Knee osteoarthritis treated by Vitamin D - many studies

Created December 2022

VitaminDWiki - Pain in two joints (e.g. both knees) 2.7 X more likely if low Vitamin D - Aug 2025

Knee Osteoarthritis associated with low Vitamin D in 56% of 26 studies - Aug 2025

Global prevalence of vitamin D deficiency among patients with knee osteoarthritis: A systematic review and meta-analysis

Nutrition and Health PDF behind paywall

Muhammad Iqhrammullah https://orcid.org/0009-0008-6745-8848 m.iqhrammullah@gmail.com, Juan Fransiscus Wira , and Radi Muharris Mulyana

Background: Low serum 25-hydroxyvitamin D (25[OH]D) levels affect bone remodeling, contributing to the development and progression of knee osteoarthritis (OA). Aim: This meta-analysis aimed to estimate the prevalence of vitamin D deficiency in patients with knee OA.

Methods: A systematic search was conducted in Europe PMC, Google Scholar, Scopus, Scilit, and Web of Science for studies published until 8 August 2024 that reported the prevalence and contributing factors of hypovitaminosis D in knee OA patients. Study quality was assessed using the Newcastle–Ottawa Scale. A random-effect meta-analysis with Freeman–Tukey double arcsine transformation estimated the pooled prevalence of vitamin D deficiency.

Results: Out of 1695 records identified, 26 studies (n = 4248 patients) met the inclusion criteria.

The pooled prevalence of vitamin D deficiency was 56.72% (95% CI: 46.93–66.25). No significant difference was observed across publication periods of 2015–2019 (p = 0.465) and 2020–2024 (p = 0.407). Patients with an average body mass index (BMI) ≥28 kg/m² had a higher prevalence (65.62%, 95% CI: 49.23–80.32) compared to those with BMI <28 kg/m² (37.63%, 95% CI: 24.72–51.48). The prevalence was significantly higher in European countries (65.92%, 95% CI: 47.17–82.43) than in the USA (p = 0.046). In Asia, the Middle East, and North Africa, prevalences were 60.96% (95% CI: 42.32–78.08) and 63.11% (95% CI: 43.8–80.47), respectively.

Conclusion: Over half of knee OA patients had vitamin D deficiency, with higher prevalence in Europe and among individuals with obesity. Targeted screening for 25(OH)D levels in knee OA patients is recommended.

Many Knee Osteoarthritis studies found that Vitamin D helps, conclusion: need better studies - umbrella analysis Jan 2025

Shining light on knee osteoarthritis: an overview of vitamin D supplementation studies

Front. Med. , 21 Jan 2025 Volume 11 - 2024 | https://doi.org/10.3389/fmed.2024.1423360

Di ZhangDi Zhang1Miaoyu YeMiaoyu Ye1Yao XuYao Xu2Luyu JiangLuyu Jiang1Yanmei HuYanmei Hu1Qi ZhangQi Zhang1Xiao HanXiao

Background: The impact of knee osteoarthritis on individuals’ daily functioning is significant. In recent years, Vitamin D supplements cure osteoarthritis has garnered attention from medical professionals and patients due to its simplicity and portability. Several systematic reviews (SRs) and meta-analyses (MAs) have examined the efficacy of vitamin D supplementation for knee osteoarthritis, yet there is variability in their methodology and quality.

Objective: To search, gather, and analyze data on the characteristics and quantitative results of SR/MA in patients with KOA treated with Vitamin D supplementation, and objectively evaluate the efficacy of supplements. Then, provides clinical evidence and recommendations the clinical use of vitamin D supplementation.

Methods: Two individuals reviewed and collected data from four databases until October 2023. AMSTAR-2, ROBIS, PRISMA 2020, and GRADE tools were used to evaluate the methodological quality, bias risk, reporting quality, and evidence strength of all SR/MA. Additionally, we applied the corrected covered area (CCA) method to measure overlap in randomized controlled trials (RCTs) cited among the SR/MA.

Results: 3 SRs and 6 MAs were included in the analysis : 3 studies were low quality by AMSTAR-2, and 6 studies were very low quality. According to ROBIS, 6 studies were high-risk and 3 were low-risk. In PRISMA 2020 reporting quality, most studies showed deficiencies in comprehensive literature search strategy, reasons for literature exclusion, data preprocessing for meta-analysis, exploration of reasons for heterogeneity, sensitivity analysis, publication bias, and disclosure of funding and conflicts of interest. Grading the quality of evidence in GRADE consisted of 5 items of moderate quality, 14 items of low quality, and 10 items of very low quality. Bias risk and imprecision were the main factors for downgrading. The calculation of RCT overlap between SR/MA using CCA showed a high degree of overlap.

Conclusion: Vitamin D supplementation may show potential efficacy in ameliorating symptoms of KOA. The evidence indicates that Vitamin D supplements for knee osteoarthritis can improve patients’ Total WOMAC scores and synovial fluid volume in the joints. Nevertheless, due to the generally low quality of current studies, future research should prioritize improving the quality of primary studies to establish the efficacy of vitamin D supplementation for KOA with more robust scientific evidence.

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Knee Osteoarthritis 1.7 more likely if low Vitamin D - Jan 2024

Relationship between serum vitamin D levels and the prevalence of knee osteoarthritis: A retrospective study on 3424 subjects

Technol Health Care. 2024 Jan 4. doi: 10.3233/THC-230802 PDF Price: EUR 27.50

Seçkin Özgür Tekeli 1, Özkan Köse 1 2, Dilek Yapar 3, Feyza Yağmur Tekeli 4, Mehmet Melih Asoğlu 1, Emre Mücahit Kartal 1

Background: The extent of the association between vitamin D deficiency and knee osteoarthritis remains inadequately understood.

Objective: This study aimed to elucidate the relationship between vitamin D levels and knee osteoarthritis through a cross-sectional analysis.

Methods: This retrospective study involved an analysis of knee radiographs and serum 25-hydroxyvitamin D3 (25-(OH) vitamin D3) levels in a cohort of 3424 individuals (2901 women and 523 men). Knee osteoarthritis severity was evaluated using the Kellgren-Lawrence radiological scoring system.

Results: Of the participants, 49.2% (n= 1,683) were diagnosed with knee osteoarthritis. Among these patients, the levels of adjusted 25-(OH) vitamin D3 were significantly lower (p< 0.001). Regression analysis revealed a significant association between vitamin D deficiency and knee osteoarthritis, with an adjusted odds ratio (OR) of 1.7 (95% CI: 1.5-2.0; p< 0.001). Notably, a stronger association was observed between vitamin D deficiency and knee osteoarthritis in women under 65 compared to those aged 65 and above.

Conclusions: The findings of this study indicate a higher prevalence of vitamin D deficiency in patients with knee osteoarthritis. Maintaining adequate serum 25-(OH) vitamin D3 levels may prevent knee osteoarthritis, especially in women below 65.

Both Vitamin D and Magnesium appear to be needed if have Knee Osteoarthritis - Oct 2023

**Investigation of the relationship between magnesium level and vitamin D, bone mineral density, and chronic diseases in patients with knee osteoarthritis

Magnes Res. 2023 Jun 1;36(2):40-48. doi: 10.1684/mrh.2023.0515 PDF behind paywall

Ebru Yilmaz 1, Sena Ünver 2

The maintenance of various physiological cellular processes requires mineral magnesium (Mg). The purpose of the study was to determine a possible association between Mg level and vitamin D levels, bone mineral density (BMD), chronic diseases, and radiographic stage in individuals with knee osteoarthritis (OA). The study included 98 individuals (62 female and 36 male) who had been diagnosed with at least grade 1 knee OA. Age, sex, smoking, body mass index (BMI), family history of osteoporosis, menopausal status, duration of menopause, the presence of chronic diseases (hypertension, diabetes mellitus, hyperlipidaemia, coronary artery disease, hypothyroidism) and radiological stage of knee OA were gathered from all patients. Also, serum calcium, Mg, alkaline phosphatase, parathyroid hormone (PTH) and 25(OH)-vitamin D levels were recorded. Additionally, dual-energy X-ray absorptiometry (DEXA) was used to measure the BMD of the lumbar vertebrae (L1-L4) and femoral neck as well as anteroposterior radiography of the knee in all patients. T scores ≤-2.5 were accepted as evidence of osteoporosis. The mean age of the study population was 59.15 ± 10.58 years.

The level of Mg significantly correlated with age, smoking, presence of chronic disease, duration of menopause, the level of vitamin D and PTH, and femoral neck T score (p<0.05). This study provides data supporting the relationship between magnesium levels and PTH and vitamin D levels, bone mineral density, and chronic disease. Future research is needed to examine the potential link between knee osteoarthritis and magnesium status.

Knee osteoarthritis pain reduced by 4,000 IU of Vitamin D for 3 months (35 ng avg.) – Dec 2022* The influence of vitamin D supplementation on the expression of mediators of inflammation in knee osteoarthritis *Immunol Res . 2022 Dec 26. doi: 10.1007/s12026-022-09354-0

Ana Divjak 1 2, Ivan Jovanovic 3, Aleksandar Matic 4 5, Aleksandra Tomic Lucic 6 7, Nevena Gajovic 3, Milena Jurisevic 8, Aleksandra Jurisic Skevin 1 2, Mirjana Veselinovic 9 10

This trial aimed to determine the possible therapeutic and immunomodulatory effects of vitamin D3 in patients with knee OA. In this open-label clinical trial, symptoms were assessed over 3 months in patients with primary knee OA receiving oral vitamin D3 4000 IU/day. Clinical response was evaluated at baseline and 3 months using WOMAC subscores and VAS. Serum levels of cytokines IL-1ß, TNF-a, IL-13, IL-17, IL-33, IL-4, and IL-10 were determined by ELISA method. Eighty patients with knee OA were included. All 80 completed the study; the median 25(OH)D3 level was 23.1 ng/ml at baseline and increased by 12.3 ng/ml after treatment. Vitamin D3 after 3 months of supplementation induced a significant reduction in VAS pain and WOMAC subscores. Using OMERACT-OARSI criteria, 86.7% of patients treated with vitamin D3 responded to treatment. At the end of 3 months, systemic values of IL-1ß (p < 0.01), IL-23 (p < 0.01), and IL-33 (p < 0.01) were significantly increased, values of TNF-a (p < 0.01), IL-13 (p < 0.01), and IL-17 (p < 0.01) were significantly decreased, while value of IL-4 was not significantly changed. No adverse events were detected. Treatment with vitamin D is associated with improvement in pain, as well as stiffness and physical function. Vitamin D supplementation increased systemic values of IL-33. Our results indicate that vitamin D3 supplementation may be used as a novel therapeutic in knee OA. Future studies are needed to investigate a potential role of IL-33 in the pathogenesis of knee OA.

Vitamin D reduces pain and cartilage destruction in knee osteoarthritis animals through inhibiting the matrix metalloprotease (MMPs) expression - May 2023

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VitaminDWiki - studies in both categories Osteoarthritis and Intervention

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Study References (2022)

  1. Orlowsky EW, Kraus VB. The role of innate immunity in* osteoarthritis *: when our first line of defense goes on the offensive. J Rheumatol. 2015;42(3):363–71. https://doi.org/10.3899/jrheum.140382

  2. Rainbow R, Ren W, Zeng L. Inflammation and joint tissue interactions in oa: implications for potential therapeutic approaches. Arthritis. 2012;2012:741582. https://doi.org/10.1155/2012/741582

  3. Wang Y, Teichtahl AJ, Pelletier JP, et al. Knee effusion volume assessed by magnetic resonance imaging and progression of knee* osteoarthritis : data from the osteoarthritis *Initiative. Rheumatology (Oxford). 2019;58(2):246–53. https://doi.org/10.1093/rheumatology/key274

  4. Wang K, Xu J, Hunter DJ, Ding C. Investigational drugs for the treatment of* osteoarthritis *. Expert Opin Invest Drugs. 2015;24:1539–56. https://doi.org/10.1517/13543784.2015.1091880

  5. Wang XB, Zhao FC, Yi LH, et al. MicroRNA-21-5p as a novel therapeutic target for* osteoarthritis *. Rheumatology (Oxford). 2019;58(8):1485–97. https://doi.org/10.1093/rheumatology/kez102

  6. Cao Y, Winzenberg T, Nguo K, Lin J, Jones G, Ding C. Association between serum levels of 25-hydroxyvitamin D and* osteoarthritis *: a systematic review. Rheumatology (Oxford). 2013;52(7):1323–34. https://doi.org/10.1093/rheumatology/ket132

  7. Aranow C. Vitamin D and the immune system. J Investig Med. 2011;59(6):881–6. https://doi.org/10.2310/JIM.0b013e31821b8755

  8. Kapoor M, Martel-Pelletier J, Lajeunesse D, et al. Role of proinflammatory cytokines in the pathophysiology of* osteoarthritis *. Nat Rev Rheumatol. 2011;7:33–42. https://doi.org/10.1038/nrrheum.2010.196

  9. Wojdasiewicz P, Poniatowski LA, Szukiewicz D. The role of inflammatory and anti-inflammatory cytokines in the pathogenesis of* osteoarthritis *. Mediators Inflamm. 2014;2014:561459. https://doi.org/10.1155/2014/561459

  10. Rai V, Radwan MM, Agrawal DK. IL-33, IL-37, and vitamin D interaction mediate immunomodulation of inflammation in degenerating cartilage. Antibodies. 2021;10(4):41. https://doi.org/10.3390/antib10040041

  11. Pavlovic S, Zdravkovic N, Radosavljevic G, et al. Interleukin-33/ST2: a new signaling pathway in immunity and immunopathology. Vojnosanit Pregl. 2012;69(1):69–77. https://doi.org/10.2298/vsp1201069p

  12. Dinarello CA. Overview of the IL-1 family in innate inflammation and acquired immunity. Immunol Rev. 2018;28:8–27. https://doi.org/10.1111/imr.12621

  13. Shipton EA, Shipton EE. Vitamin D and pain: vitamin D and its role in the aetiology and maintenance of chronic pain states and associated comorbidities. Pain Res Treat. 2015;2015:904–67. https://doi.org/10.1155/2015/904967

  14. Alkan G, Akgol G. Do vitamin D levels affect the clinical prognoses of patients with knee* osteoarthritis *? J Back Musculoskelet Rehabil. 2017;30(4):897–901. https://doi.org/10.3233/BMR-160589

  15. Zhang FF, Driban JB, Lo GH, et al. Vitamin D deficiency is associated with progression of knee* osteoarthritis *. J Nutr. 2014;144(12):2002–8. https://doi.org/10.3945/jn.114.193227

  16. Glover TL, Horgas AL, Fillinbim RB, Goodin BR. Vitamin D status and pain sensitization in knee* osteoarthritis *: a critical review of the literature. Pain Manag. 2015;5:447–53. https://doi.org/10.2217/pmt.15.43

  17. Stannus OP, Jones G, Blizzard L, Cicuttini FM, Ding C. Associations between serum levels of inflammatory markers and change in knee pain over 5 years in older adults: a prospective cohort study. Ann Rheum Dis. 2013;72(4):535–40. https://doi.org/10.1136/annrheumdis-2011-201047

  18. Kellgren JH, Lawrence JS. Radiological assessment of osteoarthrosis. Ann Rheum Dis. 1957;16(4):494–502. https://doi.org/10.1136/ard.16.4.494

  19. Bellamy N, Bell MJ, Goldsmith CH, et al. Evaluation of WOMAC 20, 50, 70 response criteria in patients treated with hylan G-F 20 for knee* osteoarthritis *. Ann Rheum Dis. 2005;64:881–5. https://doi.org/10.1136/ard.2004.026443

  20. Pham T, Van Der Heijde D, Altman RD, et al. OMERACT-OARSI initiative:* osteoarthritis Research Society International set of responder criteria for osteoarthritis *clinical trials revisited. Osteoarthr Cartil. 2004;12:389–99. https://doi.org/10.1016/j.joca.2004.02.001

  21. Jovanovic M, et al. Metabolic syndrome attenuates ulcerative colitis: correlation with interleukin-10 and galectin-3 expression. World J Gastroenterol. 2019;25:6465–82. https://doi.org/10.3748/wjg.v25.i43.6465

  22. Wu Z, Malihi Z, Stewart AW, Lawes CM, Scragg R. Effect of vitamin D supplementation on pain: a systematic review and meta-analysis. Pain Physician. 2016;19:415–27.

  23. Hussain S, Singh A, Akhtar M, et al. Vitamin D supplementation for the management of knee* osteoarthritis *: a systematic review of randomized controlled trials. Rheumatol Int. 2017;37:1489–98. https://doi.org/10.1007/s00296-017-3719-0

  24. Sanghi D, Mishra A, Sharma AC, et al. Does vitamin D improve* osteoarthritis *of the knee: a randomized controlled pilot trial. Clin Orthop Relat Res. 2013;471:3556–62. https://doi.org/10.1007/s11999-013-3201-6

  25. Jin X, Jones G, Cicuttini F, et al. Effect of vitamin D supplementation on tibial cartilage volume and knee pain among patients with symptomatic knee* osteoarthritis *: a randomized clinical trial. JAMA. 2016;315(10):1005–13. https://doi.org/10.1001/jama.2016.1961

  26. Arden NK, Cro S, Sheard S, et al. The effect of vitamin D supplementation on knee* osteoarthritis *, the video study: a randomised controlled trial. Osteoarthr Cartil. 2016;24:1858–66. https://doi.org/10.1016/j.joca.2016.05.020

  27. Mc Alindon T, Lavalley M, Schneider E, et al. Effect of vitamin D supplementation on progression of knee pain and cartilage volume loss in patients with symptomatic* osteoarthritis *. JAMA. 2013;309:155–62. https://doi.org/10.1001/jama.2012.164487

  28. Gao XR, Chen YS, Deng W. The effect of vitamin D supplementation on knee* osteoarthritis *: a meta-analysis of randomized controlled trials. Int J Surg. 2017;46:14–20. https://doi.org/10.1016/j.ijsu.2017.08.010

  29. Diao N, Yang B, Yu F. Effect of vitamin D supplementation on knee* osteoarthritis *: a systematic review and meta-analysis of randomized clinical trials. Clin Biochem. 2017;50:1312–6. https://doi.org/10.1016/j.clinbiochem.2017.09.001

  30. Zhao ZX, He Y, Peng LH, et al. Does vitamin D improve symptomatic and structural outcomes in knee* osteoarthritis *? A systematic review and meta-analysis. Aging Clin Exp Res. 2021;33(9):2393–403. https://doi.org/10.1007/s40520-020-01778-8

  31. Tateiwa D, Yoshikawa H, Kaito T. Cartilage and bone destruction in arthritis: pathogenesis and treatment strategy: a literature review. Cells. 2019;8(8):818. https://doi.org/10.3390/cells8080818

  32. Glover TL, Horgas AL, Fillingim RB, Goodin BR. Vitamin D status and pain sensitization in knee* osteoarthritis *: a critical review of the literature. Pain Manag. 2015;5(6):447–53. https://doi.org/10.2217/pmt.15.43

  33. Martens P, Gysemans C, Verstuyf A, Mathieu C. Vitamin D’s effect on immune function. Nutrients. 2020;12:1248. https://doi.org/10.3390/nu12051248

  34. Milosavljevic MZ, Jovanovic IP, Pejnovic NN, et al. Deletion of IL-33R attenuates VEGF expression and enhances necrosis in mammary carcinoma. Oncotarget. 2016;7(14):18106–15.

  35. Griesenauer B, Paczesny S. ST2/IL-33 axis in immune cells during inflammatory diseases. Front Immunol. 2017;8:475. https://doi.org/10.3389/fimmu.2017.00475

  36. Besnard AG, Togbe D, Guillou N, Erard F, Quesniaux V, Ryffel B. IL-33- activated dendritic cells are critical for allergic airway inflammation. Eur J Immunol. 2011;41(6):1675–86. https://doi.org/10.1002/eji.201041033

  37. Jovanovic I, Pejnovic N, Radosavljevic G, Arsenijevic N, Lukic ML. IL-33/ST2 axis in innate and acquired immunity to tumors. OncoImmunology. 2012;1(2):229–31. https://doi.org/10.4161/onci.1.2.18131

  38. Jovanovic I, Radosavljevic G, Mitrovic M, et al. ST2 deletion enhances innate and acquired immunity to murine mammary carcinoma. Eur J Immunol. 2011;41(7):1902–12. https://doi.org/10.1002/eji.201141417

  39. Jovanovic I, Pejnovic N, Radosavljevic G, et al. Interleukin-33/ST2 axis promotes breast cancer growth and metastases by facilitating intratumoural accumulation of immunosuppressive and innate lymphoid cells. Int J Cancer. 2014;134(7):1669–16682. https://doi.org/10.1002/ijc.28481

  40. He Z, Song Y, Yi Y, et al. Blockade of IL-33 signalling attenuates* osteoarthritis *. Clin Transl Immunol. 2020;9(10):e1185. https://doi.org/10.1002/cti2.1187

  41. De Martinis M, Ginaldi L, Sirufo MM, et al. IL-33/vitamin D crosstalk in psoriasis-associated osteoporosis. Front Immunol. 2021;11:604055. https://doi.org/10.3389/fimmu.2020.604055

  42. Sirufo MM, Ginaldi L, Martinis DE, M,. The IL-33/ST2 axis and vitamin D as a possible emerging therapeutic target in** osteoarthritis__. Rheumatology (Oxford). 2021;60(8):e300. https://doi.org/10.1093/rheumatology/keab292

  43. Annalora AJ, Jozic M, Marcus CB, Iversen PL. Alternative splicing of the vitamin D receptor modulates target gene expression and promotes ligand in dependent functions. Toxicol Appl Pharmacol. 2019;364:55–67. https://doi.org/10.1016/j.taap.2018.12.009

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