Deficiency and lack of vitamin d, polimorphism of the gene receptor of vitamin d and their influence on the intervertebral disc and back pain (literature review)

Authors

  • Vladyslav Povoroznyuk SI «D. F. Chebotarev Institute of Gerontology of the National Academy of Medical Sciences of Ukraine», Kyiv, Ukraine
  • Ninel Dedukh SI «D. F. Chebotarev Institute of Gerontology of the National Academy of Medical Sciences of Ukraine», Kyiv, Ukraine https://orcid.org/0000-0003-0307-2328
  • Tatiana Shinkarenko SI «D. F. Chebotarev Institute of Gerontology of the National Academy of Medical Sciences of Ukraine», Kyiv, Ukraine

DOI:

https://doi.org/10.15674/0030-598720183107-116

Keywords:

intervertebral disc, degeneration, vitamin D, polimorphism of the gene receptor vitamin D (VDR), risk factors, chronic back pain in lumbar spine

Abstract

Vitamin D has a pronounced metabolic effect on bone and cartilaginous tissue, which can have importance for the maintaining of a structural organization and metabolism of the intervertebral disc.

Objective: based on the analysis of literature review, we assessed the impact of the vitamin D deficiency and itʼs lack, polymorphism of the vitamin D receptor on intervertebral disc in normal and with degenerative spine diseases, as well as the manifestation of lower back pain. The review presents the data about the features of the structural organization of intervertebral disc in the normal conditions and with degeneration, risk factors contributing to the degeneration and we evaluated the effect of vitamin D on the intervertebral disc structures. It was mentioned that in patients with degenerative spine diseases, as a rule, there is the deficiency of vitamin D, which affects the prognosis of the surgical treatment. The strategy for the prevention of these diseases can be an estimation of the level of this vitamin followed by its correction. Vitamin D deficiency in patients is associated with nonspecific pain syndrome in the lumbar spine. It was found that hypovitaminosis of vitamin D leads to a violation of bone metabolism and the function of muscle tissue, increased biosynthesis of proinflammatory cytokines, affects the modulating pain sensory neurons. The mechanisms leading to these violations require further studying. Of great importance is the study of polymorphism of the receptor gene vitamin D, which is related to degeneration of intervertebral disc, which is not the same for different populations of patients. Genetic studies of polymorphism of the receptor gene vitamin D gene have crucial for understanding the mechanisms of the degeneration of the intervertebral disc. Genetic information is important for determining of the risk of patients with degenerative spine diseases, in particular, symptomatic manifestations of intervertebral disc degeneration.

Author Biographies

Vladyslav Povoroznyuk, SI «D. F. Chebotarev Institute of Gerontology of the National Academy of Medical Sciences of Ukraine», Kyiv

MD, Prof. in Orthopaedics and Traumatology

Ninel Dedukh, SI «D. F. Chebotarev Institute of Gerontology of the National Academy of Medical Sciences of Ukraine», Kyiv

Dr. Biol. Sci., Prof.

References

  1. Kaplan, W., et al. (2013) Priority medicines for Europe and the World: 2013 update. World Health Organization; Geneva, Switzerland. Available from : http://www. who.int/medicines/areas/priority_medicines.
  2. Boos, N., Weissbach, S., Rohrbach, H., Weiler, C., Spratt, K. F., & Nerlich, A. G. (2002). Classification of age-related changes in lumbar intervertebral discs. Spine, 27(23), 2631–2644. doi:https://doi.org/10.1097/00007632-200212010-00002
  3. Urban, J. P. G. (2003) Degeneration of the intervertebral disc. Arthritis Research and Therapy, 5(3), 120–130. doi: https://doi.org/10.1186/ar629
  4. Taha, M. M., Sabbah, N. A., Rezk, N. A., & Mansour, H. (2017). Vitamin D receptor expression in lumbar disc degeneration patients. Open Journal of Modern Neurosurgery, 07(02), 19–33. doi:https://doi.org/10.4236/ojmn.2017.72003
  5. Płudowski, P., Karczmarewicz, E., & Bayer, M. (2013) Practical guidelines for the supplementation of vitamin D and the treatment of deficits in Central European — recommended vitamin D intakes in the general population and groups at risk of vitamin D deficiency. Pain. Joints. Spine, 11, 7–12. (in Ukrainian)
  6. Lips, P., Hosking, D., Lippuner, K., Norquist, J. M., Wehren, L., Maalouf, G., … Chandler, J. (2006). The prevalence of vitamin D inadequacy amongst women with osteoporosis: an international epidemiological investigation. Journal of Internal Medicine, 260(3), 245–254. doi:https://doi.org/10.1111/j.1365-2796.2006.01685.x
  7. Povoroznyuk, V. V., Pludowski, P. (2014) Vitamin D deficiency and insufficiency: epidemiology, diagnosis, prevention and treatment. Kyiv. (in Ruassian)
  8. Povoroznyuk, V. V., Dedukh, N. V., Yakovenchuk, N. N. (2018) Vitamin D and osteoarthritis. Pain. Joints. Spine, 8(1), 14–23. doi: https://doi.org/10.22141/2224-1507.8.1.2018.130693 (in Ruassian)
  9. Stoker, G. E., Buchowski, J. M., Chen, C. T., Kim, H. J., Park, M. S., & Riew, K. D. (2013). Hypovitaminosis D and cervical disk herniation among adults undergoing spine surgery global. Spine Journal, 3(4), 231–236. doi:https://doi.org/10.1055/s-0033-1354252
  10. Bogunovic, L., Kim, A. D., Beamer, B. S., Nguyen, J., & Lane, J. M. (2010). Hypovitaminosis D in patients scheduled to undergo orthopaedic surgery. The Journal of Bone and Joint Surgery-American Volume, 92(13), 2300–2304. doi:https://doi.org/10.2106/jbjs.i.01231
  11. Zolfaghari, F., Faridmoayer, A., Soleymani, B., Taji, M., & Mahabadi, M. (2016). A survey of Vitamin D status in patients with degenerative diseases of the spine. Asian Spine Journal, 10(5), 834. doi:https://doi.org/10.4184/asj.2016.10.5.834
  12. Allegri, M., Montella, S., Salici, F., Valente, A., Marchesini, M., Compagnone, C., … Fanelli, G. (2016). Mechanisms of low back pain: a guide for diagnosis and therapy. F1000Research, 5, 1530. doi:https://doi.org/10.12688/f1000research.8105.2
  13. Radchenko, V., Dedukh, N., Fedotova, I. (2018) Lumbar disc herniation. In T. Sohall, L. G. Lenke, K. Abums, A. Samdani (Ed.), The Spinel principles & practice (рр. 371–383).
  14. Povoroznyuk, V. V. (2016) Pain in the lower back: modern look at the problemsу. Problems of Osteology, 19(3–4), 5–16. (in Ukrainian)
  15. Liebscher, T., Haefeli, M., Wuertz, K., Nerlich, A. G., & Boos, N. (2011). Age-related variation in cell density of human lumbar intervertebral disc. Spine, 36(2), 153–159. doi:https://doi.org/10.1097/brs.0b013e3181cd588c
  16. Tomaszewski, K. A., Saganiak, K., Gładysz, T., & Walocha, J. A. (2015). The biology behind the human intervertebral disc and its endplates. Folia Morphologica, 74(2), 157–168. doi:https://doi.org/10.5603/fm.2015.0026
  17. Sharp, C. A., Roberts, S., Evans, H., & Brown, S. J. (2009). Disc cell clusters in pathological human intervertebral discs are associated with increased stress protein immunostaining. European Spine Journal, 18(11), 1587–1594. doi:https://doi.org/10.1007/s00586-009-1053-2
  18. Oprea, M., Popa, I., Cimpean, A. M., Raica, M., Poenaru, D. V. Microscopic assessment of degenerated intervertebral disc: clinical implications and possible therapeutic challenge. Іn vivo, 29, 95–102.
  19. Adams, M. A., & Dolan, P. (2012). Intervertebral disc degeneration: evidence for two distinct phenotypes. Journal of Anatomy, 221(6), 497–506. doi:https://doi.org/10.1111/j.1469-7580.2012.01551.x
  20. Risbud, M. V., & Shapiro, I. M. (2013). Role of cytokines in intervertebral disc degeneration: pain and disc content. Nature Reviews Rheumatology, 10(1), 44–56. doi:https://doi.org/10.1038/nrrheum.2013.160
  21. Hadjipavlou, A. G., Tzermiadianos, M. N., Bogduk, N., Zindrick, M. R. (2008) The pathophysiology of disc degeneration. Journal Bone and Joint Surgery. Br., 90(10), 1261–1270. doi: https://doi.org/10.1302/0301-620X.90B10.20910
  22. Wang, J., Tang, T., Yang, H., Yao, X., Chen, L., Liu, W., & Li, T. (2007). The expression of Fas ligand on normal and stabbed-disc cells in a rabbit model of intervertebral disc degeneration: a possible pathogenesis. Journal of Neurosurgery: Spine, 6(5), 425–430. doi:https://doi.org/10.3171/spi.2007.6.5.425
  23. Elmasry, S., Asfour, S., De Rivero Vaccari, J. P., & Travascio, F. (2015). Effects of Tobacco smoking on the degeneration of the intervertebral disc: a finite element study. PLOS One, 10(8), e0136137. doi:https://doi.org/10.1371/journal.pone.0136137
  24. Mayer, J. E., Iatridis, J. C., Chan, D., Qureshi, S. A., Gottesman, O., & Hecht, A. C. (2013). Genetic polymorphisms associated with intervertebral disc degeneration. The Spine Journal, 13(3), 299–317. doi:https://doi.org/10.1016/j.spinee.2013.01.041
  25. Feng, Y., Egan, B., & Wang, J. (2016). Genetic factors in intervertebral disc degeneration. Genes and Diseases, 3(3), 178–185. doi:https://doi.org/10.1016/j.gendis.2016.04.005
  26. Gruber, H. E., Hoelscher, G., Ingram, J. A., Chow, Y., Loeffler, B., & Hanley, E. N. (2008). 1,25(OH)2-Vitamin D3 inhibits proliferation and decreases production of monocyte chemoattractant Protein-1, thrombopoietin, VEGF, and angiogenin by human annulus cells in vitro. Spine, 33(7), 755–765. doi:https://doi.org/10.1097/brs.0b013e3181695d59
  27. Colombini, A., Lanteri, P., Lombardi, G., Grasso, D., Recordati, C., Lovi, A., … Brayda-Bruno, M. (2012). Metabolic effects of vitamin D active metabolites in monolayer and micromass cultures of nucleus pulposus and annulus fibrosus cells isolated from human intervertebral disc. The International Journal of Biochemistry & Cell Biology, 44(6), 1019–1030. doi:https://doi.org/10.1016/j.biocel.2012.03.012
  28. Cannell, J. J., Grant, W. B., Holick, M. F.(2014) Vitamin D and inflammation. Dermatoendocrinol, 6 (1), e983401. doi: 10.4161/19381980.2014.983401
  29. An, J., Zhang, W., Zhang, J., Lian, L., Shen, Y., & Ding, W. (2017). Vitamin D improves the content of TGF-β and IGF-1 in intervertebral disc of diabetic rats. Experimental Biology and Medicine, 242(12), 1254-1261. doi:https://doi.org/10.1177/1535370217707744
  30. Kim, T. H., Lee, B. H, Lee, H. M, Lee, S. H, Park, J. O, Kim, H. S, Kim, S. W, Moon, S. H. Prevalence of vitamin D deficiency in patients with lumbar spinal stenosis and its relationship with pain. Pain Physician, 16(2), 165–176.
  31. Li, Q., Zhang, J., Chen, J., Fan, J., Jiang, T., Yin, J., … Yin, G. (2016). A clinical analysis of vitamin D status in patients before spinal surgery. International Surgery, 101(7–8), 367–374. doi:https://doi.org/10.9738/intsurg-d-16-00102.1
  32. Stoker, G. E., Buchowski, J. M., Chen, C. T., Kim, H. J., Park, M. S., & Riew, K. D. (2013). Hypovitaminosis D and cervical disk herniation among adults undergoing spine surgery. Global Spine Journal, 3(4), 231–236. doi:https://doi.org/10.1055/s-0033-1354252
  33. Stoker, G. E., Buchowski, J. M., Bridwell, K. H., Lenke, L. G., Riew, K. D., & Zebala, L. P. (2013). Preoperative vitamin D status of adults undergoing surgical spinal fusion. Spine, 38(6), 507–515. doi:https://doi.org/10.1097/brs.0b013e3182739ad1
  34. Waikakul, S. (2012). Serum 25-hydroxy-calciferol level and failed back surgery syndrome. Journal of Orthopaedic Surgery, 20(1), 18–22. doi:https://doi.org/10.1177/230949901202000104
  35. Plotnikoff, G. A., & Quigley, J. M. (2003). Prevalence of Severe Hypovitaminosis D in patients with persistent, nonspecific musculoskeletal pain. Mayo Clinic Proceedings, 78(12), 1463–1470. doi:https://doi.org/10.4065/78.12.1463
  36. Deyo, R. A. (1992). What can the history and physical examination tell us about low back pain? JAMA: The Journal of the American Medical Association, 268(6), 760. doi:https://doi.org/10.1001/jama.1992.03490060092030
  37. Straube, S., Moore, A. R., Derry, S., & McQuay, H. J. (2009). Vitamin D and chronic pain. Pain, 141(1), 10–13. doi:https://doi.org/10.1016/j.pain.2008.11.010
  38. Kulie, T., Groff, A., Redmer, J., Hounshell, J., Schrager, S. (2009) Vitamin D: an evidence-based review. The Journal of the American Board of Family Medicine, 22, 698–706. doi: https://doi.org/10.3122/jabfm.2009.06.090037
  39. De Torrenté de la Jara, G., Pécoud, A., & Favrat, B. (2006). Female asylum seekers with musculoskeletal pain: the importance of diagnosis and treatment of hypovitaminosis D. BMC Family Practice, 7(1). doi:https://doi.org/10.1186/1471-2296-7-4
  40. Lodh, M., Goswami, B., Mahajan, R. D., Sen, D., Jajodia, N., & Roy, A. (2014). Assessment of vitamin D status in patients of chronic low back pain of unknown etiology. Indian Journal of Clinical Biochemistry, 30(2), 174–179. doi:https://doi.org/10.1007/s12291-014-0435-3
  41. Lotfi, A., Abdel-Nasser, A. M., Hamdy, A., Omran, A. A., & El-Rehany, M. A. (2007). Hypovitaminosis D in female patients with chronic low back pain. Clinical Rheumatology, 26(11), 1895–1901. doi:https://doi.org/10.1007/s10067-007-0603-4
  42. de Souza Silva, A. V., Lacativa, P. G., Russo, L. A., De Gregório, L. H., Pinheiro, R. A., & Marinheiro, L. P. (2013). Association of back pain with hypovitaminosis D in postmenopausal women with low bone mass. BMC Musculoskeletal Disorders, 14(1). doi:https://doi.org/10.1186/1471-2474-14-184
  43. Orlyk, Т. V. (2014) The role of vitamin D in the formation of vertebral pain syndrome in women in the postmenopausal period. Medico-social problems of the family, 19(4), 50–54. (in Ukrainian)
  44. Kim, T. H., Lee, B. H., Lee, H. M., Lee, S. H., Park, J. O., Kim, H. S., Kim, S. W., Moon, S. H. (2013) Prevalence of vitamin D deficiency in patients with lumbar spinal stenosis and its relationship with pain. Pain Physician, 16(2), 165–176.
  45. Sedighi, M., & Haghnegahdar, A. (2014). Role of vitamin D3 in Treatment of Lumbar Disc Herniation—Pain and Sensory Aspects: Study Protocol for a Randomized Controlled Trial. Trials, 15(1). doi:https://doi.org/10.1186/1745-6215-15-373
  46. Çalık, Y., & Aygün, Ü. (2017). Evaluation of vitamin D levels in patients with chronic low back-leg pain. Acta Orthopaedica et Traumatologica Turcica, 51(3), 243–247. doi:https://doi.org/10.1016/j.aott.2017.03.006
  47. Tague, S. E., Clarke, G. L., Winter, M. K., McCarson, K. E., Wright, D. E., & Smith, P. G. (2011). Vitamin D deficiency promotes skeletal muscle hypersensitivity and sensory hyperinnervation. Journal of Neuroscience, 31(39), 13728–13738. doi:https://doi.org/10.1523/jneurosci.3637-11.2011
  48. Warner, A. E., & Arnspiger, S. A. (2008). Diffuse musculoskeletal pain is not associated with low vitamin D levels or improved by treatment with Vitamin D. JCR: Journal of Clinical Rheumatology, 14(1), 12–16. doi:https://doi.org/10.1097/rhu.0b013e31816356a9
  49. Block, S. R. (2004). Vitamin D deficiency is not associated with nonspecific musculoskeletal pain syndromes including fibromyalgia. Mayo Clinic Proceedings, 79(12), 1585–1586. doi:https://doi.org/10.4065/79.12.1585
  50. Ghai, B., Bansal, D., Kanukula, R., Gudala, K., Sachdeva, N., Dhatt, S. S., Kumar, V. (2017) Vitamin D supplementation in patients with chronic low back pain: an open label, single arm clinical trial. Pain Physician, 20(1), E99–E105.
  51. Al Faraj, S., & Al Mutairi, K. (2003). Vitamin D Deficiency and Chronic Low Back Pain in Saudi Arabia. Spine, 28(2), 177–179. doi:https://doi.org/10.1097/00007632-200301150-00015
  52. Garcion, E., Wion-Barbot, N., Montero-Menei, C. N., Berger, F., & Wion, D. (2002). New clues about vitamin D functions in the nervous system. Trends in Endocrinology & Metabolism, 13(3), 100–105. doi:https://doi.org/10.1016/s1043-2760(01)00547-1
  53. Calton, E. K., Keane, K. N., Newsholme, P., & Soares, M. J. (2015). the impact of vitamin D levels on inflammatory status: a systematic review of immune cell studies. PLOS ONE, 10(11), e0141770. doi:https://doi.org/10.1371/journal.pone.0141770
  54. Rosendahl-Riise, H., Spielau, U., Ranhoff, A. H., Gudbrandsen, O. A., & Dierkes, J. (2016). Vitamin D supplementation and its influence on muscle strength and mobility in community-dwelling older persons: a systematic review and meta-analysis. Journal of Human Nutrition and Dietetics, 30(1), 3–15. doi:https://doi.org/10.1111/jhn.12394
  55. Straube, S., Derry, S., Straube, C., & Moore, R. A. (2015). Vitamin D for the treatment of chronic painful conditions in adults. Cochrane Database of Systematic Reviews, 6(5), СD007771. doi:https://doi.org/10.1002/14651858.cd007771.pub3
  56. Zadro, J. R., Shirley, D., Ferreira, M., Carvalho Silva, A. P., Lamb, S. E., Cooper, C, Ferreira, P. H.( 2018) Is vitamin D supplementation effective for low back pain? a systematic review and meta-analysis. Pain Physician, 21(2), 121–145.
  57. Zhao, J., Yang, M., Shao, J., Bai, Y., & Li, M. (2015). Association between VDR FokI polymorphism and intervertebral disk degeneration. Genomics, Proteomics & Bioinformatics, 13(6), 371–376. doi:https://doi.org/10.1016/j.gpb.2015.11.003
  58. Vieira, L. A., De Marchi, P. L., Dos Santos, A. A., Christofolini, D. M., Barbosa, C. P., Fonseca, F. L., … Rodrigues, L. M. (2014). Analysis of FokI polymorphism of vitamin D receptor gene in intervertebral disc degeneration. Genetic Testing and Molecular Biomarkers, 18(9), 625–629. doi:https://doi.org/10.1089/gtmb.2014.0030
  59. Jiang, H., Qin, Z., Zong, S., He, M., Zhan, X., Xiao, Z., Wei, Q. (2017) Vitamin D receptor gene polymorphisms and lumbar disc degeneration: a systematic review and meta-analysis. European Spine Journal, 26(1), 267–277. doi: https://doi.org/10.1007/s00586-016-4771-2
  60. Pabalan, N., Tabangay, L., Jarjanazi, H., Vieira, L. A., Dos Santos, A. A., Barbosa, C. P., Rodrigues, L. M., Bianco, B. (2017) Association between the Fokl and Apal polymorphisms in the vitamin D receptor gene and intervertebral disc degeneration: a systematic review and meta-analysis. Genetic Testing and Molecular Biomarkers, 21(1), 24–32. doi: https://doi.org/10.1089/gtmb.2016.0054
  61. Chen, L., Zhao, S., Niu, F., & Bi, G. (2017). Association between vitamin D receptor gene polymorphisms and intervertebral disc degeneration: A meta-analysis. Journal of Orthopaedic Science, 22(2), 184–189. doi:https://doi.org/10.1016/j.jos.2016.11.009
  62. Xu, G., Mei, Q., Zhou, D., Wu, J., & Han, L. (2012). Vitamin D receptor gene and aggrecan gene polymorphisms and the risk of intervertebral disc degeneration — a meta-analysis. PLoS ONE, 7(11), e50243. doi:https://doi.org/10.1371/journal.pone.0050243
  63. Videman, T., Leppävuori, J., Kaprio, J., Battié, M. C., Gibbons, L. E., Peltonen, L., & Koskenvuo, M. (1998). 1998 Volvo Award Winner in Basic Science Studies. Spine, 23(23), 2477–2485. doi:https://doi.org/10.1097/00007632-199812010-00002
  64. Cheung, K. M., Chan, D., Karppinen, J., Chen, Y., Jim, J. J., Yip, S., … Song, Y. (2006). Association of the Taq I Allele in Vitamin D receptor with degenerative disc disease and disc bulge in a Chinese population. Spine, 31(10), 1143–1148. doi:https://doi.org/10.1097/01.brs.0000216530.41838.d3
  65. Weijian Chen. (2012). Association of vitamin D receptor gene polymorphism in Han people with lumbar degenerative disc disease. African Journal of Pharmacy and Pharmacology, 6(16). doi:https://doi.org/10.5897/ajpp12.114
  66. Virtanen, I. M., Karppinen, J., Taimela, S., Ott, J., Barral, S., Kaikkonen, K., Heikkilä, O., Mutanen, P., Noponen, N., Männikkö, M., Tervonen, O., Natri, A., Ala-Kokko, L. (2002) The association of lumbar disc disease with vitamin-D receptor gene polymorphism. Journal of Bone and Joint Surgery Am., 84-A, 2022–2028.
  67. Oishi, Y., Shimizu, K., Katoh, T., Nakao, H., Yamaura, M., Furuko, T., … Nakamura, T. (2003). Lack of association between lumbar disc degeneration and osteophyte formation in elderly japanese women with back pain. Bone, 32(4), 405–411. doi:https://doi.org/10.1016/s8756-3282(03)00031-0
  68. Eser, B., Cora, T., Eser, O., Kalkan, E., Haktanır, A., Erdogan, M. O., & Solak, M. (2010). Association of the polymorphisms of vitamin D receptor and aggrecan genes with degenerative disc disease. Genetic Testing and Molecular Biomarkers, 14(3), 313–317. doi:https://doi.org/10.1089/gtmb.2009.0202
  69. Yuan, H., Tang, Y., Liang, Y., Lei, L., Xiao, G., Wang, S., & Xia, Z. (2010). Matrix metalloproteinase-3 and vitamin D receptor genetic polymorphisms, and their interactions with occupational exposure in lumbar disc degeneration. Journal of Occupational Health, 52(1), 23–30. doi:https://doi.org/10.1539/joh.l8149
  70. Jiang, H., Qin, Z., Zong, S., He, M., Zhan, X., Xiao, Z., & Wei, Q. (2016). Vitamin D receptor gene polymorphisms and lumbar disc degeneration: a systematic review and meta-analysis. European Spine Journal, 26(1), 267–277. doi:https://doi.org/10.1007/s00586-016-4771-2
  71. Nong, L., Huang, Y., Zhao, S., & Xu, N. (2016). Vitamin D Receptor gene, matrix metalloproteinase 3 polymorphisms and the risk of intervertebral disc degeneration susceptibility: meta-analysis. Asian Spine Journal, 10(5), 964. doi:https://doi.org/10.4184/asj.2016.10.5.964
  72. Colombini, A., Brayda-Bruno, M., Lombardi, G., Croiset, S. J., Ceriani, C., Buligan, C., … Cauci, S. (2016). BsmI, ApaI and TaqI polymorphisms in the vitamin D receptor gene (VDR) and association with lumbar spine pathologies: an Italian case-control study. PLoS ONE, 11(5), e0155004. doi:https://doi.org/10.1371/journal.pone.0155004
  73. Cauci, S., Viganò, M., De Girolamo, L., De Luca, P., Perucca Orfei, C., Banfi, G., … Colombini, A. (2017). High Levels of Circulating Type II Collagen Degradation Marker (CTx-II) Are Associated with specific VDR polymorphisms in patients with adult vertebral osteochondrosis. International Journal of Molecular Sciences, 18(10), 2073. doi:https://doi.org/10.3390/ijms18102073

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Povoroznyuk, V., Dedukh, N., & Shinkarenko, T. (2023). Deficiency and lack of vitamin d, polimorphism of the gene receptor of vitamin d and their influence on the intervertebral disc and back pain (literature review). ORTHOPAEDICS TRAUMATOLOGY and PROSTHETICS, (3), 107–116. https://doi.org/10.15674/0030-598720183107-116

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No. 3 (2018)

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DIGESTS AND REVIEWS

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