Supplementation of hyaluronic acid injections with vitamin D improve knee function by attenuating synovial fluid oxidative stress in osteoarthritis patients with vitamin D insufficiency

Objectives There is still controversy about the effect of vitamin D supplementation on osteoarthritis (OA). The purpose of this study was to investigate the effects of vitamin D supplementation with Hyaluronic acid (HA) injection on OA. Methods We investigated serum vitamin D levels and oxidative stress (OS) in synovial fluid from patients with OA who underwent total knee arthroplasty (grade IV, n = 24) and HA injection (grade II and III, n = 40). The effects of HA injection with or without oral vitamin D supplementation on synovial fluid OS and knee pain and function were then further investigated. Finally, patients underwent HA injection were divided into two groups according to vitamin D levels (vitamin D < or > 30 ng/ml), and the efficacy of the two groups were compared. Results The results showed that the levels of glutathione peroxidase (GSH-PX) (P < 0.05) in the synovial fluid were lower in patients with stage IV OA than that in patients with stage II-III OA, while the levels of malondialdehyde (MDA) (P < 0.05) and lactate dehydrogenase (LDH) (P < 0.01) were significantly higher. Moreover, we found that age, BMI and vitamin D levels were significantly associated with the levels of oxidants and/or antioxidants in synovial fluid, and that vitamin D was significantly negatively correlated with BMI (R = −0.3527, p = 0.0043). Supplementation of HA injections with vitamin D significantly reduced the OS status in synovial fluid, attenuated knee pain and improved knee function in OA patients with vitamin D insufficiency. Conclusion We conclude that maintenance of vitamin D sufficiency may be beneficial for the treatment of OA by improving OS in synovial fluid.

[1]  L. Mounien,et al.  Vitamin D and Obesity/Adiposity—A Brief Overview of Recent Studies , 2022, Nutrients.

[2]  C. Lo,et al.  The effect of vitamin D supplementation on oxidative stress parameters: an updated meta-analysis of clinical trials. , 2022, Pharmacological research.

[3]  B. Gallego,et al.  Effectiveness of Vitamin D Supplementation on Knee Osteoarthritis - A target trial emulation study using data from the Osteoarthritis Initiative cohort. , 2022, Osteoarthritis and cartilage.

[4]  Y. Boirie,et al.  A Meta-Analysis of the Impact of Nutritional Supplementation on Osteoarthritis Symptoms , 2022, Nutrients.

[5]  N. Lane,et al.  Synovial inflammation in osteoarthritis progression , 2022, Nature Reviews Rheumatology.

[6]  F. Cuenca‐Martínez,et al.  The Role of Vitamin D in Early Knee Osteoarthritis and Its Relationship with Their Physical and Psychological Status , 2021, Nutrients.

[7]  K. Valachová,et al.  Hyaluronan as a Prominent Biomolecule with Numerous Applications in Medicine , 2021, International journal of molecular sciences.

[8]  A. Fifere,et al.  The Implication of Reactive Oxygen Species and Antioxidants in Knee Osteoarthritis , 2021, Antioxidants.

[9]  Jean L. Fry,et al.  Vitamin D Promotes Skeletal Muscle Regeneration and Mitochondrial Health , 2021, Frontiers in Physiology.

[10]  A. Mobasheri,et al.  The role of metabolism in chondrocyte dysfunction and the progression of osteoarthritis , 2020, Ageing Research Reviews.

[11]  Wan-Ching Chou,et al.  Hyaluronic acid injection reduces inflammatory and apoptotic markers through modulation of AKT by repressing the oxidative status of neutrophils from osteoarthritic synovial fluid. , 2020, International journal of biological macromolecules.

[12]  Ni Zeng,et al.  Infrapatellar Fat Pad and Knee Osteoarthritis , 2020, Aging and disease.

[13]  R. O’Keefe,et al.  LDHA-mediated ROS generation in chondrocytes is a potential therapeutic target for osteoarthritis , 2020, Nature Communications.

[14]  T. Haqqi,et al.  Oxidative stress and inflammation in osteoarthritis pathogenesis: Role of polyphenols. , 2020, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[15]  P. Brun,et al.  Anti-Inflammatory Performance of Lactose-Modified Chitosan and Hyaluronic Acid Mixtures in an In Vitro Macrophage-Mediated Inflammation Osteoarthritis Model , 2020, Cells.

[16]  Q. Liang,et al.  KLF2 Protects against Osteoarthritis by Repressing Oxidative Response through Activation of Nrf2/ARE Signaling In Vitro and In Vivo , 2019, Oxidative medicine and cellular longevity.

[17]  B. Sharma,et al.  Manganese dioxide nanoparticles protect cartilage from inflammation-induced oxidative stress. , 2019, Biomaterials.

[18]  C. Orces The Association between Body Mass Index and Vitamin D Supplement Use among Adults in the United States , 2019, Cureus.

[19]  J H Abbott,et al.  OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis. , 2019, Osteoarthritis and cartilage.

[20]  Ravinder J. Singh,et al.  Obesity Decreases Hepatic 25‐Hydroxylase Activity Causing Low Serum 25‐Hydroxyvitamin D , 2019, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[21]  S. Wimalawansa Vitamin D Deficiency: Effects on Oxidative Stress, Epigenetics, Gene Regulation, and Aging , 2019, Biology.

[22]  C. Park Vitamin D in the Prevention and Treatment of Osteoarthritis: From Clinical Interventions to Cellular Evidence , 2019, Nutrients.

[23]  C. Scirè,et al.  Osteoarthritis and its management - Epidemiology, nutritional aspects and environmental factors. , 2018, Autoimmunity reviews.

[24]  R. Tanakol,et al.  Calcitriol treatment in patients with low vitamin D levels , 2018, Archives of Osteoporosis.

[25]  M. Hamrick,et al.  Recent advances in hyaluronic acid based therapy for osteoarthritis , 2018, Clinical and Translational Medicine.

[26]  F. Flamigni,et al.  Emerging Players at the Intersection of Chondrocyte Loss of Maturational Arrest, Oxidative Stress, Senescence and Low-Grade Inflammation in Osteoarthritis , 2018, Oxidative medicine and cellular longevity.

[27]  T. Throckmorton,et al.  Hyaluronic acid injections for osteoarthritis of the knee: predictors of successful treatment , 2018, International Orthopaedics.

[28]  F. Cicuttini,et al.  Maintaining Vitamin D Sufficiency Is Associated with Improved Structural and Symptomatic Outcomes in Knee Osteoarthritis. , 2017, The American journal of medicine.

[29]  M. Bhandari,et al.  The Disease-Modifying Effects of Hyaluronan in the Osteoarthritic Disease State , 2017, Clinical medicine insights. Arthritis and musculoskeletal disorders.

[30]  F. Cicuttini,et al.  Knee effusion-synovitis volume measurement and effects of vitamin D supplementation in patients with knee osteoarthritis. , 2017, Osteoarthritis and cartilage.

[31]  S. Honsawek,et al.  Vitamin D Supplementation Improves Quality of Life and Physical Performance in Osteoarthritis Patients , 2017, Nutrients.

[32]  C. Ding,et al.  Vitamin D and osteoarthritis: disparity between observational studies and clinical trials , 2017, International journal of rheumatic diseases.

[33]  A. Mobasheri,et al.  The role of metabolism in the pathogenesis of osteoarthritis , 2017, Nature Reviews Rheumatology.

[34]  M. Akhtar,et al.  Vitamin D supplementation for the management of knee osteoarthritis: a systematic review of randomized controlled trials , 2017, Rheumatology International.

[35]  Richard F. Loeser,et al.  Ageing and the pathogenesis of osteoarthritis , 2016, Nature Reviews Rheumatology.

[36]  M. Berteanu,et al.  Short-term Administration of Alphacalcidol is Associated with More Significant Improvement of Muscular Performance in Women with Vitamin D Deficiency Compared to Native Vitamin D. , 2016, Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association.

[37]  B. Bai,et al.  Danshen prevents articular cartilage degeneration via antioxidation in rabbits with osteoarthritis. , 2016, Osteoarthritis and cartilage.

[38]  M. D. Kohn,et al.  Classifications in Brief: Kellgren-Lawrence Classification of Osteoarthritis , 2016, Clinical orthopaedics and related research.

[39]  F. Beier,et al.  Targeting oxidative stress to reduce osteoarthritis , 2016, Arthritis Research & Therapy.

[40]  A. Carr,et al.  Osteoarthritis , 2015, The Lancet.

[41]  S. Honsawek,et al.  Role of Vitamin D in Osteoarthritis: Molecular, Cellular, and Clinical Perspectives , 2015, International journal of endocrinology.

[42]  T. Sasho,et al.  Mechanical overloading causes mitochondrial superoxide and SOD2 imbalance in chondrocytes resulting in cartilage degeneration , 2015, Scientific Reports.

[43]  P. Guo,et al.  Oral vitamin D supplementation has a lower bioavailability and reduces hypersecretion of parathyroid hormone and insulin resistance in obese Chinese males , 2014, Public Health Nutrition.

[44]  L. K. Pourshahidi Vitamin D and obesity: current perspectives and future directions , 2014, Proceedings of the Nutrition Society.

[45]  P. Pinsornsak,et al.  Can levels of antioxidants in synovial fluid predict the severity of primary knee osteoarthritis: a preliminary study , 2013, SpringerPlus.

[46]  Ajai Pratap Singh,et al.  Does Vitamin D Improve Osteoarthritis of the Knee: A Randomized Controlled Pilot Trial , 2013, Clinical orthopaedics and related research.

[47]  O. Gómez-Marín,et al.  The role of vitamin D in improving physical performance in the elderly , 2013, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[48]  Ahmad Esmaillzadeh,et al.  Serum 25‐hydroxy vitamin D levels in relation to body mass index: a systematic review and meta‐analysis , 2013, Obesity reviews : an official journal of the International Association for the Study of Obesity.

[49]  Bess Dawson-Hughes,et al.  Effect of vitamin D supplementation on progression of knee pain and cartilage volume loss in patients with symptomatic osteoarthritis: a randomized controlled trial. , 2013, JAMA.

[50]  R. Heaney,et al.  Volumetric Dilution, Rather Than Sequestration Best Explains the Low Vitamin D Status of Obesity , 2012, Obesity.

[51]  N. P. Morales,et al.  Lipid peroxidation, glutathione, vitamin E, and antioxidant enzymes in synovial fluid from patients with osteoarthritis , 2009, International journal of rheumatic diseases.

[52]  E. Regan,et al.  Joint fluid antioxidants are decreased in osteoarthritic joints compared to joints with macroscopically intact cartilage and subacute injury. , 2008, Osteoarthritis and cartilage.

[53]  M. Holick Vitamin D deficiency. , 2007, The New England journal of medicine.

[54]  A. Kasperczyk,et al.  Lipid peroxidation and antioxidant enzymes in synovial fluid of patients with primary and secondary osteoarthritis of the knee joint. , 2006, Osteoarthritis and cartilage.

[55]  M. Holick,et al.  Decreased bioavailability of vitamin D in obesity. , 2000, The American journal of clinical nutrition.

[56]  J. C. Hughston,et al.  Analysis of subjective knee complaints using visual analog scales , 1991, The American journal of sports medicine.

[57]  C. Goldsmith,et al.  Validation study of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee. , 1988, The Journal of rheumatology.

[58]  M. Akbari-Fakhrabadi,et al.  The effect of vitamin D supplementation on oxidative stress parameters: A systematic review and meta‐analysis of clinical trials , 2019, Pharmacological research.