Systemic evaluation of the relationship between psoriasis, psoriatic arthritis and osteoporosis: observational and Mendelian randomisation study

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Abstract

Objectives and methods

With 432 513 samples from UK Biobank dataset, multivariable linear/logistic regression were used to estimate the relationship between psoriasis/psoriatic arthritis (PsA) and estimated bone mineral density (eBMD)/osteoporosis, controlling for potential confounders. Here, confounders were set in three ways: model0 (including age, height, weight, smoking and drinking), model1 (model0 +regular physical activity) and model2 (model1 +medication treatments). The eBMD was derived from heel ultrasound measurement. And 4904 patients with psoriasis and 847 patients with PsA were included in final analysis. Mendelian randomisation (MR) approach was used to evaluate the causal effect between them.

Results

Lower eBMD were observed in patients with PsA than in controls in both model0 (β-coefficient=−0.014, p=0.0006) and model1 (β-coefficient=−0.013, p=0.002); however, the association disappeared when conditioning on treatment with methotrexate or ciclosporin (model2) (β-coefficient=−0.005, p=0.28), mediation analysis showed that 63% of the intermediary effect on eBMD was mediated by medication treatment (p<2E-16). Patients with psoriasis without arthritis showed no difference of eBMD compared with controls. Similarly, the significance of higher risk of osteopenia in patients with PsA (OR=1.27, p=0.002 in model0) could be eliminated by conditioning on medication treatment (p=0.244 in model2). Psoriasis without arthritis was not related to osteopenia and osteoporosis. The weighted Genetic Risk Score analysis found that genetically determined psoriasis/PsA were not associated with eBMD (p=0.24 and p=0.88). Finally, MR analysis showed that psoriasis/PsA had no causal effect on eBMD, osteoporosis and fracture.

Conclusions

The effect of PsA on osteoporosis was secondary (eg, medication) but not causal. Under this hypothesis, psoriasis without arthritis was not a risk factor for osteoporosis.

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Most cited references 16

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Recent Developments in Mendelian Randomization Studies

Jie Zheng, Denis Baird, Maria-Carolina Borges … (2017)

Purpose of Review Mendelian randomization (MR) is a strategy for evaluating causality in observational epidemiological studies. MR exploits the fact that genotypes are not generally susceptible to reverse causation and confounding, due to their fixed nature and Mendel’s First and Second Laws of Inheritance. MR has the potential to provide information on causality in many situations where randomized controlled trials are not possible, but the results of MR studies must be interpreted carefully to avoid drawing erroneous conclusions. Recent Findings In this review, we outline the principles behind MR, as well as assumptions and limitations of the method. Extensions to the basic approach are discussed, including two-sample MR, bidirectional MR, two-step MR, multivariable MR, and factorial MR. We also consider some new applications and recent developments in the methodology, including its ability to inform drug development, automation of the method using tools such as MR-Base, and phenome-wide and hypothesis-free MR. Summary In conjunction with the growing availability of large-scale genomic databases, higher level of automation and increased robustness of the methods, MR promises to be a valuable strategy to examine causality in complex biological/omics networks, inform drug development and prioritize intervention targets for disease prevention in the future.

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Psoriasis.

Jacqueline E Greb, Ari M Goldminz, James Elder … (2016)

Psoriasis is a chronic, immune-mediated disorder with cutaneous and systemic manifestations and substantial negative effects on patient quality of life. Psoriasis has a strong, albeit polygenic, genetic basis. Whereas approximately half of the accountable genetic effect of psoriasis maps to the major histocompatibility complex, >70 other loci have been identified, many of which implicate nuclear factor-κB, interferon signalling and the IL-23-IL-23 receptor axis. Psoriasis pathophysiology is characterized by abnormal keratinocyte proliferation and immune cell infiltration in the dermis and epidermis involving the innate and adaptive immune systems, with important roles for dendritic cells and T cells, among other cells. Frequent comorbidities are rheumatological and cardiovascular in nature, in particular, psoriatic arthritis. Current treatments for psoriasis include topical agents, photo-based therapies, traditional systemic drugs and biologic agents. Treatments can be used in combination or as monotherapy. Biologic therapies that target specific disease mediators have become a mainstay in the treatment of moderate-to-severe disease, whereas advances in the treatment of mild-to-moderate disease have been limited.

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Prevalence of psoriasis in China: a population-based study in six cities.

Xiaolan Ding, Tinglin Wang, Yiwei Shen … (2016)

Although psoriasis occurs worldwide, the prevalence varies considerably between different peoples and regions. In China, a questionnaire-based study was carried out in 1987 and the prevalence of psoriasis was found to be 0.12%. Since then, no large-scale, population-based study has been reported. To obtain the accurate figures for the prevalence of psoriasis in China. A population-based survey was conducted in 6 cities. The cluster sampling method was used to select communities in each city. The subjects were required to fill out self-reporting questionnaires during a face-to-face interview and also received physical examination by dermatologists. 19,974 subjects were visited and 17,345 completed the questionnaires and received dermatological examination. 102 subjects (0.59%) were found to have psoriasis. After standardization, the prevalence of psoriasis was 0.47%. The prevalence of psoriasis in males and females was 0.54% and 0.44% respectively. 97.06% of the patients had psoriasis vulgaris. 28.43% of the patients reported a family history of psoriasis. 59.80% of patients experienced a negative influence on the quality of life. This population-based and dermatologist-confirmed study showed that the prevalence of psoriasis in China is 0.47%, which is higher than that reported in 1987.