Association between biologic therapy and fracture incidence in patients with selected rheumatic and autoimmune diseases: A systematic review and meta-analysis of randomized controlled trials

Lv, Fang; Hu, Suiyuan; Lin, Chu; Cai, Xiaoling; Zhu, Xiaoxi; Ji, Linong

doi:10.1016/j.phrs.2022.106278

Cited by 4 publications

(4 citation statements)

References 31 publications

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“…More than 130,000 RA patients initiating or switching to a b/tsDMARD were included in a large real-world study; it showed that the risk of non-vertebral fractures (hip, humerus, pelvis, and the wrist region) was similar between patients on adalinumab and those on any other TNF-α inhibitor, tocilizumab, abatacept, rituximab, or tofacitinib [ 96 ]. A recent meta-analysis, which included 37 RCTs (randomized controlled trials) comparing bDMARDs with placebo or csDMARDs, also did not detect a risk reduction in non-vertebral fractures, hip fractures, or major osteoporotic fractures [ 97 ]. Subgroup analyses of different bDMARDs did not change these findings.…”

Section: Proof Of Concept: Human Pharmacologic Intervention Studiesmentioning

confidence: 99%

Mechanisms of Systemic Osteoporosis in Rheumatoid Arthritis

Pietschmann

Butylina

Kerschan‐Schindl

et al. 2022

IJMS

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Rheumatoid arthritis (RA), an autoimmune disease, is characterized by the presence of symmetric polyarthritis predominantly of the small joints that leads to severe cartilage and bone destruction. Based on animal and human data, the pathophysiology of osteoporosis, a frequent comorbidity in conjunction with RA, was delineated. Autoimmune inflammatory processes, which lead to a systemic upregulation of inflammatory and osteoclastogenic cytokines, the production of autoantibodies, and Th cell senescence with a presumed disability to control the systemic immune system’s and osteoclastogenic status, may play important roles in the pathophysiology of osteoporosis in RA. Consequently, osteoclast activity increases, osteoblast function decreases and bone metabolic and mechanical properties deteriorate. Although a number of disease-modifying drugs to treat joint inflammation are available, data on the ability of these drugs to prevent fragility fractures are limited. Thus, specific treatment of osteoporosis should be considered in patients with RA and an associated increased risk of fragility fractures.

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Section: Proof Of Concept: Human Pharmacologic Intervention Studiesmentioning

confidence: 99%

Mechanisms of Systemic Osteoporosis in Rheumatoid Arthritis

Pietschmann

Butylina

Kerschan‐Schindl

et al. 2022

IJMS

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“…Despite these bone mineral density results suggesting a relationship between DMRDs and the potential for fragility fractures, studies that directly investigated the risk of nonvertebral fractures in rheumatoid arthritis found no increase in risk with conventional DMARD use [20,23] and no decreased risk with the use of a variety of targeted or biologic DMARDs [23][24][25]. However, a meta-analysis of 100 randomized controlled trials suggested that, in patients with psoriatic arthritis, there was a decreased risk of major osteoporotic fracture, hip fracture, and osteoporotic nonvertebral fracture with biologic DMARDs [26]. That analysis did not identify any change in risk in patients with rheumatoid arthritis, axial spondylarthritis, systemic lupus erythematosus, or inflammatory bowel disease with biologic DMARD treatment [26].…”

Section: Discussionmentioning

confidence: 99%

“…However, a meta-analysis of 100 randomized controlled trials suggested that, in patients with psoriatic arthritis, there was a decreased risk of major osteoporotic fracture, hip fracture, and osteoporotic nonvertebral fracture with biologic DMARDs [26]. That analysis did not identify any change in risk in patients with rheumatoid arthritis, axial spondylarthritis, systemic lupus erythematosus, or inflammatory bowel disease with biologic DMARD treatment [26]. These differences between bone mineral density and fracture risk might be explained in part by the limited ability of bone mineral density to directly predict the risk of fractures [4].…”

Section: Discussionmentioning

confidence: 99%

Long-Term Use of Immunosuppressive Agents Increased the Risk of Fractures in Patients with Autoimmune Diseases: An 18-Year Population-Based Cohort Study

Kao,

Hsu,

et al. 2023

Biomedicines

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The risk of fractures is higher in patients with autoimmune diseases, but it is not clear whether the use of immunosuppressive agents can further increase this risk. To investigate this issue, a retrospective study was conducted using data from Taiwan’s National Health Insurance Research Database. Patients diagnosed with autoimmune diseases between 2000 and 2014, including psoriatic arthritis, rheumatoid arthritis, ankylosing spondylitis, and systemic lupus erythematosus, were included in the study. A control group of patients without autoimmune diseases was selected from the same database during the same period. Patients with autoimmune diseases were divided into two sub-cohorts based on their use of immunosuppressive agents. This study found the risk of fractures was 1.14 times higher in patients with autoimmune diseases than in those without. Moreover, we found that patients in the immunosuppressant sub-cohort had a higher risk of fractures compared to those in the non-immunosuppressant sub-cohort. The adjusted sub-distribution hazard ratio for shoulder fractures was 1.27 (95% CI = 1.01–1.58), for spine fractures was 1.43 (95% CI = 1.26–1.62), for wrist fractures was 0.95 (95% CI = 0.75–1.22), and for hip fractures was 1.67 (95% CI = 1.38–2.03). In conclusion, the long-term use of immunosuppressive agents in patients with autoimmune diseases may increase the risk of fractures.

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“…However, systemic oral medications are required for moderate-to-severe plaque psoriasis [ 1 , 15 ]. Since psoriasis is a chronic disease that requires long-term medication, people with psoriasis often require lifelong therapy [ 16 ]. Consequently, all treatment plans must adhere to strict standards for patient safety.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and Key Materials of East Asian Herbal Medicine Combined with Conventional Medicine on Inflammatory Skin Lesion in Patients with Psoriasis Vulgaris: A Meta-Analysis, Integrated Data Mining, and Network Pharmacology

Kim

Baek³

et al. 2023

Pharmaceuticals

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Psoriasis is a chronic inflammatory disease that places a great burden on both individuals and society. The use of East Asian herbal medicine (EAHM) in combination with conventional medications is emerging as an effective strategy to control the complex immune-mediated inflammation of this disease from an integrative medicine (IM) perspective. The safety and efficacy of IM compared to conventional medicine (CM) were evaluated by collecting randomized controlled trial literature from ten multinational research databases. We then searched for important key materials based on integrated drug data mining. Network pharmacology analysis was performed to predict the mechanism of the anti-inflammatory effect. Data from 126 randomized clinical trials involving 11,139 patients were used. Compared with CM, IM using EAHM showed significant improvement in the Psoriasis Area Severity Index (PASI) 60 (RR: 1.4280; 95% CI: 1.3783–1.4794; p < 0.0001), PASI score (MD: −3.3544; 95% CI: −3.7608 to −2.9481; p < 0.0001), inflammatory skin lesion outcome, quality of life, serum inflammatory indicators, and safety index of psoriasis. Through integrated data mining of intervention data, we identified four herbs that were considered to be representative of the overall clinical effects of IM: Rehmannia glutinosa (Gaertn.) DC., Isatis tinctoria subsp. athoa (Boiss.) Papan., Paeonia × suffruticosa Andrews, and Scrophularia ningpoensis Hemsl. They were found to have mechanisms to inhibit pathological keratinocyte proliferation and immune-mediated inflammation, which are major pathologies of psoriasis, through multiple pharmacological actions on 19 gene targets and 8 pathways in network pharmacology analysis. However, the quality of the clinical trial design and pharmaceutical quality control data included in this study is still not optimal; therefore, more high-quality clinical and non-clinical studies are needed to firmly validate the information explored in this study. This study is informative in that it presents a focused hypothesis and methodology for the value and direction of such follow-up studies.

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Association between biologic therapy and fracture incidence in patients with selected rheumatic and autoimmune diseases: A systematic review and meta-analysis of randomized controlled trials

Cited by 4 publications

References 31 publications

Mechanisms of Systemic Osteoporosis in Rheumatoid Arthritis

Mechanisms of Systemic Osteoporosis in Rheumatoid Arthritis

Long-Term Use of Immunosuppressive Agents Increased the Risk of Fractures in Patients with Autoimmune Diseases: An 18-Year Population-Based Cohort Study

Efficacy and Key Materials of East Asian Herbal Medicine Combined with Conventional Medicine on Inflammatory Skin Lesion in Patients with Psoriasis Vulgaris: A Meta-Analysis, Integrated Data Mining, and Network Pharmacology

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