The efficacy of statins in preventing glucocorticoid-related osteonecrosis in animal models

Yang, Zhouyuan; Liu, H.; Li, D.; Xie, Xin; Qin, Tao; Ma, Jun; Kang, Pengde

doi:10.1302/2046-3758.59.2000500

Cited by 17 publications

(13 citation statements)

References 26 publications

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“…A meta-analysis suggested that statins usage decreased the risk of GC-related ON. 42 However, we still cannot determine the protective effect of statins in treating ON patients unless some high-quality clinical trials are performed. Bisphosphonates as another hot discussion pharmacologic agent may protect major joints from necrosis by inhibiting the bone resorption.…”

Section: Discussionmentioning

confidence: 99%

Risk of osteonecrosis in systemic lupus erythematosus: An 11-year Chinese single-center cohort study

Long

Zhang

You

et al. 2021

Lupus

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Objective Osteonecrosis (ON), which can lead to physical disability, is a common complication of systemic lupus erythematosus (SLE). The purpose of this study was to determine the prevalence of ON and identify possible risk factors in Chinese SLE patients. Methods SLE patients who fulfilled the 1997 American College of Rheumatology SLE classification criteria were recruited from the Peking Union Medical College Hospital. The chi-square test (χ 2 test) and multivariate regression analyses were used to evaluate risk factors. The Cox proportional-hazards model was used to construct the survival curves and estimate the simultaneous effects of prognostic factors on survival. Results We consecutively enrolled 1,158 patients, of which 88 patients (7.6%) developed ON. Among ON patients, 57.1% of patients had isolated femoral head necrosis and 42.9% had multiple joint involvement. The mean age of ON patients (24.62 ± 8.89 years) was significantly younger than SLE patients without ON (27.23 ± 10.16 years, p = 0.09). The ON group presented with a much longer disease course (10.68 ± 5.97 years, p < 0.001) and increased incidence of arthritis, kidney, and central nervous system (CNS) involvement (65.9% [ p < 0.05], 57.6% [ p < 0.05], and 16.5% [ p < 0.05], respectively, in the ON group). ON patients were more likely to be treated with glucocorticoid (GC) and to receive a high dose of prednisolone at the initial stage of SLE ( p < 0.05). The percentage of patients who received hydroxychloroquine was much higher in the control group ( p < 0.001). Cox regression analysis suggested that CNS involvement and GC therapy were two independent risk factors for ON in SLE patients. The presence of anti-phospholipid antibodies (aPLs) was a risk factor for multiple joint necrosis (odds ratio: 6.28, p = 0.009). Conclusions ON remains a serious and irreversible complication in SLE. In addition to glucocorticoid therapy, we found that CNS system involvement was a risk factor for ON, while the administration of hydroxychloroquine was a protective factor. The clinical characteristics of multiple site ON patients were distinct from isolated femoral head necrosis patients. The presence of aPLs was a risk factor for multiple site osteonecrosis.

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Section: Discussionmentioning

confidence: 99%

Risk of osteonecrosis in systemic lupus erythematosus: An 11-year Chinese single-center cohort study

Long

Zhang

You

et al. 2021

Lupus

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“…Therefore, the question remains: does reducing circulating LDL effectively reduce the risk of SONFH with steroid application? In animal models, it has been suggested that reduced circulating lipid levels can reduce the risk of SONFH (Yang Z. et al, 2016), but the clinical effect remains to be confirmed. Additionally, in the location subgroup analysis of rs1042031 results, the heterogeneity decreased significantly from 50 to 0%.…”

Section: Discussionmentioning

confidence: 99%

Lipid Transporter Activity-Related Genetic Polymorphisms Are Associated With Steroid-Induced Osteonecrosis of the Femoral Head: An Updated Meta-Analysis Based on the GRADE Guidelines

et al. 2018

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Aims: The purpose of this study was to assess the relationship between genetic variants and steroid-induced osteonecrosis of the femoral head (SONFH) in steroid use populations.Methods: We searched the public databases up to April 15, 2018. This study analyzed only the single-nucleotide polymorphisms (SNPs) that have appeared in more than three studies and assessed the level of evidence by classifying the outcomes according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach.Results: The ABCB1 rs1045642 C>T mutation had a protective effect against SONFH in the allelic model (I2 = 50.2%; OR: 0.74; 95% CI: 0.55–1.00; p = 0.046). The rs2032582 mutation in the ABCB1 gene showed no relationship to SONFH (allelic model: I2 = 63.4%; OR: 0.85; 95% CI: 0.58–1.23; p = 0.382). In ApoB rs693, four models showed that mutations can increase SONFH risk, but the allelic model did not. The ApoB rs1042031 mutation increased SONFH risk in the dominant model (I2 = 50.3%; OR: 2.90; 95% CI: 1.49–5.66; p = 0.002).Conclusion: An allelic model of ABCB1 rs1045642 showed that mutations have a protective effect against SONFH at a very low level of evidence. The mutations in ApoB rs693 and rs1042031 increase the SONFH risk with moderate levels of evidence.

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“…Anti-coagulant ingredient warfarin and hypolipidemic drug statins can significantly decrease the risk of ON induced by steroids. [ 25 – 27 ] In addition, physical therapies such as extracorporeal shockwave therapy (ESWT), hyperbaric oxygen therapy, and pulsed electromagnetic therapy have been proved to stimulate neovascularization, increase intracellular oxygen, and reduce inflammation reactions in ON lesions. [ 28 – 31 ] Implantation of autologous bone marrow mesenchymal stem cells is a promising treatment of osteonecrosis of femoral head, significantly reducing the risk of femoral head collapse and the need of total hip replacement.…”

Section: Discussionmentioning

confidence: 99%

Juvenile-onset multifocal osteonecrosis in systemic lupus erythematosus

Jin¹,

Yang²,

2021

Medicine

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Rationale: Osteonecrosis (ON) is a devastating illness that leads to bone ischemia and potential joint destruction. Systemic lupus erythematosus (SLE) is a chronic, autoimmune disease, with multi-system involvement which is closely associated with occurrence of ON. Multifocal ON, with an estimated morbidity of 3% in SLE patients, is extremely rare in juvenile subjects. Patient concerns: A 13.3-year-old female SLE patient was admitted to hospital 20 months following the SLE diagnosis because of a sudden aggravation of sore knees. She suffered from double knee joint pain and her left knee joint showed typical signs of inflammation including redness, swelling, heat, and pain. Diagnoses: The SLE patient was diagnosed with multifocal ON of her knee joint based on magnetic resonance imaging findings of bone destruction and osteoproliferation at the bilateral distal femur and proximal tibia. Interventions: The patient received high-dose methylprednisolone and intravenous cyclophosphamide pulse therapies for controlling active lupus and nephritis. Oral calcitriol and dipyridamole were administered to alleviate knee pain and inhibit thrombi formation, thereby suppressing ON progress. Outcomes: Three weeks following the treatment, the swelling in patient's left knee subsided. Her self-reporting pain score decreased from 9 to 4 and walking time increased from 45minutes to 90minutes per day. Nearly 5 weeks later, the pain in bilateral knee joints disappeared and the patient could walk without difficulties. Lessons: This patient is the youngest SLE patient who developed multifocal ON based on the reported literature. It suggests that ON can occur in young SLE patients. A combination of internal and external risk factors can promote the development of ON. The balanced approach to the application of corticosteroids and immunosuppressors in the treatment of SLE and prevention of ON is a challenging problem that deserves further exploration.

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The efficacy of statins in preventing glucocorticoid-related osteonecrosis in animal models

Cited by 17 publications

References 26 publications

Risk of osteonecrosis in systemic lupus erythematosus: An 11-year Chinese single-center cohort study

Risk of osteonecrosis in systemic lupus erythematosus: An 11-year Chinese single-center cohort study

Lipid Transporter Activity-Related Genetic Polymorphisms Are Associated With Steroid-Induced Osteonecrosis of the Femoral Head: An Updated Meta-Analysis Based on the GRADE Guidelines

Juvenile-onset multifocal osteonecrosis in systemic lupus erythematosus

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