The Effect of Aerobic Exercise on Bone Turnover Markers in Postmenopausal Patients

NCT06866561 | Completed

• 1 other identifier: HSBY-FTR-KND-01
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of the study was to evaluate the effect of light-moderate aerobic exercise on BMD in postmenopausal osteopenic women using bone formation-resorption markers. Participants were randomized into two groups as aerobic exercise and control groups and followed for 12 weeks. At the beginning and at the 12th week, bone formation-resorption markers including procollagen type 1 N-terminal propeptide (P1NP), cross-linked C-telopeptide of type 1 collagen (CTX), osteocalcin, malondialdehyde, non-bone-specific total alkaline phosphatase, 25(OH)D3 and oxidative markers such as parathyroid hormone (PTH) were evaluated in serum and whether there was a difference between the 2 groups.

Conditions

Postmenopausal Osteopenia

Keywords

postmenopausal osteoporosis; aerobic exercise; bone turnover markers

Outcome Measures

Primary Outcomes (4)

• The serum levef of Procollagen type 1 N-terminal propeptide (P1NP) (ng/ml)

  Bone turnover markers allow for the independent assessment of bone resorption and formation by measuring their concentrations in blood and urine. These markers provide early response evaluation posttreatment of osteoporosis compared to measuring BMD. The International Osteoporosis Foundation (IOF) and the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) recommend evaluating P1NP for bone formation activity and evaluating CTX-1 concentrations for bone resorption activity. In the study,the investigators chose walking exercise as an aerobic exercise that can be easily applied to people of all age groups and those with comorbidities. For these reasons, as the primary outcome of the study, the investigators aimed to measure the effects of aerobic exercise as a treatment method that can be recommended to the majority of patients, as bone turnover markers P1NP, CTX, OCN and total ALP respond quickly to treatment.

  From enrollment to the end of treatment at 12 weeks

• The serum levef of Cross-linked C-telopeptide of type I collagen (CTX) (ng/ml)

  During bone resorption, components of bone tissue are catabolized by osteoclasts. The released components are released into the bone microenvironment and secreted into the bloodstream. Some of them are also excreted in the urine. The level of C-telopeptide type 1 collagen(CTX)(ng/ml) can be measured in serum from these products. . The International Osteoporosis Foundation (IOF) and the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) recommend evaluating CTX-1 concentrations for bone resorption activity.

  From enrollment to the end of treatment at 12 weeks

• The serum levef of Osteocalcin(OCN) (ng/ml)

  During bone formation, osteoblasts fill the cavities with collagen-rich tissue and the molecules formed during their production are secreted into the blood. These products are; Type 1 procollagen N-terminal propeptide (P1NP), bone alkaline phosphatase, Osteocalcin, Type-1 procollagen C-terminal propeptide. These molecules also show bone formation activity.

  From enrollment to the end of treatment at 12 weeks

• The serum levef of nonbone-specific total alkaline phosphatase (ALP) (U/L)

  During bone formation, osteoblasts fill the cavities with collagen-rich tissue and the molecules formed during their production are secreted into the blood. These products are; Type 1 procollagen N-terminal propeptide (P1NP), bone alkaline phosphatase, Osteocalcin, Type-1 procollagen C-terminal propeptide. These molecules also show bone formation activity.

  From enrollment to the end of treatment at 12 weeks

Secondary Outcomes (8)

• Serum level of Malondİaldehyde(MDA) (ng/ml) as a Oxidative stress marker

  From enrollment to the end of treatment at 12 weeks

• Nottingham Health Profile questionnaire (NHP)

  From enrollment to the end of treatment at 12 weeks

• Visual analog scale (VAS)

  From enrollment to the end of treatment at 12 weeks

• 6-minute walk test (6MWT)

  From enrollment to the end of treatment at 12 weeks

• International Physical Activity Questionnaire (short form)(IPAQs)

  From enrollment to the end of treatment at 12 weeks

Study Arms (2)

exercise group

ACTIVE COMPARATOR

The exercise group participated in a supervised aerobic exercise program consisting of walking on a treadmill for 30 minutes per day, 3 days per week, at an intensity of 40-60% of maximal heart rate for 4 weeks.

Other: aerobic exercise; Other: cholecalciferol; Other: calcium carbonate

Control group

OTHER

The control group did not participate in any exercise program.

Other: cholecalciferol; Other: calcium carbonate

Interventions

aerobic exercise OTHER

The exercise group participated in a supervised aerobic exercise program consisting of walking on a treadmill for 30 minutes per day, 3 days per week, at an intensity of 40-60% of maximal heart rate for 4 weeks. Additionally, they were shown an exercise program at the initial assessment that included balance, posture, and endurance exercises using body weight and weights to be performed 3 days a week, with 3 sets of 10 repetitions. The control group did not participate in any exercise program.

exercise group

cholecalciferol OTHER

Participants were prescribed 2000 IU of vitamin D (cholecalciferol) daily for 12 weeks.

Control group; exercise group

calcium carbonate OTHER

Participants were prescribed 1200 mg of calcium carbonate daily for 12 weeks.

Control group; exercise group

Eligibility Criteria

• Age: 45 Years - 65 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Postmenopausal women from Türkiye aged 45-65 years,
• Bone mineral density (BMD) T-scores between -1 and -2.5 ( measured by dual-energy X-ray absorptiometry)

You may not qualify if:

• Vertebral compression fracture,
• A history of traumatic or nontraumatic fractures in the past year,
• Thyroid hormone disorders,
• Parathyroid hormone disorders,
• Liver function disorders,
• Kidney function disorders,
• Chronic heart failure,
• A history of malignancy,
• A history of rheumatological diseases,
• Corticosteroid use,
• Immunosuppressive drug use,
• Anticonvulsant and heparin use,
• Antiresorptive or anabolic agent treatments use
• Hormone replacement therapy use
• Those who could not complete sessions due to mechanical pain exacerbated during aerobic exercise on a treadmill (such as knee and hip osteoarthritis, back pain, etc)

Sponsors & Collaborators

• Bursa Yuksek Ihtisas Training and Research Hospital: lead

Study Sites (1)

Bursa Yüksek İhtisas Education and Research Hospital

Bursa, Yıldırım, 16310, Turkey (Türkiye)

Location

Related Publications (30)

• Zhou Q, Zhu L, Zhang D, Li N, Li Q, Dai P, Mao Y, Li X, Ma J, Huang S. Oxidative Stress-Related Biomarkers in Postmenopausal Osteoporosis: A Systematic Review and Meta-Analyses. Dis Markers. 2016;2016:7067984. doi: 10.1155/2016/7067984. Epub 2016 Aug 10.

  PMID: 27594735 RESULT

• Voulgaridou G, Papadopoulou SK, Detopoulou P, Tsoumana D, Giaginis C, Kondyli FS, Lymperaki E, Pritsa A. Vitamin D and Calcium in Osteoporosis, and the Role of Bone Turnover Markers: A Narrative Review of Recent Data from RCTs. Diseases. 2023 Feb 8;11(1):29. doi: 10.3390/diseases11010029.

  PMID: 36810543 RESULT

• Eastell R, Garnero P, Audebert C, Cahall DL. Reference intervals of bone turnover markers in healthy premenopausal women: results from a cross-sectional European study. Bone. 2012 May;50(5):1141-7. doi: 10.1016/j.bone.2012.02.003. Epub 2012 Feb 12.

  PMID: 22348982 RESULT

• Siwapituk W, Kitisomprayoonkul W. Bone turnover increases during supervised treadmill walking in Thai postmenopausal women. Osteoporos Sarcopenia. 2016 Mar;2(1):41-44. doi: 10.1016/j.afos.2016.02.005. Epub 2016 Mar 21.

  PMID: 30775467 RESULT

• FilipoviC TN, LazoviC MP, BackoviC AN, FilipoviC AN, IgnjatoviC AM, DimitrijeviC SS, GopCeviC KR. A 12-week exercise program improves functional status in postmenopausal osteoporotic women: randomized controlled study. Eur J Phys Rehabil Med. 2021 Feb;57(1):120-130. doi: 10.23736/S1973-9087.20.06149-3. Epub 2020 Sep 9.

  PMID: 32902207 RESULT

• Hettchen M, von Stengel S, Kohl M, Murphy MH, Shojaa M, Ghasemikaram M, Bragonzoni L, Benvenuti F, Ripamonti C, Benedetti MG, Julin M, Risto T, Kemmler W. Changes in Menopausal Risk Factors in Early Postmenopausal Osteopenic Women After 13 Months of High-Intensity Exercise: The Randomized Controlled ACTLIFE-RCT. Clin Interv Aging. 2021 Jan 11;16:83-96. doi: 10.2147/CIA.S283177. eCollection 2021.

  PMID: 33469276 RESULT

• Zhang L, Zheng YL, Wang R, Wang XQ, Zhang H. Exercise for osteoporosis: A literature review of pathology and mechanism. Front Immunol. 2022 Sep 9;13:1005665. doi: 10.3389/fimmu.2022.1005665. eCollection 2022.

  PMID: 36164342 RESULT

• Cariati I, Bonanni R, Onorato F, Mastrogregori A, Rossi D, Iundusi R, Gasbarra E, Tancredi V, Tarantino U. Role of Physical Activity in Bone-Muscle Crosstalk: Biological Aspects and Clinical Implications. J Funct Morphol Kinesiol. 2021 Jun 21;6(2):55. doi: 10.3390/jfmk6020055.

  PMID: 34205747 RESULT

• Shoback D, Rosen CJ, Black DM, Cheung AM, Murad MH, Eastell R. Pharmacological Management of Osteoporosis in Postmenopausal Women: An Endocrine Society Guideline Update. J Clin Endocrinol Metab. 2020 Mar 1;105(3):dgaa048. doi: 10.1210/clinem/dgaa048.

  PMID: 32068863 RESULT

• Eriksen EF. Treatment of osteopenia. Rev Endocr Metab Disord. 2012 Sep;13(3):209-23. doi: 10.1007/s11154-011-9187-z.

  PMID: 21710179 RESULT

• Kaplan AA. A simple and accurate method for prescribing plasma exchange. ASAIO Trans. 1990 Jul-Sep;36(3):M597-9.

  PMID: 2252761 RESULT

• Price DD, McGrath PA, Rafii A, Buckingham B. The validation of visual analogue scales as ratio scale measures for chronic and experimental pain. Pain. 1983 Sep;17(1):45-56. doi: 10.1016/0304-3959(83)90126-4.

  PMID: 6226917 RESULT

• Hunt SM, McEwen J, McKenna SP. Measuring health status: a new tool for clinicians and epidemiologists. J R Coll Gen Pract. 1985 Apr;35(273):185-8.

  PMID: 3989783 RESULT

• Kucukdeveci AA, McKenna SP, Kutlay S, Gursel Y, Whalley D, Arasil T. The development and psychometric assessment of the Turkish version of the Nottingham Health Profile. Int J Rehabil Res. 2000 Mar;23(1):31-8. doi: 10.1097/00004356-200023010-00004.

  PMID: 10826123 RESULT

• Yang S, Feskanich D, Willett WC, Eliassen AH, Wu T. Association between global biomarkers of oxidative stress and hip fracture in postmenopausal women: a prospective study. J Bone Miner Res. 2014 Dec;29(12):2577-83. doi: 10.1002/jbmr.2302.

  PMID: 24957524 RESULT

• Zhao F, Guo L, Wang X, Zhang Y. Correlation of oxidative stress-related biomarkers with postmenopausal osteoporosis: a systematic review and meta-analysis. Arch Osteoporos. 2021 Jan 5;16(1):4. doi: 10.1007/s11657-020-00854-w.

  PMID: 33400044 RESULT

• Marcucci G, Domazetovic V, Nediani C, Ruzzolini J, Favre C, Brandi ML. Oxidative Stress and Natural Antioxidants in Osteoporosis: Novel Preventive and Therapeutic Approaches. Antioxidants (Basel). 2023 Feb 3;12(2):373. doi: 10.3390/antiox12020373.

  PMID: 36829932 RESULT

• Vasikaran S, Cooper C, Eastell R, Griesmacher A, Morris HA, Trenti T, Kanis JA. International Osteoporosis Foundation and International Federation of Clinical Chemistry and Laboratory Medicine position on bone marker standards in osteoporosis. Clin Chem Lab Med. 2011 Aug;49(8):1271-1274. doi: 10.1515/CCLM.2011.602. Epub 2011 May 24.

  PMID: 21605012 RESULT

• Mohr M, Helge EW, Petersen LF, Lindenskov A, Weihe P, Mortensen J, Jorgensen NR, Krustrup P. Effects of soccer vs swim training on bone formation in sedentary middle-aged women. Eur J Appl Physiol. 2015 Dec;115(12):2671-9. doi: 10.1007/s00421-015-3231-8. Epub 2015 Aug 9.

  PMID: 26255288 RESULT

• Jain S, Camacho P. Use of bone turnover markers in the management of osteoporosis. Curr Opin Endocrinol Diabetes Obes. 2018 Dec;25(6):366-372. doi: 10.1097/MED.0000000000000446.

  PMID: 30299435 RESULT

• Lorentzon M, Branco J, Brandi ML, Bruyere O, Chapurlat R, Cooper C, Cortet B, Diez-Perez A, Ferrari S, Gasparik A, Herrmann M, Jorgensen NR, Kanis J, Kaufman JM, Laslop A, Locquet M, Matijevic R, McCloskey E, Minisola S, Pikner R, Reginster JY, Rizzoli R, Szulc P, Vlaskovska M, Cavalier E. Algorithm for the Use of Biochemical Markers of Bone Turnover in the Diagnosis, Assessment and Follow-Up of Treatment for Osteoporosis. Adv Ther. 2019 Oct;36(10):2811-2824. doi: 10.1007/s12325-019-01063-9. Epub 2019 Aug 22.

  PMID: 31440982 RESULT

• Greenblatt MB, Tsai JN, Wein MN. Bone Turnover Markers in the Diagnosis and Monitoring of Metabolic Bone Disease. Clin Chem. 2017 Feb;63(2):464-474. doi: 10.1373/clinchem.2016.259085. Epub 2016 Dec 9.

  PMID: 27940448 RESULT

• Eastell R, Szulc P. Use of bone turnover markers in postmenopausal osteoporosis. Lancet Diabetes Endocrinol. 2017 Nov;5(11):908-923. doi: 10.1016/S2213-8587(17)30184-5. Epub 2017 Jul 7.

  PMID: 28689768 RESULT

• Howe TE, Shea B, Dawson LJ, Downie F, Murray A, Ross C, Harbour RT, Caldwell LM, Creed G. Exercise for preventing and treating osteoporosis in postmenopausal women. Cochrane Database Syst Rev. 2011 Jul 6;2011(7):CD000333. doi: 10.1002/14651858.CD000333.pub2.

  PMID: 21735380 RESULT

• Todd JA, Robinson RJ. Osteoporosis and exercise. Postgrad Med J. 2003 Jun;79(932):320-3. doi: 10.1136/pmj.79.932.320.

  PMID: 12840119 RESULT

• Benedetti MG, Furlini G, Zati A, Letizia Mauro G. The Effectiveness of Physical Exercise on Bone Density in Osteoporotic Patients. Biomed Res Int. 2018 Dec 23;2018:4840531. doi: 10.1155/2018/4840531. eCollection 2018.

  PMID: 30671455 RESULT

• NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy. Osteoporosis prevention, diagnosis, and therapy. JAMA. 2001 Feb 14;285(6):785-95. doi: 10.1001/jama.285.6.785.

  PMID: 11176917 RESULT

• Tu KN, Lie JD, Wan CKV, Cameron M, Austel AG, Nguyen JK, Van K, Hyun D. Osteoporosis: A Review of Treatment Options. P T. 2018 Feb;43(2):92-104.

  PMID: 29386866 RESULT

• Consensus development conference: diagnosis, prophylaxis, and treatment of osteoporosis. Am J Med. 1993 Jun;94(6):646-50. doi: 10.1016/0002-9343(93)90218-e. No abstract available.

  PMID: 8506892 RESULT

• Deniz KN, Aksoy MK. "The effect of aerobic exercise on bone formation and resorption markers and the quality of life tests in postmenopausal osteopenic patients". BMC Musculoskelet Disord. 2025 Apr 21;26(1):385. doi: 10.1186/s12891-025-08578-z.

  PMID: 40259282 DERIVED

MeSH Terms

Conditions

Osteoporosis, Postmenopausal

Interventions

Exercise; Cholecalciferol; Calcium Carbonate

Condition Hierarchy (Ancestors)

Osteoporosis; Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids; Calcium Compounds; Inorganic Chemicals; Carbonates; Carbonic Acid; Carbon Compounds, Inorganic; Minerals

Study Officials

• Kübra Nur Deniz, M.D.

  Bursa Yuksek Ihtisas Training and Research Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Masking Details: Patients who met the inclusion criteria were randomized into 2 groups with the investigator blinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Patients who met the inclusion criteria were randomized into 2 groups with the investigator blinded. Participants in the exercise group were included in an aerobic exercise program, while patients in the control group were not included in any exercise program. All patients underwent serum marker assessment and clinical examination both at baseline and after 12 weeks of follow-up.

Study Record Dates

• First Submitted: February 20, 2025
• First Posted: March 10, 2025
• Study Start: November 15, 2022
• Primary Completion: November 15, 2023
• Study Completion: November 15, 2023
• Last Updated: March 12, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: The IPD and additional supporting information will be available for sharing 3 months after the study is published.

Locations

TU (1)