Prognostic value of the bone turnover markers in multiple myeloma
Background: Multiple myeloma (MM) is characterized by osteolytic bone disease resulting from increased osteoclast activity and reduced osteoblast function. Aim: The aim of our research was to determine connection between bone turnover markers and presence of bone lesions, their degree of severity, t...
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Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
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irk-123456789-1376072018-06-18T03:09:22Z Prognostic value of the bone turnover markers in multiple myeloma Auzina, D. Erts, R. Lejniece, S. Original contributions Background: Multiple myeloma (MM) is characterized by osteolytic bone disease resulting from increased osteoclast activity and reduced osteoblast function. Aim: The aim of our research was to determine connection between bone turnover markers and presence of bone lesions, their degree of severity, to monitor MM bone disease and to assess effectiveness of anti-myeloma treatment. Materials and Methods: Serum samples and clinical data from 123 patients with newly diagnosed MM were collected at Riga East Clinical University Hospital (Riga, Latvia) from June 2014 to June 2016. Bone lesions detected by radiography, CT scans, MRI, and PET/CT were divided into degrees from 0 to 3 (0 — no bone involvement, 1 — ≤ 3 bone lesions, 2 — ≥ 3 bone lesions, 3 — fracture). Staging was performed applying Durie/Salmon (DS) and International Staging System classifications. Progressive disease was defined as development of one or more new bone lesions. The levels of bone metabolic markers β-isomerized C-terminal telopeptide of collagen type I (β-CTX) and bone-specific alkaline phosphatase (bALP) were monitored regularly in the year. Results: Bone lesions were found in 86 (69%) patients. From these 6 (4%) patients had 1st degree, 11 (9%) had 2nd degree and 69 (56%) had 3rd degree bone lesions. Level of the bone resorption marker β-CTX in the control group was 0.41 ng/ml, which is lower than in MM patients (p < 0.001). Spearman correlation coefficient analysis found a positive and statistically significant correlation (rs = 0.51, p < 0.001) between bone lesions degree and β-CTX levels. Mean β-CTX for patients without bone lesions was 0.72 ng/ml (SD = 0.64), but for patients with 3rd degree bone lesions it was 1.34 ng/ml (SD = 0.65) difference being 38% (p < 0.001). In patients who responded to therapy after 6 months of treatment reduction of β-CTX was found compared to baseline values (M = –0.65). In contrast, in patients who did not respond to therapy, there was a statistically significant (p < 0.001) increase in β-CTX values after six months of treatment compared to baseline values (M = 0.42). Exact cutoff value of β-CTX is 0.79. When analyzing mean bALP, no significant difference between MM patients and control group was found. ANOVA statistical analysis showed no statistically significant differences in bALP levels at different degrees of bone lesions (p = 0.95) in MM patients. Analysis of bALP suitability as MM diagnostic marker using receiver operating characteristics curve showed that bALP is not applicable for clinical diagnosis of MM (AUC 0.5, p > 0.05). However, β-CTX was found to be an excellent diagnostic marker for MM (AUC 0.91; 95% confidence interval, 0.88–0.94; p < 0.001). Conclusions: Patients with MM and bone lesions have increased value of bone resorption marker β-CTX. There is a correlation between bone resorption marker and degree of bone lesions. Changes in β-CTX levels may be used to monitor the effectiveness of myeloma treatment. 2017 Article Prognostic value of the bone turnover markers in multiple myeloma / D. Auzina, R. Erts, S. Lejniece // Experimental Oncology. — 2017 — Т. 39, № 1. — С. 53-56. — Бібліогр.: 25 назв. — англ. 1812-9269 http://dspace.nbuv.gov.ua/handle/123456789/137607 en Experimental Oncology Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
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Original contributions Original contributions |
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Original contributions Original contributions Auzina, D. Erts, R. Lejniece, S. Prognostic value of the bone turnover markers in multiple myeloma Experimental Oncology |
| description |
Background: Multiple myeloma (MM) is characterized by osteolytic bone disease resulting from increased osteoclast activity and reduced osteoblast function. Aim: The aim of our research was to determine connection between bone turnover markers and presence of bone lesions, their degree of severity, to monitor MM bone disease and to assess effectiveness of anti-myeloma treatment. Materials and Methods: Serum samples and clinical data from 123 patients with newly diagnosed MM were collected at Riga East Clinical University Hospital (Riga, Latvia) from June 2014 to June 2016. Bone lesions detected by radiography, CT scans, MRI, and PET/CT were divided into degrees from 0 to 3 (0 — no bone involvement, 1 — ≤ 3 bone lesions, 2 — ≥ 3 bone lesions, 3 — fracture). Staging was performed applying Durie/Salmon (DS) and International Staging System classifications. Progressive disease was defined as development of one or more new bone lesions. The levels of bone metabolic markers β-isomerized C-terminal telopeptide of collagen type I (β-CTX) and bone-specific alkaline phosphatase (bALP) were monitored regularly in the year. Results: Bone lesions were found in 86 (69%) patients. From these 6 (4%) patients had 1st degree, 11 (9%) had 2nd degree and 69 (56%) had 3rd degree bone lesions. Level of the bone resorption marker β-CTX in the control group was 0.41 ng/ml, which is lower than in MM patients (p < 0.001). Spearman correlation coefficient analysis found a positive and statistically significant correlation (rs = 0.51, p < 0.001) between bone lesions degree and β-CTX levels. Mean β-CTX for patients without bone lesions was 0.72 ng/ml (SD = 0.64), but for patients with 3rd degree bone lesions it was 1.34 ng/ml (SD = 0.65) difference being 38% (p < 0.001). In patients who responded to therapy after 6 months of treatment reduction of β-CTX was found compared to baseline values (M = –0.65). In contrast, in patients who did not respond to therapy, there was a statistically significant (p < 0.001) increase in β-CTX values after six months of treatment compared to baseline values (M = 0.42). Exact cutoff value of β-CTX is 0.79. When analyzing mean bALP, no significant difference between MM patients and control group was found. ANOVA statistical analysis showed no statistically significant differences in bALP levels at different degrees of bone lesions (p = 0.95) in MM patients. Analysis of bALP suitability as MM diagnostic marker using receiver operating characteristics curve showed that bALP is not applicable for clinical diagnosis of MM (AUC 0.5, p > 0.05). However, β-CTX was found to be an excellent diagnostic marker for MM (AUC 0.91; 95% confidence interval, 0.88–0.94; p < 0.001). Conclusions: Patients with MM and bone lesions have increased value of bone resorption marker β-CTX. There is a correlation between bone resorption marker and degree of bone lesions. Changes in β-CTX levels may be used to monitor the effectiveness of myeloma treatment. |
| format |
Article |
| author |
Auzina, D. Erts, R. Lejniece, S. |
| author_facet |
Auzina, D. Erts, R. Lejniece, S. |
| author_sort |
Auzina, D. |
| title |
Prognostic value of the bone turnover markers in multiple myeloma |
| title_short |
Prognostic value of the bone turnover markers in multiple myeloma |
| title_full |
Prognostic value of the bone turnover markers in multiple myeloma |
| title_fullStr |
Prognostic value of the bone turnover markers in multiple myeloma |
| title_full_unstemmed |
Prognostic value of the bone turnover markers in multiple myeloma |
| title_sort |
prognostic value of the bone turnover markers in multiple myeloma |
| publisher |
Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
| publishDate |
2017 |
| topic_facet |
Original contributions |
| url |
http://dspace.nbuv.gov.ua/handle/123456789/137607 |
| citation_txt |
Prognostic value of the bone turnover markers in multiple myeloma / D. Auzina, R. Erts, S. Lejniece // Experimental Oncology. — 2017 — Т. 39, № 1. — С. 53-56. — Бібліогр.: 25 назв. — англ. |
| series |
Experimental Oncology |
| work_keys_str_mv |
AT auzinad prognosticvalueoftheboneturnovermarkersinmultiplemyeloma AT ertsr prognosticvalueoftheboneturnovermarkersinmultiplemyeloma AT lejnieces prognosticvalueoftheboneturnovermarkersinmultiplemyeloma |
| first_indexed |
2025-07-10T04:06:51Z |
| last_indexed |
2025-07-10T04:06:51Z |
| _version_ |
1837231417763823616 |
| fulltext |
Experimental Oncology ��� ������ ���� ��arc����� ������ ���� ��arc�� ��arc�� ��
PROGNOSTIC VALUE OF THE BONE TURNOVER MARKERS
IN MULTIPLE MYELOMA
D. Auzina1, 2, *, R. Erts3, S. Lejniece1, 2
1Chemotherapy and Haematology Clinic, Riga East Clinical University Hospital, Riga LV 1079, Latvia
2Department of Internal Diseases, Riga Stradins University, Riga LV 1007, Latvia
3Department of Physics, Riga Stradins University, Riga LV 1079, Latvia
Background: Multiple myeloma (MM) is characterized by osteolytic bone disease resulting from increased osteoclast activity and
reduced osteoblast function. Aim: The aim of our research was to determine connection between bone turnover markers and pres-
ence of bone lesions, their degree of severity, to monitor MM bone disease and to assess effectiveness of anti-myeloma treatment.
Materials and Methods: Serum samples and clinical data from 123 patients with newly diagnosed MM were collected at Riga East
Clinical University Hospital (Riga, Latvia) from June 2014 to June 2016. Bone lesions detected by radiography, CT scans, MRI,
and PET/CT were divided into degrees from 0 to 3 (0 — no bone involvement, 1 — ≤ 3 bone lesions, 2 — ≥ 3 bone lesions, 3 —
fracture). Staging was performed applying Durie/Salmon (DS) and International Staging System classifications. Progressive
disease was defined as development of one or more new bone lesions. The levels of bone metabolic markers β-isomerized C-termi-
nal telopeptide of collagen type I (β-CTX) and bone-specific alkaline phosphatase (bALP) were monitored regularly in the year.
Results: Bone lesions were found in 86 (69%) patients. From these 6 (4%) patients had 1st degree, 11 (9%) had 2nd degree and
69 (56%) had 3rd degree bone lesions. Level of the bone resorption marker β-CTX in the control group was 0.41 ng/ml, which
is lower than in MM patients (p < 0.001). Spearman correlation coefficient analysis found a positive and statistically significant
correlation (rs = 0.51, p < 0.001) between bone lesions degree and β-CTX levels. Mean β-CTX for patients without bone lesions
was 0.72 ng/ml (SD = 0.64), but for patients with 3rd degree bone lesions it was 1.34 ng/ml (SD = 0.65) difference being 38%
(p < 0.001). In patients who responded to therapy after 6 months of treatment reduction of β-CTX was found compared to baseline
values (M = –0.65). In contrast, in patients who did not respond to therapy, there was a statistically significant (p < 0.001) increase
in β-CTX values after six months of treatment compared to baseline values (M = 0.42). Exact cutoff value of β-CTX is 0.79. When
analyzing mean bALP, no significant difference between MM patients and control group was found. ANOVA statistical analysis
showed no statistically significant differences in bALP levels at different degrees of bone lesions (p = 0.95) in MM patients.
Analysis of bALP suitability as MM diagnostic marker using receiver operating characteristics curve showed that bALP is not
applicable for clinical diagnosis of MM (AUC 0.5, p > 0.05). However, β-CTX was found to be an excellent diagnostic marker for
MM (AUC 0.91; 95% confidence interval, 0.88–0.94; p < 0.001). Conclusions: Patients with MM and bone lesions have increased
value of bone resorption marker β-CTX. There is a correlation between bone resorption marker and degree of bone lesions.
Changes in β-CTX levels may be used to monitor the effectiveness of myeloma treatment.
Key Words: multiple myeloma, bone turnover markers, β-CTX, bALP.
�ultiple myeloma ���� is a B-cell malignancy
c�aracterized by proliferation of monoclonal plasma
cells in t�e bone marrow. Bone lesions are a very com-
mon presenting feature in patients wit� ��� wit� lytic
bone destruction being a debilitating manifestation
of t�e disease [�]. Bone disease is typical of �� and
its occurrence increases wit� t�e progression of t�e
disease. Bone disease can substantially affect patient
morbidity and quality of life [�]. �ost patients respond
to initial treatment� but eventually almost all patients
will �ave resistant relapse and die from t�e disease.
Osteolytic lesions are seen in ���8�% of patients
at diagnosis� w�ile up to ��% develop lytic lesions
during t�e course of t�eir disease [�] and may cause
skeletal-related event �SRE� wit� bone pain� pat�ologi-
cal fractures� spinal cord compression� �ypercalcemia
and need to use radiation t�erapy or bone surgery [�]�
but no tests �ave proven useful in identifying patients
wit� increased risk for it.
�� is c�aracterized by a tig�t relations�ip wit� t�e
bone microenvironment. �� cells induce a significant
alteration of t�e bone remodeling process due to t�e
increase of osteoclast formation and activation and
to t�e suppression of osteoblast differentiation lead-
ing to t�e development of osteolytic lesions [�� 4��].
Bioc�emical markers of bone turnover may represent
an alternative to evaluate t�e bone status of patients
wit� myeloma. T�e activity of bone resorption and for-
mation is reflected by bone turnover markers �BT�s�
offering information about t�e ongoing activity in bone
degradation and formation [8].
Bone markers are classified as resorption and
formation markers. Bone resorption markers are t�e
degradation products of osteoclasts or collagen deg-
radation and bone formation markers are produced
by osteoblastic cells or derived from procollagen
metabolism. Bone resorption markers are degrada-
tion products of β-isomerized C-terminal telopeptide
of collagen type I �β-CTX�� w�ic� constitutes ��%
of t�e organic bone matrix and are �ig�ly specific for
t�e degradation of type I collagen dominant in bone.
Submitted: January 20, 2017.
*Correspondence: E-mail: dauzina@inbox.lv
Abbreviations used: β-CTX — β-isomerized C-terminal telopeptide
of collagen type I; bALP — bone-specific alkaline phosphatase; BTMs —
bone turnover markers; DS — Durie/Salmon; GFR — glomerular filtration
rate; MM — multiple myeloma; SRE — skeletal-related event.
Exp Oncol ����
��� �� �����
�4 Experimental Oncology ��� ������ ���� ��arc��
Bone formation markers are products of osteoblast ac-
tivity and include bone-specific alkaline p�osp�atase
�bALP� representing membrane-bound osteoblast
enzyme t�at is produced during bone formation. T�e
aim of our researc� was to determine connection
between BT�s and presence of bone lesions� t�eir
degree of severity� to monitor �� bone disease and
to assess effectiveness of anti-myeloma treatment.
MATERIALS AND METHODS
Serum samples and clinical data from ��� patients
wit� newly diagnosed �� were collected at Riga
East Clinical University Hospital �Riga� Latvia� from
June ���4 to June ����. T�e patients enrolled in t�is
study �� ���%� female and �� �4�%� male �ad an age
range of ���8� years �median age was ��.�� years�.
Blood samples �and related data� were accessed
after informed consent from all patients. Eac� pa-
tient’s attending p�ysician decided on t�erapy regard-
less of data being researc�ed. Bone lesions at t�e time
of diagnosis were detected using eit�er conventional
radiograp�y� computed tomograp�y �CT� scans� mag-
netic resonance imaging ��RI� or positron emission
tomograp�y �PET�/CT and were divided into degrees
from � to � �� — no bone involvement� � — ≤ � bone
lesions� � — ≥ � bone lesions� � — fracture or vertebral
collapse� according to [�]. Staging was performed
applying Durie/Salmon �DS� and International Sta ging
System classification system. Progressive disease
was defined as development of one or more new bone
lesions.
Treatment included cyclop�osp�amide� bort-
ezomib� dexamet�asone� eryt�ropoietin� calcium�
vitamin D and autologous stem cell transplantation.
In addition� 4 patients were treated wit� low dose ra-
diot�erapy �up to �� Gy� in t�e course of treatment and
� underwent vertebroplasty early in t�eir treatment. All
patients wit� bone disease �excluding patients wit�
glomerular filtration rate �GFR� < �� ml/min� received
zoledronate at a dose of 4 mg every 4 weeks.
All analyzes were made wit�in t�e same laboratory.
Bioc�emical markers of bone remodeling� namely
β-CTX and bALP were measured by electroc�emilu-
minescence immunoassay ECLIA on Cobas analyzer
�Roc�e Diagnostics� Germany� and c�emilumines-
cence immunoassay on t�e LIAISON analyzer �DiaSo-
rin� Inc.� USA�� respectively. Blood samples were col-
lected at regular intervals �every � mont�s over � year�
at � o’clock in t�e morning from fasting patients. T�e
samples were immediately centrifuged.
T�e control group comprised of ���8 age and
sex matc�ed patients. Excluded from t�e study were
bot� �� patients and control group patients w�ose
conditions creates primary or secondary osteoporosis
or bone lesions� are receiving medications t�at could
potentially lead to osteoporosis and patients wit� GFR
< �� ml/min/�.�� m�. T�e study design� patients’
information and consent forms were approved by t�e
Et�ic Committee of t�e Riga Stradins University and
conducted according to t�e national et�ical guidelines
and t�e Helsinki Declaration.
Statistical analysis. IB� SPSS Statistics �� soft-
ware �IB�� USA� was used. Data were presented
as mean ��� and standard deviation �± SD� or median
��e� and interquartile range �IQR� for continuous
variables� and counts and percentages [%] for cate-
gorical variables. Comparisons were made using
t-test� �ann — W�itney test in case of non-normality
and cate gorical variables were compared by Pear-
son’s χ� test. C�anges in time were compared by us-
ing ANOVA for repeated measures. T�e relations�ips
between variables were evaluated using Spearman —
Rank correlation coefficient �rs�. Receiver operating
c�aracteristics �ROC� curve analysis was generated
to test t�e predictive discrimination of �� patients wit�
and wit�out bone lesions. T�e area under eac� ROC
curve �AUC� was calculated as a measure of overall
diagnostic power. Sensitivity �Se�� specificity �Sp��
positive �PPV� and negative predictive values �NPV�
were determined according to standard definitions.
Exact cutoff values for bone markers were determined
based on t�e best balance of Se and Sp. All tests were
considered statistically significant at p < �.��.
RESULTS AND DISCUSSION
Bone lesions were found in 8� ���.��%� patients.
From t�ese � �4%� patients �ad �st degree� �� ��%�
�ad �nd degree and �� ���%� �ad �rd degree bone le-
sions. Distribution between bone lesion localization was
as follows: ��� patients �ad spinal lesions� �� — costal�
�� — pelvic� � — �umeral� 4 — femoral and � — sternal.
T�e most common combination of localizations were
spinal wit� costal lesions toget�er �84 patients�. 8�%
of t�e vertebral fractures occurred in T�VIII�LV region
of t�e spine and ��% of t�em found in t�e T�XI�LI re-
gion. In DS system stage �� � and � were found in �4�
�� and 8� patients� respectively� but using International
Staging System classification �� patients �ad �st stage�
�� — �nd stage and �� — �rd stage ��. Hypercalcemia
was found in �� ���%� patients.
Statistical analysis s�owed t�at t�e average age
of t�e control and study groups did not differ signifi-
cantly �t-test; p > �.���. Basic demograp�ic indicators
are s�own in Table �.
Table 1. Basic demographic indicators
Indicators Control group Research group p value
Age (M ± SD) 65.01 ± 9.14 67.93 ± 9.97 > 0.05
Female/male, n (%) 846 (75.0)
282 (25.0)
70 (56.9)
53 (43.1)
> 0.05
T�e β-CTX levels in t�e control group was �.4� ng/ml
�SD = �.���� w�ic� is statistically significantly lower
t�an in �� patients �Table ��. Spearman correlation
coefficient analysis found t�at between bone lesions
degree and β-CTX level t�ere is a positive and statisti-
cally significant correlation �rs = �.��; p < �.����. �ean
β-CTX for patients wit�out bone lesions was �.�� ng/ml
�SD = �.�4�� but for patients wit� �rd degree bone le-
sions it was �.�4 ng/ml �SD = �.��� difference being
�8%.
Experimental Oncology ��� ������ ���� ��arc����� ������ ���� ��arc�� ��arc�� ��
In patients w�o responded to t�erapy� reduction
of β-CTX was found compared to baseline values �∆� =
��.���. In contrast� in patients w�o did not respond
to t�erapy� t�ere was an increase in β-CTX values
after � mont�s of treatment compared to baseline
values �∆� = �.4�� �t-test� p < �.����. Value of β-CTX
between �st and �nd collection of samples decreased
in �� ���.��%� patients� but increased in �� ��8.�4%�.
ANOVA repeated measures s�ows statistically signifi-
cant β-CTX decrease from t�e baseline value till �nd
time of samples collection �after � mont�s� — �8%� but
from �nd to �rd time �after a year of t�erapy� — ��.�%
�p < �.����.
�ean β-CTX value depending on t�e effect
of t�erapy is s�own in Table �. β-CTX cutoff value
for �� patients depending on gender and age
is �.����.8� �Table 4�. Exact cutoff value of β-CTX for
all patients not adjusted for age and sex as diagnostic
marker is �.�� ng/ml �Sp = ��% ���% CI: 88��4�; Se =
8�% ���% CI: ���8��; PPV = ��% ���% CI: ������;
NPV = ��% ���% CI: �������. Only 4�% of patients
wit� no bone lesions �ave β-CTX value greater t�an
�.��� w�ile �4% of patients wit� �st to �rd degree bone
lesions �ave β-CTX value greater t�an �.��.
Table 3. Changes of β-CTX value depending on the effect of therapy
Patients β-CTX M ± SD
(min–max)
Difference (95%
confidence inter-
val — CI), p value
Responding patients
Before treatment (n = 114) 1.12 ± 0.64 (0.11–4.09) –0.65 (0.41–0.66)
p < 0.001After 6 months therapy (n = 84) 0.47 ± 0.36 (0.03–1.77)
Non-responding patients
Before treatment (n = 9) 1.38 ± 0.74 (0.86–3.22) 0.42 (0.21–0.62)
p < 0.001After 6 months therapy (n = 9) 1.80 ± 0.92 (1.10–3.98)
W�en analyzing mean bALP� no significant difference
between �� patients and control group was found.
ANOVA statistical analysis s�owed no statistically sig-
nificant differences in bALP levels at different degrees
of bone lesions �p = �.��� in �� patients. Value of bALP
between �st and �nd collection of samples decreased
in �� ��4.��%� patients� but increased in �� ���.48%�.
Analysis of bALP suitability as �� diagnostic marker
using ROC curve s�owed t�at bALP is not applicable
for diagnosis �AUC = �.�; p > �.���. However� β-CTX
was found to be an excellent diagnostic marker for ��
�AUC = �.��; p < �.���; ��% CI: �.88��.�4� �Figure�.
Historically conventional radiograp�y — w�ole-
body X-rays — is t�e most common tec�nique for t�e
evaluation of bone disease in �� patients. However�
w�ole-body X-rays �as several limitations: it reveals
lytic disease w�en over ��% of t�e trabecular bone �as
been lost� w�ile it cannot be used for t�e assessment
of response to t�erapy and it �as very low sensitivity
for t�e pelvis and spine. T�us� w�ole-body low-dose
CT can substitute conventional radiograp�y as t�e
standard tec�nique for t�e evaluation of bone disea-
se in ��. Furt�ermore� lytic bone lesions detected
by CT and �RI �ave been included in t�e new criteria
for t�e definition of symptomatic �� [�����].
0 20 40 60 80 100
0
20
40
60
80
100
100-Specificity
Se
ns
iti
vit
y
0 20 40 60 80 100
0
20
40
60
80
100
100-Specificity
Se
ns
iti
vit
y
ba
Figure. bALP �a� and β-CTX �b� ROC curves wit� ��% CI for
all patients
T�e lesions rarely �eal and bone scans are often
negative in myeloma patients wit� extensive lytic le-
sions� offering very little in t�e follow-up of bone di-
sease [�4]. Wit� t�is strategy� substantial damage may
�ave occurred in bone before t�e patient becomes
symptomatic and progressive bone disease is detected.
Bioc�emical markers are not �armful and are
compatible wit� mont�ly monitoring. T�ey �ave t�e
potential to detect t�e destructive process as soon
as it starts and before a lesion becomes detectable
t�roug� conventional radiograp�y [8� ����8]. Data
suggest t�at BT�s are useful prognostic factors
t�at can predict patients’ risk of SREs� bone lesion
progression� and deat�. BT�s can also be used
to measure to biologic effects of antiresorptive medi-
cations �bisp�osp�onates� and to identify subgroups
of patients w�o are at �ig� risk for disease progression
and bone disease. BT�s could potentially be used
as a tool for early diagnosis of bone lesions. �ar-
kers of bone metabolism s�ould be incorporated into
clinical practice as a tool to manage malignant bone
disease of �� patients [�� �����].
REFERENCES
1. Sezer O. Myeloma bone disease: recent advances in bio
logy, diagnosis, and treatment. Oncologist 2009; 14: 276–83.
Table 2. β-CTX and bALP levels in MM patients and control group with different degrees of bone lesions at the time of diagnosis
Group n Median β-CTX (Q1–Q3) β-CTX M ± SD (min–max) Median bALP (Q1–Q3) bALP M ± SD (min–max)
Control group 1128 0.37 (0.23–0.56) 0.41 ± 0.25 (0.03–2.50) 11.40 (8.80–15.80) 13.80 (3.90–217.00)
MM patients
Bone lesion (degree — 0) 39 0.61 (0.48–0.96) 0.72 ± 0.64 10.50 (8.05–13.05) 10.84 ± 7.72
Bone lesion (degree — 1) 5 0.90 (0.66–0.98) 0.84 ± 0.18 11.80 (11.10–12.65) 11.86 ± 0.95
Bone lesion (degree — 2) 11 0.89 (0.86–1.03) 0.99 ± 0.28 11.30 (9.70–14.00) 12.10 ± 4.50
Bone lesion (degree — 3) 68 1.11 (0.96–1.50) 1.34 ± 0.65 11.20 (8.55–15.50) 12.95 ± 6.73
Table 4. β-CTX cutoff value for MM patients depending on gender and age at the time of diagnosis
Gender of patients Age of patients AUC; p value (95% CI) Cutoff value Se, % (95% CI) Sp, % (95% CI) PPV, % (95% CI) NPV, % (95% CI)
Female 51–70 0.91; p < 0.001 (0.85–0.97) 0.79 80 (63–91) 92 (79–88) 58 (43–71) 97 (94–99)
> 70 0.87; p < 0.001 (0.79–0.96) 0.82 68 (56–83) 92 (84–96) 73 (54–87) 90 (54–87)
Male 51–70 0.92; p < 0.001 (0.84–0.99) 0.79 75 (53–90) 93 (82–98) 85 (63–96) 88 (76–96)
> 70 0.80; p < 0.001 (0.67–0.94) 0.87 62 (40–81) 85 (87–98) 88 (63–98) 57 (34–78)
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