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)

Vladyslav Povoroznyuk, Ninel Dedukh, Tatiana Shinkarenko


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.


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


Kaplan, W., et al. (2013) Priority medicines for Europe and the World: 2013 update. World Health Organization; Geneva, Switzerland. Available from : http://www.

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:10.1097/00007632-200212010-00002

Urban, J. P. G. (2003) Degeneration of the intervertebral disc. Arthritis Research and Therapy, 5(3), 120–130. doi: 10.1186/ar629

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:10.4236/ojmn.2017.72003

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)

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:10.1111/j.1365-2796.2006.01685.x

Povoroznyuk, V. V., Pludowski, P. (2014) Vitamin D deficiency and insufficiency: epidemiology, diagnosis, prevention and treatment. Kyiv. (in Ruassian)

Povoroznyuk, V. V., Dedukh, N. V., Yakovenchuk, N. N. (2018) Vitamin D and osteoarthritis. Pain. Joints. Spine, 8(1), 14–23. doi: 10.22141/2224-1507.8.1.2018.130693 (in Ruassian)

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:10.1055/s-0033-1354252

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:10.2106/jbjs.i.01231

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:10.4184/asj.2016.10.5.834

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:10.12688/f1000research.8105.2

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).

Povoroznyuk, V. V. (2016) Pain in the lower back: modern look at the problemsу. Problems of Osteology, 19(3–4), 5–16. (in Ukrainian)

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:10.1097/brs.0b013e3181cd588c

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:10.5603/fm.2015.0026

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:10.1007/s00586-009-1053-2

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.

Adams, M. A., & Dolan, P. (2012). Intervertebral disc degeneration: evidence for two distinct phenotypes. Journal of Anatomy, 221(6), 497–506. doi:10.1111/j.1469-7580.2012.01551.x

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:10.1038/nrrheum.2013.160

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: 10.1302/0301-620X.90B10.20910

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:10.3171/spi.2007.6.5.425

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:10.1371/journal.pone.0136137

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:10.1016/j.spinee.2013.01.041

Feng, Y., Egan, B., & Wang, J. (2016). Genetic factors in intervertebral disc degeneration. Genes and Diseases, 3(3), 178–185. doi:10.1016/j.gendis.2016.04.005

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:10.1097/brs.0b013e3181695d59

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:10.1016/j.biocel.2012.03.012

Cannell, J. J., Grant, W. B., Holick, M. F.(2014) Vitamin D and inflammation. Dermatoendocrinol, 6 (1), e983401. doi: 10.4161/19381980.2014.983401

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:10.1177/1535370217707744

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.

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:10.9738/intsurg-d-16-00102.1

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:10.1055/s-0033-1354252

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:10.1097/brs.0b013e3182739ad1

Waikakul, S. (2012). Serum 25-hydroxy-calciferol level and failed back surgery syndrome. Journal of Orthopaedic Surgery, 20(1), 18–22. doi:10.1177/230949901202000104

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:10.4065/78.12.1463

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:10.1001/jama.1992.03490060092030

Straube, S., Moore, A. R., Derry, S., & McQuay, H. J. (2009). Vitamin D and chronic pain. Pain, 141(1), 10–13. doi:10.1016/j.pain.2008.11.010

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: 10.3122/jabfm.2009.06.090037

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:10.1186/1471-2296-7-4

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:10.1007/s12291-014-0435-3

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:10.1007/s10067-007-0603-4

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:10.1186/1471-2474-14-184

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)

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.

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:10.1186/1745-6215-15-373

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:10.1016/j.aott.2017.03.006

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:10.1523/jneurosci.3637-11.2011

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:10.1097/rhu.0b013e31816356a9

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:10.4065/79.12.1585

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.

Al Faraj, S., & Al Mutairi, K. (2003). Vitamin D Deficiency and Chronic Low Back Pain in Saudi Arabia. Spine, 28(2), 177–179. doi:10.1097/00007632-200301150-00015

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:10.1016/s1043-2760(01)00547-1

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:10.1371/journal.pone.0141770

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:10.1111/jhn.12394

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:10.1002/14651858.cd007771.pub3

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.

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:10.1016/j.gpb.2015.11.003

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:10.1089/gtmb.2014.0030

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: 10.1007/s00586-016-4771-2

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: 10.1089/gtmb.2016.0054

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:10.1016/j.jos.2016.11.009

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:10.1371/journal.pone.0050243

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:10.1097/00007632-199812010-00002

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:10.1097/01.brs.0000216530.41838.d3

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:10.5897/ajpp12.114

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.

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:10.1016/s8756-3282(03)00031-0

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:10.1089/gtmb.2009.0202

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:10.1539/joh.l8149

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:10.1007/s00586-016-4771-2

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:10.4184/asj.2016.10.5.964

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:10.1371/journal.pone.0155004

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:10.3390/ijms18102073

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