Why are patients with lupus prone to osteoporosis?

*It is only for medical professionals to read for reference and have an in-depth understanding of the causes of SLE-related osteoporosis! Systemic lupus erythematosus (SLE) is an autoimmune disease that affects multiple systems
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In recent years, studies have found that the incidence of osteoporosis in SLE patients has increased, and the decrease in bone density in SLE patients is related to disease activity and disease progression.
Disease-related inflammation, metabolism, endocrine, autoantibodies, drug effects, and genetic factors are all involved in osteoporosis Happened
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Osteoporosis, as one of the complications of SLE, is not simply caused by the influence of glucocorticoids
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Through this article, let's take a closer look at the causes of SLE-related osteoporosis
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01 Disease-related inflammation The systemic inflammation of SLE can increase bone resorption and reduce bone formation, mainly mediated by interleukin (IL)-1, IL-6, IL-17 and tumor necrosis factor (TNF)-α The reaction can promote osteoclast differentiation and inhibit osteoblast activity, resulting in bone loss
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The abnormal activation of the immune system changes the balance between osteoblasts and osteoclasts, thereby affecting bone remodeling and leading to osteoporosis
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The main role in the pathogenesis of osteoporosis is the signal transduction pathway of bone metabolism osteoprotegerin (OPG), nuclear factor-κβ receptor activator (RANK), nuclear factor-κβ receptor activator ligand (RANKL) molecules OPG/RANKL/RANK system composed of related signal transduction pathways
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Abnormal function of T and B cells leads to abnormal expression of OPG and RANKL genes, which may be one of the causes of bone loss in SLE patients
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Inflammatory factors in SLE serum can induce and promote the expression of RANKL.
After RANK is combined with the receptor RANKL, it promotes the differentiation of osteoclast precursor cells into mature osteoclasts, stimulates the activity of osteoclasts, and promotes bone resorption
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02 Metabolic factors atherosclerosis and osteoporosis are potentially linked, and serum low-density lipoprotein (LDL) levels may serve as a common risk factor for both
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Healthy female patients can maintain high bone density by reducing fat intake and controlling serum LDL levels
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Vitamin D deficiency is common in SLE patients, which is an important metabolic factor that causes bone loss in SLE
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SLE patients are intolerant to ultraviolet rays, so avoid sun exposure and use sunscreen, which reduces the synthesis of vitamin D in the skin
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Especially dark-skinned SLE patients have more melanin, which hinders ultraviolet absorption to a greater extent, leading to a further reduction in vitamin D production
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In addition, renal failure in SLE patients can lead to a decrease in 1,25-dihydroxyvitamin D levels.
Studies have found that high serum creatinine levels are related to a decrease in 1,25-dihydroxyvitamin D levels
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Up to 60% of SLE patients may have lupus nephritis and even renal insufficiency during the course of the disease
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Severe renal failure patients will have secondary hyperparathyroidism, which will promote osteoclasts and osteolysis.
Serum 1,25-dihydroxyvitamin D levels will also decrease, which will affect intestinal calcium absorption and eventually cause Loss of bone mass
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  03 Endocrine factors Menopause is a risk factor for osteoporosis and fragility fractures
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Sex hormones have a protective effect on bone metabolism, and postmenopausal SLE patients have an increased risk of osteoporosis and related fractures
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Compared with healthy people of the same sex and the same age, SLE patients have higher estrogen levels, lower androgen levels, and dehydroepiandrosterone (DHEA) levels
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Moreover, DHEA is lower in SLE disease activity than in remission
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As the age increases, the level of DHEA in most people gradually decreases, which will cause bone loss, which is also one of the reasons for the occurrence of osteoporosis in the elderly
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Postmenopausal SLE patients are more likely to develop vertebral compression fractures than before menopause
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  04 Autoantibodies A cross-sectional study of Chinese postmenopausal female SLE patients found that the hip bone mass of patients with anti-Ro antibody positive was decreased, and the hip bone mass of patients with anti-Sm antibody positive was relatively high.
Anti-dsDNA antibody and SLE bone mass Change doesn't matter much
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Of course, this finding needs to be confirmed by further studies with a larger sample size
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At present, there are few studies on bone metabolism of autoantibodies in SLE patients, and the correlation between SLE osteoporosis and other autoantibodies still needs in-depth study
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  05 Drugs influence glucocorticoids are commonly used in the treatment of SLE and its complications, and the effect on bone has a two-sided effect: on the one hand, long-term or large-scale use of glucocorticoids will promote the occurrence or development of osteoporosis; on the other hand, On the one hand, glucocorticoids can inhibit the damaging effect of systemic inflammation on bone
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In 2017, China published a study, in order to eliminate the influence of disease activity on bone density as much as possible, the study included patients with SLE in remission who took long-term low-dose hormones
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The results showed that compared with the healthy control group, the bone mineral density of those with prednisone ≤ 7.
5 mg/d and those with prednisone 7.
5-10 mg/d was reduced
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The study shows that even long-term use of prednisone ≤ 7.
5 mg/d will cause a significant decrease in bone density, suggesting that long-term use of hormones may not have a safe dose for bone density
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Disease activity can promote bone loss in SLE patients, and immunosuppressive drug therapy is particularly important
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On the one hand, immunosuppressive drugs can reduce disease activity; on the other hand, for patients who need frequent or long-term use of glucocorticoids during recurrent episodes and chronic active periods, the application of immunosuppressive drugs can help reduce the dose of glucocorticoid therapy.
And usage time
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However, the effect of immunosuppressants on osteoporosis is controversial.
Because the use of immunosuppressants usually indicates that the patient is active or has a serious illness, it is difficult to clearly determine its effect on bones
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  06 Genetic factors research has found that SLE-related osteoporosis may be related to genetic factors
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SLE patients with FOK-1 vitamin D receptor (VDR) ff genotype had higher serum vitamin D levels than those with FF genotype
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Studies have also found that SLE patients with FOK-1 VDR ff genotype have a higher spine bone density than those with FF and Ff genotypes
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  07 Conclusion If we can fully understand the risk factors and pathogenesis of SLE-related osteoporosis, it will be more helpful to protect the bone health of SLE patients
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SLE treatment is mainly to inhibit disease activity and prevent organ damage, but with the increased risk of osteoporosis and fractures in SLE patients, we should also consider bone health as a goal of SLE treatment
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The effects of various immunosuppressive agents on bone metabolism in SLE patients still need to be further clarified.
The development of treatment plans needs to take into account SLE disease activity and bone metabolism.
Drugs for preventing and treating SLE osteoporosis will also become a research hotspot in the future
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Osteoporosis in a murine model of postmenopausal lupus[J].
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[2].
Gu CY , Zhao R, Zhang XM, et al.
A meta-analysis of secondary osteoporosis in systemic lupus erythematosus: prevalence and risk factors[J].
Arch Osteoporos.
2019, 15（1).
[3].
Lai SW, Kuo YH, Liao K F.
Bone health in patients with systemic lupus erythematosus[J].
Ann Rheum Dis.
2019, doi: 10.
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[4].
Ralston SH, Schett G.
Osteoimmunology[J].
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