Научная статья на тему 'Serum level of N-terminal propeptide of type i procollagen in people of various ages and gender'

Serum level of N-terminal propeptide of type i procollagen in people of various ages and gender Текст научной статьи по специальности «Клиническая медицина»

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Ключевые слова
BONE TURNOVER MARKERS / N-TERMINAL PROPEPTIDE OF TYPE I PROCOLLAGEN / AGE / SEX / МАРКЕРИ ФОРМУВАННЯ ТА РЕЗОРБЦії КіСТКОВОї ТКАНИНИ / N-ТЕРМіНАЛЬНИЙ ПРОПЕПТИД ПРОКОЛАГЕНУ І ТИПУ / ВіК / СТАТЬ / МАРКЕРЫ ФОРМИРОВАНИЯ И РЕЗОРБЦИИ КОСТНОЙ ТКАНИ / N-ТЕРМИНАЛЬНЫЙ ПРОПЕПТИД ПРОКОЛЛАГЕНА I ТИПА / ВОЗРАСТ / ПОЛ

Аннотация научной статьи по клинической медицине, автор научной работы — Povoroznyuk V.V., Zaverukha N.V., Solonenko T.Y.

Background. The purpose of the study is to determine the serum level of N-terminal propeptide of type I procollagen (PINP) in healthy men and women of various ages. Materials and methods. The study included 1,568 individuals (1,422 females and 146 males, aged 20-89 years (mean age 60.36 ± 13.68 yrs). All patients were divided into 7 groups, by decades and according to the gerontological age classification: young age 20-44 yrs, middle age 45-59 yrs, elderly 60-74 yrs, and old 75-89 yrs. During the study, we examined the effect of such demographic characteristics, as age and gender, on serum PINP level, using the electrochemiluminescence immunoassay ECLIA on the cobas e 411 analyzer. Results. We have detected no significant effect of age on the serum variability of PINP in females (F = 1.453, p = 0.19). However, we observed a significant decrease of PINP level in the female age groups of 40-49 yrs (47.74 ± 21.31, p = 0.02), 60-69 yrs (49.76 ± 25.75, p = 0.03), 70-79 yrs (50.49 ± 26.71, p = 0.04), compared with the age group of 20-29 yrs (58.67 ± 27.46). The regression analysis revealed a significant decrease of PINP level with age in young women and men (20-44 years). When comparing serum PINP level in the oldest age group (80-89 years), we detected its increase in women (55.20 ± 28.38 ng/ml), compared with the 70-79 years group (50.49 ± 26.71 ng/ml), and its decrease in men (54.87 ± 28.24 and 39.16 ± 12.46 ng/ml, respectively). In men, we revealed significant effect of age on the serum variability of PINP (F = 3,077, p = 0.007). Conclusions. The regression analysis showed a significant decrease in PINP level with age in men and women of 20-44 years. In men, we detected a significant effect of age on the variability of serum PINP level. A comparison of serum PINP levels in the oldest age group of 80-89 revealed its increase in women, compared to the 70-79 age group, and decrease in men. The obtained results may be used as reference values for PINP level in serum among representatives of the Ukrainian population of various ages and sexes.

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Уровень N-терминального пропептида проколлагена І типа в сыворотке крови у людей разного возраста и пола

Целью исследования является определение уровня N-терминального пропептида проколлагена І типа (PINP) в сыворотке крови у здоровых мужчин и женщин всех возрастов. Материалы и методы. В исследование были включены 1568 человек (1422 лица женского и 146 мужского пола) в возрасте 20-89 лет (средний возраст 60,36 ± 13,68 года). Всех пациентов разделили на 7 групп, в соответствии с десятилетиями и геронтологической классификацией возраста: молодой возраст 20-44 года, средний 45-59 лет, пожилой 60-74 года и старческий возраст 75-89 лет. Во время исследования изучали влияние демографических характеристик (возраста и пола) на уровень PINP в сыворотке крови методом электрохемилюминесцентного иммуноанализа ECLIA на анализаторе cobas e 411. Результаты. В результате исследования у женщин не выявлено достоверного влияния возраста на вариабельность PINP в сыворотке крови (F = 1,453, р = 0,19). Выявлено достоверное снижение уровня PINP в возрастных группах: 40-49 лет (47,74 ± 21,31, р = 0,02), 60-69 лет (49,76 ± 25,75, р = 0,03), 70-79 лет (50,49 ± 26,71, р = 0,04), по сравнению с возрастной группой 20-29 лет (58,67 ± 27,46). По результатам регрессионного анализа выявлено достоверное снижение уровня PINP с возрастом у молодых женщин и мужчин (20-44 лет). При сравнении уровня PINP в сыворотке крови у представителей старшей возрастной группы (80-89 лет) обнаружено его повышение у женщин (55,20 ± 28,38 нг/мл) по сравнению с группой 70-79 лет (50,49 ± 26,71 нг/мл) и снижение у мужчин (54,87 ± 28,24 нг/мл и 39,16 ± 12,46 нг/мл соответственно). У мужчин обнаружено вероятное влияние возраста на вариабельность PINP в сыворотке крови (F = 3,08, р = 0,007). Выводы. По результатам регрессионного анализа установлено достоверное снижение уровня PINP с возрастом у мужчин и женщин 20-44 лет. Доказано вероятное влияние возраста на вариабельность PINP в сыворотке крови у мужчин. При сравнении уровня PINP в сыворотке крови у представителей старшей возрастной группы (80-89 лет) выявлено его повышение у женщин по сравнению с группой 70-79 лет и снижение у мужчин. Полученные нами результаты могут быть использованы как референтные данные уровня PINP в сыворотке крови у представителей украинской популяции разного возраста и пола.

Текст научной работы на тему «Serum level of N-terminal propeptide of type i procollagen in people of various ages and gender»

Орипнальш дослiдження / Original Researches

БШЬ.

СуГЛОБИ. JOINTS. I ХРЕБЕТ SPINE I

УДК 16.124.2-078:57.083.185]:616.12-008.331.1 DOI: 10.22141/2224-1507.10.1.2020.199719

V.V. PovoroznyukC, N.V. Zaverukha , T.Y. Solonenko Э

State Institution "D.F. Chebotarev Institute of Gerontology by the NAMS of Ukraine", Kyiv, Ukraine

Serum level of N-terminal propeptide of type I procollagen in people of various ages and gender

For citation: Bol', sustavy, pozvonocnik. 2020;10(1):1-8. doi: 10.22141/2224-1507.10.1.2020.199719

Abstract. Background. The purpose of the study is to determine the serum level of N-terminal propeptide of type I procollagen (PINP) in healthy men and women of various ages. Materials and methods. The study included 1,568 individuals (1,422 females and 146 males, aged 20-89 years (mean age 60.36 ± 13.68 yrs). All patients were divided into 7 groups, by decades and according to the gerontological age classification: young age - 20-44 yrs, middle age 45-59 yrs, elderly 60-74 yrs, and old 75-89 yrs. During the study, we examined the effect of such demographic characteristics, as age and gender, on serum PINP level, using the electrochemiluminescence immunoassay ECLIA on the cobas e 411 analyzer. Results. We have detected no significant effect of age on the serum variability of PINP in females (F = 1.453, p = 0.19). However, we observed a significant decrease of PINP level in the female age groups of 40-49 yrs (47.74 ± 21.31, p = 0.02), 60-69 yrs (49.76 ± 25.75, p = 0.03), 70-79 yrs (50.49 ± 26.71, p = 0.04), compared with the age group of 20-29 yrs (58.67 ± 27.46). The regression analysis revealed a significant decrease of PINP level with age in young women and men (20-44 years). When comparing serum PINP level in the oldest age group (80-89 years), we detected its increase in women (55.20 ± 28.38 ng/ml), compared with the 70-79 years group (50.49 ± 26.71 ng/ml), and its decrease in men (54.87 ± 28.24 and 39.16 ± 12.46 ng/ml, respectively). In men, we revealed significant effect of age on the serum variability of PINP (F = 3,077, p = 0.007). Conclusions. The regression analysis showed a significant decrease in PINP level with age in men and women of 20-44 years. In men, we detected a significant effect of age on the variability of serum PINP level. A comparison of serum PINP levels in the oldest age group of 80-89 revealed its increase in women, compared to the 70-79 age group, and decrease in men. The obtained results may be used as reference values for PINP level in serum among representatives of the Ukrainian population of various ages and sexes.

Keywords: bone turnover markers; N-terminal propeptide of type I procollagen; age; sex

Introduction

Bone tissue is a metabolically-active structure, which through its remodeling (resorption and formation) takes part in the mineral metabolism, adaptation to the mechanical loading, reacts to the changes of outer and inner environment and recovers after the traumatic injuries [1]. The bone metabolic changes are influenced by the somatic growth in the child and adolescent age, balanced nutrition and dietary flaws, ageing and menopause, metabolic bone disorders, physical activity, therapeutic and surgical interventions, co-morbidities etc. [2]. Traditionally, the bone tissue (BT)'s formation and resorption processes are evaluated by means of histological tools — biopsy with morphometric analysis. However, in the recent years, the advance of im-

munoenzyme analysis enabled the detection of BT metabolic molecular marker in the blood or urine [3].

The International Osteoporosis Foundation (IOF) and the International Federation of Clinical Chemistry Bone Marker Standards Working Group (IOF—IFCC) suggested a routine examination of N-terminal propeptide of type I procollagen (PINP) and P-isomerized C-terminal telo-peptides (P-CTx) in order to prevent fractures, forecast the risk of their occurrence, monitor efficacy of the osteotropic therapy in the osteoporotic (OP) patients [4]. At present, PINP and P-CTx are the only available, economical and highly-sensitive [1] markers of the BT formation and resorption, used in the everyday practice.

© 2020. The Authors. This is an open access article under the terms of the Creative Commons Attribution 4.0 International License, CC BY, which allows others to freely distribute the published article, with the obligatory reference to the authors of original works and original publication in this journal.

Для кореспонденци: Поворознюк Владислав Володимирович, доктор медичних наук, професор, завщувач вщдшу шшчно!' фЫолош та патологи' опорно-рухового апарату, ДУ «1нститут геронтологи' iM. Д.Ф. Чеботарьова НАМН Укра'ни», вул. Вишгородська, 67, м. Ки'в, 04114, Укра'на; e-mail: okfpodac@ukr.net

For correspondence: Vladyslav Povoroznyuk, MD, PhD, Professor, Head of the Department of clinical physiology and pathology of locomotor apparatus, State Institution "D.F. Chebotarev Institute of Gerontology by the NAMS of Ukraine', Vyshgorodska st., 67, Kyiv, 04114, Ukraine; e-mail: okfpodac@ukr.net Full list of author information is available at the end of the article.

All across the world, there has been an active study of the BT remodeling markers, singling out the most informative ones, going on for the 30 recent years [4]. There was an important impetus when an anti-osteoporotic therapy was introduced into the clinical practice in the 1990s, and the OP treatment's efficacy started to be monitored [3]. Previously, the only bone formation marker widely-used was the total alkaline phosphatase, discovered nearly 90 years ago, early in the last century. However, today it is not considered sensitive enough to testify to the BT formation in the laboratory framework [3, 5, 6].

The BT remodeling markers are divided into two groups: those in charge of the BT formation, and others in charge of its resorption. The formation markers are products of osteoblast activity, detected in the blood serum or plasma: [2]: PINP, serum procollagen I carboxyterminal propeptide (PICP), osteocalcin, alkaline phosphatase (ALP) bone isoenzyme. The resorption markers are primarily the products of collagen destruction: P-CTx, N-terminal telopeptide of Type I collagen (NTX-I), deoxypyridino-line, hydroxyproline, tartrate-resistant acid phosphatase (TRACP), cathepsin K (catK), receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG) [4, 6, 7].

The aim of our study was to determine the PINP blood serum levels of healthy men and women of various ages.

Materials and methods

The study was based at the State Institution "D.F. Chebotaryov Institute of Gerontology by the NAMS of Ukraine" and the Ukrainian Scientific-Medical Center of Osteoporosis by the NAMS of Ukraine. The study included 1,568 individuals (1,422 females and 146 males, aged 20-89 years (mean age 60.36 ± 13.68 years). All patients were divided into 7 groups, by decades and according to the gerontological age classification: young age — 20-44 years, middle age - 45-59 years, elderly - 60-74 years, and old - 75-89 years.

Among the inclusion criteria, there were the first recourse to the medical institutions and signed informed consent. Among the exclusion criteria, there were: comorbidities influencing the bone metabolism, the second PINP assaying (dynamic indexing), a history of osteotropic medications (except for calcium and vitamin D), factures of various localizations in the recent year.

During the study, we examined the effect of such demographic characteristics, as age and gender, on serum PINP level, using the electrochemiluminescence immunoassay ECLIA on the cobas e 411 analyzer. The blood serum assays were performed according to 2017 recommendations on the standardized sample processing and patient PINP assay priming [4]: blood collection at fasting, between 7.30 and 10.00 [8]. In the next 2 hours, the blood was centrifuged in the special vacuum test tubes with a distribution gel. The sample analysis was usually made at the day of collection or within the limits of 3 days after (the centrifuged serum was stored at the temperature -200C). The day before the collection, the patients were to avoid exhausting physical activities.

Statistical analysis was performed with Statistica 6.0 software. The obtained results were presented as: mean values (M) ± their standard deviations (SD). The critical level of significance in terms of statistical hypotheses' verification was considered to be 0.05 (p < 0.05). The age's influence on PINP variability was determined by one-factorial (ANOVA) dispersion analysis. The intergroup differences were evaluated by Scheffe's test. The interaction among age, sex and PINP serum levels was determined by linear regression analysis.

Results

According to the distribution of the examined subjects into 7 groups by decades (Fig. 1), the study was made of: 66 individuals (47 females and 19 males) aged 20-29 years, 101 individuals (80 females and 21 males) aged 30-39 years, 105 individuals (79 females and 26 males) aged 40-49 years, 358 individuals (334 females and 24 males) aged 50-59 years, 526 individuals (496 females and 30 males) aged 6069 years, 344 individuals (322 females and 22 males) aged 70-79 years and 68 individuals (64 females and 4 males) aged 80-89 years. The patients were distributed by their ge-rontological characteristics into the following groups: 212 individuals (158 females and 54 males) of young age, 418 individuals (382 females and 36 males) of middle age, 714 individuals (673 females and 41 males) of elderly age, and 224 individuals (209 females and 15 males) of old age.

There was no significant effect of age on the serum PINP variability; F = 1.45, p = 0.19 (Table 1; Fig. 1). While evaluating the intergroup differences, we found a significant PINP decrease in a group of 40-49 years (47.74 ± 21.31, p = 0.02), 60-69 years (49.76 ± 25.75, p = 0.03), 70 - 79 years (50.49 ± 26.71, p = 0.04), compared with the group of 20-29 years (58.67 ± 27.46) (Fig. 2 A).

By contrast, for men age played a significant role in the serum PINP variability; F = 3.08, p = 0.007 (Table 1). While evaluating the intergroup differences (Fig. 2 B), we found a significant PINP decrease in a group of 30 — 39 years (50.44 ± 20.10, p = 0.02), 40 — 49 years (42.93 ± 14.87, p < 0.001), 50 — 59 years (49.57 ± 25.03, p = 0,01), 60 — 69 years (42.31 ± 27.95, p<0.001) and 80 — 89 years

80 70 60 1 50

O)

20 10 0

20-29 30-39 40-49 50-59 60-69 70-79 80-89 Age, years

— • — Females ■ Males

Fig. 1. PINP levels in males and females according to their ages Note: PINP - N-terminal propeptide of type I procollagen.

(39.16 ± 12.46, p = 0.03), compared with the group of 2029 years (69.18 ± 27.92).

The results of regression analysis of PINP level and age (Fig.3) did not reveal any significant differences in women (r = -0.012, t = -0.44, p = 0.66) and men (r = - 0.15, t = -1.87, p = 0.06).

According to the female gerontological distribution (Fig. 4a), the serum PINP level was significantly lower in the age group of 75-89 years (54.17 ± 28.84, p<0.05), compared with the age group of 60-74 years (49.26 ± 25.38, Table 2). The males of 60-74 years had the serum PINP level of 43.85 ± 28.08, (p < 0.05), and it was significantly lower than that of the young subjects - 33.30 ± 6.88 (Fig. 4 B).

According to the regression analysis, PINP was reducing with age in young women (p < 0.05) and men (p < 0.05)

(Fig. 5 A, C). Among the women of the oldest group (75-89 years), its level increased with age (Fig. 5 B). By contrast, in men of the same age there was a negative correlation observed between PINP and age (p > 0.05) (Fig. 5 D).

Discussion

Organic matrix of the bone tissue is made of 90 % collagen type I. Synthesized by osteoblasts in the shape of its precursor - procollagen, it guarantees the bone strength. Type I procollagen has C- (carboxy) and N-(amino) terminal fragments, split away by enzymes -proteinases - with a further collagen formation, joined by the bone matrix, and penetration of C- and N-terminal fragments in the intracellular liquid and blood flow. N-terminal propeptide of type I procollagen (PINP) is the most sensitive marker of the BT

a Mean □ Mean ± SE 1 Mean ± 1,96'SE

CL

z

CL

B

□ Mean

□ Mean ± SE

I Mean ± 1,96'SE

Fig. 2. The serum PINP levels in males and females of various ages with distribution into decades:

(A) - females, (B) - males Note: PINP - N-terminal propeptide of type I procollagen; 7.

Table 1. The serum PINP levels in men and women of various ages

Age, years Women Men

Mean age, years Number of subjects, n PINP level, ng/ml Mean age, years Number of subjects, n PINP level, ng/ml

20-29 25.83 ± 2.50 47 58.67 ± 27.46 25.84 ± 2.69 19 69.18 ± 27.92

30-39 35.21 ± 2.92 80 49.54 ± 26.60 34.24 ± 3.28 21 50.44 ± 20.10

40-49 45.28 ± 2.83 79 47.74 ± 21.31 44.42 ± 3.07 26 42.93 ± 14.87

50-59 55.59 ± 2.72 334 51.91 ± 26.82 54.21 ± 2.64 24 49.57 ± 25.03

60-69 64.15 ± 2.80 496 49.76 ± 25.75 64.87 ± 2.03 30 42.31 ±27.95

70-79 74.02 ± 2.73 322 50.49 ± 26.71 74.59 ± 3.05 22 54.87 ± 28.24

80-89 82.25 ± 2.46 64 55.20 ± 28.38 82.50 ± 1.73 4 39.16 ± 12.46

Total 61.24 ± 12.99 1422 50.85 ± 26.25 51.73 ± 16.91 146 50.08 ± 25.51

Note: PINP - N-terminal propeptide of type I procollagen.

formation and reflects the bone-formation rate, has a greater stability and diagnostic value than C-terminal fragments (CTF), and it is dissolved in 6-8 minutes by the blood flow. The PINP blood rate is directly proportionate to the rate of produced osteoblasts and built-in collagen [2, 3, 12].

While interpreting the results, one should take into account all the available modified and non- modified: age, sex, a recent history of fracture, long-lasting immobilization, pregnancy, comorbidities and a previous history of anti-osteoporotic medications and some other drugs.

0 0'

A

50 60 70 Age, years

80 90 100

1^95% confidence!

B

10 20 30 40 50 60 70 80 90 Age, years

^95 % confidence

Fig.3. Regression analysis of interaction between the serum PINP level and age: (A) - females, (B) - males. Note: PINP - N-terminal propeptide of type I procollagen. A. PINP (ng/ml) = 52.277 - 0.0234 * AGE (years), r = -0.012, t = -0.44, p = 0.66. B. PINP (ng/ml) = 62.087 - 0.2320 * AGE (years), r = -0.15, t = -1.87, p = 0.06

Table 2. The serum PINP levels in men and women of various ages according to the gerontological classification

Age, years Women Men

Mean age, years Number of subjects, n PINP level, ng/ml Mean age, years Number of subjects, n PINP level, ng/ml

20-44 33.80 ± 6.37 158 51.70 ± 25.77 33.30 ± 6.88 54 55.18 ± 24.38

45-59 54.54 ± 3.78 382 51.47 ± 26.38 51.89 ± 4.07 36 47.21 ± 22.10

60-74 66.18 ± 4.24 673 49.26 ± 25.38 66.05 ± 4.13 41 43.85 ± 28.08

75-89 78.33 ± 3.14 209 54.17 ± 28.84 78.60 ± 2.78 15 55.66 ± 27.32

60 58 56 E 54

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1 52

CL

50 48 46

F = 2.07, p = 0.1

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x

2 3

Age, years

A

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F = 1.96, p = 0.12

i

1

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B

a Mean □ Mean ± SE I Mean ± 1,96'SE

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Fig.4. The serum PINP levels in males and females of various ages according to the gerontological classification:

(A) - females, (B) - males.

Note: PINP - N-terminal propeptide of type I procollagen; 1 - subjects of 20-44 years, 2 - 45-59 years, 3 - 60-74 years, 4 - 75-89 years.

Note: PINP - N-terminal propeptide of type I procollagen.

For most BT metabolism markers, the acrophase, or peak time of the highest blood rate, is similar for both sexes [13]. The BT formation marker rate in the newly-born and neonates is at its highest, compared to other age groups. By the pubertal age, their level drops down. At the beginning of sexual maturation (by Tanner's classification - I-III), the rate of markers are higher, and afterwards it starts to decline, earlier for girls, later for boys [4, 14]. According to the reference data, among the juniors the PINP rate is higher in men than in women. It is attributed to a larger BT volume and mass of men (taking into account their height and constitution) and, thus, to a faster formation and resorption of larger bones [15, 14]. Our findings did not reveal a significant PINP rate's increase in men compared to women (men — 69.18 ± 27.92, women - 58.67 ± 27.46). The absence of significant difference is, to our mind, explained by a small number of the young examined male subjects (n = 19).

With advancing age, the BT metabolism markers increase in men at a more significant rate, than in women [14]. Our findings confirm that among the older women (75-89 years) there was an increase of blood PINP blood rates with age;

however, among the similarly-aged men there was an opposite tendency. These results may be associated with a small sample of old men (n = 15) and an "assumed" low average life expectancy of male population in Ukraine. According to the 2018 data by the Statistical Service of Ukraine, an average life expectancy of men is 66.69 years while an average life expectancy of women is 76.72 years [10]. It is lower than the European one: where an average life expectancy of men is 78.3 years and an average life expectancy of women is 83.5 years [11]. J. E. Aaron et al. described the BT histomorphic alterations in men and women. The BT trabecular volume was similar for both sexes; however, it differed by the histological parameters. The men's principal BT loss factors were attributed to the reduced formation, and the women's BT loss remained unchanged. These findings enabled an assumption that the BT alterations in women is caused by an amplified resorption. The BT loss in women is primarily associated with the destruction of individual trabeculae, by contrast to the one in men who are subject to a generalized trabecular wearing-down, though it has a lower effect on mineral density and the BT quality [16]. Furthermore,

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78 80 82

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Fig. 5. Correlation and regression analysis of age and the serum PINP level interaction: (A) - females aged 20-44 years, (B) - females

aged 75-89years, (C) - males aged 20-44 years, (D) - males aged 75-89 years Note: PINP - N-terminal propeptide of type I procollagen. A. PINP (ng/ml) = 77.725 - 0.7701 * AGE (years), (r= -0.19, t = -2.42, p = 0.02); B. PINP (ng/ml) = 35.846 + 0.23397 * AGE (years), (r = 0.03, t = 0.37, p = 0.71); C. PINP (ng/ml) = 97.734 - 1.278 * AGE (years), (r = -0.36, t = -2.79, p = 0.007); D. PINP (ng/ml) = 405.50 - 4.451 * AGE (years), (r = 0.45, t = -1.83, p = 0.09).

high BT metabolism markers reveal bone microarchitecture degradation and the BT loss in men less frequently than in women. However, it may be suggested that the BT metabolism marker alterations are no predictors of fracture in men

[14].

The blood serum PINP level grows during menopause; however, its inner individual variations in the peri- and postmenopausal women are less than 10%. Our findings reveal an increase of the blood serum PINP level in the age group of 50-59 years (51.91 ± 26.82, p = 0.03), corresponding to the late postmenopausal period in Ukraine; the mean age of menopause being 48.7 years [9]. At the same time, as in case of older men, its level remains stable or increases insignificantly, usually after 70 years [4, 14, 17]. The post-menopausal women have a higher PINP level than men of a similar age.

According to the reference data, the BT formation marker level is often affected by the seasonality. It is claimed that in winter their level is higher, which is attributed to the vitamin D deficiency and secondary hyperparathyroidism. It is essential to take this fact into account interpreting these results, especially in the older people, who have a higher likelihood of the vitamin D deficiency [13].

The PINP level is higher during the lutein stage of the menstrual cycle than during the follicular stage. Szulc P. et al. (2017) recommend that the women of reproductive age should be subject to the blood sampling during the follicular stage, lasting on average from the 1st to 14th day of the menstrual cycle [4].

During pregnancy, the bone formation marker level remains intact during the first two trimesters and rapidly increases during the third trimester. After the labors, their concentration rapidly drops down; however, it remains elevated during the postpartum period, compared to the nonpregnant women of a similar age. The lactating women have a higher PINP level, compared to the non-lactating ones

[4, 18].

The serum PINP level grows dramatically during the first weeks after the fracture (by 150 % from the basic level). It reaches its maximum 12 weeks after fracture with a further decrease. The elevated PINP concentration is preserved for more than 1 year. The fractures with a larger scale of destruction and consolidation (for instance, pertrochanteric fracture) are associated with a higher BT formation and resorption markers alike. Immobilization also results in an elevated serum PINP level [4, 14].

The influence of physical activity on the PINP level depends on the sports subjects are involved in, duration and intensity of physical activity. The women who are into swimming did not report any alterations of BT metabolism markers [14], confirming the fact that the physical exercises do not affect the PINP level significantly [19].

The BT metabolism marker rates depend on the body weight. The studies show that the BT formation markers are lower in the obese people, compared to subjects with a normal BMI [14].

Disorders of the BT formation and resorption balance is observed with some endocrine diseases (hypothyroidism, hypoparathyroidism, hypopituitarism, growth hormone de-

ficiency) and HIV-infection. The PINP level is inversely correlated to the fast glomerular filtration rate, or GFR, in patients with a chronic renal insufficiency. The oral and parenteral corticosteroids depending on their doses are suppressing the bone tissue formation, unlike the inhalers affecting the BT metabolism level [4].

The women using oral estrogen-based contraceptives had the BT formation marker levels which were lower by 15-25 %; however, medroxyprogesterone acetate raises the PINP level insignificantly [4].

The PINP's advantage over other BT formation markers is its minimal circadian variability and the fact that unlike others, it is not affected by the food intake, enabling random blood samplings during the day [4].

Our study had a certain limitation: there were few men in the age group of 20-29 (n = 19) and 80-89 years (n = 4), complicating the interpretation of findings.

Conclusions

According to the regression analysis, the PINP level decreased significantly with age, both in men and women of 2044 years. A considerable age-related effect was revealed on the blood serum PINP's variability in men. While comparing the PINP's levels in the oldest group of 80-89 years, we found its reduction in women by comparison with the group of 70-79 years as well as its reduction in men. The obtained findings may be used as reference data on the serum PINP level in the Ukrainian patients of various ages and sexes.

Conflicts of interests. Authors declare the absence of any conflicts of interests and their own financial interest that might be construed to influence the results or interpretation of their manuscript.

References

1. Shetty S, Kapoor N, Bondu JD, Thomas N, Paul TV. Bone turnover markers: Emerging tool in the management of osteoporosis. Indian J Endocrinol Metab. 2016;20(6):846—852. https://doi.org/10.4103/2230-8210.192914.

2. Seibel MJ. Biochemical markers of bone turnover: part I: biochemistry and variability. Clin Biochem Rev. 2005;26(4):97—122.

3. Roodman GD, Guise TA. Bone and Cancer. In: Burr DB, Allen MR, editors. Basic and Applied Bone Biology. 2th ed. USA: Academic Press; 2019. 411-423 pp. https://doi. org/10.1016/B978-0-12-813259-3.00022-1.

4. Szulc P, Naylor K, Hoyle NR, Eastell R, Leary ET; National Bone Health Alliance Bone Turnover Marker Project. Use of CTX-I and PINP as bone turnover markers: National Bone Health Alliance recommendations to standardize sample handling and patient preparation to reduce pre-analytical variability. Osteoporos Int. 2017;28(9):2541—2556. https://doi. org/10.1007/s00198-017-4082-4.

5. Coates P. Bone turnover markers. Aust Fam Physician. 2013;42(5):285—287.

6. Povoroznyuk VV, Balatska NI. Role of bone tissue turnover markers in diagnosis of osteoporosis. Mystetstvo likuvan-nya. 2013;2—3:98—99. (in Ukrainian).

7. Povoroznyuk VV. Osteoporosis and biochemical bone turnover markers. Laboratory diagnosis. 2002;1:53-61. (in Ukrainian).

8. Redmond J, Fulford AJ, Jarjou L, Zhou B, Prentice A, Schoenmakers I. Diurnal Rhythms of Bone Turnover Markers in Three Ethnic Groups. J Clin Endocrinol Metab. 2016;101(8):3222-3230. https://doi.org/10.1210/jc.2016-1183.

9. Povoroznyuk VV, Grygorieva N.V. Menopause and osteoporosis. Mystetstvo likuvannya. 2005;3:25-30. (in Ukrainian).

10. State Statistics Service of Ukraine. Fertility, mortality, and average life expectancy tables for 2018. Kyiv; 2019. 66 p.

11. Eurostat. Life expectancy at birth in the EU: men vs. women. 2017. Available from: https://ec.europa.eu/eurostat/ web/products-eurostat-news/-/DDN-20190725-1

12. Vasikaran S, Eastell R, Bruy re O, et al. Markers of bone turnover for the prediction of fracture risk and monitoring of osteoporosis treatment: a need for international reference standards. Osteoporos Int. 2011;22(2):391-420. https://doi. org/10.1007/s00198-010-1501-1.

13. Garnero P, Szulc P. Assessment of Bone Turnover in Men Using Biochemical Markers. In: Orwoll E, Bilezikian J, Vanderschueren D, editors. Osteoporosis in Men. 2nd ed. Academic Press; 2009. 25-40 pp. https://doi.org/10.1016/B978-0-12-374602-3.00003-1.

14. Eastell R, Szulc P. Use of bone turnover markers in postmenopausal osteoporosis. Lancet Diabetes Endocri-

nol. 2017;5(11):908-923. https://doi.org/10.1016/s2213-8587(17)30184-5.

15. Kitareewan W, Boonhong J, Janchai S, Aksaranugraha S. Effects of the treadmill walking exercise on the biochemical bone markers. J Med Assoc Thai. 2011;94 Suppl 5:S10-S16.

16. Aaron JE, Makins NB, Sagreiya K. The microanatomy of trabecular bone loss in normal aging men and women. Clin Orthop Relat Res. 1987;(215):260-271.

17. Van den Berghe G, Van Roosbroeck D, Vanhove P, Wouters PJ, De Pourcq L, Bouillon R. Bone turnover in prolonged critical illness: effect of vitamin D. J Clin Endocrinol Metab. 2003;88(10):4623-4632. https://doi.org/10.1210/ jc.2003-030358.

18. Ferreira A, Alho I, Casimiro S, Costa L. Bone remodeling markers and bone metastases: From cancer research to clinical implications. Bonekey Rep. 2015;4:668. https://doi. org/10.1038/bonekey.2015.35.

19. Weiler R, Keen R, Wolman R. Changes in bone turnover markers during the close season in elite football (soccer) players. J Sci Med Sport. 2012;15(3):255-258. https://doi. org/10.1016/j.jsams.2011.09.004.

Received 24.01.2020 Revised 13.02.2020 Accepted 23.02.2020 ■

Information about authors

V.V. Povoroznyuk, MD, PhD, Professor, Head of the Department of clinical physiology and pathology of locomotor apparatus, State Institution "D.F. Chebotarev Institute of Gerontology of the NAMS of Ukraine'; Kyiv, Ukraine, ORCID iD: http://orcid.org/0000-0002-9770-4113

Nataliia Zaverukha, Junior Research Fellow at the Department of Clinical Physiology and Pathology of musculoskeletal system, State Institution "D.F. Chebotarev Institute of Gerontology of the NAMS of Ukraine", Kyiv, Ukraine, ORCID iD: http://orcid.org/0000-0002-0181-2794

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Tetiana Solonenko, Junior Research Fellow at the Department of Clinical Physiology and Pathology of musculoskeletal system, State Institution "D.F. Chebotarev Institute of Gerontology of the NAMS of Ukraine", Kyiv, Ukraine, ORCID iD: http://orcid.org/0000-0002-8443-4898

Поворознюк В.В., Заверуха Н.В., Солоненко Т.Ю.

ДУ «1нститут геронтологи теш Д.Ф. Чеботарьова» НАМН УкраУни, м. Кию, УкраУна

PiBeHb N-термшального пропептиду проколагену I типу в сироватц KpoBi

в oci6 pÍ3Horo BiKy та стат

Резюме. Метою дослщження е визначення piBM N-термь нального пропептиду проколагену I типу (PINP) у сироват-щ кровi здорових чоловтв та жшок рiзного вшу. Mamepia-ли таметоди. У дослщження були включеш 1568 ошб (1422 особи жшочо'1 та 146 — чоловiчоI стап) вшом 20—89 рошв (середнш вш — 60,36 ± 13,68 року). Усгх обстежених ошб розподшили на 7 груп вщповщно до десятирiччя та герон-толопчно! класифшацп вщу: молодий вш — 20—44 роки, середнш — 45—59 рошв, лггнш — 60—74 роки та старечий вш — 75—89 рошв. Пщ час дослщження вивчали вплив демогра-фiчних характеристик: вшу i стап на рiвень PINP у сироват-щ кровi методом електрохемшюмшесцентного iмуноаналiзу ECLIA на аналiзаторi cobas e 411. Результати. У результат дослщження в жшок не встановлено вiроriдного впливу вь ку на варiабельнiсть рiвня PINP у сироватщ кровi (F = 1,453, р = 0,19). Виявлено вiрогщне зниження рiвня PINP у жшок вшових груп: 40-49 рошв (47,74 ± 21,31, р = 0,02), 60-69 роив (49,76 ± 25,75, р = 0,03), 70-79 рошв (50,49 ± 26,71, р = 0,04), порiвняно з групою 20-29 роив (58,67 ± 27,46). За результатами регресшного аналiзу визначено вiрогщне зниження рiвня PINP iз вiком у молодих жiнок та чоловь

кiв (20—44 роки). При порiвняннi рiвня PINP у сироватщ кровi в представникiв найстаршо! вшово! групи (80—89 ро-кiв) виявлено його пщвищення в жiнок (55,20 ± 28,38 нг/мл) порiвняно з групою 70—79 рошв (50,49 ± 26,71 нг/мл) та зниження в чоловтв (54,87 ± 28,24 нг/мл та 39,16 ± 12,46 нг/мл вщповщно). У чоловiкiв доведено вiрогщний вплив вiку на варiабельнiсть рiвня PINP у сироватцi кровi (F = 3,08, р = 0,007). Висновки. За результатами регресшного аналь зу доведено вiроriдне зниження рiвня PINP iз вiком у чоловтв та жшок 20—44 роив. Виявлено вiрогщний вплив вь ку на варiабельнiсть рiвня РШР у сироватцi кровi у чоловтв. При порiвняннi рiвня РШР у сироватщ кровi в пред-ставникiв найстаршо! вiково'i групи (80—89 рошв) визначено його пщвищення в жшок порiвняно з групою 70—79 роив та зниження в чоловтв. Отримаш нами результати мо-жуть бути використанi як референтш данi рiвня PINP у сироватщ кровi в представнишв укра!нсько! популяцй рiзно-го вшу та стап.

Ключовi слова: маркери формування та резорбци истко-во! тканини; N-термiнальний пропептид проколагену I типу; вш; стать

Поворознюк В.В., Заверуха Н.В., Солоненко Т.Ю.

ГУ «Институт геронтологии имени Д.Ф. Чеботарева НАМН Украины», г. Киев, Украина

Уровень N-терминального пропептида проколлагена I типа в сыворотке крови

у людей разного возраста и пола

Резюме. Целью исследования является определение уровня N-терминального пропептида проколлагена I типа (PINP) в сыворотке крови у здоровых мужчин и женщин всех возрастов. Материалы и методы. В исследование были включены 1568 человек (1422 лица женского и 146 — мужского пола) в возрасте 20—89 лет (средний возраст — 60,36 ± 13,68 года). Всех пациентов разделили на 7 групп, в соответствии с десятилетиями и геронтологической классификацией возраста: молодой возраст — 20—44 года, средний — 45—59 лет, пожилой — 60—74 года и старческий возраст — 75—89 лет. Во время исследования изучали влияние демографических характеристик (возраста и пола) на уровень PINP в сыворотке крови методом электрохемилюминесцентного иммуноанали-за ECLIA на анализаторе cobas e 411. Результаты. В результате исследования у женщин не выявлено достоверного влияния возраста на вариабельность PINP в сыворотке крови (F = 1,453, р = 0,19). Выявлено достоверное снижение уровня PINP в возрастных группах: 40—49 лет (47,74 ± 21,31, р = 0,02), 60-69 лет (49,76 ± 25,75, р = 0,03), 70-79 лет (50,49 ± 26,71, р = 0,04), по сравнению с возрастной группой 20-29 лет (58,67 ± 27,46). По результатам регрессионного анализа выявлено достоверное снижение уровня PINP

с возрастом у молодых женщин и мужчин (20—44 лет). При сравнении уровня РШР в сыворотке крови у представителей старшей возрастной группы (80—89 лет) обнаружено его повышение у женщин (55,20 ± 28,38 нг/мл) по сравнению с группой 70—79 лет (50,49 ± 26,71 нг/мл) и снижение у мужчин (54,87 ± 28,24 нг/мл и 39,16 ± 12,46 нг/мл соответственно). У мужчин обнаружено вероятное влияние возраста на вариабельность РШР в сыворотке крови ^ = 3,08, р = 0,007). Выводы. По результатам регрессионного анализа установлено достоверное снижение уровня РШР с возрастом у мужчин и женщин 20—44 лет. Доказано вероятное влияние возраста на вариабельность РШР в сыворотке крови у мужчин. При сравнении уровня РШР в сыворотке крови у представителей старшей возрастной группы (80—89 лет) выявлено его повышение у женщин по сравнению с группой 70—79 лет и снижение у мужчин. Полученные нами результаты могут быть использованы как референтные данные уровня РШР в сыворотке крови у представителей украинской популяции разного возраста и пола.

Ключевые слова: маркеры формирования и резорбции костной ткани; ^терминальный пропептид проколлагена I типа; возраст; пол

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