A Losing Battle: Weight Regain Does Not Restore Weight Loss‐Induced Bone Loss in Postmenopausal Women
Open accessAbstract
Previously, we reported significant bone mineral density (BMD) loss in postmenopausal women after modest weight loss. It remains unclear whether the magnitude of BMD change in response to weight loss is appropriate (i.e., proportional to weight loss) and whether BMD is recovered with weight regain. We now report changes in BMD after a 1‐year follow‐up. Subjects (n = 23) in this secondary analysis were postmenopausal women randomized to placebo as part of a larger trial. They completed a 6‐month exercise‐based weight loss program and returned for follow‐up at 18 months. Dual‐energy X‐ray absorptiometry (DXA) was performed at baseline, 6, and 18 months. At baseline, subjects were aged 56.8 ± 5.4 years (mean ± s.d.), 10.0 ± 9.2 years postmenopausal, and BMI was 29.6 ± 4.0 kg/m 2. They lost 3.9 ± 3.5 kg during the weight loss intervention. During follow‐up, they regained 2.9 ± 3.9 kg. Six months of weight loss resulted in a significant decrease in lumbar spine (LS) (−1.7 ± 3.5%; P = 0.002) and hip (−0.04 ± 3.5%; P = 0.03) BMD that was accompanied by an increase in a biomarker of bone resorption (serum C‐terminal telopeptide of type I collagen, CTX: 34 ± 54%; P = 0.08). However, weight regain was not associated with LS (0.05 ± 3.8%; P = 0.15) or hip (−0.6 ± 3.0%; P = 0.81) bone regain or decreased bone resorption (CTX: −3 ± 37%; P = 0.73). The findings suggest that BMD lost during weight reduction may not be fully recovered with weight regain in hormone‐deficient, postmenopausal women. Future studies are needed to identify effective strategies to prevent bone loss during periods of weight loss.
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Some long-term data from lifestyle-based weight loss interventions suggest that lean mass and BMD may not be recovered with weight regain.
“As some long-term data from lifestyle-based weight loss interventions suggest LM (58) and BMD (59, 60) may not be recovered with weight regain, better understanding of the effects of intermittent use of GLP1Ra-based therapies on long-term change in body composition represents another important area of further inquiry.”
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MethodInfluentialEffects of a low-carbohydrate ketogenic diet on health parameters in resistance-trained women
Vargas-Molina, S., Carbone, L., Romance, R., Petro, J. L., Schoenfeld, B. J., Kreider, R. B., Bonilla, D. A., & Benítez‐Porres, J. (2021) · European Journal of Applied Physiology · doi:10.1007/s00421-021-04707-3 · Cited by 18 · see citing works
“Although an explanation for discrepancies in findings is not clear, it should be noted that the previous investigations were not performed on strength-trained participants, which may have helped promote a positive effect on BMD in our study (Villalon et al. 2011).”
ResultBone Mineral Density Changes during Weight Regain following Weight Loss with and without Exercise
Serra, M. C., & Ryan, A. S. (2021) · Nutrients · doi:10.3390/nu13082848 · Cited by 17 · see citing works
“[6] observed that elevations in the bone resorption marker, C-terminal telopeptide of type I collagen, occurring during WL remained elevated during the follow-up period despite weight regain.”
BackgroundResultWherry, S. J., Miller, R. M., Jeong, S. H., & Beavers, K. M. (2021) · Nutrients · doi:10.3390/nu13041250 · Cited by 16 · see citing works
Weight loss, weight regain and bone health
Pines, A. (2012) · Climacteric · doi:10.3109/13697137.2012.667975 · Cited by 16 · see citing works
Chmelo, E. A., Beavers, D. P., Lyles, M. F., Marsh, A. P., Nicklas, B. J., & Beavers, K. M. (2016) · Nutrition & Diabetes · doi:10.1038/nutd.2016.8 · Cited by 15 · see citing works
Hypothalamic leptin gene therapy reduces body weight without accelerating age-related bone loss
Turner, R. T., Dube, M. G., Branscum, A. J., Wong, C. P., Olson, D. A., Zhong, X. S., Kweh, M. F., Larkin, I. V., Wronski, T. J., Rosen, C. J., et al. (2015) · Journal of Endocrinology · doi:10.1530/joe-15-0280 · Cited by 14 · see citing works
“Importantly, weight regain does not restore bone and, http://joe.endocrinology-journals.org 2015 Society for Endocrinology DOI: 10.1530/JOE-15-0280 Printed in Great Britain as a consequence, weight cycling is especially deleterious to the skeletal system (Lee et al. 2010a, Villalon et al. 2011).”
BackgroundInfluentialSwift, S. N., Swift, J. M., & Bloomfield, S. A. (2014) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00588.2013 · Cited by 9 · see citing works
Legrand, M. A., Paccou, J., Lecerf, J., Thomas, T., Chapurlat, R. D., Cortet, B., Biver, E., & Papageorgiou, M. (2025) · Obesity · doi:10.1002/oby.70047 · Cited by 8 · see citing works
Gavin, K. M., Melanson, E. L., Hildreth, K. L., Gibbons, E., Bessesen, D. H., & Kohrt, W. M. (2020) · Obesity · doi:10.1002/oby.22978 · Cited by 8 · see citing works
“VO2peak was measured by indirect calorimetry during treadmill exercise as previously described (20).”
MethodSelf-citationCasey, B. A., Kohrt, W. M., Schwartz, R. S., & Pelt, R. E. V. (2014) · Obesity · doi:10.1002/oby.20703 · Cited by 7 · see citing works
Self-citationWeaver, A. A., Greene, K. A., Leng, X., Lenchik, L., Lyles, M. F., Nicklas, B. J., Baker, A. M., Helgason, B., Stapleton, J. R., Devane, K. S., et al. (2026) · Osteoporosis International · doi:10.1007/s00198-026-07845-6 · Cited by 6 · see citing works
“As bone loss does not appear to recover with weight regain [5], and may even accelerate post-WL [6], cumulative loss could potentially result in clinically meaningful increases in fracture risk [1, 2].”
Beavers, K. M., Neiberg, R. H., Johnson, K., Davis, C., Casanova, R., Schwartz, A. V., Crandall, C. J., Lewis, C. E., Pi‐Sunyer, X., & Kritchevsky, S. B. (2018) · JBMR Plus · doi:10.1002/jbm4.10086 · Cited by 5 · see citing works
“Some, but not all,((18,19)) studies suggest that the well-described 2% decline in BMD with 10% weight loss continues progressively despite weight loss maintenance,((20)) and does not return with weight regain.((7,8)) Trends observed in our BMD data are in general agreement with prior reports, although results were non…”
BackgroundResultHedges, W. P., & Bukhari, M. A. S. (2015) · European Journal of Rheumatology · doi:10.5152/eurjrheum.2015.0025 · Cited by 4 · see citing works
Erlandson, K. M., Mohaweche, R., Morrow, M., MaWhinney, S., Khuu, V., Boyd, M., Balasubramanyam, A., Melanson, E. L., & Lake, J. E. (2023) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkad363 · Cited by 4 · see citing works
Very-low-calorie diets (VLCDs) for the treatment of obesity
Sumithran, P., & Proietto, J. (2014) · Elsevier eBooks · doi:10.1533/9781782420996.4.231 · Cited by 4 · see citing works
O’Hara, L. (2014) · University of the Sunshine Coast · doi:10.25907/00425 · Cited by 4 · see citing works
Beavers, K. M., Serra, M. C., Weaver, A. A., & Houston, D. K. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-813073-5.00035-6 · Cited by 2 · see citing works
Shapses, S. A., & Sukumar, D. (2013) · Springer eBooks · doi:10.1007/978-1-4471-2769-7_4 · Cited by 2 · see citing works
Bariatric Surgery, Vitamin D, and Bone Loss
Tiffany Y, K., & Schafer, A. L. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-809963-6.00064-x · Cited by 2 · see citing works
Negative effects of semaglutide on bone in obese mice
Eisner, K., Jeromson, S., Tahboub, K., Zimmerman, E., & Wright, D. C. (2026) · Cell Reports Medicine · doi:10.1016/j.xcrm.2026.102875
“15 To assess the potential longer term impact of semaglutide-driven weight loss, we investigated bone properties following the discontinuation of semaglutide treatment or caloric restriction.”
The Effect of Bariatric Surgery on Bone Health
Moir, J., Callum, I., & Seymour, K. (2015) · Journal of Advances in Medicine and Medical Research · doi:10.9734/bjmmr/2015/16903 · Cited by 1 · see citing works
Nonpharmacologic intervention for osteosarcopenia
Waters, D. L. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-820088-9.00007-x · Cited by 1 · see citing works
Ortega‐Santos, C. P., Pinto, A. J., Whipple, M. O., Pan, Z., Boyle, K. E., Melanson, E. L., Masters, K. S., Bessesen, D. H., & Bergouignan, A. (2023) · International Journal of Clinical Trials · doi:10.18203/2349-3259.ijct20230049 · Cited by 1 · see citing works
Novel Findings in Bone Biology: Impact on Bone Health for Women
Bloomfield, S. A., & Metzger, C. E. (2013) · Springer eBooks · doi:10.1007/978-1-4614-8630-5_2
“, distal radius and proximal femur trochanter) over that observed in total body scans [ 9 ] or in cancellous compartments within the distal tibia, as separated out by peripheral quantitative computed tomography (pQCT) [ 18 ].”
BackgroundLaroche, M., Pouillès, J. M., Trémollières, F., Vallet, M., Lassoued, S., Nigon, D., & Tack, I. (2016) · Revue du Rhumatisme · doi:10.1016/j.rhum.2016.01.011
Diminished bone resorption in overweight/obese women despite vitamin D insufficiency
Laroche, M., Pouillès, J. M., Trémollières, F., Vallet, M., Lassoued, S., Nigon, D., & Tack, I. (2016) · Joint Bone Spine · doi:10.1016/j.jbspin.2016.03.001
Obesity and bone mineral measurements in postmenopausal women
Saarelainen, J. (2014) · UEF eRepo (University of Eastern Finland)
(2012) · Revue Francophone des Laboratoires · doi:10.1016/s1773-035x(12)71279-0
Bariatric surgery, vitamin D, and bone loss
Kim, T. Y., & Schafer, A. L. (2023) · Elsevier eBooks · doi:10.1016/b978-0-323-91338-6.00009-4
André, H. C. S., Roux, E. L., Jong, N. P. D., Smith, P. R., Lange, A. H., Mendez, C., Zahariev, A., Mamele, M. L., Johnson, G. C., Pan, Z., et al. (2026) · medRxiv · doi:10.64898/2026.04.14.26350871
André, H. C. S., Roux, E. L., Jong, N. P. D., Smith, P. R., Lange, A. H., Mendez, C., Zahariev, A., Mamele, M. L., Johnson, G. C., Pan, Z., et al. (2026) · Obesity · doi:10.1002/oby.70310
Functional Implications of GLP-1RA Use Beyond Obesity in Aging Adults
Mascone, S. E., Prior, S. J., & Addison, O. R. (2026) · Current Geriatrics Reports · doi:10.1007/s13670-026-00467-0
“…22–28% more likely to be prescribed GLP-1RAs than men [33, 34], which may be partially explained by menopause-related changes in body composition [35], muscle strength [36], and cardiometabolic health [37] that occur in mid-life concurrently when GLP-1RAs are most likely to be initiated [34, 38].”
- Authors
- Villalon, K. L., Gozansky, W. S., van Pelt, R. E., Wolfe, P., Jankowski, C. M., Schwartz, R. S., & Kohrt, W. M.
- Affiliations
- University of Colorado Anschutz (US)
- Corresponding author
- Villalon, Karen L.
- Venue
- Obesity
- Publisher
- Wiley
- Published
- 2011-12
- Volume
- 19
- Issue
- 12
- Pages
- 2345-2350
- ISSN
- 1930-7381 (ISSN-L)
- 1930-739X
- PMC
- PMC3760414
- OpenAlex
- W2098860050
- Cited by
- 67
- References
- 39
- Citations by year
- 2026: 7 · 2025: 1 · 2024: 1 · 2023: 6 · 2022: 2 · 2021: 5 · 2020: 5 · 2019: 4 · 2018: 6 · 2016: 7 · 2015: 6 · 2014: 9 · 2013: 5 · 2012: 3
- FWCI
- 5.70
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Obesity (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (R01AG018198, F32AG005899, K01AG019630, T32AG000279)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK048520)
- National Center for Research Resources (M01RR000051, UL1RR025780)
- Topics
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Keywords
- weight regain, weight loss, bone mineral density, bone loss, postmenopausal women, bone resorption, C-terminal telopeptide of type I collagen, lumbar spine, hip bone
- MeSH terms
- Female, Follow-Up Studies, Hip, Humans, Lumbar Vertebrae, Middle Aged, Obesity, Peptides, Biomarkers, Weight Gain, Weight Loss, Exercise, Absorptiometry, Photon, Bone Density, Osteoporosis, Postmenopausal, Body Mass Index, Bone Remodeling, Collagen Type I, Weight Reduction Programs
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