Carpel tunnel syndrome: A link with vitamin D and calcium
- Authors:
- Published online on: June 26, 2020 https://doi.org/10.3892/br.2020.1322
- Article Number: 15
Abstract
Introduction
Carpal tunnel syndrome (CTS) is one of the most common peripheral neuropathies of the upper extremities which results in significant functional disability (1). It is more common between the ages of 30 and 50 years, affects females more often than males and its occurrence is usually bilateral (2).
CTS is a condition caused by compression of the median nerve at the wrist, which runs from the forearm into the palm. The compression causes pain, numbness, tingling in the fingers or hands, particularly the thumb, index and middle fingers in addition to the loss of sensation in the fingers and weakness in the hands (1).
The exact cause and pathogenesis of CTS are unclear. The risks of developing CTS include performing repetitive work tasks, forceful angular hand movements, the use of vibrating tools (3), diabetes mellitus, rheumatoid arthritis, hypothyroidism, obesity and pregnancy (2).
CTS and vitamin D deficiency are two distinct conditions that can cause chronic pain. Several studies have investigated the association between CTS and vitamin D status. The results of these studies suggested that low vitamin D levels are associated with CTS (4-6). Vitamin D is the most commonly observed single most deficient vitamin in different populations, including in areas of the world that receive sufficient sunlight, such as Jordan (7). Vitamin D has also been shown to exert a multitude of effects on various systems, including neuroprotection, anti-inflammatory and anti-proliferative actions by regulating the transcription of vitamin D-responsive genes (8).
CTS and musculoskeletal disorders are reported to be common amongst certain occupational industries, such as those who tools which vibrate (9). Additionally, psychological symptoms are found to be higher in patients with CTS (10,11) and other neuropathic conditions which result in pain (12). However, the precipitating etiology underlying the psychological symptoms is still not well understood (12). Musculoskeletal pain (MSP), weakness, psychological symptoms and neuropathy were found to be accompanied by vitamin D deficiency (13-16). In addition to low serum vitamin D levels, low daily calcium intake was also found to be associated with psychological symptoms in patients with MSP (13), psychiatric outpatients (14), patients with none-cardiac chest pain (17) and patients with an overactive bladder (18). Therefore, the present study aimed to evaluate vitamin D levels, daily calcium intake, MSP and psychological symptoms in patients with CTS.
Materials and methods
Study population
Patients were recruited from the outpatient clinics of Neurology at King Abdulla University Hospital (KAUH), the main tertiary teaching hospital in the north of Jordan, between December 2015 and June 2016.
Patients were confirmed to have CTS clinically by neurologists and by nerve conduction study (NCS) or CTS group. All tests were performed in the same room, using the NCS system (CADWELL Industries Inc.). The CTS group was compared with an equivalent number of healthy volunteers without any complaints of pain or other issues in the upper limbs, no MSP or fatigue (control) (14). Healthy volunteers were recruited included both males and females who visited different clinics for checkups or as accompanying persons at the university campus of Jordan University of Science and Technology.
The research was performed in accordance with the Declaration of Helsinki (19) and was approved by the Institutional Review Board Committee of Jordan University of Science and Technology. Written informed consent was obtained from all participants. Any history of severe trauma to the wrist, diabetes, thyroid disorders, connective disorders and those who were on vitamin D supplements for the past two months or did not have detectable levels of vitamin D in the serum were excluded from the study. Additionally, all patients answered a self-guided questionnaire, which contained socio-demographic information.
Data were collected from 48 patients (8 males and 40 females), mean age 48.55±8.3 (age range, 22-60 years) confirmed to have CTS by NCS or CTS group. In addition, 48 sex-matched healthy subjects aged between 22 and 59 years mean age 42.33±8.3 (mean age did not differ significantly from the CTS group, P=0.853) were used as the comparison group.
Assessment of MSP
Localization and severity of MSP were determined using two questions from the Pain DETECT questionnaire (14,15,20). The first question asked participants to locate sites of usual pain by marking the area of pain on an illustration of the human body. The second question asked participants to indicate average pain intensity over the last month using a scale from 0-10 (0, no pain and 10, maximum pain). Also, the patients answered questions about the frequency of their pain (daily, 4-6 times/week, 2-3 times/week) and duration ≤3 months or >3 months. Participants were also asked if they experienced fatigue.
Assessment of psychological symptoms
The Hospital Anxiety and Depression Scale (HADS) were used to assess self-reported symptoms of anxiety and depression for the patients as well as the control. The HADS is a reliable and potentially valid measure for detecting depression and anxiety disorders in both somatic, psychiatric and primary care patients in the general population (21).
According to the total HADS score of the study, subjects were divided into three groups: Total score of 0-7, normal; 8-10, borderline abnormal; and 11-21, abnormal, clinical or a case for either anxiety or depression. A total score for anxiety and depression was calculated by adding together all the values.
Assessment of daily calcium intake
Calcium, an essential mineral in the bone is primarily found in dairy products (22-24). Therefore, milk and milk products are the major sources of dietary calcium. Dietary calcium may also be obtained from non-dairy products, such as nuts, seeds, broccoli and sardines with bones (22). Participants answered questions regarding their daily intake and type of dairy product intake. Daily intake of dairy products, such as milk, yogurt, cheddar cheese, cream cheese and labneh (a soft cream cheese made by the removal of whey from yogurt through a cheesecloth) was stratified as none, single, two, three or more dairy servings per day; where 1 serving was defined as 1 cup of milk or yogurt (300 mg calcium), 2 full tablespoons of labneh (100 mg calcium), 1-ounce of cheese (162 mg calcium) or cream cheese (20 mg calcium) (13,14,17,18).
Laboratory analysis
Non-fasting venous blood samples were drawn for analyses of serum 25-hydroxyvitamin D (25-OHD) levels. Serum 25-OHD levels were determined using a chemiluminescent assay on a Roche Modular E170 Analyzer (Roche Diagnostics). Vitamin D status was divided into four diagnostic categories according to serum 25(OH)D levels as follows: Vitamin D sufficiency (≥30 ng/ml), vitamin D insufficiency (20-<30 ng/ml), vitamin D deficiency (10-<20 ng/ml), and severe vitamin D deficiency (<10 ng/ml). Vitamin D measurements were performed at the KAUH Laboratory.
Statistical analysis
Data were analyzed using SPSS version 21.0 (IBM, Corp.). Data are presented as frequencies or the mean ± standard deviation, as appropriate. An independent samples t-test (unpaired) or Mann-Whitney U test were used as appropriate for comparisons between two groups. Spearman's rank correlation coefficient analysis was used to assess the correlation between psychological symptoms and selected parameters with non-normal data. A χ2 test was performed to determine the differences between categorical variables, and to investigate the association between psychological symptoms and categorical variables of interest. Binary logistic regression analysis was used to determine variables predictive of CTS. P<0.05 was considered to indicate a statistically significant difference.
Results
Patient characteristics
Out of the 48 patients with CTS, 22.9% (n=11) had positive CTS in the right hand, 12.5% (n=6) in the left hand, and 66.7% (n=31) of the patients had bilateral positive CST. Females represented 83.3% (n=40) of the CTS group and 75% (n=36) were married. The BMI was significantly different between patients with CTS and the control group, (P=0.009). The analysis revealed that 85.4% (n=41) of the CTS group were either overweight or obese, whereas 66.7%, n=32 of the controls were overweight or obese, (Table I). Self-reported fatigue was reported by 72.9%, (n=35) of the CTS group compared with 0% of individuals in the control.
All individuals in the CTS group exhibited MSP, 89.6% (n=43) of them had chronic pain (>3 months duration), and 70.8% (n=34) experienced pain for >1 year. The CTS group reported a variety of factors that increased pain. The most exacerbating factor was kitchen work (72.9%), followed by sleeping (68.8%), carrying a handbag (68.8%), moving/walking (50%) and washing their hair (39.6%). The average pain intensity for patients with CT was 6.33±1.74 compared with 0 for the controls.
Factors that exacerbated pain with respect to sex were not statically significant with the exception of kitchen work. Pain was significantly exacerbated by kitchen work in females (85.0%, n=34) compared with males (12.5%, n=1), P<0.001.
Occupational types for patients with CTS were as follows: 66.66% (n=32) were housewives, 8.32% (n=4) were manual workers (farmer, chief, carpenter and driver), 6.25% (n=3) were retired, 4.16% (n=2) were unemployed, 1 patient was a secretary, 2.08% (n=2) and the remaining patients were in other occupations, 12.5% (n=6). Occupational types of the control group was 18.75% academics (n=9) [professors (n=6), lecturers (n=2) and student (n=1)], laboratory technician 16.66% (n=8), university laboratory administrator 12.5% (n=6), office employee 39.58% (n=19) [office assistant (n=16) and secretary (n=3)] and others 12.48% (n=6) (Table II).
Biochemical parameters among the study population
There were significant differences in vitamin D levels between the patients with CTS and the controls (9.53±7.3 and 31.65±14.4, respectively; P≤0.001). Vitamin D deficiency (<20 ng/ml) was observed in 95.8% (n=46) of the CTS group compared with 22.9% (n=11) of the controls. Only 2.1% (n=1) of the CTS group had a normal level of vitamin D (≥30 ng/ml) compared with 60.4% (n=29) of the control (Table I).
No clinical parameters (demographics, psychological symptoms, number of pain sites, average pain severity and all other measured parameters) in the CTS patients with respect to sex were statistically significant.
Vitamin D levels amongst the CTS group (male, 11.01±6.7 ng/ml; female, 9.04±7.7 ng/ml; P=0.38), and amongst females <45 and ≥45 years of age (9.75±8.3 and 9.3±6.3, P=0.834, respectively) did not differ significantly.
Concerning total calcium intake (mg/day), the analysis showed that the median daily calcium intake was significantly lower in the CTS group compared with the controls (337.428, range, 156.40-549.470; 639.400, range, 353-780; respectively; P<0.001).
In the CTS group, 45.8% (n=22) of the participants consumed <300 mg/day calcium compared with 16.5% (n=8) in the control group, which is ~<1/4 the Recommended Dietary Allowance (1,000-1,300 mg depending on age group) (25).
Psychological symptoms
The CTS group had notably worse psychological symptoms compared with the controls. Clinical anxiety and clinical depression (HADS score, ≥11) were reported by 35.4 and 29.2% of participants in the CTS group, respectively, whereas 4.3% of controls had clinical anxiety and 2.0% of had clinical depression (Table I).
Correlation between psychological symptoms and the assessed variables
Psychological symptoms were significantly and inversely correlated with vitamin D levels and total daily calcium intake, and positively correlated with BMI. Depression was significantly and positively correlated with anxiety. The values of Spearman's correlation coefficient analysis reflect a strong correlation (>0.25) with the exception of BMI (Table III).
Logistic regression analysis for predictors of CTS among the study population
As there was only one patient with CTS+ who had normal vitamin D levels and one patient with CTS+ who had insufficient vitamin levels, continuous logistic regression analysis rather than categorical analysis was used to determine variables predictive of CTS.
Logistic regression revealed that with every unit increase in serum vitamin D levels, the odds of having CTS was decreased by 1.22x. While a one-unit increase in anxiety total score was associated with a 14% increase in the odds of having CTS after adjusting for different confounders (Table IV).
Association between NCS severity and selected parameters
Based on the NCS rating for CTS symptom severity (mild, moderate or severe), none of the measured parameters were associated with CTS severity in either or both hands, with the exception of MSP frequency. Pain frequency (daily, 4-6 times/week, 2-3 times/week) was significantly associated with CTS severity for the right hand only (P=0.012).
Discussion
In the present study, the relationship between serum vitamin D levels with MSP, psychological symptoms and daily dietary calcium intake in patients with CTS were evaluated and compared with healthy controls.
The most notable finding of the present study was the presence of a high prevalence of vitamin D deficiency, MSP, fatigue, clinical anxiety and clinical depression amongst Jordanian patients with CTS compared with healthy individuals. Additionally, serum vitamin D levels and HADS-anxiety total score were independent predictors of CTS. The majority of the CT patients were females and were housewives.
Regarding the association between vitamin D deficiency and CTS, the results are in agreement with previous studies. CTS patients had significantly lower vitamin D levels compared with the controls. This observation was in agreement with previously published studies from Tanik et al (4), Nageeb et al (5) and Gürsoy et al (26). In contrast, Lee et al (27) showed there was no difference in vitamin D levels between the patients with CTS and the controls.
There is a growing body of evidence demonstrating that vitamin D is neuroprotective. The administration of vitamin D or its metabolites has been shown to reduce neurological injury and/or neurotoxicity in a variety of animal systems by several mechanisms, including protection of neurons against oxidative stress through its antioxidant and anti-inflammatory properties (27,28). Additionally, vitamin D can regulate intraneuronal calcium homeostasis and β-amyloid deposition (28). Neuroinflammation is one of the most important processes involved in the pathogenesis of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease and Multiple Sclerosis.
In the last decade, there has been an increase in the interest in the roles of vitamin D in peripheral nerve functions. Diabetes mellitus is a clinical condition that contributes several neuropathies. Shehab et al (29) showed that diabetic peripheral neuropathy was significantly associated with vitamin D deficiency, whereas Celikbilek et al (30) reported that diabetic patients with neuropathy had lower levels of vitamin D compared with those without neuropathies.
In the present study, 95.8% of patients with CTS had vitamin D deficiency compared with 22.9% of the controls. Also, regression analysis showed that vitamin D deficiency is one of the independent risk factors of CTS. Thus, our study suggests that CTS symptoms may be triggered by low vitamin D levels.
In addition to the presence of a high prevalence of vitamin D deficiency, all CTS patients had MSP, and the majority of them experienced fatigue. MSP that is associated with vitamin D deficiency is explained by the presence of low bone density and osteomalacia in adults (16), heightened central sensitivity upon mechanical stimulation (31) and the growth of muscle fibers (32). Intestinal calcium absorption is significantly reduced to 10-15% when children and adults are vitamin D deficient (33).
The association between neuropathic pain and psychological symptoms is well recognized (34,35); however, the precipitating pathology between these symptoms remains unclear. Tekeoglu et al (10) found that the majority of patients in the CTS group had higher symptoms of depression and anxiety, compared with the control group, which significantly improved at 3 months after carpal tunnel release (36).
In the present study, in addition to MSP, there was a high prevalence of clinical anxiety and clinical depression among patients with CTS. Additionally, serum vitamin D levels and daily calcium intake were significantly inversely associated with anxiety/depression symptoms. HADS-anxiety was one of the independent risk factors associated with CTS.
In agreement with the results of the present study, a high prevalence between vitamin D deficiency and psychological symptoms among patients with MSP has been previously reported (13,37). These findings may have implications in understanding the bidirectional association between the psychological symptoms and MSP among patients with CTS. This finding also raises the question about the relation between CTS and MSP, and if vitamin D and calcium supplementation can be used to treat CTS similar to patients with MSP (13).
CTS is suggested to be provoked by repetitive movements that put stress on the arm or wrist, or specific wrist postures, but may also not be a work-related problem (38). Interestingly, 66.66% of our females with CTS were housewives, relatively consistent with previously published articles (39-41). The high incidence of CTS in housewives can be attributed to routine domestic home duties that involve repetitive movements (42).
In Jordan, wrapped grape leaves (grape leaves stuffed with rice and herbs) and stuffed zucchini which requires hollowing out zucchini using a vegetable corer, are common recipes of Jordanian cuisine that require repetitive hand movement of both hands which involves prolonged taxing hand-wrist activities, and highly repetitive wrist flexion/extension.
The association between parameters, such as sex, increased age, a high BMI and CTS have been reported in numerous studies. CTS patients have higher BMI values compared with controls (5,43,44), consistent with findings from the present study. Some 45.8% of patients with CTS were obese compared with 18.8% of the controls. This effect may be due to the fat deposition in the carpel tunnel that results in compression of the median nerve (43). Additionally, CTS was more common in women >50 years (45). The results of the present study were consistent with previous findings, 83.3% of the CTS patients were females and 75% were between 30-50 years of age. The sex differences were attributed partially to pregnancy, breastfeeding and first menopausal years (46).
In the present study, although patients with CTS had a significantly higher BMI and lower vitamin D levels compared with controls, there were no significant differences between males and females in the mean vitamin D levels amongst the CTS group, or between females aged <45 and ≥45 years. In both cases, females had significantly lower vitamin D levels compared with controls. In contrast with these results, Lee et al (27) found women with CTS >50 years had significantly lower vitamin D levels than the age-matched healthy control women. Tanik et al (4) also reported that women with CTS <40 years had significantly lower levels of vitamin D compared with the sex-matched controls.
Overall, a high incidence of vitamin D deficiency, MSP and psychological symptoms was observed. Furthermore, there was a significant negative association between anxiety/depression symptoms, vitamin D levels, and total daily calcium intake observed among patients with CTS. There was a positive association between anxiety symptoms and depression symptoms. CTS was more common in females than males, and the majority of the females were housewives. Serum vitamin D levels and HADS-anxiety total score were independent predictors of CTS.
The strengths of the present study come from its design, and the method of CTS assessment. However, the small sample size, and the fact that all the recruited participants were from Jordan are limitations of the present study. In the future, collaborative studies between institutes from different countries are required to obtain a larger and more ethnically diverse cohort for evaluation.
In conclusion, the findings of the present study demonstrated that vitamin D deficiency, MSP, and anxiety and depression are common problems in patients with CTS. Low vitamin D levels and HADS-Anxiety were significant independent predictors of CTS. Logistic regression analysis showed with every with unit increase in serum vitamin D levels, the odds of having CTS were decreased by 1.22x. While a one-unit increase in anxiety total score was associated with a 14% increase in the odds of having CTS after adjusting for different confounders. Housewives had an equivalent chance of suffering from CTS morbidity as other high-risk professions. Further studies are required to confirm if vitamin D supplementation may prevent the onset of CTS.
Acknowledgements
Not applicable.
Funding
Funding
The research was supported by funds from a Deanship of Research, Jordan University of Science and Technology (Irbid, Jordan) (grant no. 225/2014).
Availability of data and materials
The datasets used and/or analyzed during the present study are available from the corresponding author on reasonable request.
Authors' contributions
KKAR conceived and designed the study and drafted the manuscript. RMK performed the clinical assessment of patients, interpreted the patients' data and revised the manuscript critically for important intellectual content. Both authors read and approved the final manuscript.
Ethics approval and consent to participate
The Institutional Review Board Committee at Jordan University of Science and Technology (Irbid, Jordan) approved the present study (approval no. 19/78/2014). Written informed consent was obtained from all participants after discussing the purpose of the study and the procedure.
Patient consent for publication
Not applicable.
Competing interests
The authors declare that they have no competing interests.
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