NOREPOS

NOREPOS: Decoding Hip Fracture Trends Across Norway

We spoke to Professor Haakon E. Meyer about NOREPOS, a collaborative research network that delves into understanding and alleviating the burden of osteoporosisrelated hip fractures in Norway. Their research focuses on understanding declines in hip fractures, immune-bone connection, weather impacts, and predictive models.

NOREPOS (Norwegian Epidemiologic Osteoporosis Studies) is a collaborative network of researchers from five scientific institutions in Norway. Their main goal is to conduct epidemiological research with a focus on osteoporosis and its consequences.

The NOREPOS collaboration began in 1997. The collaboration includes researchers from the University of Bergen (UiB), UiT The Arctic University of Norway in Tromsø, the Norwegian University of Science and Technology (NTNU), the University of Oslo (UiO), and the Norwegian Institute of Public Health.

Norway has one of the highest incidences of hip fractures in the world. In Norway, every hour witnesses two forearm fractures and one new hip fracture. These fractures are not just painful. Hip fractures cause increased morbidity and all-cause mortality, reduce function, and increase the risk of death. Hip fractures do not only affect individuals but they cause a significant economic burden on society. In Norway, they’re among the costliest diagnoses. Despite declining hip fracture risk over the past decades, due to the increasing elderly population, a rise in

fractures is expected. NOREPOS aims to understand why Norway has the world’s highest hip fracture rates and how these rates vary across groups in the population. This knowledge is crucial for planning healthcare and prevention strategies.

NOREPOS uses data from large populationbased epidemiologic studies conducted in Norway. These studies include data on health status such as height, weight, hip/ waist circumferences, heart rate, and blood pressure; health behaviors, sociodemographic factors, general health, and disease. They also collect data from fracture registers, examining hip and forearm fractures. The NORHip database contains data on almost 240,000 hip fractures treated in Norwegian hospitals from 1994 up to date, linked to other databases for comprehensive analysis and validated against local hip fracture registries.

Novel Aspects of an Old Problem

The recently completed research project (2018-2023), funded by the Research Council of Norway, used the NORHip database in combination with health studies and registries cover the entire population. The project had

three main objectives: firstly, uncovering the factors that have contributed to the decline in hip fracture incidence in the past two decades. Secondly, exploring the link between the immune system and bone metabolism, and how the immune system might affect bone health and fracture risk. Thirdly, by studying weather, climate, air pollution, and demographics, the project aimed to figure out why fracture risks differ across regions.

Hip-IMPACT Model

In Norway, the annual number of hip fractures treated in hospitals is comparable to the annual number of patients treated for myocardial infarction. However, despite observed declines in age-adjusted hip fracture rates in Europe and North America, the increasing life expectancy and growth of the population aged over 60 predict a potential rise in fracture numbers that surpasses the decline in age-specific incidence. In a previous study, the researchers demonstrated a 27% decrease in age-adjusted hip fracture rates in Norway between 1999-2019. Understanding the forces behind these trends is vital to reducing the future burden of hip fractures on

healthcare systems and society at large. In this study, the researchers aimed to understand how much osteoporosis treatments and secular changes in lifestyle factors influenced the observed decline in hip fracture incidence during the mentioned period.

The Hip-IMPACT model examines data from different periods to determine how changes in various risk factors and treatments contribute to the decrease in hip fracture incidence. It was developed in collaboration with the University of Liverpool, building upon their IMPACT model initially created to analyze cardiovascular disease mortality. This study is the first to measure the influence of both treatment changes and risk factors on hip fracture rates at a population level. The researchers found that osteoporosis medications played a modest role in reducing hip fractures, explaining around one-fifth of the decline. The decline in hip fracture incidence was primarily influenced by

changes in major risk factors and preventive measures, accounting for over two-thirds of the observed decrease. Increased population BMI, particularly among men, accounted for a significant proportion of this decrease, highlighting the importance of low body weight as a modifiable risk factor. The rise in individuals with total hip prostheses which precludes fracture in the operated hip, contributed significantly to the decline, especially in women. An increased number of physically active individuals and lower smoking rates also contributed to fewer hip fractures. It is crucial to understand how changes in risk factors and treatment changes impact hip fractures. This information can be used to guide public health advice and make policy adjustments aimed at managing the expected increase in hip fractures. The researchers plan to implement the Hip IMPACT model in Denmark, and hopefully in other countries as well.

The Connection Between Immune Function and Bone Metabolism

“Osteoimmunology” is a term that highlights the connection between bone health and the immune system. The researchers are studying the long-term risk of osteoporosis and hip fracture across the size of immune response measured by the tuberculin skin test in a massive population-wide cohort. The researchers aimed to determine whether a stronger post-vaccination immune response correlates with a higher risk of hip fracture or lower bone mineral density three to four decades later. The team studied 244,607 individuals who participated in the nationwide tuberculosis screening and BCG vaccination program (between 1963 and 1975), to see if their tuberculin skin test (TST) results after BCG vaccination when they were young, were linked to hip fracture risks later in life (from 1994 to 2013). Additionally, they assessed bone mineral density (BMD) at a mean age of 52 years using dual-energy X-ray absorptiometry (DXA) scans in a subsample. The study found that men who tested positive on the tuberculin skin test (TST) after getting the BCG vaccine in their younger years had a slightly higher risk of experiencing a hip fracture later in life. This connection might be related to immune-mediated bone loss.

Interestingly, this association wasn’t observed in women. Understanding the TST response is complicated because it involves various immunological mechanisms. While the study highlighted these trends in men, there’s still

uncertainty about the precise meaning of the TST response. Immune system activity is impacted by dietary patterns. The researchers are now studying the association between dietary inflammatory patterns and risk of hip fracture in the large US Nurses’ Health Study. This is done in collaboration with researchers at Harvard T.H. Chan School of Public Health in Boston, USA.

Additionally, the researchers explored the connection between immune response after BCG vaccination and risk of primary total hip arthroplasty due to idiopathic osteoarthritis or rheumatoid arthritis. They found that among women, a strong immune response was associated with a lower risk of hip replacement due to osteoarthritis. For men, the data suggested an increased risk, though it wasn’t statistically significant. Variations in immune responses and unexplored factors create the need for further research to better understand this connection.

differences in hip fracture rates across different counties or seasons solely based on geographic factors. More investigation into climate-related factors could provide better insights.

Another NOREPOS study investigated the potential link between cold outdoor temperatures and the risk of forearm and hip fractures. They linked hospital records of forearm and hip fractures to monthly average temperatures. Their findings revealed a higher risk of both forearm and hip fractures when temperatures fell below 0°C compared to higher temperatures. For forearm fractures, the highest risk was for temperatures just below 0°C. Moreover, individuals faced increased mortality post-hip fracture during colder temperatures. This study suggests a connection between cold temperatures and higher risks of fractures and mortality, shedding light on environmental factors influencing bone health.

“NOREPOS aims to understand why Norway has the world’s highest hip fracture rates and how these rates vary across population groups. This knowledge is crucial for planning healthcare and prevention strategies.”

NOREPOS-Climate

In the NOREPOS-Climate project, the researchers are exploring the connections between weather conditions, air quality, and fractures in Norway. By using nationwide data on fractures and weather info from the Norwegian Meteorological Institute, along with air pollution estimates from Aarhus University, they are investigating how factors like cold temperatures and air quality might relate to forearm and hip fractures.

One NOREPOS study examined if living at different elevations and distances from the coast might clarify the differences in hip fracture rates across geographical areas. In Norway, areas situated at higher elevations and farther from the coastline showed an increased risk of hip fractures. Researchers included all hip fracture patients admitted to Norwegian hospitals between 2009 and 2018 in their analysis, combining individual data on residential elevation and distance to the coast with population demographics. Their findings revealed that higher elevation and greater distance from the coast in Norway correlated with increased hip fracture risks, among women. Despite these findings, the study couldn’t explain the previously observed

NOREPOS

Norwegian Epidemiologic Osteoporosis Studies

Project Objectives

The project aims to decipher the causes behind Norway’s high hip fracture rates and their variation across demographics. The knowledge gained from this project is used to inform targeted healthcare strategies mitigating societal and individual burdens.

Project Funding

The NOREPOS network has received two substantial grants from the Research Council of Norway, in 2008 and 2017, respectively.

Project Partners

Prof. Martin O’Flaherty, University of Liverpool, UK.

Prof. Bo Abrahamsen, University of Southern Denmark.

Colleagues at the Norwegian Institute of Public Health and the universities in Oslo, Bergen, Trondheim and Tromsø.

Contact Details

Professor Haakon E. Meyer, MD PhD

Department of Community Medicine and Global Health

Faculty of Medicine, University of Oslo &

Senior Medical Officer

Norwegian Institute of Public Health

T: +47 480 82 702

E: h.e.meyer@medisin.uio.no

W: http://www.norepos.no/ W: https://pubmed.ncbi.nlm.nih.gov/25278275/

Predicting Injury Based on Extreme Weather Events

The team aims to predict the incidence of fractures influenced by meteorological factors, such as frequent “freeze-thaw” cycles. By analyzing weather patterns alongside demographic data (age, gender, immigrant background), the goal is to predict the daily number of fractures in individuals over 40 years old during severe weather events. This could lead to localized “fracture forecasts” for each municipality and hospital catchment area. This predictive model aims to offer a “fracture forecast” specific to each area, aiding municipalities and hospitals in preparing for potential surges in fractures. It could guide timely actions like enhanced snow clearance and hospital staffing adjustments, reducing both health impacts and the environmental footprint of these responses. Moreover, it could inform individuals through weather apps about when to use safety measures like spikes during icy conditions, potentially preventing several hundred fractures annually. Ultimately, this innovative approach seeks to anticipate and minimize the impact of extreme weatherrelated fractures on both community health and environmental resources.

Kjeldgaard HK, Holvik K, Abrahamsen B, Tell GS, Meyer HE, O’Flaherty M. Explaining declining hip fracture rates in Norway. A population-based modelling study. The Lancet Regional Health - Europe, Volume 30, 2023,100643, ISSN 2666-7762, https://doi.org/10.1016/j.lanepe.2023.100643. (https://pubmed.ncbi.nlm.nih.gov/37215491/)

Dahl J, Holvik K, Heldal E, Grimnes G, Hoff M, Finnes TE, Apalset EM, Meyer HE. Individual Variation in Adaptive Immune Responses and Risk of Hip Fracture – A NOREPOS Population-Based Cohort Study. Bone Miner Res. 2020; 35:2327-2334. doi: 10.1002/jbmr.4135. (https://pubmed.ncbi.nlm.nih.gov/32697001/)

Professor Haakon E. Meyer

Professor Haakon E. Meyer is a professor of epidemiology at the Section for Preventive Medicine and Epidemiology, at the Faculty of Medicine University of Oslo. He is a senior medical officer at the Norwegian Institute of Public Health in Oslo, Norway, and is the leader of the NOREPOS collaboration.

Project participants linked with the Hip-IMPACT model: From left to right: Prof. Haakon E. Meyer, researcher Kristin Holvik, Prof. Martin O’Flaherty, University of Liverpool, post doc Helena Kjeldgaard (Photo: Espen K. Olsen).