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Peer-reviewedCC BYMedicine

Additive effects of active vitamin D3 or vitamin E administration on therapeutic lower-limb home exercise for knee osteoarthritis: A pilot prospective randomized controlled trial.

4 affiliations
  1. 1Department of Orthopaedics, Juntendo University Faculty of Medicine, Bunkyo-ku, Tokyo, Japan.
  2. 2Department of Orthopaedic Surgery, Juntendo University, Tokyo Koto Geriatric Medical Center, Koto-ku, Tokyo, Japan.
  3. 3Department of Orthopaedic Surgery, Medical Technology Innovation Center, Clinical Research & Trial Center, Graduate School of Health and Sports Science, Juntendo University, Bunkyo-ku, Tokyo, Japan.
  4. 4Department of Regenerative Medicine for Locomotive Organ, Faculty of Medicine, Juntendo University, Tokyo, Japan.

Abstract

Background

Quadriceps weakness, inflammation, and reduced physical function are common in knee osteoarthritis (OA), and lower limb exercise therapy is an established non-pharmacological treatment. Vitamin D3 (vit D3) and vitamin E (vit E) have been proposed as adjunctive therapies; however, clinical findings are inconsistent. We aimed to examine whether combining lower limb home exercises with oral active vit D3 or vit E supplementation provides additive benefits compared with home exercise alone in women with symptomatic knee OA.Methods

Eighty-eight postmenopausal women with knee OA (Kellgren-Lawrence grade 2-4; 71.9 ± 5.6 years) were randomly assigned to receive therapeutic lower limb home exercise only, home exercise with active vit D3 administration, or home exercise with vit E administration. Participants performed isometric lower limb exercises twice daily for 24 weeks. Subsequently, they were assessed using the Japanese knee osteoarthritis measure (JKOM) as the primary outcome. Secondary outcomes were short-form health survey, grip strength, quadriceps muscle strength, 10-m walk test, inflammatory markers, bone mineral density, and body composition. For data analyses, we used paired and independent t tests, analysis of variance, and analysis of covariance, adjusting for age, body mass index, and Kellgren-Lawrence grade.Results

Eighty participants completed follow-up. All groups showed significant improvements in JKOM score, quadriceps muscle strength, and 10-m walk test. Grip strength improved significantly only in the group that received active vit D. No significant between-group differences were observed in JKOM scores, short-form health survey-36, muscle strength, or physical performance. Inflammatory markers decreased significantly in the vit E group, although between-group differences were not observed. No other significant between-group differences were found, except in bone mineral density.Conclusions

Administering active vit D3 or vit E for 24 weeks as an adjunct to lower limb home exercises did not yield significant additive effects on symptoms, muscle strength, or physical performance in women with knee OA. Exercise therapy alone remained effective, and vitamin supplementation showed nutrient-specific trends.

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BibTeX
@article{kanazawa2026additive,
  title = {{Additive effects of active vitamin D3 or vitamin E administration on therapeutic lower-limb home exercise for knee osteoarthritis: A pilot prospective randomized controlled trial.}},
  author = {Hiroaki Kanazawa and Hisashi Kurosawa and Masashi Nagao and Masato Koike and Kei Miyagawa and Yu Ozaki and Yoshiyuki Iwase and Muneaki Ishijima},
  journal = {Medicine},
  year = {2026},
  month = oct,
  doi = {10.1097/md.0000000000051197},
  url = {https://europepmc.org/article/MED/42888606},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Additive effects of active vitamin D3 or vitamin E administration on therapeutic lower-limb home exercise for knee osteoarthritis: A pilot prospective randomized controlled trial.
AU  - Hiroaki Kanazawa
AU  - Hisashi Kurosawa
AU  - Masashi Nagao
AU  - Masato Koike
AU  - Kei Miyagawa
AU  - Yu Ozaki
AU  - Yoshiyuki Iwase
AU  - Muneaki Ishijima
PY  - 2026
DA  - 2026/10/01
JO  - Medicine
DO  - 10.1097/md.0000000000051197
UR  - https://europepmc.org/article/MED/42888606
AB  - Background  Quadriceps weakness, inflammation, and reduced physical function are common in knee osteoarthritis (OA), and lower limb exercise therapy is an established non-pharmacological treatment. Vitamin D3 (vit D3) and vitamin E (vit E) have been proposed as adjunctive therapies; however, clinical findings are inconsistent. We aimed to examine whether combining lower limb home exercises with oral active vit D3 or vit E supplementation provides additive benefits compared with home exercise alone in women with symptomatic knee OA.Methods  Eighty-eight postmenopausal women with knee OA (Kellgren-Lawrence grade 2-4; 71.9 ± 5.6 years) were randomly assigned to receive therapeutic lower limb home exercise only, home exercise with active vit D3 administration, or home exercise with vit E administration. Participants performed isometric lower limb exercises twice daily for 24 weeks. Subsequently, they were assessed using the Japanese knee osteoarthritis measure (JKOM) as the primary outcome. Secondary outcomes were short-form health survey, grip strength, quadriceps muscle strength, 10-m walk test, inflammatory markers, bone mineral density, and body composition. For data analyses, we used paired and independent t tests, analysis of variance, and analysis of covariance, adjusting for age, body mass index, and Kellgren-Lawrence grade.Results  Eighty participants completed follow-up. All groups showed significant improvements in JKOM score, quadriceps muscle strength, and 10-m walk test. Grip strength improved significantly only in the group that received active vit D. No significant between-group differences were observed in JKOM scores, short-form health survey-36, muscle strength, or physical performance. Inflammatory markers decreased significantly in the vit E group, although between-group differences were not observed. No other significant between-group differences were found, except in bone mineral density.Conclusions  Administering active vit D3 or vit E for 24 weeks as an adjunct to lower limb home exercises did not yield significant additive effects on symptoms, muscle strength, or physical performance in women with knee OA. Exercise therapy alone remained effective, and vitamin supplementation showed nutrient-specific trends.
SN  - 0304-5412
SN  - 1536-5964
ER  -