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Randomized Controlled Trial
. 2025 Aug 24;40(9):1035-1044.
doi: 10.1093/jbmr/zjaf058.

Effects of vitamin D3, omega-3s, and a simple home exercise program on incident vertebral fractures: the DO-HEALTH randomized controlled trial

Melanie Kistler-Fischbacher  1   2 , Gabriele Armbrecht  3 , José A P Da Silva  4   5 , Caroline de Godoi Rezende Costa Molino  1   2 , Robert Theiler  2 , René Rizzoli  6 , Bruno Vellas  7   8 , Bess Dawson-Hughes  9 , John A Kanis  10 , Lorenz C Hofbauer  11 , Endel John Orav  12 , Reto W Kressig  13 , Andreas Egli  1   2 , Guido A Wanner  14 , Heike A Bischoff-Ferrari  1   2 ; DO-HEALTH Research Group
Collaborators, Affiliations
Randomized Controlled Trial

Effects of vitamin D3, omega-3s, and a simple home exercise program on incident vertebral fractures: the DO-HEALTH randomized controlled trial

Melanie Kistler-Fischbacher et al. J Bone Miner Res. .

Abstract

Vertebral fractures (VFs) are among the most common osteoporotic fractures. The effect of vitamin D3, omega-3s or a simple home exercise program (SHEP) on VFs is unclear. We examined whether vitamin D3, omega-3s, or SHEP, alone or in combination, over 3 years, reduce the incidence rate of VFs among European older adults. DO-HEALTH is a multi-center, 2 × 2 × 2 factorial design, randomized controlled trial, which included older adults (≥70 years) free from major health events in the 5 years prior to enrollment. The study interventions were vitamin D3 (2000IU/d), omega-3s (1 g/d), and SHEP (3 × 30 min/wk), applied alone or in combination. Quantitative and qualitative VF assessment was determined from lateral thoracolumbar DXA scans. The primary outcome for this analysis was the incidence rate (IR) of total VFs, defined as the number of any new and progressed VFs over the 3-year follow-up. Sensitivity analyses were conducted for only new VFs and only VF progressions. Negative binomial regression models were fit, adjusted for age, sex, prior fall, BMI, study site and participants' follow-up time. 1488 participants (mean age 74.9 years; 77% had low bone mass or osteoporosis; 43.8% had 25(OH)D levels <20 ng/mL) were included. There were 93 incident VFs, of which 58 were new VFs and 35 were progressions. None of the three treatments reduced the IR of total VFs overall, however, the IR was reduced with SHEP compared to the control exercise program in women (IR ratio 0.52, 95% CI 0.28, 0.98). In the sensitivity analysis for VF progressions, SHEP reduced the IR (IR ratio 0.34, 95% CI 0.16, 0.75). Among generally healthy older adults, vitamin D3 and omega-3s supplementation did not reduce the incidence rate of VFs. SHEP reduced the incidence rate of total VFs in women and of VF progressions overall. Exercise may play a role in the prevention of VFs.

Keywords: Vertebral morphology; community-dwelling older adults; low bone mass; nutritional supplements; osteoporosis; prevention; vertebral deformity; vertebral fracture progression.

Plain language summary

Vertebral fractures are one of the most common consequences of osteoporosis. Vitamin D, omega-3 fatty acids (omega-3s), and exercise are simple but promising strategies to improve bone health and reduce fracture risk, however, their effect on vertebral fractures in healthy older adults across a 3-year duration was unclear. In this study, we examined whether daily vitamin D supplementation (2000 IU/d), daily omega-3 s supplementation (1 g/d) or a simple home exercise program performed three times per week, either applied alone (eg, only vitamin D supplements) or in combination (eg, vitamin D and omega-3s supplements) would reduce the number of new vertebral fractures over 3 years. We included 1488 healthy older adults from Switzerland, Germany, France, and Portugal who were at least 70 years of age and who had not experienced any major health events in the 5 years before study start. Taking omega-3s or vitamin D supplements showed no benefit. The simple home exercise program reduced the number of new fractures in women, and reduced the number of vertebral fractures that progressed in their severity (ie, collapsed further). Exercise may therefore play a role in the prevention of vertebral fractures.

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Conflict of interest statement

J.A.K. is a director of Osteoporosis Research Ltd that maintains FRAX. L.C.H. has received honoraria for advisory boards or educational lectures from Amgen, Ascendis, BluePrint, and UCB to himself, and support for clinical trials from Ascendis and Amolyt to his institution. H.A.B.-F. reports as the PI of the DO-HEALTH trial, grants from the European Commission (Grant Agreement No. 278588), from the University of Zurich, from NESTEC, from PFIZER Consumer Healthcare, from Streuli Pharma, plus non-financial support from DSM Nutritional Products and from Roche Diagnostics. Furthermore, H.A.B.-F. reports speaker fees from Wild, Pfizer, Vifor, Mylan, Roche Diagnostics, and independent and investigator initiated grants from Pfizer and from Vifor, outside the submitted work. M.K.-F., G.A., J.A.P.D., C.G., R.T., R.R., B.V., B.D.-H., E.J.O., R.W.K., A.E., and G.A.W. declare no conflicts of interest.

Figures

Graphical Abstract
Graphical Abstract
Figure 1
Figure 1
Treatment effects on the incidence rate of total VFs over the 3-year follow-up. Analyses adjusted for age, linear spline at age 85 years, sex, prior fall, BMI, and study site. N = 1369.
See this image and copyright information in PMC

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References

    1. Kanis JA, Norton N, Harvey NC, et al. SCOPE 2021: a new scorecard for osteoporosis in Europe. Arch Osteoporos. 2021;16(1):82. 10.1007/s11657-020-00871-9 - DOI - PMC - PubMed
    1. Kemmler W, Häberle L, von Stengel S. Effects of exercise on fracture reduction in older adults: a systematic review and meta-analysis. Osteoporos Int. 2013;24(7):1937-1950. 10.1007/s00198-012-2248-7 - DOI - PubMed
    1. Dong Y, Peng R, Kang H, et al. Global incidence, prevalence, and disability of vertebral fractures: a systematic analysis of the global burden of disease study 2019. Spine J. 2022;22(5):857-868. 10.1016/j.spinee.2021.12.007 - DOI - PubMed
    1. Rizkallah M, Bachour F, Khoury ME, et al. Comparison of morbidity and mortality of hip and vertebral fragility fractures: which one has the highest burden? Osteoporos Sarcopenia. 2020;6(3):146-150. 10.1016/j.afos.2020.07.002 - DOI - PMC - PubMed
    1. Koelé MC, Lems WF, Willems HC. The clinical relevance of hyperkyphosis: a narrative review. Front Endocrinol (Lausanne). 2020;11:5. 10.3389/fendo.2020.00005 - DOI - PMC - PubMed

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