International Journal of Medical Sciences And Clinical Research
88
https://theusajournals.com/index.php/ijmscr
VOLUME
Vol.05 Issue05 2025
PAGE NO.
88-91
10.37547/ijmscr/Volume05Issue05-18
The Prognostic Value of Markers of Bone Metabolism
Kim Oksana Vladislavovna
Samarkand State Medical University, Uzbekistan
Received:
31 March 2025;
Accepted:
29 April 2025;
Published:
31 May 2025
Abstract:
Biomarkers of bone metabolism, including biomarkers of bone collagen, have attracted great scientific
interest. Numerous international studies indicate the importance of these markers in assessing the degree of bone
tissue damage, which have not only diagnostic but also prognostic value.
Keywords:
Biomarkers of bone metabolism, bone tissue, acute hematogenous osteomyelitis, collagen.
Introduction:
Today,
acute
hematogenous
osteomyelitis (CGO) remains a serious problem in
childhood. According to WHO, the annual incidence of
acute respiratory viral infections among children
ranges from 2 to 13 cases per 100,000 population,
depending on the region, age and quality of medical
care. In developed countries such as the USA, Canada
and Western European countries, the incidence of
osteomyelitis in children remains relatively stable
–
about 5-7 cases per 100,000 children per year.
However, in Africa, South Asia, and Latin America, the
incidence of CSOs is significantly higher, reaching 15-20
cases per 100,000 children. In addition, numerous
studies indicate an increase in the incidence of
osteomyelitis, which is associated with the growth of
antibiotic
–
resistant bacterial strains (for example,
MRSA - methicillin-resistant Staphylococcus aureus), as
well as insufficient vaccination against hemolytic
streptococcus and pneumococcus, a high incidence of
injuries among children, limited access to medical care
and untimely treatment of bacterial infections, high
survival newborn children with immunodeficiency due
to the development of neonatology.
The purpose of the study
In this regard, the purpose of our study was to study
biomarkers of bone metabolism, namely type I
procollagen aminotherminal propeptide (PINP) and
type I collagen carboxytherminal telopeptide (β
-
CrossLabs) in children with acute hematogenous
osteomyelitis.
METHODS
The study was conducted at the Samarkand State
Medical University, a children's multidisciplinary
surgical hospital. For the
study, we took 60 sick children, who were divided into
6 groups. Group 1 included sick children aged 0-28
days, group 2: 1-11 months, group 3: 1-4 years, group
4: 5-9 years, group 5: 10-14 years, and group 6: 15-19
years. Children from the control group were assigned
to each study group. Concentrations of type I
procollagen aminotherminal propeptide (PINP) and
type I collagen carboxytherminal telopeptide (β
-
CrossLabs), as well as levels of calcium, phosphorus,
and alkaline phosphatase were studied in all children.
These indicators were determined on the 1st day of
admission, on the 7th day after surgical treatment, and
in the long-term period after treatment (after 6
months). To study these indicators, methods of enzyme
immunoassay and biochemical analysis were carried
out.
RESULTS AND DISCUSSION
Bone tissue is a highly specialized metabolically active
mineralized connective tissue. Its structural and
functional integrity is ensured by two multidirectional
processes, such as the formation and resorption of
bone tissue, the intensity of which is determined by the
activity of the cellular elements of bone, that is,
osteoblasts, osteoclasts and osteocytes. Osteoblasts
are responsible for formation, osteoclasts for
resorption, osteocytes for maintaining the structural
and functional activity of mature bone tissue. The
most important biopolymer of bone tissue is protein,
type 1 collagen, which makes up more than 90% of the
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International Journal of Medical Sciences And Clinical Research (ISSN: 2771-2265)
mass of the organic bone matrix, which plays a key role
in the mineralization of the intercellular matrix of bone
tissue, as well as in ensuring the strength properties of
bone.
Thus, the metabolic state of the main bone protein,
collagen, is determined by the intensity and direction
of its synthetic or, conversely, catabolic processes. This
indicates that shifts in bone collagen metabolism
directly reflect the general trend of metabolic
processes in bone tissue. The balance between the
synthesis and breakdown of bone collagen is a complex
multi-stage process involving both extracellular and
intracellular stages. The levels of bone formation or
bone breakdown can be assessed by analyzing the
components of bone collagen released into the blood.
Thus, markers of type 1 collagen synthesis include the
amino terminal propeptide procollagen type 1 (PINP
–
from English N-terminal propeptide of type 1 collagen).
Under the action of catabolic factors, mainly
osteoclasts,
amino-
and
carboxytherminal
telopeptides, called N-terminal (NTX-1) and C-terminal
telopeptides (CTX-1), are cleaved from the type 1
collagen molecule. In this case, CTX -1 can have 2 forms:
alpha- CTX and beta- CTX. Beta
–
CTX contains beta-
isomerized aspartic acid (beta-CrossLaps, from the
English beta- isomerized carboxy-terminal cross-linking
region of collagen type 1). It is a beta-isomerized
carboxytherminal fragment of a type 1 collagen
molecule, which is a specific marker of bone resorption.
Bone tissue in young children contains less collagen and
more non-collagen proteins, and is also rich in
glycosaminoglycans. The majority of collagen in
children is soluble, poorly resistant to heat and the
action of collagenolytic enzymes; at the same time,
biosynthesis proceeds at a high rate. With age, the
relationship of collagen with non
–
collagen proteins
increases
-
proteoglycans,
glycoproteins,
phosphoproteins. As a result, the solubility of collagen
decreases, the mechanical strength of collagen fibers
increases, resistance to denaturing factors and
collagenase; the mineral component of bone increases
significantly. As a result of the implementation of the
above
–
mentioned
mechanisms,
a
pronounced
anabolic effect in the exchange of bone collagen is
manifested, which may explain the increase in the
concentration of the bone formation marker P1NP on
all days of observation after surgery, especially in the
group of young and middle-aged children.
In the first group of children (0-28 days old), the level
of the marker of bone collagen resorption before
surgery and on the 7th day after surgery practically did
not differ from the data of the control group (1,115
ng/ml) and amounted to 1,144 ng/ml (P>0.05) and
1,232 ng/ml (P>0.05), respectively. 6 months after
surgery, the content of -CrossLaps in blood serum
increased by 119.3% compared with the control group
and amounted to 2.446 ng/ml (P=0.001). The amount
of type I collagen formation marker in bone tissue
increased significantly before surgery, on day 7 after
surgery, and after 6 months of follow-up, respectively,
from 6.31 ng/ml (in the control) to 9.58 ng/ml
(P=0.012), 10.25 ng/ml (P=0.012), and 15.77 ng/ml
(p=0.001), respectively.
The results of the studied indicators in the 2nd group of
children (1-11 months) indicate an increase in both
resorption markers and markers of type I collagen
formation in the blood serum. Thus, the content of -
CrossLaps was increased both before surgery (by
110.2%; P=0.002) and on days 7 and 60 after surgery by
275.7% (P=0.001), respectively. Noteworthy is the
significant increase in the studied indicator from 0.766
ng/ml (in the control) to 2.878 ng/ml (P=0.001) on the
7th day after surgery.
The concentration of the N-terminal propeptide
procollagen type I (PINP) during these observation
periods also increased by 117.4% (P=0.003), 152.5%
(P=0.001) and 123.8% (P=0.001), respectively. In the
group of children aged 1 to 4 years, there was a
maximum increase in the concentration of BNP in the
blood serum both before surgery and on the 7th day
after surgery. During these periods, the level of the
analyzed indicator increased by 11.4 and 9.2 times,
respectively, compared with the control group. At the
same time, the content of -CrossLaps increased,
although not as pronounced. Thus, the concentration
of the marker of bone collagen resorption increased
from 0.86 ng/ml (in the control) to 1.413 ng/ml
(P=0.001) before surgery and 1.617 ng/ml (P=0.001) on
day 7 after surgery. Similarly to the changes in bone
collagen metabolism in group 3, there were shifts in the
content of the studied markers in children aged 5 to 9
years in the first 7 days of observation.
Thus, the level of procollagen type I N-terminal
propeptide (PINP) was increased before surgery from
2.89 ng/ml (in the control) to 16.95 ng/ml (P=0.001). On
day 7 after surgery, PINP decreased slightly to 12.62
ng/ml, but was 4.5 times higher than the control values
(P=0.001). 6 months after surgery, the studied marker
remained significantly elevated and amounted to 22.76
ng/ml (P=0.001). The content of -CrossLaps in the
analyzed group before surgery did not differ from the
control, increased by 44.6% (P=0.021) on the 7th day
after surgery and increased significantly by more than
5 times on the 6th month of follow-up. A distinctive
feature of type I bone collagen metabolism in group 4
was a significant increase in the concentration of
markers of both osteogenesis and its resorption in the
long-term period after surgery. At the same time, the
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International Journal of Medical Sciences And Clinical Research (ISSN: 2771-2265)
PINP content increased more significantly than the
level of -CrossLaps, which indicates an increase in
synthetic processes over its breakdown in bone
collagen metabolism.
In the group of children aged 10 to 14 years, the level
of the marker of bone collagen formation PINP
increased over time. Thus, before surgery, the PINP
content was increased by 3.74 times (P=0.001)
compared with the control group; after surgery, on day
7, it increased by 4.78 times (P=0.001), and after 6
months
–
by 5.59 times (P=0.001). The amount of the
bone resorption marker -CrossLaps varied in phases:
it was increased by 24.5% (P=0.036) before surgery, did
not differ from the data of the control group a week
after surgery, and increased again by 49.5% (P=0.001)
after 6 months of follow-up.
The opposite changes, in contrast to the shifts in group
5, were noted in the indicators of type I collagen
metabolism in children aged 15-19 years, where there
was a significant increase in -CrossLaps, a marker of
bone resorption, both before surgery and in the
dynamics of observations after surgery. Thus, the
content of the studied marker before surgery was
increased by 59.8% (P=0.002) compared with the
control; 3.9 times on the 7th day after surgery
(P=0.001), 10.5 times after 6 months (P=0.001). At the
same time, the increase in PINP in the dynamics of
observations was not so significant: before surgery, it
increased from 11.60 ng/ml (in the control) to 13.46
ng/ml (P>0.05), on the 7th day after surgery to 15.02
ng/ml (P=0.001) and after 6 months to 16.59 ng/ml
(P=0.002). Thus, the dynamics of changes in the
content of markers of bone collagen metabolism in the
blood serum of children aged 15 to 19 years indicates a
pronounced resorption of type I collagen both in the
initial stages after surgery and in the long term.
In addition to bone biomarkers (PINP and -CrossLaps),
we also studied the content of calcium, phosphorus
and alkaline phosphatase, since these biochemical
parameters also reflect bone metabolism and have not
only diagnostic value, but recent studies indicate their
prognostic value, since together with the main bone
markers they can predict the outcome of the disease.
In group 1, the calcium level on day 1 was 1.81 mmol/L,
followed by a moderate increase by day 7 (1.91
mmol/L) and a further increase by month 6-7 (1.98
mmol/l). Despite the statistically insignificant
difference between the 1st and 7th days (p > 0.05), the
tendency to increase calcium levels by the 6th-7th
month may indicate a positive dynamics of the
inflammatory process. In children of group 2 (1-11
months), the initial calcium level was 1.93 mmol/l,
slightly higher than in newborns, and significantly (p <
0.05) increases by day 7 (1.99 mmol/l). The maximum
value (2.05 mmol/l) is recorded by the 6th-7th month,
which, while improving the clinical picture, indicates a
favorable prognosis.
In the age group of 1-4 years and 5-9 years, the increase
in Ca from day 1 to day 7 (1.97 → 1.99 mmol/l and 1.90
→ 1.96 mmol/l, respectively) is small a
nd does not
always reach statistical significance (p = 0.06 for 1-4
years, p = 0.08 for 5-9 years). However, a further
increase by the 6th-7th month (to an average of 2.2 and
2.0 mmol/l, respectively) correlates with an
improvement in radiological and clinical parameters (p
< 0.05). A moderate increase in calcium on the
background of adequate antibacterial therapy may
reflect a decrease in the activity of the inflammatory
process and the restoration of bone metabolism,
especially if other biochemical markers (alkaline
phosphatase, phosphorus) are normalized in parallel.
In the 10-14-year-old group, the intake calcium level
(2.43 mmol/L) is the highest among all ages, while by
day 7 it decreases to 2.03 mmol/l (p < 0.05), and by
month 6-7 it increases again to about 2.2 mmol/L. A
sharp decrease in the acute period may indicate an
intense
inflammatory
process
and
metabolic
restructuring of bone tissue. In the age group of 15-19
years, initially (2.25 mmol/l) there was a slightly
increased calcium, which decreased to 1.93 mmol/l by
day 7 (p = 0.04). The increase by 6-7 months (2.05
mmol/l) indicates the restoration of mineral balance.
The practical significance lies in the fact that
maintaining low calcium values for longer than 2-3
weeks may signal a prolonged course of inflammation,
the formation of sequestration, or insufficient
effectiveness of therapy. Thus, in patients with acute
osteomyelitis, the dynamics of total calcium during the
acute period and the rehabilitation period can serve as
an additional criterion for predicting the outcome of
the disease. An increase in the indicator by the 6th-7th
month, especially in combination with a decrease in the
level of inflammatory markers, is considered a sign of a
favorable outcome and effective therapy. In turn,
insufficient growth or repeated decrease in calcium
should alert the doctor and encourage an expanded
diagnostic search (X-ray, MRI) and, if necessary,
correction of therapeutic measures.
CONCLUSIONS
Thus, we can conclude that the determination of
markers of type I bone collagen metabolism is the most
informative for assessing bone resorption, formation
and regeneration, which can be used not only in the
diagnosis of acute kidney injury, but also in monitoring
treatment, as well as predicting the outcome of the
disease.
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International Journal of Medical Sciences And Clinical Research (ISSN: 2771-2265)
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