INTRODUCTION:

Vitamin D is a hormone and essential nutrient for bone metabolism and neuromuscular function^[1], stimulates osteoblast activity, increases intestinal absorption of calcium from diet, regulates phosphorus levels and it also potentially influences the pain pathways that are associated with changes in cortical, immunological, hormonal, and neuronal levels.^[2]Without the presence of activated vitamin D, normal bone metabolism is altered so that only 10% of calcium and 60% of phosphorus is absorbed^[3], this exacerbates osteoporosis and osteopenia and also might lead to osteomalacia. Vitamin D deficiency has been reported in populations with several different types of chronic musculoskeletal pain such as osteoarthritis, rheumatoid arthritis, osteoporosis, soft tissue rheumatism, low back pain, and arthralgia^[4-7].

Vitamin D deficiency is associated with musculoskeletal pain, loss of type II muscle fibres, and proximal muscle atrophy.^[8,9]Plotnik of and Quigley^[2] found that 89% of subjects with chronic musculoskeletal pain were deficient in Vitamin D. Vitamin D insufficiency is highly prevalent in older osteoporotic patients, who are particularly vulnerable to the bone weakening due to vitamin D insufficiency.^[10,11]

The majority of studies demonstrate the beneficial role of vitamin D as a therapeutic agent to maintain bone density in older patients with osteoporosis. Current guidelines recommend the prevention of osteoporosis in the elderly via pharmacological and non-pharmacological measures, including vitamin D and calcium supplementation in addition to osteoporosis treatment.^[12,13,14]

The aim of the present study was to evaluate the effectiveness of oral nanosolution of vitamin D3 in pain management of some neuro spinal disorders. The objectives of the study were to evaluate the improvement in vitamin-D levels, to evaluate the improvement of pain score in patients post treatment with vitamin-D formulation.

MATERIAL AND METHODS:

Study site and study design:

This was a panel study where in the pain scores were collected repeatedly at different times from same individuals. The study duration was two years i.e. from 2017 to 2019. The study was conducted at RK Hospitals, Gajuwaka, Visakhapatnam.

Ethical Considerations:

Permission was approved from Institutional Ethical Committee to conduct this study (RK/IEC/59/2017). The aim and objective of the study was clearly explained to the patients. A patient consent form was obtained from patients who are willing to co-operate the study.

Participants:

Inclusion criteria:

1. Patients who are diagnosed with myofacial syndrome, back pain, osteopenia and osteoporosis.

2. Patients with vitamin D deficiency.

Exclusion criteria:

1. Patients with normal vitamin D levels.

2. Patients diagnosed with other neuro spinal disorders.

3. Patients with insufficient findings.

Sampling technique and sample size:

Purposive and convenience sampling technique was employed to select the subjects. The estimated sample size was 377. But due to loss to follow up (86) and due to insufficient data (22), the sample size taken was 269.

Study Instrument:

Numeric Rating Scale (NRS) for Pain was an 11 item (0-10) pain intensity rating scale in which the respondent asked to select a numerical value between 0 and 10 that bests describe their intensity. ‘0’ indicates “no pain” and ‘10’ indicates “worst possible pain”. Higher score indicates high pain intensity.

Data collection:

Patients satisfying inclusion criteria were selected. Patient’s socio-demographic details and clinical history was noted down. The pain score was calculated from them initially using numeric rating scale for pain. Vitamin-D levels were noted down from lab reports. Again, patient’s pain score was calculated after 6 weeks of follow up. The dose of oral nano solution of Vit-D3 was 60,000IU once a week on empty stomach. According to Vitamin-D council, the vitamin-D status was categorised as below:

Vitamin-D status	Blood Level
Deficient	0-30 ng/ml
Insufficient	31-39 ng/ml
Sufficient	40-80 ng/ml
Toxic	>150 ng/ml

Data analysis:

Frequency and percentages were calculated for qualitative data. Mean and standard deviation was calculated for quantitative data. Non-parametric tests were employed for qualitative data and quantitative data (with non-Gaussian distribution) to find out statistically significant relation between the variables. Vitamin-D levels and pain scores within the group were compared using Wilcoxon test. p-value <0.05 was considered as statistically significant. p-value <0.01 was considered as statistically highly significant.

RESULTS AND DISCUSSION:

Figure 1: Age wise distribution of patients

Patients with age group between 36-50 years were high in generalised back pain (78.26%), osteopenia (44.82%), osteoporosis (43.42%) and myofacial syndrome (37%). The mean age of patients in myofacial syndrome, generalised back pain, osteopenia and osteoporosis was 41.45±13.92 years, 40.41±13.00 years, 41.34±13.88 years and 42.88±13.69 years respectively.

Figure 2: Gender wise distribution of patients

Females were predominantly higher than males in myofascial syndrome (58.69%), generalized back pain (52.80), osteopenia (55.17%) and osteoporosis (55.26%).

Table 1: Vitamin-D levels before and after treatment

S. No.	Name of the disease	Before (Mean± SD)	After (Mean± SD)
1	Myofascial syndrome	15.30±6.76	44.15±9.49
2	Generalised Back Pain	13.32±5.18	42.36±7.84
3	Osteopenia	21.74±7.82	46.26±8.34
4	Osteoporosis	18.54±6.04	43.76±7.83

Table 2: Pain scores before and after treatment

S. No	Name of the disease	Before (Mean±SD)	After (Mean±SD)
1	Myofascial syndrome	7.32±1.82	1.45±1.60
2	Generalised Back Pain	7.50±1.67	1.82±1.88
3	Osteopenia	7.44±1.85	1.91±1.81
4	Osteoporosis	7.10±1.86	1.73±1.68

The vitamin-D levels and pain scores had been considerably improved after treatment in all four neurospinal disorders as shown in Table 1 and Table 2.

Table 3: Comparison of Vitamin-D levels and Pain scores within the disorders

S. No	Name of disease	Vitamin-D levels		Pain Score
S. No	Name of disease	z-statistic	p-value	z-statistic	p-value
1	Generalized back pain	-8.19	<0.0001	8.15	<0.0001
2	Myofascial syndrome	-5.9	<0.0001	5.9	<0.0001
3	Osteopenia	-6.62	<0.0001	6.62	<0.0001
4	Osteoporosis	-7.57	<0.0001	7.57	<0.0001

In our study patients with age group 36-50 years were most commonly affected in the four groups. Patients with age group 41-50 years were most commonly affected in myofascial syndrome.^[15] The age group showing the highest incidence was the 20-40 year age group, although children can also have MPD syndrome. ^[16]The average age of women suffering from osteopenia and osteoporosis was 59.2±10.5 years in a study.^[17] Females were more commonly affected than males in our study.

There is increase in mean vitamin-D levels after six weeks in all the four groups. In India current recommendations for correction of vitamin D level, is by giving 60,000 IU of oral Vitamin D on a weekly basis for 8 weeks.^[18,19] In a study by Manek each subject planned to receive 60,000 IU of nano particle based vitamin D, once weekly, for 8 weeks orally and it was observed that patients who have received vitamin D3 therapy for at least 4 weeks period, the improvement (serum 25 [OH] D >30 ng/ml) was seen in 84.2% (n=32) patients at the end of 4 weeks itself and 39.5% (n=15) patients at the end of 8 weeks.^[20] A published literature suggests that vitamin D3 granules eight weeks of vitamin D3 60,000 IU/week oral granules supplementation increased serum 25 (OH) D to optimal levels in most of the subjects with Vitamin D deficiency.^[21] It has been reported that approximately 50% of orally ingested vitamin D3 is absorbed.^[22]In-vitro study done on rat intestine showed that average absorption of Nano particle-based vitamin D was 77.83±0.24%. The predicted human absorption may be more than 90%. This study also showed that nano particle-based vitamin D absorbed through various parts of rat small intestine like duodenum, jejunum, and ileum.^[23]

There was very high statistically significant relationship between Vitamin –D levels and pain scores in all the four groups (p<0.0001). Few studies linked low levels of vitamin D and the incidence of both acute and chronic pain.^[24-27]Few studies reported a link between Vitamin D deficiency and musculoskeletal symptoms like muscle weakness, pain, bone pain.^[28-30]Clinical studies of vitamin D supplementation in patients with known vitamin D deficiency have shown mixed results in improving pain scores.^[31] Low 25(OH) D levels have been found to be related to heightened central sensitivity (particularly augmented pain processing) upon mechanical stimulation in chronic pain patients.^[32]Research suggests that nanoformulation will help improve the bioavailability of fat-soluble nutrients.^[23] Few research studies suggested that nanoformulation of vitamin-D may enhance therapeutic efficacy, photo- stability and bio-degradation of vitamin D supplements. ^[23,33,34]

The available literature on randomized double-blind placebo-controlled trails of vitamin D supplementation in treating chronic pain conditions was limited. Mixed results were reported on the improvement of pain with vitamin-D supplementation. Infra red therapy and a session of soft tissue massage was found to be effective in the improvement of chronic low back pain.^[41] Aceclofenac in combination with thiocolchicoside was effective in reducing the acute low back pain than aceclofenac monotherapy.^[42]

Table 4: Literature review of some studies on Vitamin D and pain outcome

Author	Condition	Dose of Drug	Pain Outcome	Improvement with vitamin D
Warner and Arnspiger^[35]	Diffuse Musculoskeletal Pain	50,000 ergocalciferol per week for 3 months	There was no correlation between vitamin D level and pain on VAS (r 0.038) or FPS (r 0.298) at 3-month follow-up	No
Di Munno et al^[36]	Polymyalgia Rheumatica	35,000 IU for 25 days	Subjective pain on movement significantly decreased in both groups over time, but there was no difference between groups	No
Wepner et al^[37]	Severe pain from Fibromyalgia syndrome	2400 IU or 1200 IU per day	A marked reduction in pain was noted over the treatment period in the treatment group. Variance analysis of the 2 groups at 4 time points showed a significant group effect in visual analog scale scores. This also was correlated with scores on the physical role functioning scale of the Short Form-36.	Yes
McAlindon et al^[38]	Symptomatic knee OA pain	2000 IU daily with dose escalation to elevate serum levels to more than 36ng/ml	Vitamin D supplementation for 2 years at a dose sufficient to elevate 25(OH)D serum levels to more than 36ng/ml when compared to placebo, did not reduce knee pain or cartilage volume loss in patients with symptomatic Osteo Arthritis	No
Sakalli et al^[39]	Pain in the elderly	300,000IU via p.o and parenteral	Megadose vitamin D administration increases quality of life, decreases pain, and improves functional mobility when given via oral or intramuscular routes in the elderly	Yes
Schreuder et al^[40]	Nonspecific musculoskeletal pain	150,000IU vitamin D₃p.o for 6 weeks	Patients in vitamin D group were significantly more likely than their counterparts in the placebo group to report pain relief 6 weeks after treatment (34.9 vs. 19.5%, P= 0.04). The former was also more likely to report an improved ability to walk stairs (21.0 vs. 8.4%, P= 0.008).	Yes

CONCLUSION:

Our study concluded that oral nano formulation of vitamin-D with 60,000 IU weekly for six weeks was effective in treating pain in some musculoskeletal diseases.

CONFLICTS OF INTEREST:

The authors declare no conflict of interest.

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Received on 27.01.2020 Modified on 08.04.2020

Research J. Pharm. and Tech. 2021; 14(1):6-10.

DOI: 10.5958/0974-360X.2021.00002.0