Detection of individuals at risk of osteoporosis through registers
The aim of this study is to investigate the association of previous conditions or diseases (determined using the International Classification of Diseases (ICD-10 code)) and osteoporotic fractures in the Danish population with the aim of ultimately developing tools for identifying and treating persons at high risk of sustaining their first major osteoporotic fracture.
Osteoporosis is the most common bone disease in humans. It is characterized by low bone mass and micro-architectural deterioration of bone of the skeleton leading to bone fragility and a predisposition to fractures. Osteoporosis is a major cause of morbidity and mortality, particularly in post-menopausal women and older men. The remaining lifetime risk of a major osteoporotic fracture (clinical spine, hip, forearm or humeral fracture) is approximate 46% in women and 22 % in men. Still osteoporosis is undiagnosed and under-treated in Denmark as in many other countries. In Denmark, it have been estimated that it is only around 25% of all persons with a high risk of osteoporotic fractures (defined as three or more risk factors) that are referred to DXA examination, and controversy, a relatively high proportion of examinations are performed in persons with a low risk of osteoporotic fractures. This is supported entirely by similar studies from other countries. Prognoses from the Danish Bone Society indicate that an unchanged effort in detecting and treating of osteoporosis will lead to an increase in the number of hip fractures of 85%, reflecting the large increase in the number of Danes aged 60 or over in the next 25 years. It is therefore of great societal interest to improve methods for early case finding in osteoporosis.
Though osteoporosis is commonly associated with menopause and ageing, many common conditions and diseases are also known to be associated with osteoporosis and increased risk of fracture, e.g. diabetes, chronic lever disease etc. Many of these conditions are included in national guidelines for clinical practice for the diagnosis and treatment of osteoporosis. Secondary osteoporosis are present in both genders, and evaluations for underlying causes reveals that up to 30% of post-menopausal women and 50-80% of men are found to have secondary factors contributing to osteoporosis. The most important conditions found in the studies were History of low-energy fracture, parental hip fracture, smoking ect, however, there could possibly be other common (or more uncommon) conditions and diseases that is related to osteoporotic fracture - which no one have suggested yet. The best performing algorithm for identifying persons at high risk of fracture, for the purpose of preventing the first major osteoporotic fracture event, would potentially include not only common risk factors whose influence on fracture risk could be small or modest but also rarer risk factors provided they strongly increased the risk of fracture in affected subjects.
Danish registers are particularly useful for fracture studies because of their coverage of the entire population and the availability of consistently coded long term data. Denmark has a large array of high quality national registers that provide a unique opportunity to perform large population-based studies linking information about diagnoses, medications, etc. at the individual level. Overall, the aim of this study was to investigate the association of previous conditions or diseases (determined using the International Classification of Diseases (ICD-10 code)) and osteoporotic fractures in the Danish population with the aim of ultimately developing tools for identifying and treating persons at high risk of sustaining their first major osteoporotic fracture.
Description of the cohort
We conducted a nationwide population-based case-control study through Danish registers.
First, the Danish Civil Registration system was used to identify candidates for possible inclusion in the study population. We extracted all Danish citizens (men and women) aged 45 years and above the 1th of January 2013. The Danish National Register was used to retrieve information on fractures and other conditions or diseases in the period 1995-2013.
We used Danish National Registers to identify our cases; all individual in the country who were diagnosed through a hospital contact (in- or outpatient) as having a major osteoporotic fracture (MOF) during 2013 (1. of January to the 31. of December 2013). MOF were defined as hip, clinical vertebral, wrist or humerus fracture (ICD-10 codes: S120, S121, S122, S220, S221, S320, T08, S422, S423, S720, S721, S722, S525, S526).
All individual with a MOF before the first of January were excluded.
The cases were matched against six controls each on time-at-risk, sex and year of birth and the index date of the control was set to the index date of the case (date of first MOF in 2013), excluding any later diagnoses of the control from analyses. Controls had to be alive on the index date of their respective fracture case.
Exposures (ICD-codes to define secondary osteoporosis):
The exposures in the study are all potential ICD-10 codes admitted at Danish hospitals that each individual have obtained from 1995 up to indexdate. We used ICD-10 codes at level 2 (e.g. DS10) and obtained the codes from the Danish National Registers
Data and biological material
Register data from the following databases will be linked for identification of the cohort and to extract information on fractures and other conditions or diseases: Danish Civil Registration system, The National Patient Registry and The Death Cause Registry.
Later we will provide information on Medical Product Statistics Registry and data concerning social economic status e.g. through OPENs authorization to Statistics Denmark
The study does not collect biological material.
Collaborating researchers and departments
OPEN, Institute of Clinical Research, University of Southern Denmark/OUH Odense University Hospital
- Professor Bo Abrahamsen, PhD
IST - Research Unit of General Practice
- Professor Jens Søndergaard
Publications associated with the project
Skjødt MK, Möller S, Hyldig N, Clausen A, Bliddal M, Søndergaard J, Abrahamsen B, Rubin KH. Validation of the Fracture Risk Evaluation Model (FREM) in predicting major osteoporotic fractures and hip fractures using administrative health data. Bone. 2021 Jun;147:115934. doi: 10.1016/j.bone.2021.115934. Epub 2021 Mar 20. PMID: 33757901.
Möller S, Skjødt MK, Yan L, Abrahamsen B, Lix LM, McCloskey EV, Johansson H, Harvey NC, Kanis JA, Rubin KH, Leslie WD. Prediction of imminent fracture risk in Canadian women and men aged 45 years or older: external validation of the Fracture Risk Evaluation Model (FREM). Osteoporos Int. 2021 Oct 1. doi: 10.1007/s00198-021-06165-1. Epub ahead of print. PMID: 34596704.