Systemic Osteoporosis Major Complication of Psoriatic Arthritis

Systemic Osteoporosis Major Complication of Psoriatic Arthritis CAMELIA CIACLI 1, M. COJOCARU 2 1 Vasile Goldis West University, Faculty of Medicine, Arad, Romania 2 Titu Maiorescu University, Faculty of Medicine, Bucharest, Romania Objectives. Determination of bone mineral density in patients with psoriatic arthritis and its correlation with the development of the disease. Methods. Three groups of patients were recruited: group 1 patients with psoriasis arthritis; group 2 patients with rheumatoid arthritis, group 3 control group. Group 1 was divided into: group 1A patients with disease duration < 5 years and group 1B patients with disease duration > 5 years. Bone mineral density was determined for total hip by dual X-ray absorptiometry (DXA). Results. In the group 1A BMD values of total femur were between -1.32 and -1.68 DS; in the group 1B BMD values of total femur were between 1B -1.58 and - 1.77DS; in the group 2 BMD values of total femur were between -2.51 and -3.41 DS and in the control group BMD values of total femur were between 0.29 and 1.3 DS. In patients with psoriatic arthritis, the duration of arthritis was negatively correlated with BMD values of total femur. In conclusion, psoriatic patients with longer duration of disease may be at a risk for osteoporosis, which can require preventative treatment efforts. Key words: Psoriatic arthritis, Bone mineral density. Periarticular osteoporosis is one of the early changes detected by radiological examinations of patients with psoriatic arthritis. The exact mechanism underlying bone mass loss is not yet fully elucidated but apparently contributes to this: synovial resorbing of cytokines is responsible for bone destruction, periarticular vascularization growing and immobilization of the affected joint [1, 2]. With the introduction in clinical practice of DEXA (dual energy x ray absorptiometry) this was the gold standard in determining bone mineral density. This method has shown that patients with psoriatic arthritis have changes like local osteoporosis or systemic osteoporosis which leads to an increased risk of fracture. That osteoporosis is even more accentuated as the disease is more active and longer [3, 4]. Nowadays it is a special interest for the study of psoriatic arthritis (disease that until recently was not recognized as a disease in its own right) reflected in the studies that have demonstrated the existence of a bone mineral density correlation between the period of evolution of the disease and the degree of disease activity [5, 6], from the reality that in rheumatoid arthritis, osteoporosis is a clinical characteristic of the disease. The results of these studies have revealed the presence of osteoporosis and osteopenia at femoral neck level at 33% to 41% of patients with psoriatic arthritis; bone mineral density determined from the femoral neck correlates with disease activity and the period of its evolution [7, 8]. MATERIALS AND METHODS The study was conducted on three groups of patients: group 1 (patients with psoriatic arthritis diagnosed on the basis of CASPAR criteria (The Classification Criteria for Psoriatic Arthritis) is made up of 27 patients (n = 27), of which 15 men and 12 women with ages between 30 50 years. Depending on the duration of the disease Group 1 was divided into two subgroups: 1A (n = 11 patients, 6 women and 5 men diagnosed with psoriatic arthritis for less than 5 years) 1B (n = 16 patients, 7 women and 9 men diagnosed with psoriatic arthritis for over 5 years). Group 2 (patients with rheumatoid arthritis diagnosed according to American Association of Rheumatology criteria) consists of 21 patients (n = 21) of which 13 men and 8 women aged 25 52 years. Control group (patients under 50 years without inflammatory diseases and osteoarticular degenerative diseases) was composed of 20 patients (n = 20) of which 9 women and 11 men. ROM. J. INTERN. MED., 2012, 50, 2, 173 178

174 Camelia Ciacli and M. Cojocaru 2 The patients were examined at the International Medical Center Arad (Euromedic Romania). Criteria for inclusion. Patients between the ages of 27 50 years diagnosed with psoriatic arthritis based on CASPAR criteria (The Classification Criteria for Psoriatic Arthritis) and rheumatoid arthritis diagnosed according to American Association of Rheumatology criteria. All patients had a period of approximately 36 months of the disease, also they were in acute phase of the disease and they have not taken NSAIDs drug treatment with at least one month prior to inclusion in the study. For all these patients was conducted a general clinical examination, laboratory testing with investigations to exclude the presence of other autoimmune associated disorders or a neoplasia process, or with a systemic infection. Exclusion criteria. Patients with: ankylosing spondylitis, Reiter syndrome, other bone metabolism diseases diagnosed on the basis of a detailed anamnesis, clinical examination and laboratory investigation forms (Paget Disease, Cushing Syndrome, Hodgkin s lymphoma, etc.), alcohol consumers, intestinal inflammatory diseases (Crohn), syndrome of malnutrition, vitamin D deficiency or treatment on bone with impact on metabolism, patients who have received in the last 12 months with methotrexate or corticosteroids, other disorders requiring treatment for long time (over 6 months) with corticosteroids, patients who have received nutritional supplement with calcium or vitamin D, sustained with physical activity in the past 12 months, women under 40 years of age in the early postmenopausal period by different etiology (surgical or medicinal). Bone mineral density was measured at the level of the right femoral neck by DEXA method (dual energy x-ray absorptiometry). For standardization, the results are reported in the form of the T score expressed in standard deviations (DS). T score was calculated by comparing mineral density of bone with the media of bone mineral density of young and healthy adult, same-sex. Thus, osteopenia is defined based on a T-score between-1 and-2 and osteoporosis with the score T -2.5 according to WHO criteria. Statistical analysis of the data in this study and statistical graphics has been done with Microsoft Office Excel 2007 using: descriptive statistics Items: arithmetic mean ± standard deviation (mean ± SD); elements of differential statistics: Student test and Pearson test: Student Test has been used to compare the data from the two groups with the control group. The values of the coefficients: p 1A (Group 1A and the Control group), p 1B (between the control group and group 1B) and p 2 (between the control group and group 2); p < 0.05 has a significant statistical value; Pearson-Test was used to compare the data from the same group analysis. The correlation coefficients: r 1A (group 1A) and r 1B (group 1B), r 2 (group 2); r 3 (control group); r > 0.5 respectable correlation (positive or negative). RESULTS Within the group 1A (n = 11 patients with disease onset under 5 years) the score T at the level of right femoral neck had limits ranging from -1.32 and -1.68 DS (average -1.55 ± 0.11 DS), and the difference between having a significant statistical average (p 1A < 0.01-S, statistically significant) compared with control group. Within the group 1B (n = 16 patients with disease onset over 5 years) the score T at the level of right femoral neck had limits between -1.58 and -1.77DS (average -1.68 ± 0.06), and the difference between having a significant statistical average (p 1B < 0.01-S, statistically significant) compared with control group. Within the group 2 (n = 21) the score T at the level of right femoral neck had limits of between -2.51 and -3.41 DS (average -2.93 + 0.3 DS), and the difference between the average values intensely statistically significant (p2 < 0. 001-ES, statistical significant) compared to the control group. Within the control group (n = 20) the score T at the level of right femoral neck had limits between 0.29 and 1.3 DS (average 0. 82 + 0. 32 DS) (Table I, Fig. 1). The duration of evolution of psoriatic arthritis is an important factor that determines the appearance of periarticular osteoporosis. In our study of the evolving importance of disease occurrence of osteopenia / periarticular osteoporosis is presented below. (Table II, Figs. 3, 4, 5).

3 Systemic Osteoporosis and Psoriatic Arthritis 175 Table I The score T at the level of right femoral neck had limits on analyzed patients groups PARAMETER (average ± ds) Femoral T score (DS) Group 1 A (n = 11) -1.55 ± 0.11 p 1A < 0.01 Group 1B (n = 16) -1.68 ± 0.06 p 1B < 0.01 Control Group Group 2 (n = 20) (n = 21) 0.82 ± 0.32-2.93 ± 0.3 p 2 < 0.001 Fig. 1. The evolution of the disease to analyze lots of patients. Fig. 2. Comparison of femoral neck s T scores levels in patients taken under study. Table II Comparison between the evolution of the disease and bone mineral density of patients analyzed lots PARAMETER (average ± GROUP 1A GROUP1B GROUP 2 DS) (n = 11) (n = 16) (n = 21) Evolution period (years) 2.91 ± 1.3 8.0 ± 1.47 3.4 ± 0.98 Femoral neck T score (DS) -1.55 ± 0.11 p 1A < 0.01 r 1A = -0.708-1.68 ± 0.06 p 1B < 0.01 r 1B = -0.728-2.93 ± 0.3 p 2 < 0.001 r 2 = -0.732

176 Camelia Ciacli and M. Cojocaru 4 Fig. 3. The correlation between the femoral neck T score and the evolution of the disease from group 1A (n = 11). Fig. 4. The correlation between the femoral neck T score and the evolution period of group 1B (n = 16). Fig. 5. The correlation between the femoral neck T score and evolution period of disease in group 2 (n = 21).

5 Systemic Osteoporosis and Psoriatic Arthritis 177 Analyzing the results from the patients groups with psoriatic arthritis it can be noticed a strong negative correlation: r 1A = -0.708 (R 1A 2 = 0.5026 on the group 1A); r 1B = -0.728 (R 1B 2 = 0.5313 from lot 1B) between femoral T score levels decrease and increase of evolution period of disease in rheumatoid arthritis it can be seen a strong negative correlation r 2 = -0.732 (R 22 = 0.5354 from lot 2) during the early years of disease evolution. DISCUSSION Psoriatic arthritis from clinical point of view creates difficulties to diagnosis because of clinical diversity forms and similarity with other arthritis. Accordingly, paraclinical examinations are particularly useful in any evolutionary stage of the disease, especially because some parameters have a prognostic and diagnostic value. Evolution of psoriatic arthritis is characterized by the existence of activation period of the disease along with periods of remission. Studies cited in the literature, on the evolution of of psoriatic arthritis, have highlighted the fact that to a large number of patients, the disease causes the joints destruction with severe impairment of their function; at a rate of about 7% of patients with psoriatic arthritis have been necessary musculoskeletal surgery. Psoriatic arthritis affects the quality of life handicap that has been added to the other one psoriatic skin injuries [9]. Bone remodeling is a physiological process that has as a purpose replacing old bone with new one. To the resorption process the primary role is played by osteoclasts, while the role of bone formation is reserved to osteoblasts. This remodeling is maintaining the bone mass during normal adult life. The imbalance of remodeling process has repercussions on the architecture and bone mass and can lead to long-term loss of skeletal integrity structure and fractures; therefore, these are major causes of morbidity and mortality during aging. To maintain the proper remodeling process to its best level requires it is necessary to exist tight interaction between the bone cells, bone marrow and bone matrix, interactions which are soluble factors to consolidate or integrate into the bone matrix. Comparative studies cited in the literature on this subject have inconsistent results. Thus, studies made by Frediani on patients with psoriatic and rheumatoid arthritis have shown that periarticular bone mineral density is significantly lower in the second group [10]. Harrison has demonstrated that the degree of periarticular osteoporosis is the same for both groups [11] and that to the appearance of periarticular osteoporosis contribute also increases of periarticular vascularization [12]. By examining the prevalence of medullar edema which shows the hyperemia, Jevtic demonstrated that it is correlated with the presence of periarticular osteopenia detected by DEXA [13], while Harrison has not found any correlation between synovial hyperemia and periarticular osteoporosis; also it was not identified any correlation between these parameters and the number of affected joints. For the first time Harrison proposes the hypothesis that the primordial site of inflammation in psoriatic arthritis is extrasinovial [11]. The limits of these studies include the small number of patients in the study, which is due to the difficulty of recruiting patients with recent psoriatic arthritis (less than 5 years) given the low incidence of such disorders. CONCLUSIONS Analyzing the results obtained from the study we may conclude that: in psoriatic arthritis appears to be a reduction of periarticular mineral bone density; this reduction of mineral bone density evaluated by determination of femoral neck T score the (DS) with DEXA method is more accentuated as the disease is older and more active; there is a strong negative correlation of femoral neck T-score with the evolution period of the disease; reducing the bone mineral density is more accentuated in rheumatoid arthritis since the early years of disease s evolution; the determination of bone mineral density by DEXA method can be used to determine early periarticular osteoporosis (which confers an increased risk of fractures in asymptomatic patients) and for therapeutic intervention in good time. Obiective. Determinarea densităţii minerale osoase la pacienţii cu artrită psoriazică şi corelarea acesteia cu dezvoltarea bolii. Metode. Au fost selecţionate trei grupuri de pacienţi: grupa 1 pacienţii cu artrită psoriazică, grupa 2 pacienţii cu artrită reumatoidă, grupa 3 grup de

178 Camelia Ciacli and M. Cojocaru 6 control. Grupa 1 a fost împărţită în: grupa 1A pacienţi cu durata bolii < de 5 ani şi 1B pacienţii cu durata bolii > de 5 ani. Densitatea minerală osoasă a fost calculată pentru întreg şoldul prin absorbţiometrie duală de tip raze X (DXA). Rezultate. La grupul 1A valorile BMD ale femurului au fost între -1,32 şi -1,68 DS, în grupul 1B valorile BMD ale femurului au fost între -1,58 şi -1,77 DS; la grupul 2 valorile DMO ale femurului au fost între -2,51 şi -3,41 DS şi în grupul de control valorile DMO ale femurului au fost între 0,29 şi 1,3 DS. La pacienţii cu artrită psoriazică, durata artritei a fost negativ corelată cu valorile DMO ale femurului. În concluzie, pacienţii cu psoriazis cu o durată mai mare a bolii pot prezenta risc de osteoporoză, ceea ce poate necesita eforturile unui tratament preventiv. Corresponding author: Camelia Ciacli, Vasile Goldiş West University, Arad, Herodot Str., 7, Arad, Romania, Tel. 0744 635081, E-mail: cciacli@yahoo.com REFERENCES 1. FREDIANI B., ALLEGRI A., FALSETTI P. et al., Bone mineral density in patients with psoriatic arthritis. J Rheumatol 2001; 28: 138 43. 2. WRIGHT V., MOLL J.M.H., Seronegative polyarthritis. Amsterdam: Elsevier North Holland Publishing Company; 1976. 3. RITCHIE D.M., BOYLE J.A., MCINNES J.M. et al., Clinical studies with an articular index for the assessment of joint tenderness in patients with rheumatoid arthritis. Q J Med 1968; 37: 393 406. 4. NOLLA J.M., FITER J., ROZADILLA A. et al., Bone mineral density in patients with peripheral psoriatic arthritis. Rev Rhum Engl Ed 1999; 66: 457 60. 5. MILLARD T.P., ANTONIADES L., EVANS A.V., SMITH H.R., SPECTOR T.D., BARKER J.N., Bone mineral density of patients with chronic plaque psoriasis. Clin Exp Dermatol 2002; 26: 446 8. 6. JEVTIC M., WALSH N.C., GRAVALLESE E.M., Bone loss in inflammatory arthritis: mechanisms and treatment strategies. Curr Opin Rheumatol 2004; 16: 419 22. 7. RITCHLIN C.T., HAAS-SMITH S.A., LI P., HICKS D.G., SCHWARZ E.M., Mechanisms of TNF- - and RANKL-mediated osteoclastogenesis and bone resorption in psoriatic arthritis. J Clin Invest 2003; 111: 821 31. 8. SIMONET W.S., LACEY D.L., DUNSTAN C.R., Osteoprotegerin: a novel secreted protein involved in the regulation of bone density.cell 2003; 89: 309 19. 9. SOKOLL K.B., HELLIWELL P.S., Comparison of disability and quality of life in rheumatoid and psoriatic arthritis. J Rheumatol 2001; 28: 1842 46. 10. FREDIANI B., ALLEGRI A., FALSETTI P. et al., Bone mineral density in patients with psoriatic arthritis. J Rheumatol 2001; 28: 138 43. 11. HARRISON B.J., HUTCHINSON C.E., ADAMS J., BRUCE I.N., HERRICK A.L., Assessing periarticular bone mineral density in patients with early psoriatic arthritis or rheumatoid arthritis. Ann Rheum 2002; 61: 1007 11. 12. MILLARD T.P., ANTONIADES L., EVANS A.V., SMITH H.R., SPECTOR T.D., BARKER J.N., Bone mineral density of patients with chronic plaque psoriasis. Clin Exp Dermatol 2002; 26: 446 8. 13. JEVTIC M., WALSH N.C., GRAVALLESE E.M., Bone loss in inflammatory arthritis: mechanisms and treatment strategies. Curr Opin Rheumatol 2004; 16: 419 22. Received March 12, 2012