The effect of a Pulmonary Rehabilitation programme on 10-year risk of fragile fracture (FRAX® score) in patients with COPD: protocol for a randomised controlled trial

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Daskalakis" }, { "@type": "Person", "name": "I. Patsaki" }, { "@type": "Person", "name": "E. Skordilis" }, { "@type": "Person", "name": "A. Evangelodimou" }, { "@type": "Person", "name": "E. Grammatopoulou" } ], "publisher": { "@type": "Organization", "name": "F1000Research", "logo": { "@type": "ImageObject", "url": "https://f1000research.com/img/AMP/F1000Research_image.png", "height": 480, "width": 60 } }, "image": { "@type": "ImageObject", "url": "https://f1000research.com/img/AMP/F1000Research_image.png", "height": 1200, "width": 150 }, "description": " Background Chronic Obstructive Pulmonary Disease (COPD) is associated with increased fracture risk due to systemic inflammation, physical inactivity, and corticosteroid use. Pulmonary Rehabilitation (PR) improves physical function and quality of life in Chronic Obstructive Pulmonary Disease (COPD), but its effect on fracture risk remains unexplored. Objective To evaluate the effect of a PR program on the 10-year fracture risk (FRAX score), Bone Mineral Density (BMD), and secondary outcomes in COPD patients. Methods 10 patients with stable COPD, aged 55–80 years, will be enrolled in a single-centre, randomized controlled trial. Participants will be randomized to a PR group (exercise, dietary counselling, respiratory physiotherapy and standard medical care) or a control group (standard medical care). Outcomes will include the scores of the Fracture Risk Assessment Tool (FRAX®), the Bone Mineral Density-BMD (via DEXA), the BODE index [Body Mass Index-BMI, Airflow Obstruction (FEV1% pred), Dyspnoea (MRC sale), and exercise capacity (6MWT), the COPD Assessment Test (CAT), the Nijmegen Questionnaire-NQ, and the Borg dyspnoea scale, assessed at baseline and at 12 months. Statistical analysis will use 2×2 ANOVA repeated measures with Bonferroni adjustment. Anticipated Results PR is expected to reduce FRAX scores, improve BMD, mitigate mortality index, dysfunctional breathing patterns, and the impact of COPD in the participants’ health and daily life compared to standard care. Conclusion This trial will provide novel insights into PR’s role in fracture prevention for COPD patients, addressing a critical gap in holistic disease management. Trial registration: Australian New Zealand Clinical Trials Registry (ANZCTR). Trial id: ACTRN12623001282673, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=384352&showOriginal=true&isReview=true Date submitted: 9/07/2023 Date registered: 8/12/2023 Protocol version: 28/10/2024 " } { "@context": "http://schema.org", "@type": "BreadcrumbList", "itemListElement": [ { "@type": "ListItem", "position": "1", "item": { "@id": "https://f1000research.com/", "name": "Home" } }, { "@type": "ListItem", "position": "2", "item": { "@id": "https://f1000research.com/browse/articles", "name": "Browse" } }, { "@type": "ListItem", "position": "3", "item": { "@id": "https://f1000research.com/articles/14-874/v1", "name": "The effect of a Pulmonary Rehabilitation programme on 10-year risk..." } } ] } Home Browse The effect of a Pulmonary Rehabilitation programme on 10-year risk... ALL Metrics - Views Downloads Get PDF Get XML Cite How to cite this article Daskalakis A, Patsaki I, Skordilis E et al. The effect of a Pulmonary Rehabilitation programme on 10-year risk of fragile fracture (FRAX® score) in patients with COPD: protocol for a randomised controlled trial [version 1; peer review: awaiting peer review] . F1000Research 2025, 14 :874 ( https://doi.org/10.12688/f1000research.166015.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Study Protocol The effect of a Pulmonary Rehabilitation programme on 10-year risk of fragile fracture (FRAX® score) in patients with COPD: protocol for a randomised controlled trial [version 1; peer review: awaiting peer review] A. Daskalakis https://orcid.org/0000-0001-9943-7672 1,2 * , I. Patsaki https://orcid.org/0000-0003-0614-2723 1 , E. Skordilis 3 , A. Evangelodimou 1 , E. Grammatopoulou 1 * A. Daskalakis https://orcid.org/0000-0001-9943-7672 1,2 * , I. Patsaki https://orcid.org/0000-0003-0614-2723 1 , [...] E. Skordilis 3 , A. Evangelodimou 1 , E. Grammatopoulou 1 * * Equal contributors PUBLISHED 04 Sep 2025 Author details Author details 1 Laboratory of Advanced Physiotherapy, Department of Physiotherapy, University of West Attica, Egaleo, 122 43, Greece 2 Department of Orthopaedic Surgery, General Oncologic Hospital ‘’St. Anargyroi’’, Kifisia, Greece 3 School of Physical Education and Sport Sciences, National and Kapodistrian University of Athens, Dafni, Greece A. Daskalakis Roles: Conceptualization, Investigation, Writing – Original Draft Preparation I. Patsaki Roles: Methodology, Visualization E. Skordilis Roles: Data Curation, Methodology A. Evangelodimou Roles: Visualization E. Grammatopoulou Roles: Conceptualization, Methodology, Supervision, Writing – Review & Editing OPEN PEER REVIEW REVIEWER STATUS AWAITING PEER REVIEW This article is included in the HEAL1000 gateway. Abstract Background Chronic Obstructive Pulmonary Disease (COPD) is associated with increased fracture risk due to systemic inflammation, physical inactivity, and corticosteroid use. Pulmonary Rehabilitation (PR) improves physical function and quality of life in Chronic Obstructive Pulmonary Disease (COPD), but its effect on fracture risk remains unexplored. Objective To evaluate the effect of a PR program on the 10-year fracture risk (FRAX score), Bone Mineral Density (BMD), and secondary outcomes in COPD patients. Methods 10 patients with stable COPD, aged 55–80 years, will be enrolled in a single-centre, randomized controlled trial. Participants will be randomized to a PR group (exercise, dietary counselling, respiratory physiotherapy and standard medical care) or a control group (standard medical care). Outcomes will include the scores of the Fracture Risk Assessment Tool (FRAX ® ), the Bone Mineral Density-BMD (via DEXA), the BODE index [Body Mass Index-BMI, Airflow Obstruction (FEV 1 % pred), Dyspnoea (MRC sale), and exercise capacity (6MWT), the COPD Assessment Test (CAT), the Nijmegen Questionnaire-NQ, and the Borg dyspnoea scale, assessed at baseline and at 12 months. Statistical analysis will use 2×2 ANOVA repeated measures with Bonferroni adjustment. Anticipated Results PR is expected to reduce FRAX scores, improve BMD, mitigate mortality index, dysfunctional breathing patterns, and the impact of COPD in the participants’ health and daily life compared to standard care. Conclusion This trial will provide novel insights into PR’s role in fracture prevention for COPD patients, addressing a critical gap in holistic disease management. Trial registration: Australian New Zealand Clinical Trials Registry (ANZCTR). Trial id: ACTRN12623001282673, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=384352&showOriginal=true&isReview=true Date submitted: 9/07/2023 Date registered: 8/12/2023 Protocol version: 28/10/2024 READ ALL READ LESS Keywords COPD, Pulmonary Rehabilitation, Fracture Risk, FRAX Score, Bone Mineral Density Corresponding Author(s) A. Daskalakis ( [email protected] ) Close Corresponding author: A. Daskalakis Competing interests: No competing interests were disclosed. Grant information: The author(s) declared that no grants were involved in supporting this work. Copyright: © 2025 Daskalakis A et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite: Daskalakis A, Patsaki I, Skordilis E et al. The effect of a Pulmonary Rehabilitation programme on 10-year risk of fragile fracture (FRAX® score) in patients with COPD: protocol for a randomised controlled trial [version 1; peer review: awaiting peer review] . F1000Research 2025, 14 :874 ( https://doi.org/10.12688/f1000research.166015.1 ) First published: 04 Sep 2025, 14 :874 ( https://doi.org/10.12688/f1000research.166015.1 ) Latest published: 04 Sep 2025, 14 :874 ( https://doi.org/10.12688/f1000research.166015.1 ) Introduction Chronic Obstructive Pulmonary Disease (COPD) is a widespread, chronic, and progressively worsening disease characterized by persistent respiratory symptoms ( Singh et al., 2019 ). The disease is not limited to the lungs but also affects other systems, such as the muscular, skeletal, hematopoietic, and endocrine systems, leading to conditions like cachexia, osteoporosis, normocytic anaemia, diabetes mellitus, and metabolic syndrome ( Parker et al., 2005 ). For the treatment of COPD, a global network of experts has developed guidelines focusing on smoking cessation, routine influenza and pneumococcal vaccinations, pharmacological therapy, rehabilitation, education, self-management, supportive care, palliative care, and end-stage patient care. Additional measures include various types of oxygen therapy and ventilation support strategies ( Singh et al., 2019 ). Pharmacological treatment for COPD varies based on whether the patient is in a stable condition or experiencing an exacerbation. In stable COPD, drugs used include short- or long-acting bronchodilators (SABA/LABA), short- or long-acting antimuscarinic drugs (SAMAs/LAMAs), methylxanthines, inhaled or oral anti-inflammatory drugs, PDE4 inhibitors, long-term antibiotics, and mucolytic or antioxidant drugs ( Singh et al., 2019 ). Pulmonary Rehabilitation (PR) programmes are essential for managing COPD. Their comprehensive design includes personalized therapeutic and educational interventions that address both short-term and long-term management of COPD, as well as its biological, mental, and social complications ( Singh et al., 2019 ; Spruit et al., 2013 ; Dyspnea, 1999 ). Since the initial joint statement by the American Thoracic Society (ATS) and the European Respiratory Society (ERS) ( Celli et al., 2004 ), extensive data have demonstrated the effectiveness of pulmonary rehabilitation (PR) in reducing dyspnoea, enhancing exercise capacity, and managing chronic obstructive pulmonary disease (COPD) over the long term ( Spruit et al., 2013 ; Dyspnea, 1999 ). A PR program is designed to provide individualized rehabilitation tailored to the specific needs of each COPD patient. The structure of a PR program should be based on the initial patient evaluation, disease severity, and any existing comorbidities ( Spruit et al., 2013 ; Dyspnea, 1999 ). Chronic Obstructive Pulmonary Disease (COPD) not only affects respiratory function but also has significant extrapulmonary consequences. Among these systemic complications, secondary osteoporosis is particularly notable. While the occurrence of secondary osteoporosis is documented in COPD, their causal relationship has not yet been clarified. There appears to be a correlation between osteoporosis and body mass index in COPD patients, as well as pulmonary hyperinflation. Primarily, cachexia is most strongly associated with osteoporosis, likely due to common pathophysiological pathways such as systemic inflammation, reduced fitness, and other factors related to proteolysis ( Scanlon et al., 2004 ). Secondary osteoporosis has been investigated in COPD patients engaged in a pulmonary rehabilitation program. One study indicated that bone mineral density remained unchanged after one year; however, it improved in patients who underwent lung volume reduction surgery compared to those who did not ( Mineo et al., 2005 ). Another longitudinal study over three years observed a worsening of osteoporosis and the development of fragility fractures in the spine. Additionally, vitamin D deficiency was linked to decreased bone mineral density, inflammation, and myopathy ( Graat-Verboom et al., 2011 ). Furthermore, there was a correlation between worsening FEV 1 and the incidence of osteoporotic fractures, likely attributable to the reduced physical activity associated with increased airflow obstruction, which exacerbates osteoporosis ( Graat-Verboom et al., 2011 ). The relationship between osteoporosis and reduced physical activity in COPD patients was similarly demonstrated in a study by Silva et al. (2011) . Osteoporosis manifests as reduced bone density and structural alterations in bone tissue, resulting in increased fragility and susceptibility to low-energy fractures, known as fragility fractures. The spine, hip, and distal radius are particularly prone to such fractures. Preventing fragility fractures is essential, given their association with a mortality rate of up to 20%, and the fact that only 30% of affected individuals achieve complete healing ( Sernbo & Johnell, 1993 ). The globally accepted FRAX ® statistical algorithm serves as a clinical tool for calculating the risk of fragility fractures. This algorithm considers various factors, including age, gender, body mass index (BMI), bone mineral density (DEXA), history of previous fragility fractures, family history of parental hip fractures, smoking history, corticosteroid use, and other risk elements ( Ogura-Tomomatsu et al., 2012 ; Dennison et al., 2012 ; Graat-Verboom et al., 2011 ). Anti-osteoporotic therapy in Greece is recommended if the 10-year fracture risk is estimated to be ≥5% for the hip or ≥15% for a major osteoporotic fracture at another site, to mitigate this risk ( Lyritis et al., 2013 ). Objective of the proposed trial The primary objective of this study is to determine the effect of a PR program on fragility fracture risk and on bone density. Secondary improvements are expected in mortality index, dysfunctional breathing patterns, and in the impact of COPD in the participants’ health and daily living. Methods Study design The study will be a single blind randomized controlled trial (RCT), conducted in accordance with the CONSORT statement. A flowchart of the study according to the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials guidelines is presented in Figure 1 . Figure 1. Flowchart of the study in accordance with the SPIRIT statement. Study setting The Pulmonary Rehabilitation (PR) Programme will take place at Sotiria Hospital for Chest Diseases in Athens, Greece, where participants will be recruited. The hospital’s research committee has approved the protocol (23934/10-9-2020). Participants in the intervention group will enrol in the PR program offered by the outpatient department of the 2nd Pulmonology Clinic at the same hospital. Interventions and assessments will take place at Sotiria Hospital in Athens (Greece). Recruitment procedures The participants will be recruited by a qualified pulmonologist, the director (pulmonologist) of the 2 nd Pulmonology Clinic, at the out-patient department of Sotiria Hospital for Chest Diseases in Athens, Greece. The secretariat of the 2 nd Pulmonology Clinic will provide to all participants information regarding (a) the study’s objectives, methods, and specifics, (b) the voluntary nature of their participation, (c) their right to withdraw from the study at any time even after consenting, and (d) their option to decline answering specific questions if they so choose and will review and sign an informed consent form. The consent declaration pertains to personal data privacy and the protection of participants’ rights. Randomization and blinding procedures On the day of the recruitment procedure, the above-mentioned secretariat will be involved in the randomization process. The eligible sample will be randomly assigned to two groups by using sealed, sequentially numbered, and opaque envelopes to ensure concealed allocation. These envelopes will be opened by the primary researcher, who is responsible for the study’s coordination and the only person who will know the allocation of the participants (single blinding procedure). Participants and eligibility The eligible volunteers will be invited to participate in the study. The pneumonologist at the out-patient department will conduct the lung function testing, diagnose stable COPD (no active exacerbation) ( Agustí et al., 2023 ) and define the eligibility of the volunteers, who will meet the inclusion criteria. Inclusion criteria: Greek patients (both males and females, aged 55-80 years) with stable COPD (stages I-VI) from the Attica region, seeking care at the outpatient department of Sotiria Hospital for Chest Diseases in Athens, Greece. Exclusion criteria: Patients meeting any of the following criteria will be excluded from the trial: a) Use of anti-osteoporotic drug therapy within three years prior to randomisation, b) Oral or intravenous corticosteroid therapy within three months prior to randomisation, c) Charlson Comorbidity Index (CCI) >5, d) Thyroid disorders, including untreated hyperthyroidism, over-treated hypothyroidism, and primary hyperparathyroidism, e) Excessive alcohol consumption, f ) Diagnosis of rheumatoid arthritis, and g) Diagnosis of coeliac disease. Participants’ characteristics The participants will be people (both males and females, aged 55-80 years) with stable COPD (stages I-VI) from the Attica region, seeking care at the outpatient department of Sotiria Hospital for Chest Diseases in Athens, Greece. Sample size The calculation of the minimum sample size for detecting significant differences between groups was based on the effect size of 1.15 for the femoral neck BMD ( Shehab & Osama, 2017 ). Specifically, with an effect size of 1.15, power size of 0.85, and α = 0.05, the minimum sample size was found to be eight ( Celli et al., 2004 ): four ( ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories, 2002 ) individuals allocated in the experimental group and four ( ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories, 2002 ) in the control group. However, considering a 15% possible dropout or exclusion, the minimum sample size was reconsidered to be 10. Initial assessment The pulmonologist at the out-patient department, will conduct pulmonary function testing (FEV 1 , FVC, PEF), provide the diagnosis of stable COPD and an informative printed material to all volunteers as well. A qualified physical therapist, with at least five years of experience in the assessment and management of COPD patients, will supervise the following clinical tests and questionnaire’s measurements in all participants: a) the six-minute walking distance test (6MWT), ( ATS, 2002 ), b) the BODE index ( Celli et al., 2004 ), c) the CAT questionnaire ( Jones et al., 2009 ), d) the Nijmegen Questionnaire ( van Dixhoorn & Duivenvoorden, 1982 ), and e) the Borg Scale ( Borg, 1982 ). A qualified radiologist, with at least five-year experience, will conduct the measurements of BMD and calculate the FRAX score. All tests will be performed in a random order, during the initial assessment. The above research colleagues will deliver the collected data to the secretariat of the 2nd Pulmonology Clinic at Sotiria Hospital, who in turn, will send them to the statistician. Interventions Both groups will receive printed informative materials detailing COPD management, including the importance of prophylactic measures such as medical follow-up, regular exercise, vaccination, proper use of medication, and self-drainage techniques. The materials, developed by the hospital’s physician and physiotherapist, are based on the GOLD report ( Singh et al., 2019 ) and the ATS/ERS official statement ( Celli et al., 2015 ). Intervention group: The intervention group will engage in the standardized PR program of the Sotiria Hospital that spans 12 weeks. It will consist of 36 sessions (three ( Akyea et al., 2019 ) sessions per week) and four ( ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories, 2002 ) counselling sessions of one-hour duration with health professionals from the hospital’s PR team. Particularly, the standardized Pulmonary Rehabilitation (PR) program is structured as follows: 1. Medical Evaluation and Follow-up: • Initial and Final Medical Evaluation: Each patient will undergo maximum exercise testing at the start and the end of the study. The tests will be conducted by the same specialist of the PR. • Weekly Medical Follow-ups: The specialized pulmonologist of the PR will adjust medications based on the GOLD ( Agustí et al., 2023 ) guidelines, in collaboration with the patient’s personal physician. 2. Nurse Counselling: • Symptom Evaluation and measurements of SpO 2 levels, and blood pressure. • Inhaler and Nebulizer Training: Demonstrations will ensure correct usage of inhalers and nebulizers. 3. Tailored Exercise Training, supervised by the physiotherapist of the PR: • Interval Aerobic Exercise (30 s work-30s rest): 40 minutes at 100% maximum workload. • Continuous Submaximal Aerobic Exercise: 10-20 minutes on a treadmill at a Borg dyspnoea scale rating of 3-4 and 60% maximum heart rate. • Resistance Training: Exercises at 60-120% of one repetition maximum (1-RM). 4. Respiratory Physiotherapy: • Methods: Diaphragmatic breathing, pursed-lip breathing, ergonomic techniques, and self-drainage methods for bronchial secretion clearance, lasting 15 minutes at the end of each session. 5. Dietary Counselling: • Assessment: The specialized dietitian of the PR will evaluate dietary habits using a one-week food diary. • Body Composition Analysis: Bioelectrical Impedance Analysis will be used to inform personalized dietary plans addressing issues like cachexia or obesity. • Goals: Encourage balanced diets that minimize metabolic CO 2 production, reducing respiratory strain, and promote long-term healthy eating habits (Spruit, 2014). 6. Psychological Counselling: • Therapy Sessions: The specialized psychologist of the PR will provide weekly face-to-face counselling using Cognitive Behavioural Therapy (CBT) for conditions such as anxiety and depression. • Medication Referral: Patients requiring pharmacotherapy will be referred to a psychiatrist. • Family Involvement: Family members will be trained to support disease management ( Yohannes, 2024 ). 7. Program Adherence Monitoring: • Tracking: The respiratory nurse of the PR programme will monitor attendance and participation, while each patient will maintain a personal checklist documenting his/her engagement in program activities. Upon completion of the program, the participants of the intervention group will engage in a six-month post-rehabilitation (maintenance) supervised exercise program (exercise at a lower frequency than the initial program and continuation of other above mentioned specialists’ support), conducted twice a week with the same healthcare personnel. Finally, for the remaining three months of the present study, the intervention group will follow the guidelines for COPD management strategies, provided in the informative material. Control group The control group will receive the standardized COPD therapy (drug management and regular follow-ups), as prescribed by the pulmonologist at the outpatient department and were instructed to follow the written informative material for COPD management strategies for all 12 months duration of the study. Outcome measures Primary outcomes: - FRAX ® score ( Kanis et al., 2008 ; Akyea et al., 2019 ) and the: - Bone Mineral Density (BMD) (Dual-energy X-ray absorptiometry-DXA) ( Sakurai-Iesato et al., 2017 ). Secondary outcomes: - BODE index [Body Mass Index-BMI ( World Health Organization, 2000 ), Airflow Obstruction (FEV 1 % pred), Dyspnoea Medical Research Council (MRC) dyspnoea scale ( Bestall et al., 1999 ), and exercise capacity (six Minute Walk Test-6MWT) ( Pessoa et al., 2014 , Celli et al., 2004 ). - COPD Assessment Test (CAT) ( Jones et al., 2009 ). - Nijmegen questionnaire – NQ for Dysfunctional Breathing screening ( Van Dixhoorn & Duivenvoorden, 1985 ; Daskalakis et al., 2025 ). - Borg dyspnoea scale ( Borg, 1982 ). There will be two measurements (0, 12 months). The SPIRIT schematic protocol of the study is presented in Table 1 . Table 1. Standard protocol items: recommendations for interventional trials of this study (SPIRIT). Enrolment Allocation Post Allocation Close-out TIME POINT -t1 0 t1 (month 1) t2 (month 2) t3 (month 3) t4 (month 12) ENROLLMENT: Eligibility screen x Informed consent x Demographic information x Allocation x Intervention PR programme ASSESMENTS Pulmonary function x Primary outcomes: FRAX score x x BMD x x Secondary outcomes: BODE index x x ○ BMI x x ○ FEV 1 x x ○ MRC x x ○ 6MWT x x CAT x x NQ x x Borg scale x x Primary outcome measures - The Fracture Risk Assessment Tool (FRAX ® ) is a valid tool that calculates the 10-year probability of a major osteoporotic fracture (MOF) (hip, spine, humerus and wrist fracture) and the 10-year probability of a hip fracture ( Kanis et al., 2018 ). The FRAX incorporates multiple risk factors to estimate the likelihood (% 10-year probability) of fractures, accounting for variables like age, sex, body mass index (BMI), smoking status, and history of previous fractures, among others. The tool has been validated for general population ( Kanis et al., 2008 ) and is available in 31 languages ( Kanis et al., 2018 ). It has been validated in COPD population ( Akyea et al., 2019 ). In the present study, the 10-year probability of suffering major osteoporotic and hip fractures was calculated using the total hip neck BMD and the Geek version of the fracture risk assessment tool (FRAX ® ) ( https://frax.shef.ac.uk/FRAX/tool.aspx?country=49 ). The accuracy of FRAX in COPD population to detect the fracture risk is high (76.1%, 95% CI 74.9% to 77.2%). The sensitivity of the risk scores for any Major Osteoporotic Fractures (MOF) (using >20% risk as cut-off ) was found to be 25.4%. The sensitivity of the risk scores for hip fracture (using >3% cut-off ) was found to be 78.1% ( Akyea et al., 2019 ). - The Dual-energy X-ray absorptiometry (DEXA) is the gold standard tool for assessing BMD and diagnosing osteoporosis, and it also plays a role in the FRAX ® tool algorithm ( Kanis et al., 2008 ). This method uses low-dose X-rays to measure the density of bones (gr/cm 2 ), with results often presented in terms of a T-score that indicates how much the participant’s bone density deviates from the average for their age and gender. In general population, DEXA’s precision errors are 2-3% for repeated measurements at the spine, 3-5% at the hip and <2% for total body calcium determinations ( WHO, 1994 ). DEXA procedure has been validated in COPD population ( Sakurai-Iesato et al., 2017 ). Specifically, the BMD has shown negative correlation with CAT score (r = -0.31, p = 0.03) and the severity of emphysema (LAV%) (r = -0.34, p = 0.02), and positive correlations with the body mass index (BMI) (r = 0.37, p < 0.01) and FEV 1 % (r = 0.51, p < 0.001) ( Sakurai-Iesato et al., 2017 ). In the present study, all DEXA measurements will be conducted in the hip neck of non-dominant side, using the same well-functioning and calibrated DEXA machine (Hologic QDR Explorer, SN: 90785). - The BODE is a multidimensional tool that evaluates the severity of COPD based on four factors: BMI, airflow obstruction (FEV 1 ), dyspnoea (MRC Dyspnoea Scale), and exercise capacity (6-MWT). The BODE index is a powerful predictor of mortality in COPD patients and will be utilized to assess the clinical severity of COPD for the participants. Patients with elevated BODE scores have faced a higher mortality risk. Specifically, the hazard ratio for death from any cause increased by 1.34 for each one-point rise in the BODE score (95% confidence interval, 1.26 to 1.42; P < 0.001). Similarly, the hazard ratio for death from respiratory causes was found to be 1.62 (95% CI, 1.48-1.77; p < 0.001) ( Celli et al., 2004 ). In the present study the online BODE calculation will be used ( https://www.mdcalc.com/calc/3916/bode-index-copd-survival ). ○ Body Mass Index (BMI) is a widely used method to assess body fat based on an individual’s weight and height. It is calculated by dividing a person’s weight in kilograms by the square of their height in meters (kg/m 2 ). According to the World Health Organization ( WHO, 2000 ), adults are classified as follows, based on BMI: underweight (<18.50 kg/m 2 ), normal weight (18.50–24.99 kg/m 2 ), overweight (25.00–29.99 kg/m 2 ), and obese (≥30.00 kg/m 2 ). In COPD, different BMI categories are linked to distinct clinical manifestations and comorbidity patterns of the disease. Specifically, patients with BMI 30 kg/m 2 have shown a higher prevalence of systemic hypertension, hyperlipidemia, sleep apnea, diabetes mellitus, chronic renal failure, congestive heart failure, gout, venous insufficiency, degenerative joint disease, and pulmonary hypertension ( Divo et al., 2014 ). For the present study, BMI will be measured using a manual hospital weight scale and a stadiometer for height measurement. ○ The Spirolab III spirometer (Medical International Research, Inc. USA) will be used to measure lung function. For the purposes of the present study, FEV 1 % of the predicted value was measured as an indicator of airway obstruction, based on the norms of Knudson, Slatin, Lebowitz and Burrows (1976) . For the validity and reliability of the measurements: a) the device was calibrated before each evaluation with the help of a flow-volume syringe, b) each attempt by the test subjects lasted at least 6 seconds, at least three acceptable attempts were performed and the best was recorded, and c) the test subjects did not consume short-acting β2-agonists at least 4 hours before the test ( Halpin et al., 2021 ). ○ The MRC scale ( Bestall et al. 1999 ; Stenton, 2008 ): estimates. the disability related to shortness of breath, by determining the occurrence of shortness of breath when it should not occur or by quantifying the limitations in exercise. The MRC scale consists of 5 suggestions-items with a score of each proposal ranging from 1 (no shortness of breath) to 5 (very high shortness of breath). The MRC scale has shown high reliability (98% agreement rate among observers) and validity (convergent validity: high correlation with other dyspnoea scales, and divergent validity: high correlation with lung function, 6MWT, MRC and shuttle distance, SGRQ and CRQ scores, mood state and EADL) ( Mahler & Wells, 1988 ; Dyspnoea, 1999 ; Bestall et al., 1999 ). ○ The 6-minute Walking Test (6MWT) ( Solway et al., 2001 ) is a standardized test, best tolerated by participants, and representative of daily activities. It has been tested in many clinical populations for its validity and reliability ( Solway et al., 2001 ). The 6MWT has been widely used to assess functional exercise capacity in patients with COPD ( Pessoa et al., 2014 ). It is a simple and practical test that requires only a 30-meter hallway and does not need specialized exercise equipment or technician training ( ATS, 2002 ). A threshold distance of 350 meters is commonly used; patients who walk less than 350 meters have shown a 66% mortality rate, while those who walk more than 350 meters have a mortality rate of 30.6% ( Cote et al., 2008 ). Furthermore, mortality risk increases with every 100-meter decrease in walking distance. A change in 6-minute walk distance is considered clinically significant when a patient improves by at least 50 meters following an intervention ( ATS, 2002 ). In the present study, the 6MWT will be conducted according to the ATS (2002) guidelines , which have standardized instructions and procedures and corridor length. The participants will be instructed to walk up and down a 30-meter indoor straight corridor as many times as they can, without running. The heart rate and the saturation of oxygen will be monitored throughout the test with a pulse oximeter (Beurer PO45, Ulm, Germany). Dyspnoea and fatigue levels will be recorded before and after the test with the Borg Scale. The total distance walked will be recorded in meters at the end of six minutes. The 6MWT has demonstrated excellent intra- and inter-rater reliability (ICC = 0.98 ( Hansen et al., 2018 ) and validity ( Cote et al., 2008 ) in patients with COPD. - The COPD Assessment Test (CAT) is a validated tool for measuring the impact of COPD on a patient’s quality of life and assessing the severity of symptoms. It is consisted of eight ( Celli et al., 2004 ) items that assess various dimensions of the disease, including cough, phlegm production, breathlessness, and overall activity levels ( Jones et al., 2009 ). The CAT has been firstly validated in the USA, Europe and China and later translated and validated in more than 100 languages other than English. The CAT score ranges from 0 to 40 and had been categorized into four severity bands: Low Impact (CAT score 1 to 10), Medium Impact (11 to 20), High Impact (21 to 30), Very High Impact (31 to 40). In COPD patients, CAT has also shown convergent validity (correlation with SGRQ: r = 0.16, p = 0.005) ( Jones et al., 2011 ) and excellent internal consistency (Cronbach’s alpha = 0.88) as well as test re-test reliability (ICC = 0.80) in stable COPD patients ( Jones et al., 2009 ). In present study, the official Greek translation of CAT will be used and a permission to use has been obtained from the copyright holder (Mapi Research Trust special terms No110747). - The Nijmegen Questionnaire (NQ) is a validated tool for screening hyperventilation in the general population ( van Dixhoorn & Duivenvoorden, 1982 ), asthma ( Grammatopoulou et al., 2014 ), and dysfunctional breathing (DB) in individuals with COPD ( Daskalakis et al., 2025 ). The NQ consists of 16 items related to DB symptoms, each rated on a 5-point Likert scale ranging from ‘never’ (0) to ‘very often’ ( ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories, 2002 ), yielding a maximum total score of 64. Cut-off scores are set at 23 points for the general population and >17 points for individuals with asthma ( Grammatopoulou et al., 2014 ). The items are organized into three dimensions: shortness of breath, peripheral tetany, and central tetany. The NQ has recently been validated in a Greek COPD population. A three-factor structure comprising all 16 items was extracted using principal component analysis, explaining 74.70% of the variance, a high internal consistency (Cronbach’s alpha = 0.94) and a cut-off score of >23 with 95.92% sensitivity and 94.29% specificity ( Daskalakis et al., 2025 ). In the present study, the Greek version of the NQ ( Grammatopoulou et al., 2014 ) will be used. - The Modified Borg Scale is a simple, valid, and non-proprietary tool widely used in both clinical and research settings to assess the symptom of shortness of breath (dyspnoea) ( Borg, 1982 ). The scale ranges from 0 (no dyspnoea) to 10 (maximum or extreme dyspnoea). As a subjective tool, it captures the patient’s perception of breathlessness, making it particularly useful for evaluating respiratory function in conditions such as COPD ( Neder et al., 2011 ). The Borg assesses breathlessness at rest and during exercise. The minimally clinically important difference (MCID) is 1 point ( Ries, 2005 ). A cut-off score of 3 points has been proposed as the threshold, at which dynamic hyperinflation may be initiated in patients with COPD ( de Freitas et al., 2023 ). The Borg scale has shown also divergent validity in COPD patients (correlations with PEFR (r = -0.42, p < 0.001) ( Kendrick et al., 2000 ). Additionally, exertional dyspnoea measured using the Borg Scale after the 6-minute walk distance test (6-MWDT) shows a significant correlation with ΔIC (change in inspiratory capacity) (r = -0.49, p < 0.00001) ( Marin et al., 2001 ). During maximal exercise testing in COPD patients, the within-subject coefficient of variation (CV) for the Borg score was found to be 13.9% ± 9.0% (range: 6% to 31%), which did not differ significantly from physiological parameters such as minute ventilation (VE): 8.2% ± 4.1% (range: 4% to 15%) and oxygen uptake (VO 2 ): 5.2% ± 3.4% (range: 1% to 10%) ( Mador et al., 1995 ). In the present study, the Greek version of the Modified Borg Scale will be used to assess the sensation of breathlessness. Anticipated dates of trial commencement and completion The study is in progress. Data collection methods Data on outcomes before and after the intervention will be meticulously collected by the above-mentioned research colleagues (a pneumonologist, a physiotherapist and a radiologist), sent to the secretariat and forwarded to the statistician. Throughout the study, the supervisor Professor of the main researcher (PhD candidate at the Physiotherapy dept of the University of West Attica-UNIWA) will oversee the data collection process. Data management Evaluation data will be retrieved from a predefined spreadsheet containing baseline characteristics and securely stored in a protected database by the supervisor. Physical copies of evaluation forms signed informed consent documents, and other non-electronic records will be securely maintained within the study setting. To safeguard data integrity, monthly backups of all entries will be performed until the trial concludes. Once the study is completed, the finalized dataset will be forwarded to the statistician for analysis. Statistical analysis The Statistical Package for the Social Sciences (IBM Corp., SPSS, version 29, Armonk, NY, USA) will be used for the purposes of the study. The reliability of repeated measurements (test-retest reliability) will be tested, with the intraclass correlation coefficient (ICC), to examine the degree of association across the assessments (0 and 12 months) for the entire sample ( Thomas & Nelson, 1996 ). The interaction between the intervention (intervention group, control group) and time (0, 12 months) for each variable will be assessed with 2x2 ANOVA repeated measures with Bonferroni correction. Levene’s test will be utilized to assess the homogeneity of variance. T-test parameter estimates will be conducted to evaluate differences between the intervention and control groups at each time point. Eta-squared will be used to express the total variance explained by the interaction between intervention and time. The statistical significance level will be set at 0.05. Monitoring Data monitoring A data monitoring committee consisted of members from the UNIWA Physiotherapy Department will periodically observe the collected data in predetermined time periods. Harms Experienced clinical staff will conduct the assessments as well as the PR intervention. Any adverse event will be immediately reported to the UNIWA committee throughout the trial. Auditing The experiment will be evaluated monthly. If any deviation or alteration is observed from the protocol, it will be recorded and addressed accordingly. Ethics and dissemination Research ethics approval The Ethics Committee of UNIWA approved the present study under protocol no. 3094-06/04/2021. The ethics approval was obtained on 6th April 2021 from the University of West Attica. The study fully adheres to the Helsinki Declaration’s “Ethical Principles of Medical Research Involving Human Subjects.” Any protocol modifications will be promptly disclosed to the Ethics Committee. The trial is registered at the ANZCTR database with identification number ACTRN12623001282673. Protocol amendments The study has already been modified and accepted in accordance with the suggestions from the UNIWA Ethics Committee. No further modifications are permitted. Consent Before involvement in the study, all participants will sign a consent containing a short form of the protocol and a confidentiality statement. The written informed consent, which must be signed by the main researcher, the participant, and two witnesses, will also grant permission for the publication of study results, with the clear understanding that participants may withdraw from the study at any time without consequence. Confidentiality At the time of randomization, every participant will get a code number that will secure blinding and confidentiality of the participants. A confidentiality statement will be included in the consent form and will be signed accordingly. Participants’ confidentiality will be maintained throughout the study. No personal information will be disclosed. Access to data The primary researcher, the supervisor and the statistician will have access to the data. Ancillary and post-trial care The entire procedure and the study protocol will be overseen by professionals and the physiotherapy dept of the UNIWA committee. After the trial, participants will be monitored for approximately four weeks to address any potential harms or issues that will arise, and they will be able to contact the main researcher. Discussion It is well established that Pulmonary Rehabilitation-PR programs improve physical condition, functional ability (6MWDT) ( Spruit et al., 2013 ; Dyspnea, 1999 ), and health-related quality of life (SF-36, SGRQ) ( Schroff et al., 2017 ). Patients with COPD undergoing PR showed significant improvements in dyspnoea, fatigue, emotional function, and mastery in COPD patients ( McCarthy et al., 2015 ). PR also seems to alleviate symptoms of dyspnoea and fatigue (Borg scale) ( Casaburi et al., 1991 ) and reduce the risk of future COPD exacerbations, as evidenced by a lower rate of rehospitalization at 1-year follow-up ( Kjærgaard et al., 2020 ). Mineo et al., (2005) found that PR is less effective for bone density in COPD patients compared to lung volume reduction surgery (LVRS). The researchers proposed that surgical correction of chest abnormalities due to COPD may reduce the hypermetabolic-catabolic state of COPD patients and positively influence bone metabolism, an effect not observed in the PR group in their study. Conversely, Li et al. (2022) identified PR as a crucial component in osteoporosis treatment. Additionally, exercise improves the general condition and increases bone mineral density (BMD) in COPD patients ( Sadeghi et al., 2021 ). Aerobic exercise is general noted as a key stone on bone quality, improving bone mineral density in patients with COPD ( Abd El-Kader et al., 2016 ), while resistance training is widely documented for the positive effect on both muscle and bone tissue ( Lippi et al., 2022 ). The later evidence follows a well-established connection between muscles and bones, which shares common genetic, molecular and mechanical pathways. Indeed, systematic inflammation and cytokines increase muscle and bone catabolism whether, muscle activation triggers anabolic activity in adjacent bones ( Zhang & Sun, 2021 ). As a result, muscle dysfunction in COPD is linked to osteoporosis and sarcopenia, requiring common measures to address both. Pulmonary Rehabilitation is a proposed therapy for sarcopenia in COPD and expected that it will have a positive effect on bone quality ( Kim et al., 2019 ) and maybe on fragility fracture risk (FRAX score). With reference to the known literature, up to now no study has investigated the effect of PR on FRAX score in COPD patients. The present study will be the first known randomized controlled trial (RCT) to examine the effectiveness of Pulmonary Rehabilitation on the FRAX score in the COPD population. This clinical population has been limitedly investigated for the systematic manifestation of COPD in bone health, despite the increasing comorbidity and mortality of fragility fractures in COPD patients. The study aims to enhance research towards patients with COPD who are at risk of bone fractures, improve their functionality and daily life, and provide further evidence for the necessity of managing the systematic manifestation of the disease. This protocol uses randomization, concealed allocation, and valid tools for the COPD people, and examiner’s blinding. Despite the rigorous design, recruiting participants from a single hospital limits external validity. Study status The present study is in progress. Study dissemination The findings of this study will be presented at an international conference and published in an indexed journal. Conclusions This RCT will be novel, as, for the first time, it will provide evidence of the effect of Pulmonary Rehabilitation on the FRAX score in individuals with COPD. Pulmonary Rehabilitation is the cornerstone in COPD long-term management and its potential effect on fragility fracture risk will be an added value. Furthermore, by identifying patients at risk, the initiation of therapy could help prevent fragility fractures. Data availability Underlying data This article does not have associated data. Reporting guidelines Figshare: SPIRIT checklist for ‘The effect of a Pulmonary Rehabilitation programme on 10-year risk of fragile fracture (FRAX ® score) in patients with COPD: protocol for a randomised controlled trial’, https://doi.org/10.6084/m9.figshare.29271077.v2 ( Daskalakis, 2025 ). Data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0). References Abd El-Kader SM, Al-Jiffri OH, Ashmawy EM, et al. : Treadmill walking exercise modulates bone mineral status and inflammatory cytokines in obese asthmatic patients with long term intake of corticosteroids. Afr. Health Sci. 2016; 16 (3): 798–808. PubMed Abstract | Publisher Full Text | Free Full Text Agustí A, Celli BR, Criner GJ, et al. : Global Initiative for Chronic Obstructive Lung Disease 2023 Report: GOLD Executive Summary. Am. J. Respir. Crit. Care Med. 2023; 207 (7): 819–837. PubMed Abstract | Publisher Full Text | Free Full Text Akyea RK, McKeever TM, Gibson J, et al. : Predicting fracture risk in patients with chronic obstructive pulmonary disease: a UK-based population-based cohort study. BMJ Open. 2019; 9 (4): e024951. Published 2019 Apr 3. PubMed Abstract | Publisher Full Text | Free Full Text ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories: ATS statement: guidelines for the six-minute walk test [published correction appears in Am J Respir Crit Care Med. 2016 May 15;193(10):1185. doi: 10.1164/rccm.19310erratum.]. Am. J. Respir. Crit. Care Med. 2002; 166 (1): 111–117. PubMed Abstract | Publisher Full Text Bestall JC, Paul EA, Garrod R, et al. : Usefulness of the Medical Research Council (MRC) dyspnoea scale as a measure of disability in patients with chronic obstructive pulmonary disease. Thorax. 1999; 54 (7): 581–586. PubMed Abstract | Publisher Full Text | Free Full Text Borg GA: Psychophysical bases of perceived exertion. Med. Sci. Sports Exerc. 1982; 14 (5): 377–381. PubMed Abstract | Publisher Full Text Casaburi R, Patessio A, Ioli F, et al. : Reductions in exercise lactic acidosis and ventilation as a result of exercise training in patients with obstructive lung disease. Am. Rev. Respir. Dis. 1991; 143 (1): 9–18. PubMed Abstract | Publisher Full Text Celli BR, Cote CG, Marin JM, et al. : The body-mass index, airflow obstruction, dyspnoea, and exercise capacity index in chronic obstructive pulmonary disease. N. Engl. J. Med. 2004; 350 (10): 1005–1012. Publisher Full Text Celli BR, Decramer M, Wedzicha JA, et al. : An official American Thoracic Society/European Respiratory Society statement: research questions in COPD. Eur. Respir. Rev. 2015; 24 (136): 159–172. PubMed Abstract | Publisher Full Text | Free Full Text Celli BR: MacNee W; ATS/ERS Task Force. Standards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper [published correction appears in Eur Respir J. 2006 Jan;27(1):242]. Eur. Respir. J. 2004; 23 (6): 932–946. PubMed Abstract | Publisher Full Text Cote CG, Casanova C, Marín JM, et al. : Validation and comparison of reference equations for the 6-min walk distance test. Eur. Respir. J. 2008; 31 (3): 571–578. PubMed Abstract | Publisher Full Text Daskalakis A, Patsaki I, Haniotou A, et al. : Dysfunctional Breathing, in COPD: A Validation Study. J. Clin. Med. 2025; 14 (7): 2353. Published 2025 Mar 29. PubMed Abstract | Publisher Full Text | Free Full Text Daskalakis A: The effect of a Pulmonary Rehabilitation programme on 10-year risk of fragile fracture (FRAX ® score) in patients with COPD: protocol for a randomised controlled trial. figshare. 2025. Publisher Full Text de Freitas APVM , Belo LF, Martinez L, et al. : Use of the Borg dyspnoea scale to identify dynamic hyperinflation during the 6-minute walking test in individuals with moderate-severe COPD: A pilot study. Pulmonology. 2023; 29 (4): 335–337. PubMed Abstract | Publisher Full Text Dennison EM, Compston JE, Flahive J, et al. : Effect of co-morbidities on fracture risk: findings from the Global Longitudinal Study of Osteoporosis in Women (GLOW). Bone. 2012; 50 (6): 1288–1293. PubMed Abstract | Publisher Full Text | Free Full Text Divo MJ, Cabrera C, Casanova C, et al. : Comorbidity Distribution, Clinical Expression and Survival in COPD Patients with Different Body Mass Index. Chronic Obstr. Pulm. Dis. 2014; 1 (2): 229–238. Published 2014 Sep 25. PubMed Abstract | Publisher Full Text | Free Full Text Dyspnoea.: Mechanisms, assessment, and management: a consensus statement. American Thoracic Society (ATS). Am. J. Respir. Crit. Care Med. 1999; 159 (1): 321–340. Publisher Full Text Graat-Verboom L, van den Borne BE , Smeenk FW, et al. : Osteoporosis in COPD outpatients based on bone mineral density and vertebral fractures. J. Bone Miner. Res. 2011; 26 (3): 561–568. PubMed Abstract | Publisher Full Text Grammatopoulou EP, Skordilis EK, Georgoudis G, et al. : Hyperventilation in asthma: a validation study of the Nijmegen Questionnaire--NQ. J. Asthma. 2014; 51 (8): 839–846. PubMed Abstract | Publisher Full Text Halpin DMG, Criner GJ, Papi A, et al. : Global Initiative for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease. The 2020 GOLD Science Committee Report on COVID-19 and Chronic Obstructive Pulmonary Disease. Am. J. Respir. Crit. Care Med. 2021; 203 (1): 24–36. PubMed Abstract | Publisher Full Text | Free Full Text Hansen H, Beyer N, Frølich A, et al. : Intra- and inter-rater reproducibility of the 6-minute walk test and the 30-second sit-to-stand test in patients with severe and very severe COPD. Int. J. Chron. Obstruct. Pulmon. Dis. 2018; 13 : 3447–3457. Published 2018 Oct 18. PubMed Abstract | Publisher Full Text | Free Full Text Jones PW, Harding G, Berry P, et al. : Development and first validation of the COPD Assessment Test. Eur. Respir. J. 2009; 34 (3): 648–654. Publisher Full Text Jones PW, Tabberer M, Chen WH: Creating scenarios of the impact of COPD and their relationship to COPD Assessment Test (CAT™) scores. BMC Pulm. Med. 2011; 11 : 42. Published 2011 Aug 11. PubMed Abstract | Publisher Full Text | Free Full Text Kanis JA, Johansson H, Harvey NC, et al. : A brief history of FRAX. Arch. Osteoporos. 2018; 13 (1): 118. Published 2018 Oct 31. PubMed Abstract | Publisher Full Text | Free Full Text Kanis JA, McCloskey EV, Johansson H, et al. : Case finding for the management of osteoporosis with FRAX--assessment and intervention thresholds for the UK [published correction appears in Osteoporos Int. 2009 Mar;20(3):499-502]. Osteoporos Int. 2008; 19 (10): 1395–1408. PubMed Abstract | Publisher Full Text Kendrick KR, Baxi SC, Smith RM: Usefulness of the modified 0-10 Borg scale in assessing the degree of dyspnoea in patients with COPD and asthma. J. Emerg. Nurs. 2000; 26 (3): 216–222. PubMed Abstract | Publisher Full Text Kim SH, Shin MJ, Shin YB, et al. : Sarcopenia Associated with Chronic Obstructive Pulmonary Disease. J. Bone Metab. 2019; 26 (2): 65–74. PubMed Abstract | Publisher Full Text | Free Full Text Kjærgaard J, Juhl CB, Lange P, et al. : Adherence to early pulmonary rehabilitation after COPD exacerbation and risk of hospital readmission: a secondary analysis of the COPD-EXA-REHAB study. BMJ Open Respir. Res. 2020; 7 (1): e000582. PubMed Abstract | Publisher Full Text | Free Full Text Knudson RJ, Slatin RC, Lebowitz MD, et al. : The maximal expiratory flow-volume curve. Normal standards, variability, and effects of age. Am. Rev. Respir. Dis. 1976; 113 (5): 587–600. PubMed Abstract | Publisher Full Text Li Y, Gao H, Zhao L, et al. : Osteoporosis in COPD patients: Risk factors and pulmonary rehabilitation. Clin. Respir. J. 2022; 16 (7): 487–496. PubMed Abstract | Publisher Full Text | Free Full Text Lippi L, Folli A, Curci C, et al. : Osteosarcopenia in Patients with Chronic Obstructive Pulmonary Diseases: Which Pathophysiologic Implications for Rehabilitation? Int. J. Environ. Res. Public Health. 2022; 19 (21): 14314. Published 2022 Nov 2. PubMed Abstract | Publisher Full Text | Free Full Text Lyritis GP, Rizou S, Galanos A, et al. : Incidence of hip fractures in Greece during a 30-year period: 1977-2007. Osteoporos Int. 2013; 24 (5): 1579–1585. PubMed Abstract | Publisher Full Text Mador MJ, Rodis A, Magalang UJ: Reproducibility of Borg scale measurements of dyspnoea during exercise in patients with COPD. Chest. 1995; 107 (6): 1590–1597. PubMed Abstract | Publisher Full Text Mahler DA, Wells CK: Evaluation of clinical methods for rating dyspnoea. Chest. 1988; 93 (3): 580–586. Publisher Full Text Marin JM, Carrizo SJ, Gascon M, et al. : Inspiratory capacity, dynamic hyperinflation, breathlessness, and exercise performance during the 6-minute-walk test in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 2001; 163 (6): 1395–1399. PubMed Abstract | Publisher Full Text McCarthy B, Casey D, Devane D, et al. : Pulmonary rehabilitation for chronic obstructive pulmonary disease. Cochrane Database Syst. Rev. 2015; 2015 (2): CD003793. Published 2015 Feb 23. PubMed Abstract | Publisher Full Text | Free Full Text Mineo TC, Ambrogi V, Mineo D, et al. : Bone mineral density improvement after lung volume reduction surgery for severe emphysema. Chest. 2005; 127 (6): 1960–1966. PubMed Abstract | Publisher Full Text Neder JA, et al. : Dyspnoea scales: Psychometric properties of the Borg Dyspnoea scale for individuals with chronic respiratory diseases. Eur. Respir. J. 2011; 38 (4): 901–909. Obesity: preventing and managing the global epidemic. Report of a WHO consultation. World Health Organ. Tech. Rep. Ser. 2000; 894 : i–253. PubMed Abstract Ogura-Tomomatsu H, Asano K, Tomomatsu K, et al. : Predictors of osteoporosis and vertebral fractures in patients presenting with moderate-to-severe chronic obstructive lung disease. COPD. 2012; 9 (4): 332–337. PubMed Abstract | Publisher Full Text Parker CM, Voduc N, Aaron SD, et al. : Physiological changes during symptom recovery from moderate exacerbations of COPD. Eur. Respir. J. 2005; 26 (3): 420–428. PubMed Abstract | Publisher Full Text Pessoa BV, Arcuri JF, Labadessa IG, et al. : Validity of the six-minute step test of free cadence in patients with chronic obstructive pulmonary disease. Braz. J. Phys. Ther. 2014; 18 (3): 228–236. PubMed Abstract | Publisher Full Text | Free Full Text Ries AL: Minimally clinically important difference for the UCSD Shortness of Breath Questionnaire, Borg Scale, and Visual Analog Scale. COPD. 2005; 2 (1): 105–110. PubMed Abstract | Publisher Full Text Sadeghi H, Jehu DA, Daneshjoo A, et al. : Effects of 8 Weeks of Balance Training, Virtual Reality Training, and Combined Exercise on Lower Limb Muscle Strength, Balance, and Functional Mobility Among Older Men: A Randomized Controlled Trial. Sports Health. 2021; 13 (6): 606–612. PubMed Abstract | Publisher Full Text | Free Full Text Sakurai-Iesato Y, Kawata N, Tada Y, et al. : The Relationship of Bone Mineral Density in Men with Chronic Obstructive Pulmonary Disease Classified According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Combined Chronic Obstructive Pulmonary Disease (COPD) Assessment System. Intern. Med. 2017; 56 (14): 1781–1790. PubMed Abstract | Publisher Full Text | Free Full Text Scanlon PD, Connett JE, Wise RA, et al. : Loss of bone density with inhaled triamcinolone in Lung Health Study II. Am. J. Respir. Crit. Care Med. 2004; 170 (12): 1302–1309. PubMed Abstract | Publisher Full Text Sernbo I, Johnell O: Consequences of a hip fracture: a prospective study over 1 year. Osteoporos Int. 1993; 3 (3): 148–153. Publisher Full Text Shehab MAEK, Osama HAJ: Influence of Aerobic Exercise Training on Bone Mineral Status among Chronic Obstructive Pulmonary Disease Patients. Int. J. Pul. Res. Sci. 2017; 2 (1): 555577. Publisher Full Text Silva DR, Coelho AC, Dumke A, et al. : Osteoporosis prevalence and associated factors in patients with COPD: a cross-sectional study. Respir. Care. 2011; 56 (7): 961–968. Publisher Full Text Singh D, Agusti A, Anzueto A, et al. : Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease: the GOLD science committee report 2019. Eur. Respir. J. 2019; 53 (5): 1900164. Published 2019 May 18. Publisher Full Text Mohsen SM, Chakroun S, Chaker A, et al. : Body mass index in COPD: what relationship? Eur. Respir. J. 56 (suppl 64). Publisher Full Text Schroff P, Hitchcock J, Schumann C, et al. : Pulmonary Rehabilitation Improves Outcomes in Chronic Obstructive Pulmonary Disease Independent of Disease Burden. Ann. Am. Thorac. Soc. 2017; 14 (1):26–32. PubMed Abstract | Publisher Full Text | Free Full Text Solway S, Brooks D, Lacasse Y, et al. : A qualitative systematic overview of the measurement properties of functional walk tests used in the cardiorespiratory domain. Chest. 2001; 119 (1): 256–270. PubMed Abstract | Publisher Full Text Spruit MA, Singh SJ, Garvey C, et al. : An official American Thoracic Society/European Respiratory Society statement: key concepts and advances in pulmonary rehabilitation [published correction appears in Am J Respir Crit Care Med. 2014 Jun 15;189(12):1570]. Am. J. Respir. Crit. Care Med. 2013; 188 (8): e13–e64. PubMed Abstract | Publisher Full Text Stenton C: The MRC breathlessness scale. Occup. Med. (Lond.). 2008; 58 (3): 226–227. Publisher Full Text Thomas JR, Nelson JK:Research Methods in Physical Activity.Human Kinetics.1996. ISBN:0880114819, 9780880114813. van Dixhoorn J , Duivenvoorden HJ: The Nijmegen Questionnaire for assessment of dysfunctional breathing. Psychosom. Med. 1982; 44 (2): 181–184. van Dixhoorn J , Duivenvoorden HJ: Efficacy of Nijmegen Questionnaire in recognition of the hyperventilation syndrome. J. Psychosom. Res. 1985; 29 (2): 199–206. PubMed Abstract | Publisher Full Text WHO: Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Report of a WHO study group. WHO Technical Report Series 843. Geneva; 1994. Yohannes AM: Psychosocial Support in Pulmonary Rehabilitation. Respir. Care. 2024; 69 (6): 664–677. Published 2024 May 28. PubMed Abstract | Publisher Full Text | Free Full Text Zhang L, Sun Y: Muscle-Bone Crosstalk in Chronic Obstructive Pulmonary Disease. Front. Endocrinol (Lausanne). 2021; 12 : 724911. Published 2021 Sep 28. PubMed Abstract | Publisher Full Text | Free Full Text Comments on this article Comments (0) Version 1 VERSION 1 PUBLISHED 04 Sep 2025 ADD YOUR COMMENT Comment Author details Author details 1 Laboratory of Advanced Physiotherapy, Department of Physiotherapy, University of West Attica, Egaleo, 122 43, Greece 2 Department of Orthopaedic Surgery, General Oncologic Hospital ‘’St. Anargyroi’’, Kifisia, Greece 3 School of Physical Education and Sport Sciences, National and Kapodistrian University of Athens, Dafni, Greece A. Daskalakis Roles: Conceptualization, Investigation, Writing – Original Draft Preparation I. Patsaki Roles: Methodology, Visualization E. Skordilis Roles: Data Curation, Methodology A. Evangelodimou Roles: Visualization E. Grammatopoulou Roles: Conceptualization, Methodology, Supervision, Writing – Review & Editing Competing interests No competing interests were disclosed. Grant information The author(s) declared that no grants were involved in supporting this work. Article Versions (1) version 1 Published: 04 Sep 2025, 14:874 https://doi.org/10.12688/f1000research.166015.1 Copyright © 2025 Daskalakis A et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Download Export To Sciwheel Bibtex EndNote ProCite Ref. Manager (RIS) Sente metrics Views Downloads F1000Research - - PubMed Central info_outline Data from PMC are received and updated monthly. - - Citations open_in_new 0 open_in_new 0 open_in_new SEE MORE DETAILS CITE how to cite this article Daskalakis A, Patsaki I, Skordilis E et al. The effect of a Pulmonary Rehabilitation programme on 10-year risk of fragile fracture (FRAX® score) in patients with COPD: protocol for a randomised controlled trial [version 1; peer review: awaiting peer review] . 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