KLINICZNO-PATOGENETYCZNE ASPEKTY NIEDOBORU MASY KOSTNEJ U PACJENTÓW Z WSPÓŁWYSTĘPUJĄCĄ CHOROBĄ ZWYRODNIENIOWĄ STAWÓW ORAZ PRZEWLEKŁYM ZAPALENIEM TRZUSTKI

Liliy S. Babinets, Tatiana H. Maevska, Olga I. Kriskiv, Liudmyla S. Tsybulska, Iryna B. Chornomydz, Oksana Ya. Drapak

SHII “I. Ya. Horbachevsky Ternopil state medical university of the Ministry of public health of Ukraine”, Ternopil, Ukraine

ABSTRACT

Introduction: Pathology of the musculoskeletal system creates a number of important and complex medical problems affecting the economic situation of society, health and quality of life of individuals and their families. One of these problems and the most common disease of the joints which is diagnosed in 20% of the population of the planet is osteoarthritis (OA).

The aim: The article deals with modern views on the problem of comorbidity of osteoarthritis, chronic pancreatitis and osteodefiсiency. Dual energy X-ray densitometry data were analyzed, as well as indicators of activation of lipid peroxidation (malonic aldehyde), antioxidant protection system (superoxide dismutase and SH-group, ceruloplasmin, сatalase) and tissue destruction (oxyproline).

Materials and Methods:The complex examination of 72 patients was made. Patients were divided into two groups: 30 patients with OA and 42 – with OA in combination with CP. The control group included 20 apparently healthy individuals. Evaluation of CT scan was performed using Dual Energy X-Ray Absorptiometry – DXA by Lunar corp. (Madison, WI) – Lunar DPX-A No. 2589 in the lumbar region of the vertebral column. The evaluation of the indicators was carried out in accordance with WHO recommendations (WHO, Geneva, 1994) [1]. The study of LPO was carried out on the level of malonic aldehyde (MA). To assess AOP, we determined SOD, ceruloplasmin (CPN); SH-groups; catalase. The endogenous intoxication and the level of degradation of the connective tissue in the body was estimated by levels of free oxyproline. The influence of CP on the state of LPO-AOP was established by the following clinical characteristics of CP: age of the patients, structural condition of the pancreas with the help of the method of ultrasound, expressed in points. Excretory function of the pancreas was investigated on the level of fecal α-elastase ( by ELISA test using the kits BIOSERV ELASTASE 1-ELISA).

Results: During the examination of the mineral bone density by the dual energy X-ray densitometry it was discovered that the presence of CP in patients with OA led to a significant reduction of BMD and deterioration of the bone tissue (BT): the proportion of patients with normal bone decreased from 67% to 16%, the number of patients with osteopenia increased from 10% to 67%; patients with OP appeared – 17%.Besides, the increased degradation of bone tissue in OA with CP was accompanied by strengthening of oxidative changes (by MA-level), weakening of the antioxidant defense (SOD and SH-groups), the increase in the severity of inflammation and endotoxemia (levels of catalase and ceruloplasmin), as well as increased degradation of connective and bone tissue in the joints and progression of fibrosis in tissue (the level of oxyproline).

Conclusions: It was found out that the presence of CP in patients with OA led to a significant reduction of BMD and the deterioration of the bone tissue. It was discovered that during the combined course of OA and CP with osteopenia there occurs the weakening of the AOP (by SOD and SH-groups) and a relatively high level of LPO activation (by MA-level) as well as the increased deterioration in connective and bone tissue and aggravation of osteopenia which is indicated by the increased levels of oxyproline.

Wiad Lek 2017, 71, 6 cz. I, 1067-1071

Introduction

Pathology of the musculoskeletal system creates a number of important and complex medical problems affecting the economic situation of society, health and quality of life of individuals and their families. One of these problems and the most common disease of the joints which is diagnosed in 20% of the population of the planet is osteoarthritis (OA). In Ukraine it is officially registered more than 500, 000 patients with OA. According to statistics, now every third resident suffers from OA of certain joints [2, 3, 4]. The prevalence of OA in the population (6.3 %) correlates with age and reaches the maximum settings (13,9%) in individuals aged over 45 [5, 6]. OA is a polyetiologic disease based on the affection of all the components of the joint, primarily, the cartilage and subchondral bone [7, 8]. The pathogenesis of OA consists of a number of interconnected chains that results in the formation of degenerative and destructive processes in the cartilage and bone tissue. In addition, recently conducted studies have revealed a relatively high frequency of disorders of internal organs (including gastrointestinal tract disorders) in patients with OA. According L. B. Lazebnik and V. N. Drozdov, [9] the combination of the manifest OA and the diseases of the GI tract is quite frequent. It was also found that these patients were reported to have more than 5 diseases per each person examined. This gave the right to the authors to form the problem of polymorbidity with OA [8, 9]. In cases of the GI tract diseases, in particular, with the progression of chronic pancreatitis (CP) as a long-term inflammatory disease of the pancreas complicated by fibrosis, calcification, exocrine and endocrine insufficiency, the formation of osteodeficiency (OD) is frequent [10, 11, 12]. In CP the absorption and metabolism of vitamin D and its metabolites is impaired, as well as malabsorption of calcium and other minerals occurs. Therefore, patients with CP undoubtedly constitute a risk group regarding the appearance or worsening of the disorders in the bone tissue (BT). In CP, as well as in OA, the activation of lipid peroxidation (LPO) and reduction of antioxidant protection (AOP) occur, endogenous intoxication develops, which also leads to the changes of the bone tissue (BT) in the form of its enlargement (osteosclerosis) or reduction (osteopenia and osteoporosis (OP)) [13].

The reduction of bone mineral density (BMD) and its demineralization is a major cause of disability in the elderly. The development of osteodeficient conditions (OP and osteopenia) may be asymptomatic for years[14, 15]. Densitometry as the main method of early diagnosis allows to reveal liability to the disease, its depth, and to take the complex of medical and preventive measures in advance to avoid serious consequences. OA, osteopenia and OP are extremely important for their medical and social impact diseases of musculoskeletal system which were selected among the five most relevant ones during the Bone and Joint Decade – 2000 to 2010. An increase in the frequency of each of them is associated with age, dysfunction of the gastrointestinal tract and its diseases, in particular, in CP. In addition, they have their own characteristics and are continuously growing, which makes relevant the study of the problem of comorbid course of OA, CP and OD [16, 17, 18].

The aim

The aim of the study was to analyze the condition of bone mineral density, as well as the relationship of osteodeficiency and clinical characteristics of chronic pancreatitis and parameters of the lipid peroxidation (LPO) and antioxidant protection (AOP) in patients with osteoarthritis in combination with chronic pancreatitis.

Materials and methods

72 patients with OA who were treated in the day patient department of the Ternopil City Municipal Hospital #2 were the object of the study. Patients were divided into two groups: 30 patients with OA and 42 – with OA in combination with CP. Among the patients there were 47 women (65%) and 25 men (35%). The average age of patients was (57,3±5,1) years. The control group included 20 apparently healthy individuals. The diagnosis of OA was established on the basis of unified diagnostic criteria [7, 19], the radiographic stage of OA was established by J. H. Kellgren and J. S. Lawrence. The study included the patients with disorders of the hip and knee joints without synovitis with radiological stage I-III. The diagnosis of СP was verified in accordance with generally accepted clinic criteria [7]. The patients in remission phase without diabetes were included in the study. Evaluation of CT scan was performed using Dual Energy X-Ray Absorptiometry – DXA by Lunar corp. (Madison, WI) – Lunar DPX-A No. 2589 in the lumbar region of the vertebral column. We analyzed the following parameters: BMD of the lumbar region L1-L4 with intervertebral spaces taking into account osteoarthritic changes in g/cm2 within the accuracy of 0.02 g/cm2; relative indicators – T (peak bone mass) – BMD in reference to healthy young persons aged 20-45 in units of SD (standard deviations) – the units of standard deviation and the index T in % from the level of BMD of healthy young individuals [17]. The degree of BT density was determined by T-ratio (osteopenia, osteosclerosis or OP). The evaluation of the indicators was carried out in accordance with WHO recommendations (WHO, Geneva, 1994) [1]: T above (+1) – osteosclerosis; T in range (-1)-(+1) – normal CT scan; (-1) to(-2,5) – osteopenia; T lower (-2,5) – OP.

The study of LPO was carried out on the level of malonic aldehyde (MA) (determined by the reaction of V. M. Orkhevychwith with thiobarbituric acid). To assess AOP, we determined SOD (for its ability to compete with nitrotetrazolium blue for superoxide anions); ceruloplasmin (CPN) (in the serum of blood by Rowin); SH-groups (using Boyer’s method with n-mercurbenzol Na); catalase (by the level of splitting of hydrogen peroxide and determining the ratio of catalase number relating to the number of erythrocytes in 1 ml of blood). The endogenous intoxication and the level of degradation of the connective tissue in the body was estimated by levels of free oxyproline (according to the method of Stegtmann in modification of Osadchuk M. A., Kuznetsova T. P. and co-authors). The influence of CP on the state of LPO-AOP was established by the following clinical characteristics of CP: age of the patients, structural conditionof the pancreas with the help of the method of ultrasound, expressed in points. Excretory function of the pancreas was investigated on the level of fecal α-elastase ( by ELISA test using the kits Bioserv Elastase 1-Elisa).

The results were processed statistically using standard PC software packages Microsoft Excel and Statistica for Windows 6.0 (Stat Soft inc., USA) and evaluated by Student’s criteria. Assessment of the relationships was carried out on the basis of the multiple correlation coefficient R according to generally accepted statistics criteria: R < 0,3 – a weak relationship; R = 0.3 to 0.5 – moderate; R > 0.5 to 0.7 – significant; R > 0,7-0,9 – strong; R > 0,9 – very strong, close to functional connection.

Results and discussion

When assessing BMD of the patients with OA in group I it was discovered that 67.0% of patients had normal BMD, 23,0% – osteosclerosis, 10,0% – with osteopenia (Fig.I).

During the examination of group II (OA+ CP) the condition of the patients’ bones was defined in the following way: 67% – osteopenia, 17% OP and 16% – normal BMD (Fig. II). Thus, it was found that the presence of CP in patients with OA led to a significant reduction of BMD and deterioration of the bone tissue (BT): the proportion of patients with normal bone decreased from 67% to 16%, the number of patients with osteopenia increased from 10% to 67%; patients with OP appeared – 17%.

Table I shows the data of the parameters of the LPO-AOP in the comparison group of the patients with OA depending on the presence of accompanying СP.

It was noted that the group of patients with OA+CP has a reliably higher gain level of LPO in terms of MA (5,42 %) and a decrease in the AOP by the level of SH-group, SOD (by 4.31%), increased activity of ceruloplasmin and catalase (12,77%), as well as an increase in the level of the marker of the destruction of connective tissue and endotoxemia – oxyproline in comparison with similar indicators of patients with OA. Thus, the increased degradation of bone tissue in OA with CP was accompanied by strengthening of oxidative changes (by MA-level), the weakening of the antioxidant defense (SOD and SH-groups), the increase in the severity of inflammation and endotoxemia (levels of catalase and ceruloplasmin), as well as increased degradation of connective and bone tissue in the joints and progression of fibrosis in tissue (the level of oxyproline).

The study analyzed the relationships between the main parameters of CP (age of the patients, duration of the comorbid course of CP and OA, the level of fecal α-elastase structural condition of the pancreas and ultrasound criteria in points) and BMD (by densitometric index T%) with the index of LPO-AOP in patients with combined course of CP and OA accompanied by osteopenia. Table. II shows the data of correlation and regression analysis between the above mentioned parameters.

It was found that with increasing age of patients, duration of the course of combined diseases, OA and CP,the parameter of ultrasound points, as well as the reduced levels of α-elastase and the degree BMD there was an accumulation of oxyproline in the serum, as evidenced by correlation of the average strength between these parameters. This therefore states the presence of progression of destruction of bone and cartilage, as well as tissue of the pancreas in patients with combined course of OA and CP with osteopenia.

Conclusions

1. The presence of CP in patients with OA led to a significant reduction of BMD and the deterioration of the bone tissue: the proportion of patients with normal bone decreased from 67% to 16%, the proportion of the patients with osteopenia increased from 10% to 67%, the patients with OP – 17% – appeared.

2. The deterioration of the bone during OA with CP was accompanied by strengthening of oxidative changes (by MA-level), the weakening of the antioxidant defense (SOD and SH-groups), the increase of the severity of inflammation and endotoxemia (by the level of catalase and ceruloplasmin), as well as the increased deterioration of connective and bone tissue in the joints and progression of fibrosis in the tissue of the pancreas ( by the level of oxyproline).

3. The accumulation of oxyproline in serum occurs (medium strength correlation between these parameterswas found) with increasing age of the patients, duration of the course of OA combined with CP, the index of the ultrasound investigation of the pancreas, as well as with the reducing of the levels of α-elastase and the degree of BMD. This therefore states the presence of progression of destruction of bone and cartilage, as well as tissue of the pancreas in patients with combined course of OA and CP with osteopenia.

Prospects for further research. Hereafter, it is planned to deepen the study of clinico-pathogenic peculiarities of combined course of osteoarthritis, chronic pancreatitis and osteodeficiencies.

References

1. World Health Organization:Assessement of fracture risk and its application to screening for postmenopausal osteoporosis. WHO Technical Report Series 843. WHO, Geneva,1994.

2. Vertkin A, Naumov A Deforming osteoarthritis: a strategy for the management of patients with somatic pathology, Russian medical magazine– 2007.

3. Gayko G, Brusco A, Kalashnikov A, Features of pathological changes of the femoral head in patients with osteoarthritis of the hip joint Pain. Joints. Spine. 2014;1(2):9-13.

4. Fernandes L., Lund H., Mallen C.D. [et al.], EULAR recommendations for the non-pharmacological core management of hip and knee osteoarthritis, Ann. Rheum. Dis. – doi: 10.1136/annrheumdis-2012-202745.

5. Gaidam, J, The state of health of the Ukrainian population and provide medical assistance: analytically – statistical Handbook /In: Gaydayev Y, Kowalska V, Kornatsky V. Kiev: 2012. 97.

6. Nasonova V, Osteoarthritis – the problem of multimorbidity. Ukrainian medical magazine . 2009; 6:81. 84.

7. Mostovoy U. Modern classification and treatment of common diseases of internal organs, ed. by – 14-e Izd., EXT. and pererab – Vinnytsia, 2012, 576.

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12. Wright S, Lochan K, Imrie C, Baker I, Nesbitt A, Kilner R. Charnley Quality of life and functional outcome at 3, 6 and 12 months after acute necrotising pancreatitis, Intensive Care Med.2009;8:37-44.

13. Tkachenko L, Katerenchuk I, Yarmola T, Pustovoit A, Smolinski A. Lesions of the gastrointestinal tract in osteoarthritis. – The world of medicine and biology. 2010;2:183-186.

14. Kazimirko, V, Kovalenko , Flegontova V. Involutional osteoarthritis and osteoporosis. – Donetsk, 2011; 4: 319-328.

15. Castaneda S., Roman-Blas J, Largo R. et al. Subchondral bone as a key target for osteoarthritis treatment, Biochem. Pharmacol. – 2012; 83:315-323.

16. Alekseeva L, Benevolensky L. Osteoarthritis and osteoporosis: guidelines for osteoporosis. Moscov: Binom; 2003, 503.

17. Kovalenko V, Bortkevich O. Osteoporosis. A practical guide. – Kiev: Morion, 2003, 448 p.

18. Smetnik V. The problem of osteoporosis: new therapeutic solutions and long-term clinical efficacy. Consilium Medicum. 2010; 6:13-16.

19. Unified clinical Protocol of primary, secondary (specialized) medical care and rehabilitation. The Ministry of health of Ukraine 10.09.2014 № 6

ADDRESS FOR CORRESPONDENCE

Liliya Babinets

SHEI “I. Ya. Horbachevsky Ternopil state medical

university of the Ministry of the public health of Ukraine”

Tatarska Str., 15/11, 46011 Ternopil, Ukraine

tel: +380673520743

e-mail: lilyanet@tut.by

Received: 20.06.2017

Accepted: 12.10.2017

Fig.1. BMD of the patients with OA

Fig.2. BMD of the patients with OA+CP

Table I. LPO-AOP of patients of the comparison group (M±M)

Index of LPO-AOP

Comparison group

Control group

(n=20)

Group I (ОА)

(n=30)

Group II (ОА+CP)

(n=42)

МА,

mmol/l

2,86±0,01

6,27±0,11

(p<0,05)*

6,61±0,14

(p<0,01)*

SH-group,

mmol/l

61,57±0,17

38,80±0,64

(p<0,001)*

36,27±0,60

(p<0,01)*

(p<0,05)**

SOD, c.u.

63,57±0,91

40,29±0,60

(p<0,001)*

38,55±0,70

(p<0,01)*

Catalase, %

15,48±0,06

55,12±0,99

(p<0,01)*

62,16±0,98

(p<0,01)*

(p<0,001)**

Ceruloplasmin,

mg/l

243,60±2,73

617,66±12,09

(p<0,05)*

631,14±11,12

(p<0,01)*

Oxyproline, μmol/l

30,89±0,17

76,57±2,11

(p<0,001)*

89,85±2,25

(p<0,05)*

(p<0,001)**

Notes: 1.* – possible difference regarding control group;

2.** – possible difference regarding the patients with OA.

Table. II. Correlation between the indicators of LPO-AOP in patients with OA+CP and the main characteristics of CP and BMD

Pairs in regressive relationship

Patient’s age,
years

The duration of the course of OA+CP, years

The level of α-elastase, μg/g

Ultrasound, points

T (%)

Oxyproline, μmol/l

0,454

n=28

р<0,01

0,448

n=28

р<0,01

-0,479

n=28

р<0,01

-0,495

n=28

р<0,01

-0,342

n=28

р<0,01

МА, mmol/l

0,403

n=28

р<0,001

0,457

n=28

р<0,01

-0,348

n=28

р<0,05

0,342

n=28

р<0,05

-0,368

n=28

р<0,01

SHgroup, mmol/l

0,385

n=28

-0,289

n=28

0,281

n=28

-0,393

n=28

р<0,05

-0,310

n=28

р<0,01

SOD, c.u.

-0,428

n=28

р<0,01

-0,395

n=28

р<0,01

0,327

n=28

р<0,05

0,321

n=28

р<0,05

0,366

n=28

р<0,01

Catalase, %

-0,483

n=28

р<0,05

0,424

n=28

р<0,05

-0,373

n=28

р<0,05

-0,393

n=28

р<0,05

-0,369

n=28

р<0,05

Ceruloplasmin,

mg/l

0,302

n=28

р<0,01

0,439

n=28

р<0,05

-0,522

n=28

р<0,05

0,358

n=28

р<0,05

-0,459

n=28

р<0,05

Note: nnumber of pairs in correlation analysis;

р – ступінь достовірності кореляційної залежності.