What we do
About our project
Background
Osteoarthritis (OA) is by far the most frequent rheumatic disease and after menopausal age, a steep rise in knee OA-incidence is seen in women. During and after menopause, many metabolic changes other than a drop in estrogen levels occur that could influence the OA process. This sex difference suggests female specific pathways that lead to OA, however, at present, such sex specific pathways have never been investigated, and no sex specific risk profiles or treatment strategies are available.
Hypothesis
We hypothesize that sex-specific factors, influenced by menopause, play a key role of in the development of OA. Identification of the mechanism behind a female specific pathway will further increase the possibilities for sex specific treatment or prevention of this debilitating disease in elderly women.
Methods
We will use the full spectrum of data available within the complete Rotterdam Study (15000 persons from age 45 years). The cohort has regular 5-year follow-up measurements and a mean follow-up duration of 10 years. The main joint under study is the knee, but the other joints will also be explored. The data will be analyzed with sex stratified multivariable regression models for identification of specific OA factors that might contribute to the unknown female specific pathway. Next, Structural Equation Modeling will be used to construct more complex models. These pathways will be validated in international and national replication cohorts.
Further in-depth analyses of sex specific pathways will be done in a sub-cohort of the Rotterdam Study of 2600 persons of age 45-60. This focus cohort is specifically suited for in depth pathway analysis, due to the omics data available. The identification of the female specific pathways will deliver female specific modifiable risk factors and molecular targets, and possibly intermediate outcomes, for sex specific treatment.
Osteoarthritis (OA) is by far the most frequent rheumatic disease and after menopausal age, a steep rise in knee OA-incidence is seen in women. During and after menopause, many metabolic changes other than a drop in estrogen levels occur that could influence the OA process. This sex difference suggests female specific pathways that lead to OA, however, at present, such sex specific pathways have never been investigated, and no sex specific risk profiles or treatment strategies are available.
Hypothesis
We hypothesize that sex-specific factors, influenced by menopause, play a key role of in the development of OA. Identification of the mechanism behind a female specific pathway will further increase the possibilities for sex specific treatment or prevention of this debilitating disease in elderly women.
Methods
We will use the full spectrum of data available within the complete Rotterdam Study (15000 persons from age 45 years). The cohort has regular 5-year follow-up measurements and a mean follow-up duration of 10 years. The main joint under study is the knee, but the other joints will also be explored. The data will be analyzed with sex stratified multivariable regression models for identification of specific OA factors that might contribute to the unknown female specific pathway. Next, Structural Equation Modeling will be used to construct more complex models. These pathways will be validated in international and national replication cohorts.
Further in-depth analyses of sex specific pathways will be done in a sub-cohort of the Rotterdam Study of 2600 persons of age 45-60. This focus cohort is specifically suited for in depth pathway analysis, due to the omics data available. The identification of the female specific pathways will deliver female specific modifiable risk factors and molecular targets, and possibly intermediate outcomes, for sex specific treatment.
Our research focus
Primary outcomes
The primary two OA outcomes measures for the analysis are incident structural knee OA (Kellgren & Lawrence degree 2 or more) and incident clinical OA. Clinical OA is defined as structural OA with the occurrence of site-specific joint pain. Also hip OA and hand OA (for hand OA combined, and for joint groups PIP, DIP and, thumb separately) according to the same definitions will be modeled.
Secondary outcomes
Secondary outcomes are quantitative outcome measures, such as KL sum scores, WOMAC pain score.
The primary two OA outcomes measures for the analysis are incident structural knee OA (Kellgren & Lawrence degree 2 or more) and incident clinical OA. Clinical OA is defined as structural OA with the occurrence of site-specific joint pain. Also hip OA and hand OA (for hand OA combined, and for joint groups PIP, DIP and, thumb separately) according to the same definitions will be modeled.
Secondary outcomes
Secondary outcomes are quantitative outcome measures, such as KL sum scores, WOMAC pain score.
Funds & Grants
ZonMw (849200003).
Collaborations
Internal collaborations
Department of Orthopedics
Department of Radiology
Department of Internal Medicine
Department of Epidemiology
Department of General Practice
External collaboration
Department of Musculoskeletal Genetics, Univesity of Nottingham
Department of Orthopedics
Department of Radiology
Department of Internal Medicine
Department of Epidemiology
Department of General Practice
External collaboration
Department of Musculoskeletal Genetics, Univesity of Nottingham
Our team
Dr. J. B. J. van Meurs (co-promotor), j.vanmeurs@erasmusmc.nl
Dr. J.H. Waarsing, e.waarsing@erasmusmc.nl
Dr. D. Schiphof, d.schiphof@erasmusmc.nl
Dr. M. Kavousi, m.kavousi@erasmusmc.nl
Dr. E. H. Oei, e.oei@erasmusmc.nl
Dr. A. M. Valdes, ana.valdes@nottingham.ac.uk
Prof. Dr. P.J.E. Bindels, p.bindels@erasmusmc.nl
Prof. S.M.A. Bierma-Zeinstra (promotor), s.bierma-zeinstra@erasmusmc.nl
Contact address for the project: i.szilagyi@erasmusmc.nl.
Dr. J.H. Waarsing, e.waarsing@erasmusmc.nl
Dr. D. Schiphof, d.schiphof@erasmusmc.nl
Dr. M. Kavousi, m.kavousi@erasmusmc.nl
Dr. E. H. Oei, e.oei@erasmusmc.nl
Dr. A. M. Valdes, ana.valdes@nottingham.ac.uk
Prof. Dr. P.J.E. Bindels, p.bindels@erasmusmc.nl
Prof. S.M.A. Bierma-Zeinstra (promotor), s.bierma-zeinstra@erasmusmc.nl
Contact address for the project: i.szilagyi@erasmusmc.nl.
