Short summary

ROSE is a randomised population-based study, including 20,904 Danish women aged 65-81 years, investigating the effectiveness of a two-step screening programme for osteoporosis, using a questionnaire based on FRAX^® followed by DXA-scan. Further, the study is expected to provide knowledge about cost-effectiveness, patient preferences of screening programme to prevent fractures.

Rationale

Osteoporosis is highly prevalent, especially in post-menopausal women. Approximately 46% of all women and 26% of all men will experience at least one osteoporotic fracture after the age of 50 years. The disease often leads to fractures, chronic pain, decreased activity of daily living, and increased mortality. Moreover, the health-related quality of life is reduced in patients after hip and vertebral compression fractures. Osteoporosis is asymptomatic until fractures occur, but can be diagnosed using dual-energy X-ray absorptiometry (DXA), which measures the bone mineral density (BMD). Osteoporosis can be effectively treated as several pharmaceutical therapies decrease the risk of fractures.

In Denmark (as in other countries), a case-finding strategy has been adopted by the health care systems to identify individuals with increased risk of osteoporosis. Individuals with one or more risk factors for osteoporotic fracture or individuals with a low energy fracture may be referred for a DXA scan by their general practitioners (GP). However, current evidence suggests that this strategy does not perform well. Osteoporosis is under-diagnosed and under-treated in Denmark and probably also elsewhere. In theory, population screening for the disease could remedy this.

The aim of the ROSE study is to investigate the effectiveness of a two-step population based osteoporosis screening programme using FRAX^® based on self-administered questionnaire to select women for DXA followed by the standard osteoporosis treatment according to national guidelines and delivered by GPs in the Region of Southern Denmark. Secondary aims are to clarify whether the screening programme is cost-effective and to assess the patients' preferences, experience and acceptance of the screening programme. Moreover, sub-studies allow assessment of the effectiveness of FRAX^® alone or combined with individual clinical risk factors in the prediction of fractures and the impact of socioeconomic factors for participation and outcome. In this paper the study design and the baseline characteristics of the study population are described.

Description of the cohort

A total of 35,000 women aged 65-80 years living in the Region of Southern Denmark were selected at random from the background population using the Danish Civil Registration system (comprising all inhabitants in Denmark) in 2010 to participate in the present two-step screening study. Before recruitment, the women were randomised 1:1 to a screening or a control group using a computerized random-number-programme stratified according to area of residence and age. The women were continually invited to the study by mail through a period from February 2010 to November 2011.

Step 1: Fracture risk assessment: Participants in both groups were posted the same self-administered questionnaire comprising questions on risk factors for osteoporosis and fractures, perceived risk of fractures etc. and a pre-paid return envelope. The information letter for the screening group included information on a later DXA scan in participants with intermediate-high risk of fracture and women were given the possibility to mark if they were not interested in having a DXA scan. Based on the returned questionnaires, the individual participants' 10-year probability of major osteoporotic fractures (calibrated to Denmark) was calculated using a programmed call of the FRAX^© website.

Step 2: DXA assessment: Women in the screening group with a 10-year probability of major osteoporotic fractures ?15 % were invited to a DXA scan. Diagnostic work-up following current standard guidelines and treatment were carried out in general practice. Women with osteoporosis were advised to see their GPs to discuss anti-osteoporotic treatment.  The DXA scans were performed in four hospitals throughout the Region of Southern Denmark: Odense University Hospital, Odense; Hospital of Funen, Nyborg; Hospital of Southwest Denmark, Esbjerg, and Sygehus Lillebælt, Kolding.

Data and biological material

Questionnaire data:

The questionnaire containing a total of 25 items and was constructed to enable calculation of the 10-year probability of major osteoporotic fractures using FRAX©. Therefore, it comprised items on anthropometry, history of osteoporosis and fractures, menopause, risk factors for osteoporosis and fractures, and conditions associated with secondary osteoporosis. Moreover, we included questions on self-rated health and perceived risk of fractures.

Primary outcome:

Incident clinical fractures, defined as major osteoporotic fractures (hip, vertebral, humerus and forearm fractures) are the primary outcome. The ascertainment of these is performed by annually follow-up utilizing the Danish National Patient Registry (NPR) starting in 2013 for both the screening and control group.

Register data:

The cohort have been enriched with full National Patient Registry and socioeconomic data from Statistic Denmark

DXA results:

Finally the study have DXA results on all the women in the screening group with FRAX ?15 % that accepted the possibility the have a DXA scan (5064 women)

Collaborating researchers and departments

OPEN Odense Patient data Explorative Network, Odense University Hospital

• Postdoc Katrine Hass Rubin, PT, MHS, PhD

Institute of Clinical Research, University of Southern Denmark, Odense

• Head of institute and Professor Kim Brixen, MD, PhD

National Institute of Public Health, University of Southern Denmark, Copenhagen

• Adjunct Teresa Holmberg. Phd

Department of Medical Endocrinology, Odense University Hospital

• Postdoc Mette Juel Rothmann, MHS, PhD
• Consultant Pernille Hermann

Department of Endocrinology, Hospital of Southwest Denmark, Esbjerg

• Consultant Jeppe Gram

COHERE, Department of Business and Economics, University of Southern Denmark, Odense

• Professor Mickael Bech, PhD

Department of Internal Medicine, Kolding Hospital

• Consultant Ole Rasmussen

Department of Medical Endocrinology, Oslo University Hospital Aker, Norway

• PhD-student Mikkel Høiberg, MD

Section Biomedical Imaging, Department of Diagnostic Radiology, University Hospital Schleswig-Holstein, Kiel, Germany

• Professor Claus C Glüer
• Researcher Reinhard Barkmann

Publications associated with the project

The Risk-Stratified Osteoporosis Strategy Evaluation study (ROSE): A Randomized Prospective Population-Based Study. Design and Baseline Characteristics. Rubin KH, Holmberg T, Rothmann MJ, Høiberg M, Barkmann R, Gram J, Hermann AP, Bech M, Rasmussen O, Glüer CC, Brixen K. Calcif Tissue Int. 2015 Feb; 96(2): 167-79.

Non-participation in systematic screening for osteoporosis-the ROSE trial. Rothmann MJ, Möller S, Holmberg T, Højberg M, Gram J, Bech M, Brixen K, Hermann AP, Glüer CC, Barkmann R, Rubin KH. Osteoporos Int. 2017 Sep 5. doi: 10.1007/s00198-017-4205-y

Effectiveness of a two-step population-based osteoporosis screening program using FRAX: the randomized Risk-stratified Osteoporosis Strategy Evaluation (ROSE) study. Rubin KH, Rothmann MJ, Holmberg T, Høiberg M, Möller S, Barkmann R, Glüer CC, Hermann AP, Bech M, Gram J, Brixen K3. Osteoporos Int. 2017 Dec 7. doi: 10.1007/s00198-017-4326-3

Socioeconomic status and risk of osteoporotic fractures and the use of DXA scans: data from the Danish population-based ROSE study. Holmberg T, Möller S, Rothmann MJ, Gram J, Herman AP, Brixen K, Tolstrup JS, Høiberg M, Bech M, Rubin KH. Osteoporos Int. 2018 Nov 21. doi: 10.1007/s00198-018-4768-2.

Use of antiosteoporotic medication in the Danish ROSE population-based screening study. Høiberg MP, Rubin KH, Holmberg T, Rothmann MJ, Möller S, Gram J, Bech M, Brixen K, Hermann AP. Osteoporos Int. 2019 Mar 26. doi: 10.1007/s00198-019-04934-7.