|Year : 2014 | Volume
| Issue : 3 | Page : 556-561
Study of bone mineral density in patients with systemic lupus erythematosus
Hassan Abd El-Hady1, Mahmoud Abd-El Aziz Kora1, Samar Gaber Soliman2, Ahmed Ragheb1, Enas Sobhei Zahran MBBCh 1
1 Department of Internal Medicine, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Physical Medicine and Rehabilitation Unit, Faculty of Medicine, Menoufia University, Menoufia, Egypt
|Date of Submission||08-Oct-2013|
|Date of Acceptance||08-Dec-2013|
|Date of Web Publication||26-Nov-2014|
Enas Sobhei Zahran
Department of Internal Medicine, Faculty of Medicine, Menoufia University, Shebin Al-Kom, Menoufia
Source of Support: None, Conflict of Interest: None
The aim of the study was to investigate bone mineral density (BMD) in systemic lupus erythematosus (SLE) patients, either newly diagnosed or treated.
As a consequence of the chronic course of SLE, osteoporosis can be a further clinical challenge in these patients. SLE-related medications can increase bone turnover, which eventually weakens bone architecture, and subsequently reduces bone strength and increases the risk for fractures, but there is good evidence that the disease per se can lead to reduced bone mass through several mechanisms such as reduced motility, renal impairment, and the systemic effect of bone-resorbing cytokines.
Materials and methods
In this study, we examined 30 lupus patients diagnosed with SLE. Patients were divided into two groups. Group II included 15 newly diagnosed patients and group III included 15 treated lupus patients. Patients diagnosed with SLE met four or more criteria of the American College of Rheumatology (ACR) for SLE. SLE Disease Activity Index (SLEDAI) and SLE International Collaboration Clinics/ACR (SLICC/ACR) index were calculated for all patients. Ten healthy adults were included as the control group (group I). Dual-energy X-ray absorptiometry was performed in all studied patients in addition to routine investigations.
The total patient number was 30. Ninety-three percent of patients were female and in the age group of 17-30 years. There was a significant reduction in BMD in diagnosed lupus patients (groups II and III) compared with healthy adults of the same age and sex. Forty percent of newly diagnosed lupus patients had osteopenia. Sixty percent of treated patients had osteopenia and 20% had osteoporosis. There was no difference among lupus patients with low BMD as regards steroid dose, SLEDAI, and SLICC/ACR index.
BMD was reduced in SLE patients as compared with healthy age-matched and sex-matched controls. It decreased in both newly diagnosed (40%) and treated lupus patients (80%). BMD in lupus patients was not affected by the duration of disease, corticosteroid doses, or SLEDAI and SLICC/ACR index.
Keywords: bone mineral density, dual-energy X-ray absorptiometry scan, systemic lupus erythematosus
|How to cite this article:|
El-Hady HA, Abd-El Aziz Kora M, Soliman SG, Ragheb A, Zahran ES. Study of bone mineral density in patients with systemic lupus erythematosus. Menoufia Med J 2014;27:556-61
|How to cite this URL:|
El-Hady HA, Abd-El Aziz Kora M, Soliman SG, Ragheb A, Zahran ES. Study of bone mineral density in patients with systemic lupus erythematosus. Menoufia Med J [serial online] 2014 [cited 2020 Feb 24];27:556-61. Available from: http://www.mmj.eg.net/text.asp?2014/27/3/556/145512
| Introduction|| |
Systemic lupus erythematosus (SLE) is an autoimmune disorder that affects multiple organ systems including the skin, kidneys, and brain. The exact cause is unknown, but genetic factors, ethnic origin, environmental factors, and medications may all be involved in its development  . Clinical features are highly variable, ranging from skin and joint involvement to organ involvement and life-threatening complications. SLE is typically associated with a waxing and waning clinical course, but some patients have continuous disease activity. SLE manifests in a unique way in each patient and treatment should be tailored to the type and severity of organ system involvement  .
Osteoporosis (OP) is a disease characterized by reduced bone mass and increased skeletal fragility. Normal bone growth and remodeling entail a tightly coupled process of bone resorption and new bone formation. OP-related bone loss occurs when bone resorption exceeds bone formation  . The WHO defined OP as a systemic skeletal disease characterized by low bone mass with microarchitectural deterioration of bone tissue, thus increasing bone fragility and susceptibility to fracture. For screening purposes, OP was defined by the WHO as a bone mineral density (BMD) at any site equal to or greater than 2.5 SD below the fracture-resistant mean peak bone mass of young adulthood  .
Individuals with lupus are at increased risk for OP. There is an increase in the incidence of fracture among individuals with SLE. In fact, women with lupus may be nearly five times more likely to experience a fracture from OP compared with normal individuals  . Pathogenetically, SLE could result in bone loss through several mechanisms, which in part depend on the disease itself and in part are treatment related. Disease-dependent mechanisms include reduced physical activity due to long-standing disabling arthritis or myopathy, renal failure, endocrine dysfunctions, and the systemic effects of proinflammatory bone-resorbing cytokines. Besides glucocorticoids, which are the mainstay of treatment in SLE, several other medications can contribute to bone loss in these patients, such as azathioprine, cyclophosphamide (CYP), and cyclosporine, and no definite data exist on the possible detrimental effect of low-dose methotrexate and long-term use of anticoagulants on the skeleton. Finally, counseling to avoid sunshine exposure can induce vitamin D deficiency, thus contributing to reduced bone mass  . Improved survival of SLE patients over the past decades has brought morbidity as the outcome measure into focus. OP contributes to morbidity in SLE, and OP with fractures is one of the parameters in the accumulated organ damage index for the disease  .
The aim of this work was to study BMD in patients with SLE, either treated or untreated.
| Materials and methods|| |
This study follows the ethical standards of our institution. Informed consents from all patients and controls were obtained in accordance with the local ethical committee. These patients were divided into two groups. Group II consisted of 15 newly diagnosed lupus patients and group III consisted of 15 treated lupus patients. Patients diagnosed with SLE met four or more criteria of American College of Rheumatology (ACR) for SLE  . SLE Disease Activity Index (SLEDAI) and SLE International Collaboration Clinics/ACR (SLICC/ACR) index were calculated for all patients. Ten healthy adults were included as controls (group I). Treated lupus patients received treatment in the form of corticosteroid (prednisolone) and immunosuppressive drugs [azathioprine, CYP, and mycophenolate mofetil (MMF)]. In all, 100% of treated lupus patients were on steroids, 86.6% were treated with azathioprine, and 6.7% were treated with CYP or MMF.
We excluded from our study patients with renal impairment (serum creatinine>1.4), patients with parathyroid disorders or other endocrinal disorders, those with prolonged immobilization, with chronic liver disease, other connective tissue diseases, malignant diseases, pregnant women, and breastfeeding women.
All patients and controls were subjected to medical history taking and complete physical examination. All patients underwent the following investigations: analysis of urine, blood urea, and serum creatinine, serum electrolytes (Na + , K + , and Ca 2+ ), serum phosphate, complete blood count, liver profile (alanine transaminase, aspartate aminotransferase, serum total and direct bilirubin, prothrombin time and concentration, serum albumin, serum alkaline phosphatase, and fasting blood glucose), antinuclear antibody, anti-dsDNA, C3, C4, erythrocyte sedimentation rate, C-reactive protein, and special investigations such as serum intact parathyroid hormone (PTH) and dual-energy X-ray absorptiometry (DEXA) scan.
Data were collected, tabulated, and statistically analyzed with an IBM compatible personal computer with SPSS statistical package version 11.
- Descriptive statistics: Such as percentage (%), mean (x), and SD were determined.
- Analytical statistics : These were ascertained using the χ2 -test, Fisher's exact test, the Mann-Whitney U-test, the Kruskal-Wallis test, and analysis of variance (F), with a level of significance as follows: P-value less than 0.05 was considered significant, P-value less than 0.001 as highly significant, and P-value greater than 0.05 as nonsignificant.
| Results|| |
There was a significant difference between the studied groups as regards BMD expressed in DEXA scan results (T score and Z score). It was significantly lower in groups II and III than in group I ([Table 1]).
In group II, six (40%) patients had osteopenia and nine (60%) patients had average BMD. In group III, nine (60%) patients had osteopenia, three (20%) had OP, and three (20%) had average BMD. Forty percent of newly diagnosed lupus patients and 80% of treated lupus patients had low BMD ([Table 2]).
|Table 2: Distribution of studied lupus patient according to results of DEXA scan in groups II and III |
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According to duration of treatment, distribution of the studied treated lupus patients (Group III) with low BMD expressed as abnormal DEXA scan results (osteopenia or OP) showed the following: Thirty three percent of these patients received treatment within ≤3 months, 41.7% received treatment within >3 months -6 months and 25% received treatment within >6 months -1 year ([Table 3]).
|Table 3: Distribution of the studied treated lupus patients (group III) with abnormal DEXA scan results (osteopenia or osteoporosis) according to duration of treatment |
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As regards the dose of steroid and type of immunosuppressive drugs, 33% of patients with low BMD received prednisolone of 10 mg or less or greater than 10-20 mg, 25% received prednisolone greater than 20-30 mg, and 8.3% received prednisolone greater than 30-40 mg; 77% of patients with osteopenia received azathioprine, and 11.1% received CYP or MMF. All patients with OP received azathioprine. Among patients with low BMD, 83.3% received azathioprine and 8.3% received CYP or MMF. All patients who received pulse steroid therapy had low BMD; 44% of patients with osteopenia and 66.6% of patients with OP received pulse steroid therapy. Among patients with low BMD, 50% received pulse steroid therapy and 50% did not ([Table 4]).
|Table 4: Distribution of treated lupus patients with low BMD expressed in abnormal DEXA scan results according to dose of steroid and type of immunosuppressive drug |
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The distribution of the newly diagnosed and treated lupus patients with low BMD expressed in abnormal DEXA scan results in terms of the SLICC/ACR damage index was as follows: four (66.6%) newly diagnosed lupus patients with low BMD had a score of 0 and two (33.3%) patients had a score greater than 0; nine (75%) treated lupus patients with low BMD had a score of 0 and three (25%) patients had a score greater than 0; 72% of patients with low BMD had a score of 0 and 27.7% had a score greater than 0 ([Table 5]).
|Table 5: Distribution of the studied lupus patients (groups II and III) with low BMD expressed as abnormal DEXA scan results (osteopenia and osteoporosis) according to SLICC/ACR damage index |
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The distribution of the newly diagnosed and treated lupus patients with low BMD expressed in abnormal DEXA scan results with respect to SLEDAI was as follows: 16% of newly diagnosed lupus patients with osteopenia had a score of 0-10, 50% had a score greater than 10-20, and 33.3% had a score greater than 20-30; 44% of treated lupus patients with osteopenia had a score of 0-10, 44.4% had a score greater than 10-20, and 11.1% had a score greater than 20-30; 33% of treated lupus patients with OP had a score of 0-10 and 66.6% had a score greater than 10-20; 33 lupus patients with low BMD had a score of 0-10, 50% had a score greater than 10-20, and 16.7% had a score greater than 20-30 ([Table 6]).
|Table 6: Distribution of the studied lupus patients (groups II and III) with abnormal DEXA scan (osteopenia or osteoporosis) according to SLEDAI |
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The correlation coefficient (r) between the DEXA scan parameter (T score) and clinical and laboratory parameters in both newly diagnosed and treated lupus patients showed the following results. There were no significant correlations as regards age, Ca, PO 4 , serum creatinine, Hb, and platelet count. A significant correlation was found between T score and alkaline phosphatase and a significant negative correlation between T score and intact PTH in newly diagnosed lupus patients ([Table 7]).
|Table 7: Correlation between DEXA scan parameters (T score) and clinical and laboratory parameters in newly diagnosed lupus patients (group II, n = 15) and treated lupus patients (group III, n = 15) |
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The correlation coefficient (r) between DEXA scan parameter (Z score) and clinical and laboratory parameters in both newly diagnosed and treated lupus patients gave the following results. There were no significant correlations as regards age, Ca 2+ , PO4 3ˉ , serum creatinine, Hb, and platelet count. However, a significant correlation was found between Z score and alkaline phosphatase and a significant negative correlation between Z score and intact PTH in newly diagnosed lupus patients ([Table 8]).
|Table 8: Correlation between DEXA scan parameters (Z score) and clinical and laboratory parameters in newly diagnosed lupus patients (group II, n = 15) and treated lupus patients (group III, n = 15) |
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| Discussion|| |
OP is common in SLE patients. Inflammation or SLE-related medications can increase bone turnover, which eventually weakens bone architecture, reduces bone strength, and increases the risk for fractures  .
The present study demonstrated a significant difference between diagnosed lupus patients and normal healthy adults of the same age and sex as regards DEXA scan results (T score and Z score). Patients with SLE had lower BMD compared with normal adults of the same age and sex. Bone loss in SLE is heterogeneous and likely a multifactorial process involving both traditional and lupus-related risk factors that may be due to the disease itself or due to its treatment. In accordance with our results, Almehed et al.  in a cross-sectional study of SLE patients showed that low BMD and OP is more common in SLE than in the general population. Also, Sinigaglia et al.  demonstrated that SLE patients had significantly lower BMD compared with healthy individuals of the same age.
In treated lupus patients, no relation was observed between low BMD expressed in abnormal DEXA scan results and duration of treatment or steroid dose. A similar observation was noticed by Pineau et al.  . In addition, So et al.  concluded that corticosteroid use was not associated with OP. In contrast, Sinigaglia et al.  demonstrated a significant difference among treated lupus patients with abnormal DEXA scan results as regards the duration of treatment, especially steroid treatment. SLE patients with OP had a higher cumulative steroid intake and longer steroid exposure. Compeyrot-Lacassagne et al.  showed that osteopenia and OP are common in SLE and are associated more closely with increased disease duration than with cumulative corticosteroid dose.
As regards the use of immunosuppressive drugs, 83% of treated lupus patients with low BMD received azathioprine and 8.3% received CYP or MMF. All patients with OP received azathioprine. Schmidt et al.  reported that treatment with azathioprine is a risk factor for low BMD. Ponnapakkam et al.  showed that most chemotherapeutics reduce BMD and increase the risk for fractures by causing gonadal suppression, which in turn increases bone removal. CYP also has a direct effect of inhibiting bone formation and removal, making the resulting bone loss particularly difficult to treat with antiresorptive therapy. In contrast, Florιn et al.  reported that azathioprine does not seem to affect BMD by itself. However, by being steroid-saving, it seems to conserve bone mineral mass.
The present study demonstrated that all patients who received pulse steroid therapy had low BMD. Haris et al.  demonstrated that methylprednisolone pulse causes immediate, profound suppression of osteoblast function, and significant increase in osteoclast activity, suggesting uncoupling of bone formation and resorption. Haugeberg et al.  concluded that treatment with intravenous pulses of methylprednisolone leads to a high rate of bone loss.
We found that reduction in BMD is not affected by disease activity (SLEDAI). The reason is probably that indexes used to evaluate disease activity are only measured at one point in time. Also, Garcνa-Carrasco et al.  found no significant correlation between disease activity and BMD. Similarly Pineau et al.  concluded that disease activity was not associated with OP. Sinigaglia et al.  found that in 84 premenopausal patients with SLE no significant differences in BMD were detected between patients according to the clinical pattern or activity index.
With respect to the relation between diagnosed lupus patients with low BMD expressed as abnormal DEXA scan results and SLICC/ACR damage index, we found no relation between the presence of low BMD and SLICC/ACR damage index. A similar observation was noticed by Bhattoa et al.  . In contrast, Sinigaglia et al.  found that patients with a high damage index had a significantly lower BMD.
Our study showed no significant correlation between DEXA scan parameters (T score and Z score) and age, Ca 2+ , serum creatinine, Hb, and platelet count. In contrast, Siffledeen et al.  showed that high platelet counts were consistently predictive of low BMD in female but not in male patients. Also, Korkmaz et al.  found a significant correlation between Hb values and femur T score, femur BMD, spine T score, and spine BMD values of the study population in bivariate correlation analysis.
Our study showed no significant correlation between DEXA scan parameters (T score and Z score) and PO4 3ˉ. However, Figueiredo et al.  reported that higher serum phosphate levels and lower hip BMD are independent bone parameters.
Our study demonstrated a significant correlation between DEXA scan parameters (T score and Z score) and alkaline phosphatase in newly diagnosed lupus patients. Also, Marwaha and Sripathy  reported that the only bone mineral parameter that had a significant influence on BMD was alkaline phosphatase.
A significant correlation was found between DEXA scan parameters (T score and Z score) and intact PTH in newly diagnosed lupus patients. A similar observation was found by Kota et al.  . In contrast, Goubraim et al.  found that intact PTH levels did not correlate with any of the BMD parameters.
| Conclusion|| |
BMD is reduced in SLE patients as compared with healthy, age-matched controls. It decreases in both newly diagnosed (40%) and treated lupus patients (80%). There was no correlation between BMD and duration of disease, corticosteroid doses, SLEDAI, and SLICC/ACR damage index.
- Further studies on a larger number of patients have to be conducted.
- Strategies to counteract bone loss must be applied soon after the disease onset. This includes effective treatment of the underlying disease, modification of any known risk factor for OP, use of corticosteroids at the lowest useful dose, and the pharmacological treatment of OP in all patients with evidence of bone loss.
- Lupus patients should be regularly followed up by means of a DEXA scan for early detection of bone loss.
| Acknowledgements|| |
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8]