INTERACTION BETWEEN RESISTANCE TRAINING AND ESTROGEN SIGNALING PATHWAYS IN MAINTAINING BONE HOMEOSTASIS IN PERI-MENOPAUSAL WOMEN

Magdalena Grzechowiak; Aleksandra Anna Purpura; Zuzanna Przybylska; Wiktor Rolski; Paulina Michalska; Bartłomiej Przystaś; Mikołaj Piotr Hobot; Gabriela Patrycja Dobosz; Sebastian Podeszwa

doi:10.31435/ijitss.2(50).2026.5579

Authors

Magdalena Grzechowiak Medical University of Silesia in Katowice, Poland https://orcid.org/0009-0001-8486-0352
Aleksandra Anna Purpura Medical University of Silesia in Katowice, Poland https://orcid.org/0009-0006-3893-7730
Zuzanna Przybylska Medical University of Silesia in Katowice, Poland https://orcid.org/0009-0001-3329-4602
Wiktor Rolski Medical University of Silesia in Katowice, Poland https://orcid.org/0009-0005-1439-4842
Paulina Michalska Medical University of Silesia in Katowice, Poland https://orcid.org/0009-0007-4141-5906
Bartłomiej Przystaś Medical University of Silesia in Katowice, Poland https://orcid.org/0009-0009-6121-3839
Mikołaj Piotr Hobot Medical University of Silesia in Katowice, Poland https://orcid.org/0009-0001-2829-6005
Gabriela Patrycja Dobosz Medical University of Silesia in Katowice, Poland https://orcid.org/0009-0009-4012-9101
Sebastian Podeszwa Medical University of Silesia in Katowice, Poland https://orcid.org/0009-0000-2973-5324

DOI:

https://doi.org/10.31435/ijitss.2(50).2026.5579

Keywords:

Resistance Training, Bone Mineral Density, Estrogen, Peri-Menopause, Bone Homeostasis, Osteoporosis

Abstract

Background. The permanent cessation of ovarian activity during menopause leads to a significant decline in circulating estrogen, which is fundamental for maintaining bone homeostasis. This deficiency disrupts the cellular equilibrium by increasing RANKL expression and reducing osteoprotegerin (OPG) production, which enhances osteoclast-mediated bone resorption and accelerates the loss of bone mineral density (BMD). Trabecular bone, particularly in the lumbar spine, is most vulnerable to these early pathophysiological changes.

Aim. The goal of this review is to evaluate resistance training as a synergistic factor that provides the site-specific mechanical loading necessary to counteract accelerated bone loss and stimulate osteogenic adaptation during the menopausal transition.

Material and methods. A literature review was conducted using major scientific databases including PubMed, Scopus, Web of Science, and Google Scholar. The search included studies published up to 2025. Keywords related to resistance training, peri-menopausal women, bone mineral density (BMD), and estrogen deficiency were used. Original research articles, randomized controlled trials, systematic reviews, and meta-analyses investigating the effects of mechanical loading on skeletal health and bone homeostasis during the menopausal transition were included.

Results. Clinical findings demonstrate that progressive resistance training, particularly at moderate-to-high intensities (≥ 70–85% of one-repetition maximum), significantly increases BMD in the lumbar spine and femoral neck. These adaptations are mediated through mechanotransduction pathways, where mechanical strain activates the canonical Wnt/beta-catenin signaling pathway by inhibiting sclerostin (SOST), a negative regulator of bone formation. Estrogen and its receptors (ERα) appear to augment these pathways, suggesting a "mutual coupling" that enhances the skeletal response to exercise.

Conclusions. Resistance training is a scientifically supported, non-pharmacological pillar for enhancing public health and quality of life in menopausal women by reducing the risk of fragility fractures and alleviating vasomotor symptoms. Structured and supervised resistance programs should be prioritized as a first-line recommendation in clinical practice to maintain skeletal integrity and independence in the aging female population.

References

Sowers, M. R., & La Pietra, M. T. (1995). Menopause: Its epidemiology and potential association with chronic diseases. Epidemiologic Reviews, 17(2), 287–304. https://doi.org/10.1093/oxfordjournals.epirev.a036192

World Health Organization. (2022). Menopause. https://www.who.int/news-room/fact-sheets/detail/menopause

Khosla, S., Oursler, M. J., & Monroe, D. G. (2012). Estrogen and the skeleton. Trends in Endocrinology & Metabolism, 23(11), 576–581. https://doi.org/10.1016/j.tem.2012.03.008

Ji, M. X., & Yu, Q. (2015). Primary osteoporosis in postmenopausal women. Chronic Diseases and Translational Medicine, 1(1), 9–13. https://doi.org/10.1016/j.cdtm.2015.02.006

Manolagas, S. C. (2000). Birth and death of bone cells: Basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis. Endocrine Reviews, 21(2), 115–137. https://doi.org/10.1210/edrv.21.2.0395

Riggs, B. L., Khosla, S., & Melton, L. J. (2002). Sex steroids and the construction and conservation of the adult skeleton. Endocrine Reviews, 23(3), 279–302. https://doi.org/10.1210/edrv.23.3.0465

Pacifici, R. (1996). Estrogen, cytokines, and pathogenesis of postmenopausal osteoporosis. Journal of Bone and Mineral Research, 11(8), 1043–1051. https://doi.org/10.1002/jbmr.5650110802

Lanyon, L. E., & Skerry, T. M. (2001). Postmenopausal osteoporosis as a failure of bone's adaptation to functional loading. Journal of Bone and Mineral Research, 16(11), 1937–1947. https://doi.org/10.1359/jbmr.2001.16.11.1937

Robling, A. G., & Turner, C. H. (2009). Mechanical signaling in bone. Current Osteoporosis Reports, 7(4), 131–136. https://doi.org/10.1007/s11914-009-0022-5

Frost, H. M. (1987). Bone "mass" and the "mechanostat": A proposal. The Anatomical Record, 219(1), 1–9. https://doi.org/10.1002/ar.1092190103

Wolff, J. (1986). The law of bone remodeling (P. Maquet & R. Furlong, Trans.). Springer-Verlag. (Original work published 1892). https://doi.org/10.1007/978-3-642-71031-5

Westcott, W. L. (2012). Resistance training is medicine: Effects of strength training on health. Current Sports Medicine Reports, 11(4), 209–216. https://doi.org/10.1249/JSR.0b013e31825dabb8

Huovinen, V., Ivaska, K. K., Kiviranta, R., Bucci, M., Lipponen, H., Sandboge, S., Raiko, J. R., Tulokas, S., Solin, O., Hannukainen, J. C., & Nuutila, P. (2016). Bone formation is increased by a weight-bearing exercise intervention in postmenopausal women. Bone, 83, 174–181. https://doi.org/10.1016/j.bone.2015.11.005

Watson, S. L., Weeks, B. K., Weis, L. J., Harding, A. T., Horan, S. A., & Beck, B. R. (2018). High-intensity resistance and impact training improves bone mineral density and physical function in postmenopausal women with osteopenia and osteoporosis: The LIFTMOR randomized controlled trial. Journal of Bone and Mineral Research, 33(2), 211–220. https://doi.org/10.1002/jbmr.3284

Gomez-Cabello, A., Ara, I., González-Agüero, A., Casajús, J. A., & Vicente-Rodríguez, G. (2012). Effects of training on bone mass in older adults: A systematic review. Sports Medicine, 42(4), 301–325. https://doi.org/10.2165/11597670-000000000-00000

Zhao, R., Zhao, M., & Xu, Z. (2015). The effects of differing resistance training modes on the preservation of bone mineral density in postmenopausal women: A meta-analysis. Osteoporosis International, 26(5), 1605–1618. https://doi.org/10.1007/s00198-015-3034-0

Shojaa, M., von Stengel, S., Kohl, M., Schoene, D., & Kemmler, W. (2020). Effects of dynamic resistance exercise on bone mineral density in postmenopausal women: A systematic review and meta-analysis with special emphasis on exercise parameters. Osteoporosis International, 31(8), 1427–1444. https://doi.org/10.1007/s00198-020-05441-w

Järvinen, T. L., Kannus, P., & Sievänen, H. (2003). Estrogen and bone—a reproductive and locomotive perspective. Journal of Bone and Mineral Research, 18(11), 1921–1931. https://doi.org/10.1359/jbmr.2003.18.11.1921

Bonewald, L. F. (2011). The amazing osteocyte. Journal of Bone and Mineral Research, 26(2), 229–238. https://doi.org/10.1002/jbmr.320

Klein-Nulend, J., Bacabac, R. G., & Bakker, A. D. (2012). Mechanical loading and how it affects bone cells: The role of the osteocyte. Journal of Musculoskeletal & Neuronal Interactions, 12(4), 166–175. https://pubmed.ncbi.nlm.nih.gov/23196291/

Santos, A., Bakker, A. D., & Klein-Nulend, J. (2009). The role of osteocytes in bone mechanotransduction. Osteoporosis International, 20(6), 1027–1031. https://doi.org/10.1007/s00198-009-0858-5

Galea, G. L., Lanyon, L. E., & Price, J. S. (2017). Sclerostin's role in bone's adaptive response to mechanical loading. Bone, 96, 38–44. https://doi.org/10.1016/j.bone.2016.10.008

Hofbauer, L. C., & Schoppet, M. (2004). Clinical implications of the osteoprotegerin/RANKL/RANK system for bone and vascular diseases. JAMA, 292(4), 490–495. https://doi.org/10.1001/jama.292.4.490

Li, X., Ominsky, M. S., Warmington, K. S., Morony, S., Gong, J., Cao, J., Gao, Y., Shalhoub, V., Tipton, B., Haldankar, R., Chen, Q., Winters, A., Boone, T., Paszty, C., & Ke, H. Z. (2009). Sclerostin antibody treatment increases bone formation, bone mass, and bone strength in a rat model of postmenopausal osteoporosis. Journal of Bone and Mineral Research, 24(4), 578–588. https://doi.org/10.1359/jbmr.081206

McLeod, K. M., & Johnson, C. S. (2011). A comparative review of selected guidelines for the prevention and treatment of osteoporosis. British Columbia Medical Journal, 53(3), 130–137. https://bcmj.org/articles/comparative-review-selected-guidelines-prevention-and-treatment-osteoporosis

Kemmler, W., Häberle, L., & von Stengel, S. (2013). Effects of exercise on fracture risk in community-dwelling older women: A meta-analysis. Osteoporosis International, 24(12), 3013–3021. https://doi.org/10.1007/s00198-013-2439-9

Fiatarone Singh, M. A. (2002). Exercise to prevent and treat frailty and violence in the elderly. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 57(5), M262–M282. https://doi.org/10.1093/gerona/57.5.m262

Winters-Stone, K. M., & Snow, C. M. (2006). Skeletal response to resistance exercise at the hip and spine in postmenopausal women: A meta-analysis. Bone, 39(6), 1226–1235. https://doi.org/10.1016/j.bone.2006.06.008

Borer, K. T. (2005). Physical activity in the prevention and amelioration of osteoporosis in women: Interaction of mechanical, hormonal and dietary factors. Sports Medicine, 35(9), 779–830. https://doi.org/10.2165/00007256-200535090-00004

Moreira, L. D. F., Oliveira, M. L. D., Lazzaretti-Castro, M., & Teixeira, L. R. (2014). Physical exercise and osteoporosis: Effects of different types of exercises on bone and physical function of postmenopausal women. Arquivos Brasileiros de Endocrinologia & Metabologia, 58(5), 514–522. https://doi.org/10.1590/0004-2730000003374

Robling, A. G., Castillo, A. B., & Turner, C. H. (2006). Biomechanical and molecular regulation of bone remodeling. Annual Review of Biomedical Engineering, 8, 455–498. https://doi.org/10.1146/annurev.bioeng.8.061505.095721

Picorelli, A. M., Pereira, L. S., Pereira, D. S., Felício, D., & Sherrington, C. (2021). Adherence to exercise programs for older people with osteoporosis: A systematic review. Journal of Clinical Medicine, 10(12), 2719. https://doi.org/10.3390/jcm10122719

Giggins, O. M., Persson, U. M., & Caulfield, B. (2013). Biofeedback in rehabilitation: A review with a focus on real-time feedback. Journal of NeuroEngineering and Rehabilitation, 10, 60. https://doi.org/10.1186/1743-0003-10-60

Milton, K., Cavill, N., Chalkley, A., Foster, C., Gomersall, S., Hagstromer, M., & Bull, F. C. (2021). Eight investments that work for physical activity. Journal of Physical Activity and Health, 18(6), 625–630. https://doi.org/10.1123/jpah.2021-0112

Skelton, D. A., & Mavroeidi, A. (2018). How do we inform and motivate the "at risk" to be more active? The challenge of osteoporosis. Journal of Clinical Medicine, 7(4), 74. https://doi.org/10.3390/jcm7040074