he Analysis of the Effect of Systemic Lupus Erythematosus Selected Indicators and Its Treatment on Bone Mineral Density

Introduction. The lesions of the bone and joint system start to appear during the first ten years of disease in 25.0 % of patients with SLE. The prevalence of osteopenia ranges from 4.0 to 74.0 % and the prevalence of osteoporosis – from 3.0 to 48.0 %. The main reasons for such disappointing statistics are chronic autoimmune inflammation and prolonged treatment with glucocorticoids (GCs), which coupled with traditional osteoporosis triggers like age, smoking, changes in hormone levels, lead to the rapid loss of bone mass. However, the issue of osteoporosis and factors affecting the condition of bone tissue in patients with SLE has not been studied sufficiently. The aim of study. The objective is to analyze the effect of SLE selected indicators and its treatment on bone mineral density. Materials and methods. The study involved 123 women aged 21 to 51 years (average age at the time of the survey – 40.37 ± 0.95). The average duration of the disease was 7.35 ± 0.27. The average total amount of exacerbations (in years) was 9.97 ± 0.60, the average total duration of exacerbations (in days) was 148.80 ± 10.24. 100.0 % of patients received methylprednisolone at the daily dose of (based on prednisolone) 5.0 – 30.0 mg (average daily dose was 11.04 ± 0.46 mg, average total dose was 31.40 ± 1.92 g). The average duration of GC treatment was consistent with the average duration of the disease. The control group included 25 practically healthy premenopausal women of the corresponding age. To achieve the stated objective, the first step was to determine bone mineral density by means of dual energy X-ray absorptiometry in treatment and control groups and compare the obtained results. The second step was to study the relationship between bone mineral density and the disease activity according to the SLE Disease Activity Index (SLEDAI) score. Patients with SLE were divided into groups according to their T-scores (a group with unaffected bone mineral density, a group with osteopenia and osteoporosis) and according to the SLEDAI scores (groups: no activity, mild activity, moderate activity, high activity, very high activity). The third step was to determine the relationships between bone mineral density scores and the SLICC / ACR Damage Index scores, the duration of the disease, the number and duration of exacerbations, the average and total doses of glucocorticoids. Results. According to the results of lumbar spine DXA scans among the women of the treatment group, 75.7 % of them had decreased bone mineral density. However, only 32.0 % of women in the control group had decreased bone mineral density (p < 0.001). According to the results of proximal femur DXA scans among the women of the treatment group, 35.5 % of them had decreased bone mineral density. However, only 16.0 % of women in the control group had decreased bone mineral density (p < 0.05) The average T-scores obtained due to lumbar spine DXA scans in both groups were significantly different and were lower in patients with SLE. The average T-scores obtained due to proximal femur DXA scans in both groups did not have a significant difference. According to percentile distribution, T-scores in treatment group was in the range (-2.02) – (-1.21), in control group (-1,08) -1,08); the medians were -0.1 and (-0.3) respectively. According to the results of our study, there is no statistical validity of the difference between groups divided by T-scores, which suggests that there is no relationship between the activity of SLE and the state of bone mineral density. The analysis of the correlation between bone mineral density scores and SLICC/ACR Damage Index scores reveals that there is a reliable association ((r = (- 3.40), p < 0.001). An inverse relationship was found between bone mineral density and the duration of disease ((r = (-0.36), p <0.01), the total number of exacerbations ((r = (- 0.49), p < 0.001) and the total duration of exacerbations ((r = (- 0.56), p < 0.001). Similar associations were also revealed by the results of analysis of relationship between bone mineral density and GC treatment, which was measured by the average dose ((r = (- 0.59), p < 0.001) and the total dose ((r = (- 0.52), p < 0.001). Conclusions. The analysis of the effect of SLE selected indicators and its treatment on bone mineral density revealed that: 1) the percentage of women with decreased bone mineral density was significantly higher in the treatment group than in the control group (lumbar spine DXA scans – 75.7 % (35.5 %), proximal femur DXA scans – 35.5 % (16.0 %), respectively), and the average T-scores for lumbar spine scans were significantly lower in patients with SLE than in the control group – (-1.41) ± 1.15 and (-0.55) ± 0.99, respectively. 2) there is no reliable correlation between bone mineral density and the disease activity according to SLEDAI; 3) there is a inverse relationship between the bone mineral density and SLICC / ACR Damage Index, the duration of disease, the total number and duration of SLE exacerbations, as well as the total dose of glucocorticoids

Characteristics of Bone Tissue in Postmenopausal Women with Systemic Lupus Erythematosus

Introduction. Osteoporosis is one of the most common systemic diseases of the skeletal system that is characterized by decreased bone mass per unit volume, increased bone fragility and risk of fractures. The prevalence of low bone mineral density in patients with systemic lupus erythematosus (SLE) is high, compared to the general population: osteopenia is diagnosed in 25.0–75.0 % of patients with SLE and osteoporosis – in 1.4–68.0 % of patients with SLE. According to the results of prospective studies, it was found that the combination of increases in bone resorption markers or bone formation markers in postmenopausal women with low bone mineral density (BMD) is associated with the increased risk of fractures – by a factor of 2.0–2.5. Aim. To characterize bone tissue in postmenopausal women with systemic lupus erythematosus. Materials and methods. SLE patients were randomized in the study, stratified by sex and postmenopausal status. 71 women (experimental group) aged 47 to 68 years (mean age at the time of the study – 54.08 ± 0.72 years) with SLE diagnosed according to the criteria set by the American College of Rheumatology (1982, 1997) were included in the study. The mean disease (SLE) duration was 13.83 ± 0.97 years; all the women at the time of the study were in postmenopausal status. 100.0 % of the patients received methylprednisolone at a dose of 8.0 to 24.0 mg/day (mean dose – 11.94 ± 0.55 mg/day) and calcium supplements at a daily dose of 1000.0 mg in conjunction with vitamin D supplement at a daily dose of 400.0 IU. The mean duration of glucocorticoid treatment in conjunction with calcium and vitamin D supplements corresponded to the mean duration of disease. The control group comprised 30 almost healthy women aged 49 to 62 years (mean age at the time of the study – 54.67 ± 0.79 years) in postmenopausal status. Two bone formation markers (osteocalcin and P1NP) and one bone resorption biochemical marker (β-crossLaps) were used to assess the rate of bone remodeling. The ultrasound bone densitometry of the calcaneus was conducted in order to evaluate the structural and functional state of bone tissue. The densitometry was performed using the ultrasound bone densitometer SONOST–2000 (OsteoSys Co., Ltd, Seoul, Korea). The statistical analysis was performed using Statistica 6.0 package (Stat Soft Inc, USA). Results and discussion. In all patients with SLE (100.0 %), changes in bone tissue were found: the first stage of osteopenia – in 16 patients (22.5 %), the second stage of osteopenia – in 19 patients (26.8 %), the third stage of osteopenia – in 24 patients (33.8 %), osteoporosis – in 12 patients (16.9 %). Osteocalcin levels were significantly elevated (by 19.76 ± 1.11; p < 0.001) in SLE patients, compared to the control group, and P1NP levels were higher, but not statistically significantly. β-crossLaps marker was significantly higher in patients with SLE, compared to the control group (by 0.15 ± 0.03, p < 0.001). According to the results of ultrasound densitometry, all patients with SLE were divided into four groups depending on the degree of BMD loss: the first group included patients with the first stage of osteopenia; the second group included patients with the second stage of osteopenia; the third group included patients with the third stage of osteopenia; and the fourth group – patients with osteoporosis. Patients of the 1st group had statistically significantly higher levels of bone formation marker – osteocalcin (by 18.94 ± 2.15; p < 0.001) – and bone resorption marker – β-crossLaps (by 0.06 ng/ml ± 0.04, p < 0.05), compared to the control group. Patients of the 2nd group had significantly higher levels of two bone remodeling markers – osteocalcin (by 17.96 ng/ml ± 1.87; p < 0.001) and β-crossLaps (by 0.08 ng/ml ± 0.03, p < 0.01); a lower level of bone formation marker – P1NP (by 3.93 mcg/L ± 1.98; p < 0.05), compared to the control group. Patients of the 3rd group had significantly increased levels of osteocalcin, P1NP and β-crossLaps (by 21.04 ng/ml ± 4.04, p < 0.001; 0.69 ng/ml ± 6.49, p < 0.05 ; and 0.25 ng/ml ± 0.04, p < 0.001, respectively), compared to the group of almost healthy women. Patients of the 4th group had significantly higher levels of two bone remodeling markers: osteocalcin (by 20.38 ng/ml ± 1.8; p < 0.001) and β-crossLaps (by 0.16 ng/ml ± 0.05, p < 0.001), compared to the control group. Conclusions. The results of bone densitometry and the obtained levels of bone remodeling biochemical markers associated with the defects in both osteoblast and osteoclast functions show that all patients with SLE in postmenopausal status who comprised experimental group had indeed changes in bone tissue

Сomparative Evaluation of Bone Mineral Density Based upon the Results of Ultrasound Osteodensitometry, X-ray Osteodensitometry, and Dual-Energy X-ray Absorptiometry Tests in Premenopausal Women with Systemic Lupus Erythematosus

Introduction. Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the chronic inflammation and multisystemic damages, accompanied by lesions in osteoarticular system, including secondary osteoporosis (OP) ­ an important risk factor for low­energy fractures. The most common noninvasive osteoporosis tests currently in use in Ukraine include ultrasound densitometry and X­ray densitometry (dual­energy X­ray absorptiometry (DXA) and hand bone X­ray densitometry). The objective is to compare diagnostic values of bone mineral density tests that employ ultrasound densitometry, X­ray osteodensitometry, and dual­energy X­ray absorptiometry in premenopausal women with SLE. Materials and methods. The study randomly included 51 women aged between 21 and 53 (mean age at the time of the study – 38.21 ± 1.66) which were diagnosed with SLE according to the criteria of the American College of Rheumatology (1982, 1997); all women at the time of the study were premenopausal. 100.0 % of the patients received methylprednisolone at a dose of 4.0 to 24.0 mg/day (average dose – 11.12 ± 0.81 mg/day) and calcium supplements at a dose of 1000.0 mg/day in combination with vitamin D at a daily dose of 400.0 IU. The average duration of treatment with glucocorticoids and calcium supplements corresponded to the average disease duration. Bone mineral density was assessed through calcaneus ultrasound bone densitometry performed with SONOST-2000 device (OsteoSys Co., Ltd, Seoul, Korea), hand bone X­ray densitometry performed with “ARM­Osteoloh” application, and dual­energy X­ray absorptiometry of lumbar spine and proximal femur performed with dual­energy X­ray absorptiometer (Stratos, France). Statistical analysis of the obtained results was carried out in MS Excel and IBM SPSS Statistics applications. Results and their discussion. The results of ultrasound densitometry among 51 patients with SLE were as follows: 13 (25.49 %) women were diagnosed with osteoporosis (average T­score ­(­2.77) ± 0.08); 26 (50.98 %) women were diagnosed with osteopenia (average T­score ­ (­1.81) ± 0.08), 6 of them (11.76 %) ­ with the first degree of osteopenia (average T­score ­ (­1.25) ± 0.04), 9 of them (17.65 %) ­ with the second degree of osteopenia (average T­score ­ (­1.74) ± 0.06), 11 of them (21.57 %) ­ with third degree of osteopenia (average T­score ­ (­2.17) ± 0.02); 12 (23.53 %) women had normal BMD (average T­score ­ (­0.7) ± 0.07). The results of hand bone X­ray densitometry among all patients with SLE showed changes in bone mineral density. 20 (39.22 %) women were diagnosed with osteoporosis (average T­score ­ (­3.03) ± 0.08); 23 (45.09 %) women ­ with osteopenia (average T­score ­ (­2.01) ± 0.08), 4 of them (7.84 %) ­ with the first degree of osteopenia (average T­score ­ (­1.2) ± 0.11), 19 of them (37.25 %) ­ with the third degree of osteopenia (average T­score ­ (­2.18) ± 0.03); 8 women (15.69 %) had normal BMD (average T­score ­ (­0.38) ± 0.01). The results of lumbar spine bone density test employing dual­energy X­ray absorptiometry (DXA) were as follows: 16 (31.37 %) patients with SLE were diagnosed with osteoporosis (average T­score ­ (­3.14) ± 0.13); 21 (41.18 %) patients were diagnosed with osteopenia (average T­score ­ (­1.56) ± 0.13), 10 of them (19.61 %) ­ with the first degree of osteopenia (average T­score ­ (­1.14) ± 0.03), 7 of them (13.73 %) ­ with the second degree of osteopenia (average T­score ­ (­1.70) ± 0.07), 4 of them (7.84 %) ­ with the third degree of osteopenia (average T­score ­ (­2.35) ± 0.03); 14 patients (27.45 %) had normal levels of BMD (average T­score ­ (­0.36) ± 0.15). The results of proximal femur bone density test employing DXA were as follows: only 12 (23.53 %) patients with SLE were diagnosed with osteopenia (average T­score ­ (­1.28) ± 0.08), 5 of them (9.80 %) ­ with the first degree of osteopenia (average T­score ­ (­1.03) ± 0.03), 3 of them (5.86 %) ­ with the second degree of osteopenia (average T­score ­ (­1.65) ± 0.04), 4 of them (7.84 %) ­ with the third degree of osteopenia (average T­score ­ (­2.05) ± 0.03); 39 patients (76.47 %) had normal levels of BMD (average T­score ­ (0.2) ± 0.14). The findings demonstrate direct correlation between T­score results obtained by ultrasound heel bone densitometry and T­score results obtained by lumbar spine DXA (r = 0.72, p < 0.001) as well as T­score results obtained proximal femur DXA (r = 0.38, p < 0.05). The findings also indicate direct relationship between the results of BMD tests employing hand bone X­ray densitometry and lumbar spine DXA (r = 0.56, p < 0.001) as well as proximal femur DXA (r = 0.37, p < 0.05). There is also direct correlation between the results of the BMD tests obtained by ultrasound heel bone densitometry and X­ray hand bone densitometry (r = 0.7, p < 0.001). Both ultrasound heel bone densitometry and X­ray hand bone densitometry identified 89.0 % of patients who had lowered BMD levels according to the results of lumbar spine DXA and 100.0 % of patients who had lowered BMD levels according to the results of proximal femur DXA (sensitivity – 0.89 and 0.1 respectively). Ultrasound densitometry demonstrated higher specificity compared to X­ray osteodensitometry: it identified 57.0 % of the patients who had normal BMD levels according to the results of lumbar spine DXA and 31.0 % of the patients who had normal BMD levels according to the results of proximal femur DXA (specificity ­ 0,57 and 0,31 respectively). X­ray osteodensitometry identified 29.0 % of the patients who had normal BMD levels according to the results of lumbar spine DXA and 21.0 % of the patients who had normal BMD levels according to the results of proximal femur DXA (specificity ­ 0,29 and 0,21, respectively). Conclusions. The study demonstrated that both ultrasound heel bone densitometry and X­ray hand bone densitometry are highly sensitive compared to dual­energy X­ray absorptiometry and acceptable methods for diagnosis of osteoporosis in patients with SLE