Biomedicine and Chemical Sciences

Chronic low back pain is often progressive and the cause may be difficult to ascertain. Vitamin D deficiency has been correlated with chronic musculoskeletal pain including low back pain.^1-5 A high prevalence of Vitamin D deficiency has been reported in patients with chronic low back pain in comparison to the general population.^6-9 Two probable theories have been postulated- Firstly, the diffuse musculoskeletal pain, weakness and paraesthesia may be caused by hypovitaminosis D and secondly, hypovitaminosis D could play a role in the development of modic changes by increasing the susceptibility to inflammation in the vertebral end plates.

Vitamin D has a significant role to play in bone metabolism and neuro muscular function. The supplementation with calcium and Vitamin D has demonstrated Vitamin D’s effectiveness in lowering the risk of fracture in osteoporotic patients. Recent research has shown a much broader role of Vitamin D and increasing number of investigations are being performed to show the effects of hypovitaminosis D and Vitamin D supplementation on different health aspects. Physiologically, Vitamin D plays a crucial role in the maintenance of extracellular calcium levels,which is a pre requisite for adequate musculoskeletal function^10-13

The rationale of our study is to find the beneficial role of vitamin D supplementation in addition to the standard treatment of chronic low back pain

MATERIALS AND METHODS:

Study design: Hospital based prospective Cohort study

Sample Size: 100

Study Sample Collection: Male and female patients between the age groups 18-70 years attending the Out Patient Department of Orthopaedics, KMCH presenting with chronic low back ache. The patients were asked to complete the baseline pain related questionnaire. The questionnaires included VAS (Visual Analogue Score) to measure chronic low back pain intensity, functional disability using MODQ (Modified Oswestry Disability Questionnaire)¹⁴, work status.

Duration of study; 1 year (May 2024- May 2025)

Inclusion Criteria: Patients of both genders aged 18-70 years with chronic low back pain ≥ 12 weeks with or without leg pain.

Exclusion criteria: Patients were excluded if they had evidence of other causes of neuropathy or painful inflammatory conditions like Diabetes Mellitus, Rheumatoid arthritis and symptomatic osteoarthritis of the hip and knee. Patients diagnosed with epilepsy, psychiatric diseases, substance abuse, metabolic bone diseases like hypo or hyperparathyroidism, chronic renal disease, medical or surgical disorders affecting Vitamin D metabolism( gastric surgery, chronic liver disease, renal failure, intestinal malabsorption, systemic infection, cancers etc) were also excluded. Patients on corticosteroids or bisphosphonates or teriparatide , pregnant and lactating mothers were also excluded. Patients taking Vitamin D supplements during the past 3 months were also excluded from our present study.

Definition of Vitamin D levels :

Vitamin D₃ deficiency was graded based on Holick’s classification as follows- Vitamin D₃ deficiency was defined as a 25(OH) D₃ level of ≤ 20ng/ml. Vitamin D insufficiency as >20 – 29ng/ml and normal level as ≥30 ng/ml.

Data Collection Method:

Only those patients meeting the inclusion criteria were enrolled from the OPD. Informed Consent was taken from each patient to assess the Vitamin D levels. Blood samples taken from Median Cubital Vein and those patients found to be having Vitamin D deficiency or insufficiency were started with Oral dose of Vitamin D₃ (60000IU) once weekly for 12 weeks. Repeat Serum Vitamin D₃ was checked after 12 weeks. Those patients with inadequate Vitamin D₃ levels even after 12 weeks were continued with Oral dose of Vitamin D₃ (60000IU) until Vitamin D₃ levels became normal. General follow up of patients was done at 3 months and 6 months respectively. The patients were assessed at baseline and at each follow up for pain intensity by using VAS (Visual Analogue Score) and functional disability by using Modified Oswestry Disability score.

Statistical Analysis: All the statistical tests were performed using SPSS software and analysis done using chi square test. P- Value of <0.05 was considered statistically significant.

RESULTS:

Table 1 : Baseline demography characteristics

Table 2  : Age( in years) characteristics

Table 3 : Vitamin D status at baseline among men and women

*Deficient Vit D levels < 20ng/ml

*Insufficient Vit D levels (21- 29ng/ml )

*Sufficient Vit d levels ≥30ng/ml

Table 4 : Table showing mean Vitamin D levels at baseline and after supplementation

*comparison between baseline and after treatment done by paired t- test

Table 5  : Clinical efficacy analysis

Results analysis:  A total of 100 potentially eligible patients were screened for study participation. 19 patients were ineligible due to normal Vitamin D levels. Hence, 81 patients were included in the study. 30 patients (37 %) were male and 51 patients (63%) were female. The mean age (SD) of the male patients was 45.7 yrs (SD =13.8) and among the females was     41.5 yrs ( SD = 17.4). Prior to inclusion into this study, the participants Mean (SD) VAS and MODQ was found to be 8 (3.56) [VAS range from 0-10]  and  45( 11.42) [MODQ range from 0 to 50]  respectively showing that the majority of the patients had severe pain  and disability at the onset of the study.

Baseline Mean (SD) Vitamin D level was found to be 18.05 ng/ml (SD= 5.73). 48 patients (59.3%) were found to have deficient Vitamin D levels at baseline and   33 patients (40.7%) were Vitamin D insufficient. Serum Vitamin D levels increased significantly to 31.07 ng/ml  (SD=11.55) post supplementation ( P <0.01) at 3 months and 40.67ng/ml (SD=9.45) at 6 months respectively( P value<0.01).

Significant reduction in pain score was observed post supplementation. The Mean VAS score at 3months and 6 months decreased to 3 (2.35) and 2 (2.12) respectively ( P value<0.001 ,which was statistically significant). The mean MODQ at 3 months and 6 months decreased to 31(9.67) and 23 (8.55) respectively ( P value <0.001, statistically significant).

DISCUSSION

Chronic low back pain is one of the most common disorder of spine in adults all over the world¹⁵. It causes hindrance in daily activities, thereby decreasing social functioning and thus decreases the quality of lifestyle. It has also been observed that insufficient and deficient levels of Vitamin D are significantly involved in severe chronic spinal diseases and chronic painful disorders^16-17. Vitamin D is involved in Calcium homeostasis and is needed for the proper functioning of bones, muscles and nerves. It also has anti-inflammatory properties. Multiple factors like geographical location, sunlight exposure, malnutrition and ethnicity affects the serum levels of Vitamin D.

Vitamin D plays a key role in the etiology and progression of various chronic pain conditions and associated co-morbidities by exerting anatomic, neurological, hormonal and immunological influences on pain expression. Vitamin D deficiency is known to induce muscle weakness and pain in adults as well as children^18-19. Vitamin D is also known to have immunomodulatory property. Vitamin D supplementation is often associated with improvement in bone density and musculoskeletal pain by reducing the synthesis of inflammatory cytokines and increasing the anti-inflammatory cytokines^20-21.

Vitamin D suppresses Tumour Necrosis Factor Alpha( TNF-α), Macrophage Colony Stimulating factor (M -CSF) and Nitric Oxide synthase in astrocytes and microglia. TNF-α has been implicated at both the peripheral and central levels of pain sensitization. M-CSF is a cytokine that stimulates proliferation, differentiation and survival of monocytes and macrophages. Macrophages can release many inflammatory mediators including pro-inflammatory cytokines particularly TNF-α and interleukin-1 beta, Nerve growth Factor, Nitric Oxide and prostanoids.

CONCLUSION:

The findings of our study provides information regarding the association of vitamin D3 deficiency and patients with chronic low back pain, which is associated with diminished functional capacity. Clinical guidelines for the management of chronic low back pain should include an evaluation of the patient's vitamin D3 status, along with recommendations for appropriate vitamin D3 supplementation for individuals who are found to be deficient in vitamin D3.

REFERENCES:

1. Dionne CE, Dunn KM, Croft PR, Nachemson AL, Buchbinder R, Walker BF, Wyatt M, Cassidy JD, Rossignol M, Leboeuf-Yde C, Hartvigsen J, Leino-Arjas P, Latza U, Reis S, Gil Del Real MT, Kovacs FM, Oberg B, Cedraschi C, Bouter LM, Koes BW, Picavet HS, van Tulder MW, Burton K, Foster NE, Macfarlane GJ, Thomas E, Underwood M, Waddell G, Shekelle P, Volinn E, Von Korff M. A consensus approach toward the standardization of back pain definitions for use in prevalence studies. Spine (Phila Pa 1976) 2008; 33:95-103.
2. Holick MF, Chen TC. Vitamin D deficiency: A worldwide problem with health consequences. Am J Clin Nutr 2008 87:1080S-1086S.
3. Lips P, Bouillon R, van Schoor NM, Vanderschueren D, Verschueren S, Kuchuk N, Milisen K, Boonen S. Reducing fracture risk with calcium and vitamin D. Clin Endocrinol (Oxf ) 2010; 73:277-285.
4. Lips P. Vitamin D deficiency and secondary hyperparathyroidism in the elderly. Consequences for bone loss and fractures and therapeutic implications. Endocr Rev 2001; 22:477-501.
5. Holick MF, Siris ES, Binkley N, Beard MK, Khan A, Katzer JT, Petruschke RA,Chen E, de Papp AE. Prevalence of Vitamin D inadequacy among postmenopausal North American women receiving osteoporosis therapy. J Clin Endocrinol Metab 2005; 90:3215-3224.
6. Leavitt SB. Vitamin D – a neglected ‘Analgesic’ for chronic musculoskeletal pain; editorial an evidence-based review & clinical practice guidance. Pain Treat Top 2008; 6:2-50.
7. Schwalfenberg G. Improvement of chronic back pain or failed back surgery with vitamin D repletion: A case series. J Am Board Fam Med 2009; 22:69-74.
8. Waikakul S. Serum 25-hydroxy-calciferol level and failed back surgery syndrome. J Orthop Surg (Hong Kong) 2012; 20:18-22.
9. McBeth J, Pye SR, O’Neill TW, Macfarlane GJ, Tajar A, Bartfai G, Boonen S, Bouillon R, Casanueva F, Finn JD, Forti G, Giwercman A, Han TS, Huhtaniemi IT, Kula K, Lean ME, Pendleton N, Punab M, Silman AJ, Vanderschueren D, Wu FC; EMAS Group. Musculoskeletal pain is associated with very low levels of vitamin D in men: results from the European Male Ageing Study. Ann Rheum Dis 2010; 69:1448-1452.
10. Harinarayanan CV, Joshi SR. Vitamin D status in India – its implications and remedial measures. J Assoc Physicians 2009; 57:40-48.
11. Harinarayan CV, Ramalakshmi T, Prasad UV, Sudhakar D, Srinivasarao PV, Sarma KV, Kumar EG. High prevalence of low dietary calcium, high phytate consumption, and vitamin D deficiency in healthy south Indians. Am J Clin Nutr 2007; 85:1062-1067.
12. Lewis PJ. Vitamin D deficiency may have role in chronic low back pain. 2005;
13. 331:109.
14. Heidari B, Shirvani JS, Firouzjahi A, Heidari P, Hajian-Tilaki KO. Association between nonspecific skeletal pain and vitamin D deficiency. Int J Rheum Dis 2010; 13:340-346.
15. Fairbank JC, Pynsent PB. The Oswestry Disability Index. Spine (Phila Pa 1976) 2000; 25:2940-2952.
16. Kim TH, Lee BH, Lee HM, Lee SH, Park JO, Kim HS, Kim SW, Moon SH. Prevalence of vitamin D deficiency in patients with lumbar spinal stenosis and its relationship with pain. Pain Physician 2013; 16:165-176.
17. Plotnikoff GA, Quigley JM. Prevalence of severe hypovitaminosis D in patients with persistent, nonspecific musculoskeletal pain. Mayo Clin Proc 2003; 78:1463-1470.
18. Muir SW, Montero-Odasso M. Effect of vitamin D supplementation on muscle strength, gait and balance in older adults: A systematic review and meta-analysis. J Am Geriatr Soc 2011; 59:2291-2300.
19. Rkain H, Bouaddi I, Ibrahimi A, Lakhdar T, Abouqal R, Allali F, Hajjaj-Hassouni N. Relationship between vitamin D deficiency and chronic low back pain in postmenopausal women. Curr Rheumatol Rev 2013; 9:63-67.
20. Lotfi A, Abdel-Nasser AM, Hamdy A, Omran AA, El-Rehany MA. Hypovitaminosis D in female patients with chronic low back pain. Clin Rheumatol 2007; 26:1895-1901.
21. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM; Endocrine Society. Evaluation, treatment, and prevention of vitamin D deficiency: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2011; 96:1911-1930.
22. Grant WB. Overweight/obesity and vitamin D deficiency contribute to the global burden of low back pain. Ann Rheum Dis 2014; 73:e48.