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The association between vitamin D level and chronic pain and depression in premenopausal women/Premenopozal eriskin kadinlarda vitamin D duzeyi ile kronik agri ve depresyon arasindaki iliski.


One of the most significant symptoms decreasing the quality of life related to musculoskeletal disorders is pain. No underlying pathology is encountered in the majority of pains originating from disorders of the musculoskeletal system, and pains from the musculoskeletal system that are not based on a specific or underlying mechanical reason are called non-specific pains of the musculoskeletal system (1-4). Chronic non-specific musculoskeletal system pain and depression are serious public health problems, because the changes by chronic non-specific musculoskeletal system pain and depression affect not only the patient but also his/her family, employer, and related healthcare professionals. An interactive correlation is present between chronic pain and depression; chronic pain may lead to depression, or depressive patients may be encountered with the complaint of pain (5,6). Vitamin D is reported to have pro-apoptotic, anti-inflammatory, and immune-modulatory features and obtains calcium homeostasis. In addition to studies reporting the association between vitamin D deficiency and non-specific musculoskeletal system pain (7) and depression (8,9), there are also other studies reporting no association between non-specific musculoskeletal system pain (10) and depression (11,12). In our study, we aimed to investigate the association between vitamin D level and non-specific musculoskeletal system pain and depression in premenopausal women.

Material and Methods

The study was performed in the outpatient clinic of the Physical Medicine and Rehabilitation Department of Konya Training and Research Hospital between September 2012 and April 2013. Two hundred eighteen premenopausal women who were admitted to the clinic due to non-specific musculoskeletal pains (e.g., low back, back, knee, shoulder, extremities, arthralgia, and common body pain) within the last 6 months and without underlying specific medical challenges (e.g., arthritis, trauma, depression, lumbar disc hernia, infection, neoplasm, metastasis, osteoporosis, rheumatoid arthritis, fracture, neurological disorders, and serious spinal pathology) were consecutively included into the study. Approval was obtained from the local ethical board of Meram Medical School of Necmettin Erbakan University. Those accepting to participate were informed, and their consents were obtained.

With common musculoskeletal system pain for at least 6 months, 21 8 premenopausal women were included into the study. Those with systemic disorders, major psychiatric diseases, history of antidepressant and anxiolytic drug intake, fibromyalgia, polymyalgia rheumatica, ankylosing spondylitis, rheumatoid arthritis, diffuse idiopathic skeletal hyperostosis, multiple myeloma, metastatic and metabolic bone diseases, a disorder or history of disorder affecting vitamin D metabolism (such as gastric surgery, chronic liver disease, renal failure, intestinal malabsorption), and the use of drugs affecting the levels of vitamin D, parathormone, alkaline phosphatase, and calcium, cigarette smokers, those drinking alcohol regularly, within the menopausal cycle, and those with restricted mobility were excluded.

If necessary, laboratory and monitoring methods were used in order to have differential diagnostic criteria of chronic pain. Detailed history was obtained from each patient, and each participant was physically examined. Levels of pain severity and depression were respectively determined with the 0-10 visual analog scale (VAS) and Beck Depression Inventory (BDI), and levels of parathormone, alkaline phosphatase, and calcium were measured. In order to determine vitamin D levels, 25(OH)D was investigated in blood samples drawn in the morning. 25-OH-D3 is the best clinical marker to show the condition of vitamin D, because it indicates total vitamin D taken together with cutaneous synthesis and diet (13-15). The threshold value of vitamin D still remains controversial in the literature. For maximum calcium absorption and optimal health status, levels are suggested to be over 30 ng/mL. However, 20 ng/mL is described as the threshold value of serum 25(OH)D preventing secondary hyperparathroidy, increased bone formation-resorption, and loss of bone mineral density (13).

In our study, the threshold value of serum 25(OH)D was accepted as 20 ng/mL, and all participants were categorized as group 1--the deficient group (<20 ng/mL), and group 2--the normal group ([greater than or equal to]20 ng/mL). The Beck Depression Inventory (BDI), a valid and reliable method to measure depression level in society, is a 21--item survey evaluating items related to the symptoms of depression, such as hopelessness, irritability, cognitive problems, feelings of guilt or being punished, and physical symptoms, including fatigue, weight loss, and lack of sexual desire. A BDI score [greater than or equal to]17 is consistent with the presence of depression (16). In our study, those with a BDI score of 17 and over were evaluated in favor of depression.

Statistical Analysis

All statistical analyses were performed using the IBM SPSS Release version 20. Appropriateness of variables to normal distribution rates was investigated with visual and analytical methods. Descriptive statistical data were presented as mean, standard deviation, numbers, and percentage. In the comparison of clinical features of participants with deficient and normal vitamin D levels, data appropriate for normal distribution rates were compared with student's t-test, and those inappropriate for normal distribution were compared with Mann Whitney U-test. In the comparison of frequencies, chi-square test was used. In order to define the linear association between independent variables and vitamin D level, Spearman's rho correlation coefficients were calculated. The statistical significance level was accepted as p<0.05. As correlation coefficients, the correlations between 0-0.25 were assessed as "none," between 0.25-0.50 as "weak-moderate," between 0.50-0.75 as "severe," and between 0.75-1.00 as "much severe."


Of 214 participants, 174 (79.8%) presented with vitamin D deficiency (group 1), while the level of vitamin D was within normal limits in 44 (20.2%) (group 2). The socio-demographic and clinical data of all participants are presented in Table 1. While a statistically significant difference was observed in both groups as to VAS and BDI scores (p<0.001 and p=0.001, respectively), no statistically significant difference was found as to age, body mass index (BMI), level of income, duration of complaints, educational status, family type, and profession (p>0.05) (Table 1). Depression level was 41.4% in group 1, whereas the rate was 20.5% in group 2 (p<0.001). In terms of levels of serum parathormone, alkaline phosphatase, and calcium, no significant difference was detected between groups 1 and 2 (p>0.05) (Table 2). While a negative correlation was found between the groups as to vitamin D level and VAS and BDI scores (r=-0.601, p<0.001 and r=-0.361, p<0.001, respectively), no correlation was determined between the groups as to age, BMI, level of income, duration of complaints, and number of children (p>0.05). However, a positive correlation was present between VAS and BDI scores (p<0.001 r=-0.470).


Vitamin D deficiency is a common problem both in Turkey and across the world. The most significant source of vitamin D is sunlight. Vitamin D deficiency develops due to insufficient exposure to sunlight and poor absorption of vitamin D via dieting, and the most marked finding is pain. The pain generally starts in the low back and may extend to the pelvis, hip, back, and costas (17,18). It is reported that non-specific musculoskeletal pain due to vitamin D deficiency originates from insufficient Ca-P and from the fact that poorly organized bone matrix presses outward onto the periost (19). Although non-specific musculoskeletal pain is one of the most common complaints of admissions to physical medicine and rehabilitation departments in daily practice, vitamin D deficiency is not considered frequently in the differential diagnosis, and high cost-effective diagnostic and therapeutic modalities are applied. In studies, however, it is reported that a low level of vitamin D is a common symptom in those with non-specific and chronic musculoskeletal pain. Especially, the association between low level of vitamin D and pain in osteomalacia is well established (20-24). Moreover, there are also studies reporting that a definite improvement is seen at the level of pain after vitamin D supplementation in patients with non-specific and chronic musculoskeletal system pain and vitamin D deficiency (25-27). As consistent with the literature, our study indicates that vitamin D deficiency is a frequent finding in premenopausal women with non-specific musculoskeletal pain, and the level of pain is strongly associated with the level of vitamin D. Therefore, because its treatment is easy and pleasing when diagnosed, vitamin D deficiency as an underlying effect should be differentiated in musculoskeletal system pains with unknown etiology.

Depression is an important public health challenge due to its high prevalence and the loss of ability it causes (28). The prevalance of major depressive disorders was reported to be 21.3% in women (29). Lifelong prevalence of depression is higher in women, compared to men (30). It is emphasized that one of the reasons of depression leading to disorders in all fields of life is also vitamin D deficiency (8,9,19,31-35). In a systematic review and meta-analysis performed recently in 31,424 individuals, an association was reported between depression and low levels of vitamin D (33). In a study where the patients with vitamin D deficiency were included, Kaya et al. (27) treated the patients with vitamin D and calcium and reported that a significant alteration was observed in BDI scores 6 months after the follow-up. However, as well as studies reporting an association between depression and vitamin D deficiency, other studies reporting no correlation between depression and vitamin D deficiency are also present (12,13,36-38). Upon evaluating BDI[greater than or equal to]17 in favor of depression, the rates of depression were 41.4% in group 1 and 20.5% in group 2 in our study. In a previous study performed by Yilmaz et al. (39), the rate of depression was 8.3% in healthy women. The fact that the depression rate was also higher in group 2 within normal limits in our study is considered to arise from the fact that the patients with chronic non-specific musculoskeletal system pain constituted our study group and from the association between chronic pain and depression. It is reported that one of the disorders in which depression is commonly encountered is chronic pain syndrome, and at least 30% of such patients display major depression (6). Also, many neurons in the amygdala region of the brain and playing a key role in emotional status are reported to be associated with pain (40). In our study, vitamin D deficiency and level of depression seem to be associated at a moderate level. However, considering the association between chronic pain and depression, we consider that more comprehensive studies are needed to suggest an association between vitamin D deficiency and depression.

Our study also has various limitations. First, because only women patients were included into the study, our findings can not be generalized to the whole population. Also, levels of depression in our participants were not evaluated via structured psychiatric interviews. So, further studies of both genders, including more participants to reflect a major part of the population, are needed.


As a result, our study indicates that vitamin D deficiency is a widespread finding in premenopausal women with chronic non-specific musculoskeletal pain and that vitamin D level is associated with level of pain and depression. Thus, vitamin D deficiency should be taken into account in premenopausal women, and the deficiency should be corrected, if any.

DOI: 10.5152/tftrd.2014.59244

Acknowledgements: Authors would like to thank Numan Duran for language editing.

Conflict of Interest: No conflict of interests was declared by the authors.

Financial Disclosure: The authors declared that this study has received no financial support.

Ethics Committee Approval: Ethics committee approval was received for this study from the ethics committee of Necmettin Erbakan University Faculty of Medicine.

Informed Consent: Written informed consent was obtained from patients who participated in this study.

Peer-review: Externally peer-reviewed.

Author Contributions: Concept S.B., H.Y.; Design H.Y., S.B., G.K. Supervision--H.Y., S.B., G.K.; Funding--H.Y., S.B., G.K.; Data Collection and/or Processing--H.Y., S.B.; Analysis and/or Interpretation --H.Y., S.B.; Literature Review--H.Y.; Writer--H.Y.; Critical Review--H.Y., S.B., G.K.; Other--H.Y., S.B., G.K.

Etik Komite Onayi: Bu calisma icin etik komite onayi Necmettin Erbakan Universitesi Meram Tip Fakultesi'nden alinmistir.

Hasta Onami: Yazili hasta onami bu calismaya katilan hastalardan alinmistir.

Hakem degerlendirmesi: Dis bagimsiz.

Yazar Katkilari: Fikir--S.B., H.Y.; Tasarim--H.Y., S.B., G.K.; Denetleme--H.Y., S.B., G.K.; Kaynaklar--H.Y., S.B., G.K.; Veri toplanmasi ve/veya islemesi--H.Y., S.B.; Analiz ve/veya yorum --H.Y., S.B.; Literatur taramasi--H.Y.; Yaziyi yazan--H.Y.; Elestirel Inceleme--H.Y., S.B., G.K.; Diger--H.Y., S.B., G.K.

Tesekkur: Yazarlar dil duzenlemesi icin Numan Duran'a tesekkur eder.

Cikar Catismasi: Yazarlar cikar catismasi bildirmemislerdir.

Finansal Destek: Yazarlar bu calisma icin finansal destek almadiklarini beyan etmislerdir.


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Halim YILMAZ [1], Said BODUR [2], Gulten KARACA [1]

[1] Department of Physical Medicine and Rehabilitation, Konya Training and Research Hospital, Konya, Turkey

[2] Department of Public Health, Balikesir University Faculty of Medicine, Balikesir, Turkey

Address for Correspondence / Yazisma Adresi: Halim Yilmaz, MD, The Department of Physical Medicine and Rehabilitation, Konya Training and Research Hospital, Konya, Turkey. Phone: +90 505 854 46 14 E-mail:

Received/Gelis Tarihi: May/Mayis 2013 Accepted/Kabul Tarihi: September/Eylul 2013
Table 1. Socio-demographic and clinical data of patients

                              25(OH)D<20             25(OH)D>20
                               (n=174)                 (n=44)

Age (year)                39.3 [+ or -] 9.6      42.1 [+ or -] 8.8
BMI (kg/[m.sup.2])        27.8 [+ or -] 5.9      26.6 [+ or -] 4.7
Level of income
  (dollar/month)         620.5 [+ or -] 353.4   678.0 [+ or -] 420.8
Number of
  living children          2.5 [+ or -] 1.5       2.2 [+ or -] 1.0
Duration of
  complaints (month)      18.5 [+ or -] 17.5     18.0 [+ or -] 22.4
VAS scores                 7.6 [+ or -] 1.8       4.7 [+ or -] 2.1
BDI scores                14.9 [+ or -] 8.9      10.4 [+ or -] 8.8
Marital status                  n (%)                  n (%)
  Married                    158 (90.8%)             42 (95.5%)
  Single                     16 (% 9.2%)              2 (4.5%)
Employed                      29 (16.3%)             9 (20.9%)
Unemployed                   145 (83.7%)             35 (79.1%)
Type of family
Core family                  107 (61.5%)             31 (70.5%)
Combined family               67 (38.5%)             13 (30.5%)
Educational status
Illiterate                    11 (6.3%)               3 (6.8%)
Primary (8 years)            132 (75.9%)             29 (72.7%)
High school (11 years)        15 (8.6%)               3 (6.8%)
College ([greater than
  or equal to] 12yrs)         16 (9.2%)               6 (13.7%)


Age (year)                              0.092
BMI (kg/[m.sup.2])                      0.205
Level of income
  (dollar/month)                        0.187
Number of
  living children                       0.109
Duration of
  complaints (month)                    0.298
VAS scores                              <0.001
BDI scores                              0.001
Marital status           [chi square]
  Married                   1.002       0.539
Employed                    0.350       0.656
Type of family
Core family                 1.214       0.298
Combined family
Educational status          0.884       0.829
Primary (8 years)
High school (11 years)
College ([greater than
  or equal to] 12yrs)

BMI: body mass index; BDI: beck depression inventory; VAS: visual
analog scale

Table 2. Laboratory findings of patients

                        25(OH)D<20          25(OH)D >20         p
                         (n=174)               (n=44)

25-OH-D3 (ng/mL)     9.3 [+ or -] 3.4    33.4 [+ or -] 14.5   <0.001
Parathormone        63.9 [+ or -] 28.7   58.2 [+ or -] 28.7    0.351
  phosphatase       77.3 [+ or -] 29.7   75.5 [+ or -] 28.3    0.814
Calcium              9.3 [+ or -] 0.4     9.4 [+ or -] 0.4     0.073
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Article Details
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Title Annotation:Original Article/Orijinal Makale
Author:Yilmaz, Halim; Bodur, Said; Karaca, Gulten
Publication:Turkish Journal of Physical Medicine and Rehabilitation
Article Type:Report
Geographic Code:7TURK
Date:Jun 1, 2014
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