More than 200 million women worldwide live with osteoporosis, and this number is projected to continue increasing sharply. At the Faculty of Dentistry, Universitas Gadjah Mada, dr. Rini Maya Puspita, M.Sc. sought to answer a fundamental question: how much can exercise help protect the bones of women experiencing estrogen loss? She addressed this question through a systematic review and meta-analysis published in the international journal Physiology International in April 2026, involving 29 studies from around the world that examined various types of physical exercise in rat models of postmenopausal osteoporosis.
Bones That Lose Their Protection
When women enter menopause, estrogen levels in the body decline dramatically. This hormone is not merely a regulator of the reproductive cycle; it also protects the bones. Estrogen suppresses the activity of osteoclasts, the cells that break down bone, while promoting the activity of osteoblasts, the cells that build new bone. When estrogen levels decrease, this balance is disrupted. More bone is destroyed than rebuilt, and bone mineral density (BMD) begins to decline.
This condition is known as postmenopausal osteoporosis. In the United States alone, 54 million adults over the age of 50 experience the condition, with women accounting for 80% of cases. Hip fractures caused by osteoporosis are associated with a 20% mortality rate within the first year. Treatment costs reach USD 17.9 billion annually in the United States alone.
Medications such as bisphosphonates and denosumab are available and can reduce fracture risk by 40–70%. However, fewer than 30% of high-risk patients actually receive them because of cost, side effects, or simple non-adherence. Consequently, non-pharmacological approaches, particularly exercise, have become increasingly attractive for further investigation.
Female Rats Without Ovaries as a Research Model
To study postmenopausal osteoporosis in the laboratory, scientists use female rats whose ovaries have been surgically removed, a procedure known as ovariectomy (OVX). This procedure mimics menopause: without ovaries, the rats stop producing estrogen, and their bones begin to thin in a pattern similar to that observed in humans.
Dr. Rini and her team, which also included Prof. Denny Agustiningsih from the Department of Physiology, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, and Prof. Nunuk Purwanti from the Department of Biomedical Sciences, Faculty of Dentistry, Universitas Gadjah Mada, searched three major scientific databases: Scopus, PubMed, and ScienceDirect. Of the 1,264 articles identified, only 29 studies met the strict criteria for qualitative analysis, and 14 of these provided sufficient data for statistical meta-analysis.
The studies examined five types of exercise: treadmill running (55%), swimming (14%), resistance exercise such as stair climbing (7%), jumping or plyometric exercise (17%), and downhill running (7%). The intervention periods ranged from 4 to 36 weeks.
“Exercise interventions significantly mitigate OVX-induced bone loss, improve BMD, and positively influence biomarkers of bone remodeling, supporting its role as a potential non-pharmacological strategy for managing postmenopausal osteoporosis.” — dr. Rini Maya Puspita, M.Sc., and colleagues, in the study conclusion
What Happens Inside the Bones
The meta-analysis showed that OVX rats without intervention experienced a clear reduction in BMD at three skeletal sites: the vertebrae, femur, and tibia. The measured mean differences ranged from 0.03–0.04 g/cm², with p-values far below 0.0001, indicating that these differences were highly unlikely to have occurred by chance.
Exercise partially reversed this bone loss. Significant increases in BMD were observed in the vertebrae and femur following exercise interventions. Moderate-intensity treadmill exercise produced the strongest effects on the vertebrae and femur, while jumping exercise produced consistent benefits at both sites. The principle is mechanically plausible: the impact and loading generated during jumping or running provide physical stimuli to the bones, encouraging osteoblasts to become more active.
Beyond altering bone density, exercise also affected biological markers (biomarkers) that reflect bone formation and resorption. Markers of bone resorption such as TRAP, CTX-1, and NTX, which increased following ovariectomy, decreased toward normal levels after physical exercise. Conversely, markers of bone formation such as osteocalcin (OCN), alkaline phosphatase (ALP), and P1NP showed normalization. Exercise also reactivated the Wnt/β-catenin signaling pathway, which had been suppressed by estrogen deficiency, reduced the expression of RANKL, which stimulates osteoclast activity, and increased the activity of the antioxidant enzyme SOD to counter oxidative stress.
Another interesting finding was that exercise stimulated the expression of the CYP19 aromatase enzyme in bone cells. This enzyme converts androgens into estrogen in local tissues, allowing bones to continue receiving estrogen even when the ovaries are no longer functioning.
Promising Evidence, but Caution Is Still Needed
The research team was transparent about the limitations of the findings. All data came from animal models rather than humans, and there are physiological differences between laboratory rats and postmenopausal women that cannot simply be overlooked. Assessment using the GRADE framework placed the strength of evidence in the Very Low to Low categories, mainly because many studies did not transparently report their randomization and blinding procedures.
Nevertheless, the direction of the findings was consistent. Across the various types and intensities of exercise and the different bone sites examined, exercise consistently showed beneficial rather than harmful effects. This strengthens the argument that physical activity deserves to be positioned as a complementary strategy, rather than merely an alternative, in the management of postmenopausal osteoporosis.
The remaining questions are no longer simply whether exercise helps, but what dose is most effective, which type of exercise is optimal for particular patient groups, and how exercise programs can be designed so that older women can consistently incorporate them into real-world life. These are the next research priorities, and FKG UGM appears unlikely to stop here.
Authors: Achmad Zam Zam Aghasy, DDS, M.Kes.; Hazra Alifia Muharam
Photo: Freepik
Source DOI: https://doi.org/10.1556/2060.2026.00710