DXA, in a Hologic QDR 1000, according to the standard of
an extensive male control population study [22]. From these values we
considered the existence of osteoporosis in male patients if BMD in lumbar
spine and / or femoral neck was , 0.710 g / cm 2 or , 0.580 g / cm 2 respectively
(maximum peak 2 2.5 S.D.). Osteopenia was defined in male population as
102 C. Acebes et al. / Clinica Chimica Acta 289 (1999) 99 – 110

values of BMD between 0.710–0.900 g / cm 2 for the lumbar spine and 0.580–
0.770 g / cm 2 for the femoral neck (range between maximum peak and 2 1 S.D.
and 2 2.5 S.D.). The peak of bone mass in the Spanish female population is
1.03160.104 g / cm 2 for lumbar spine and 0.84060.110 g / cm 2 for the femoral
neck [23].
Serum samples were drawn in the morning after an overnight fast. Two-hour
fasting morning urine samples (after the first voiding was discarded) were also
collected. Sera were separated from blood by centrifugation at 48C not more
than 1 h after sample collection and without delay were frozen in glass tubes at
2 608C until use. Aliquots of urine were also kept at 2 608C in glass tubes until
use.
Serum PICP was assayed by a RIA (Orion Diagnostica, Finland) [11]. Intra-
and inter-assay coefficients of variation of the method were less than 5 and 10%,
respectively. Sensitivity of the method was 1.2 mg / l.
Serum PINP was measured by an RIA (Orion Diagnostica, Finland) [24].
Intra- and inter-assay coefficients of variations of the method were less than 6
and 10%, respectively. Sensitivity of the method was 1.2 mg / l.
Urinary Pyr and Dpyr were assayed by HPLC, with a reverse phase column
and fluorimetric detection, after sample purification through a cellulose column
(CHROM-LINKSE, Bio-Rad, Italy). This method is a modification of that of
Black et al. [25]. Free Pyr (FPyr) and free Dpyr (FDpyr) were directly analysed.
For the determination of total (free and peptide bound) Pyr (TPyr) and total
Dpyr (TDpyr) urine was previously submitted to acid-hydrolysis at 1008C for 14
h. Intra-and inter-assay coefficients of variation of the method were less than 3.6
and 10.2%, respectively, for Pyr and 6.3 and 12%, respectively, for Dpyr.
Sensitivity of the method was 5 pmol / ml.
NTX determination was performed by ELISA (OsteomarkE, OSTEX) [14].
This assay utilises microwells as the solid-phase onto which NTX has been
absorbed. NTX in the sample competes with the solid-phase NTX for binding
sites of a monoclonal antibody labelled with horseradish peroxidase. Intra- and
inter-assay coefficients of variation of the method were less than 5 and 9%,
respectively. Sensitivity of the method was 20 nmol / l of bone collagen
equivalents (BCE).
Urinary CTX was assessed by ELISA (CrossLapsE, Osteometer, Denmark)
[13].The antigen, an eight amino acid sequence of the C-telopeptides of a-chain
of Type I collagen (EKAHD-b-GGR, b isomer), that is coated on the microwell,
and the soluble peptide present in the sample, compete for binding with an
antibody raised to this sequence. Intra- and inter-assay coefficients of variation
of the method were less than 9 and 12%, respectively. Sensitivity of the method
was 50 mg / l.
Values of all urinary markers were expressed as urinary creatinine ratios.
Urinary creatinine was measured using Jaffe´ reaction.
 C. Acebes et al. / Clinica Chimica Acta 289 (1999) 99 – 110 103

Serum concentrations of BSP were determined by a newly developed RIA

described elsewhere [26]. The coefficients of variation were 7.0% for intra-assay
variability and 9.1% for inter-assay variability. The lower detection limit in the
present RIA was 0.7 ng / ml. Spiking of human samples with purified BSP
resulted in a mean recovery of 99.4% (range 92–108%).
Statistical analysis of differences between groups was performed by Mann–
Whitney test. Linear regression between different parameters was also calcu-
lated. The diagnostic accuracy, measured as sensitivity and specificity, was
assessed by the Receiver Operating Characteristic (ROC) plots [27]. Statistical
differences between areas under ROC curves were also performed. All the
statistical studies were made with the MedCalc Software program (Belgium).

3. Results

According to the diagnostic criteria for osteoporosis and osteopenia for male
and female population indicated in Methods, none of the 13 male patients of our
group whose BMD was included in the study presented osteoporosis, but seven
of them (7 / 13) presented osteopenia. With respect to the two female patients
included in this study, neither of them presented osteoporosis nor osteopenia,
according to the maximum peak of bone mass in Spanish female population.
All the patients studied presented a normal renal function, in accordance with
their levels of creatinine clearance.
We did not find significant differences between controls and patients with AS
in the levels of PINP and PICP, the biochemical markers of bone formation
studied (Table 1). By contrast, levels of all the biochemical markers of bone
resorption studied in patients with AS, except for CTX were significantly higher
than those of control group (Table 2).
Among the biochemical parameters studied in AS which differ significantly
with respect to those of controls, FDpyr / Cr, FPyr / Cr and TPyr / Cr showed the
highest discrimination between patients and controls, as can be observed from
the ROC curves (Fig. 1). Areas under ROC curves were: FDpyr / Cr (99.7%),

Table 1
Biochemical markers of bone formation in patients with ankylosing spondylitis (AS)a
Controls AS patients Significance b
PINP (mg / l) 3569 41617 p 5 0.306
PICP (mg / l) 127622 129634 p 5 0.817
a
All values are the mean6S.D.; PINP, aminoterminal propeptide of procollagen I; PICP,
carboxyterminal propeptide of procollagen I.
b
Statistical significance between groups by Mann–Whitney test.
104 C. Acebes et al. / Clinica Chimica Acta 289 (1999) 99 – 110

Table 2
Biochemical markers of bone resorption in patients with ankylosing spondylitis (AS)a
Controls AS patients Significance b
(n 5 18) (n 5 18) (p 5)
FPyr / Cr (nM / mM) 17.965.2 39.2613.6 0.000
FDpyr / Cr (nM / mM) 4.460.8 8.962.5 0.000
TPyr / Cr (nM / mM) 39.5610.7 74.0625.2 0.000
TDpyr / Cr (nM / mM) 9.162.9 13.265.4 0.0118
NTX / Cr (nMBCE c / mM) 32619 59635 0.0086
CTX / Cr (mg / mmol) 174690 2046123 0.5974
BSP (ng / ml) 8.462.1 11.1064.1 0.0235
a
All values are the mean6S.D. Cr, urinary creatinine; FPyr, urinary free pyridinolines; FDpyr,
urinary free deoxypyridinolines; TPyr, urinary total pyridinolines; TDpyr, urinary total deox-
ypyridinolines; NTX, urinary aminoterminal crosslinked telopeptides of collagen I; CTX, urinary
carboxyterminal telopeptide of collagen I; BSP, serum bone sialoprotein.
b
Statistical significance between groups by Mann–Whitney test.
c
Bone collagen equivalents.

Fig. 1. ROC plots of urinary free deoxypyridinoline / creatinine (FDpyr / Cr) (– ? –), free
pyridinoline / creatinine (FPyr / Cr) (———), total pyridinoline / creatinine (TPyr / Cr) ( ? ? ? ), total
deoxypyridinoline / creatinine (TDpyr / Cr) (– ? ? –), and aminoterminal crosslinked telopeptides of
collagen I (NTX / Cr) (- - -), and serum bone sialoprotein (BSP) (———) in 18 patients with
ankylosing spondylitis and 18 healthy sex and age matched controls. On the X-axis the percentage
of true negative fraction or 100-specificity is plotted and on the Y-axis the true positive percentage
or sensitivity.
 C. Acebes et al. / Clinica Chimica Acta 289 (1999) 99 – 110 105

Table 3
Linear correlations ( p) between biochemical markers of bone remodeling in controls and patients
with ankylosing spondylitis a
PINP PICP FPyr FDpy TPyr TDpyr NTX CTX BSP
PINP 0.0061 0.2257 0.8958 0.1320 0.8719 0.1001 0.0207 0.0065
PICP 0.1248 0.9937 0.4498 0.7640 0.7371 0.0907 0.0373 0.2660
FPyr 0.0245 0.0365 0.0000 0.0583 0.6990 0.0373 0.0037 0.0500
FDpyr 0.0100 0.0322 0.0000 0.3455 0.9583 0.1700 0.1028 0.1173
TPyr 0.0230 0.2753 0.0001 0.0007 0.2532 0.2913 0.0271 0.1572
TDpyr 0.0532 0.3518 0.0772 0.0122 0.0001 0.1609 0.076 0.1821
NTX 0.0707 0.2120 0.0205 0.0152 0.0020 0.0072 0.0086 0.0599
CTX 0.0001 0.5617 0.0757 0.0148 0.0023 0.0008 0.0025 0.0008
BSP 0.4938 0.1132 0.1106 0.3773 0.3049 0.9107 0.2583 0.7983
From the middle line (o): controls (n 5 18), up → right; ankylosing spondylitis (n 5 18),
a

down←left. Statistical significant correlations ( p , 0.05) are in italic (MedCal software).

FPyr / Cr (96.9%), TPyr / Cr (94.1%), BSP (74.9%), TDpyr / Cr (74.6%) and

NTX / Cr (73%). Although the highest area under ROC curves corresponds to
FDpyr / Cr, areas under ROC curves of FPyr / Cr and TPyr / Cr were not
significantly different from that of FDpyr / Cr ( p 5 0.271 and p 5 0.174,
respectively). On the other hand, areas under BSP,TDpyr / Cr and NTX / Cr ROC
curves were significantly lower than under FDpyr ( p 5 0.002, p 5 0.003 and
p 5 0.002 respectively). FDpyr / Cr sensitivity was 95% with a specificity of
100%. FPyr / Cr sensitivity was 61% and TPyr / Cr sensitivity was 65% (Fig. 1).
Table 3 shows the linear correlations found between the biochemical markers
of bone turnover studied in controls and in patients with AS. Levels of Dpyr / Cr,
the marker which shows the greatest difference between the two groups,
correlates with all the biochemical markers of bone formation and resorption
studied, with the exception of BSP, in patients with AS. However, BSP
correlates significantly with FPyr and CTX, both biochemical markers of bone
resorption, and with PINP, biochemical marker of bone formation in control
subjects. On the other hand, we did not find significant correlations between the
t-score of BMD and the biochemical markers of bone turnover studied.
The molar ratio of urinary TPyr with respect to TDpyr (TPyr / TDpyr) was
calculated in patients with AS and in controls. TPyr / TDpyr was 6.0961.84
(mean6S.D.) in AS patients, a value significantly higher ( p 5 0.0036) than that
found in controls (4.4861.06).

4. Discussion

Although we did not find osteoporosis in our group of patients with AS, we
106 C. Acebes et al. / Clinica Chimica Acta 289 (1999) 99 – 110

found a decrease of bone mass, reflected in the percentage of osteopenia found

among the male patients (7 / 13 5 54%). This value is significantly higher than
the normal percentage of osteopenia in a control Spanish male control
population (from 15.6% between 22–44 years to 28.7% in the group of 70–80
years) [22]. Although the degree of bone loss could seem minor than that
observed in previous reports about AS [4], it is important to take into account
that we have not included values of BMD of patients with radiological evidence
of syndesmophites or osteophytes, which constitute an important interference in
the determination of bone densitometry. These patients are, probably, those with
the most advanced disease, and with the highest degree of osteopenia, and it is
possible that the minor degree of mobility could contribute to their bone loss.
Although values of BMD of these patients have not been included in the
mathematical calculations, their levels of biochemical markers of bone turnover
were included. On the other hand, in a recent work, Bronson et al. [8] have
shown that posteroanterior (PA) DEXA (the position used in our work) does not
accurately measure vertebral body BMD in severe AS, and that osteopenia was
better appreciated in lateral scans. This could be the reason why we have not
found a greater level of bone loss in our group of patients.
The causes of the osteopenia in AS remain unknown. According to the results
of the present work about PINP and PICP, the levels of osteoblast activity in AS
patients do not differ significantly from those of controls. Our results agree with
those of Marhoffer et al. [7] who found normal levels of alkaline phosphatase
and osteocalcin in AS, and with those of Bronson et al. [8] who reported normal
values of alkaline phosphatase, osteocalcin and PICP in this pathology, but
disagree with the studies of Szejnfeld [5] and Hanson [3] who reported a lack of
bone formation in these patients through the determination of alkaline phospha-
tase and histomorphometric studies. Other authors [28] found in patients with
this pathology an elevation in alkaline phosphatase.
The results of the present work show that Pyr and Dpyr are the biochemical
markers of bone resorption that present the highest significant differences
between controls and patients with AS. These results agree with those of
Marhoffer et al. [7], who found an increase of FPyr levels in AS, although these
authors did not determine other biochemical markers of bone resorption. In a
recent work, Bronson et al. [8] found a slightly elevation in the levels of FPyr
and FDpyr in patients with AS, but they reported that this elevation was due
only to the high levels in four patients (from 19 subjects). However, in our
series, we have observed a very little overlapping between controls and patients
in the levels of FPyr and FDpyr. In the case of FDpyr only the levels of two
patients overlapped with those of two controls in the upper limit of normality.
The differences between the results of the above authors [8] and ours, could be
explained by the different method used in the determination of FDpyr (ELISA in
Bronson’s report and HPLC in our case), because the number and age
distribution of patients were very similar in the two works.
 C. Acebes et al. / Clinica Chimica Acta 289 (1999) 99 – 110 107

It has been demonstrated that results about the usefulness of Pyr or Dpyr in
the study of a pathology or in the follow-up of a treatment could depend on the
method used, because the behaviour of peptide-bound crosslinks is not the same
as that of free crosslinks [29]. In the present work, in terms of absolute values of
area under the ROC curves, values of FDpyr present the highest discrimination
between controls and patients, but areas of FPyr and TPyr do not present a
significant difference with that of FDpyr. However, area under ROC curve of
TDpyr is significantly lower than the others. So, in this case, determination of
free and total Pyr would present the same sensitivity to detect alterations in bone
remodeling in AS, but the determination of FDpyr presents a better sensitivity
than TDpyr. We cannot explain the reason why the determination of FDpyr is
better that TDpyr in the study of this pathology, a fact that does not occur
between total and free Pyr.
At this point it is interesting to interpret which could be the tissue of origin of
the crosslinks that have been found increased in the patients with AS. With
respect to the increase observed in Dpyr levels, as Dpyr is only present in
significant quantities in bone, it is clear that the increase of this component in
urine must be due to an increase in bone resorption. If the levels of Pyr found
were elevated in the same proportion as those of Dpyr, although Pyr can be
derived from other collagen sources, we would have to assume that the elevation
observed in Pyr levels was also due to bone matrix resorption. But we have
found a significant increase in the molar ratio TPyr / TDpyr in patients with AS
with respect to control subjects (6.09 vs. 4.48) A similar fact was found
previously by Robins et al. [30] in patients with rheumatoid arthritis. The
elevation of Pyr with respect to Dpyr could indicate that a part of Pyr could
come from other sources different from bone matrix. Robins et al. [30]
explained this finding in rheumatoid arthritis by (1) a source from cartilage
erosions, due to the fact that Pyr is present in higher concentrations in cartilage
than in any other tissues, and (2) an increased turnover of synovial tissue, that
also contains appreciable amounts of Pyr. The first fact could be applied to AS,
but cartilage erosions are infrequent in this disease. However, Pyr is also present
in the intervertebral disks and ligaments [31] and these could be the most
important source of Pyr in AS taking into account the selective affection of these
structures (entheses) that occurs in this disease.
Levels of NTX in AS patients were also significantly elevated with respect to
those of controls, but the sensitivity of this determination in order to detect bone
remodeling alterations in AS was less significant than that of Dpyr and Pyr
according to the values of areas under ROC curves. This could be due to the fact
that NTX assay could reflect level of collagen type I peptides rather than being
specific for bone collagen, keeping in mind that collagen type I is present in
skin, tendon and bone [31].
It is very interesting to emphasise that levels of CTX (in this case the
b-isomer) in AS patients are not significantly different from those of controls,
108 C. Acebes et al. / Clinica Chimica Acta 289 (1999) 99 – 110

although this octapeptide is involved in the formation of pyrinidoline crosslinks

in the C-terminal telopeptide zone of collagen. However, in this case the
presence of one cross-link is not necessary for the assay reactivity and for this
reason the CTX assay can detect degradation of telopeptides at any stage of
collagen biosynthesis, including intracellular degradation of newly synthesised
collagen, and, as in the case of NTX, the assay can also detect collagen I type
peptides from other tissues than bone [31]. However, Pyr and Dpyr only express
the degradation of mature collagen and not any biosynthetic intermediates.
In the present study, we have for the first time demonstrated significantly
elevated concentrations of circulating immunoreactive BSP in patients with AS.
In previous studies [15,16], we have shown elevated levels of serum BSP in
patients with a variety of metabolic osteopathies, but also in individuals with
metastatic bone disease or multiple myeloma. In all cases, changes in serum
BSP concentrations were closely related to the urinary excretion of pyridinium
crosslinks, indicating that serum BSP values reflect accelerated bone resorption
rather than bone formation. Although high amounts of BSP have been
demonstrated mainly in active osteoblasts [32,33], other studies have shown that
resorbing osteoclasts express BSP binding integrins [34,35]. In the present work
we found that BSP correlates significantly with Pyr and CTX, both biochemical
markers of bone resorption, and also with PINP, biochemical marker of bone
formation, in control healthy subjects, although this last correlation could be due
to the coupling of bone formation and resorption in healthy controls. In patients
with AS, the lack of correlation between BSP and other markers of bone
turnover suggests that bone sialoprotein could also reflect a different process.
This should be further evaluated in a larger set of patients.
In conclusion, we have found osteopenia, accompanied by a normal formation
and a significant increase of bone resorption in patients with AS. FDpyr, FPyr
and TPyr seem to present the best sensitivity for the study of alterations of bone
resorption in this pathology, although NTX, TDpyr and BSP also show
significant differences. Due to the little overlapping between values of urinary
FDpyr of controls and patients, we suggest the use of this marker to get an
adequate evaluation of bone metabolism in AS. On the other hand, the elevation
in the molar ratio of urinary TPyr / TDpyr in AS compared to controls indicates
that in this pathology there is a type I-collagen degradation in tissues different
from bone.

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