Original Article Fibromyalgia Syndrome: Is It Related to Vitamin D Deficiency in Premenopausal Female Patients? Muyesser Okumus, MD, Mine Koybası, MD, Figen Tuncay, MD, Esma Ceceli, MD, Figen Ayhan, MD, Rezan Yorgancioglu, MD, and Pinar Borman, MD ---
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From the Ankara Training and Research Hospital, Department of Physical Medicine and Rehabilitation, Ankara, Turkey. Address correspondence to Dr. Muyesser Okumus, sehit veli kara sok 25/10 esertepe etlik, Kecioren Ankara, Turkey. E-mail: drmuyesser@ hotmail.com Received July 31, 2011; Revised September 25, 2011; Accepted September 26, 2011. 1524-9042/$36.00 Ó 2013 by the American Society for Pain Management Nursing doi:10.1016/j.pmn.2011.09.006
ABSTRACT:
There are a number of studies that have evaluated the relationship between fibromyalgia (FM) and vitamin D deficiency with conflicting results. The aim of this study was to assess vitamin D deficiency in patients with FM and to evaluate the relationship with the common symptoms of FM and levels of serum vitamin D. Forty premenopausal female fibromyalgia patients and 40 age- and sex-matched control subjects were included in the study. The demographic characteristics of all subjects, including age, sex, and body mass index, were recorded. The number of tender points was recorded, and the intensity of the widespread pain of the subjects was measured by the visual analog scale. The activities of daily living component of the Fibromyalgia Impact Questionnaire (FIQ-ADL), was used to assess physical functional capacity. Serum vitamin D was measured in both groups, and vitamin D levels .05). The incidence of vitamin D deficiency was similar between the patient and control groups (67.5% vs. 70%). Vitamin D levels significantly correlated with pain intensity (r ¼ L0.653; p ¼ .001) and FIQ-ADL scores in the FM group (r ¼ L0.344; p ¼ .030). In conclusion, the results of this study indicate that deficiency of vitamin D is not more common in premenopausal female patients with FM than in control subjects without FM. However, the association between pain and vitamin D levels in FM Pain Management Nursing, Vol 14, No 4 (December), 2013: pp e156-e163
Vitamin D and Fibromyalgia
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patients emphasizes that hypovitaminosis of vitamin D in the FM syndrome may have an augmenting impact on pain intensity and functional status. Future studies are needed to show the effect of vitamin D supplementation in the reduction of pain intensity and disability in patients suffering from this chronic condition. Ó 2013 by the American Society for Pain Management Nursing
Fibromyalgia (FM) is a chronic nonarticular rheumatic disorder characterized by widespread pain, stiffness, fatigue, sleep disorders, and a well defined pattern of tender points (Wolfe, Ross, Anderson, Russel, & Herbert, 1995). FM syndrome causes both physical and psychologic impairment and affects the quality of life of patients (Borman & Celiker, 1999). It predominantly affects women and is associated with work disability resulting in a negative socioeconomic impact (Borman & Celiker, 1999; Mannerkorpi & Ekdahl, 1997). Vitamin D deficiency is common in patients with various types of musculoskeletal symptoms, and this deficiency is found in a high proportion of patients referred to rheumatology units (Al-Allaf, Mole, Paterson, & Pullar, 2003; Serhan, Newton, Ali, Walford, & Singh, 1999; Swezey & Adams, 1999). The complaints of patients with FM resemble those of patients with vitamin D deficiency. Vitamin D deficiency may cause an unusual skeletal pain unresponsive to analgesics similarly to the FM syndrome (Al Faraj & Al Muttairi, 2003; Gloth, Lindsay, Zelesnick, & Greenough, 1991; Serhan et al., 1999; Swezey & Adams, 1999). There are a number of studies that have evaluated the relationship between FM and vitamin D deficiency with conflicting results (Armstrong, Meenagh, Bickle, Lee, Curan, & Finch, 2007; Badsha, Daher, & Ooi Kong, 2009; Bhatty, Shaikh, Irfan, Kashif, Vaswani, Sumbhai, & Gunpat, 2010; Block, 2004; de Rezende Pena, Grillo, & das Chagas Medeiros, 2010; Heidari, Shirvani, Firouziahi, Heidari, & Hajian-Tilaki, 2010; Plotnikoff & Quigley, 2003; Tandeter, Grynbaum, Zuili, Shany, & Shyartzman, 2009; Ulusoy, Sarica, Arslan, Ozyurt, Cetin, Bırgul, & Yıldırım, 2010; Warner & Arnspiger, 2008). Some studies have reported a positive association between vitamin D and FM symptoms (Armstrong et al., 2007; Badsha et al., 2009; Bhatty et al., 2010; Plotnikoff & Quigley, 2003) and others no association (Block, 2004; de Rezende Pena, Grillo, & das Chagas Medeiros, 2010; Heidari et al.,2010; Tandeter et al., 2009; Ulusoy et al., 2010; Warner & Arnspiger, 2008). The aim of the present study was to comparatively determine vitamin D deficiency in FM patients and control subjects with localized pain. We also aimed to assess the relationship between serum vitamin D levels and the common symptoms of FM.
MATERIALS AND METHODS Forty premenopausal female patients who fulfilled the American College of Rheumatology (ACR) criteria for FM syndrome (Wolfe, Smythe, Yunus, Bennett, Bombardier, Goldenberg, Tugwell, Campbell, Abeles, Clark, et al., 1990) were recruited from the Rheumatology unit outpatient clinics. Physical Medicine and Rehabilitation Clinic, Ankara Training and Research Hospital, between November and March 2009. The inclusion criteria for the FM group were generalized pain in both upper and lower extremities and both left and right sides of the body. Seventy-eight female patients with widespread pain were assessed for eligibility during the study period, and 68 patients fulfilled the ACR criteria for FM; 14 patients were excluded owing to postmenopausal status, ten were excluded owing to comorbid conditions, and four refused to participate in the study. Forty age-similar (2 years) premenopausal control subjects who were admitted for mechanical localized low back pain or tendinitis, and who had volunteered to participate in the study, were also included. We obtained informed consent from each of the patients The inclusion criterion for the control group was localized pain either in the low back or in one of the shoulders, elbows, wrists, knees, or ankles due to tendinitis. Exclusion criteria for both patient and control groups were having concomitant inflammatory rheumatic diseases, inflammatory bowel disease, liver and kidney diseases, osteoporosis, thyroid or parathyroid diseases, or cancer. All of the subjects previously or currently treated with systemic steroids or other demineralizing agents were also excluded, and the study was approved by the Ethics Committee of the hospital. The demographic characteristics of FM patients and control subjects, including age, sex, and body mass index (BMI), were recorded. Height and weight were measured and BMI calculated in kg/m2 as an index of body fat in both patients and control subjects. All subjects completed a questionnaire including questions on menarche age, number of pregnancies, lactation duration, and FM-related symptoms, including muscle weakness, sleep disturbance, fatigue, and tingling. All of the participants underwent a complete physical examination comprising tender point evaluation. All the tender points were algometrically measured by
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using a Fischer tissue compliance meter, a manually operated mechanical device that can also be used a pressure algometer (Fischer, 1987). The apparatus has a force pressure handle connected to a rubber disc and is calibrated in kg/cm2. Pressure was applied vertically on the 18 tender points and increased at a rate of 1 kg/s. Subjects were asked to say ‘ yes’’ when pain was experienced. Self-reported pain of the subjects during the last week was measured using a visual analog scale (VAS) that ranged from 0 to 10. The activities of daily living component of the Fibromyalgia Impact Questionnaire (FIQ-ADL) was used to assess the physical functional capacity in all subjects (Burckhardt, Clark, & Bennett, 1991). The responses to the FIQ-ADL were scaled from 0 (‘‘always able to do’’) to 3 (‘‘never able to do’’). The items were added together and divided by the number of valid scores to yield one physical functioning score (Jensen, Wittrup, Bliddal, DanneskioldSamsoe, & Faber, 2003). Laboratory tests for measurement of serum calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), and parathyroid hormone were determined by routine methods for subjects in both groups. Serum vitamin D (25-hydroxy vitamin D) was measured in both groups by a radioimmunoassay method (Gamma-C12; Berthold, Wilberg, Germany). All samples for vitamin D level measurements were collected between November and March, which corresponds to the winter season in our country. Serum samples were tested in duplicate and the results expressed in nmol/L. Vitamin D levels
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From the Ankara Training and Research Hospital, Department of Physical Medicine and Rehabilitation, Ankara, Turkey. Address correspondence to Dr. Muyesser Okumus, sehit veli kara sok 25/10 esertepe etlik, Kecioren Ankara, Turkey. E-mail: drmuyesser@ hotmail.com Received July 31, 2011; Revised September 25, 2011; Accepted September 26, 2011. 1524-9042/$36.00 Ó 2013 by the American Society for Pain Management Nursing doi:10.1016/j.pmn.2011.09.006
ABSTRACT:
There are a number of studies that have evaluated the relationship between fibromyalgia (FM) and vitamin D deficiency with conflicting results. The aim of this study was to assess vitamin D deficiency in patients with FM and to evaluate the relationship with the common symptoms of FM and levels of serum vitamin D. Forty premenopausal female fibromyalgia patients and 40 age- and sex-matched control subjects were included in the study. The demographic characteristics of all subjects, including age, sex, and body mass index, were recorded. The number of tender points was recorded, and the intensity of the widespread pain of the subjects was measured by the visual analog scale. The activities of daily living component of the Fibromyalgia Impact Questionnaire (FIQ-ADL), was used to assess physical functional capacity. Serum vitamin D was measured in both groups, and vitamin D levels .05). The incidence of vitamin D deficiency was similar between the patient and control groups (67.5% vs. 70%). Vitamin D levels significantly correlated with pain intensity (r ¼ L0.653; p ¼ .001) and FIQ-ADL scores in the FM group (r ¼ L0.344; p ¼ .030). In conclusion, the results of this study indicate that deficiency of vitamin D is not more common in premenopausal female patients with FM than in control subjects without FM. However, the association between pain and vitamin D levels in FM Pain Management Nursing, Vol 14, No 4 (December), 2013: pp e156-e163
Vitamin D and Fibromyalgia
e157
patients emphasizes that hypovitaminosis of vitamin D in the FM syndrome may have an augmenting impact on pain intensity and functional status. Future studies are needed to show the effect of vitamin D supplementation in the reduction of pain intensity and disability in patients suffering from this chronic condition. Ó 2013 by the American Society for Pain Management Nursing
Fibromyalgia (FM) is a chronic nonarticular rheumatic disorder characterized by widespread pain, stiffness, fatigue, sleep disorders, and a well defined pattern of tender points (Wolfe, Ross, Anderson, Russel, & Herbert, 1995). FM syndrome causes both physical and psychologic impairment and affects the quality of life of patients (Borman & Celiker, 1999). It predominantly affects women and is associated with work disability resulting in a negative socioeconomic impact (Borman & Celiker, 1999; Mannerkorpi & Ekdahl, 1997). Vitamin D deficiency is common in patients with various types of musculoskeletal symptoms, and this deficiency is found in a high proportion of patients referred to rheumatology units (Al-Allaf, Mole, Paterson, & Pullar, 2003; Serhan, Newton, Ali, Walford, & Singh, 1999; Swezey & Adams, 1999). The complaints of patients with FM resemble those of patients with vitamin D deficiency. Vitamin D deficiency may cause an unusual skeletal pain unresponsive to analgesics similarly to the FM syndrome (Al Faraj & Al Muttairi, 2003; Gloth, Lindsay, Zelesnick, & Greenough, 1991; Serhan et al., 1999; Swezey & Adams, 1999). There are a number of studies that have evaluated the relationship between FM and vitamin D deficiency with conflicting results (Armstrong, Meenagh, Bickle, Lee, Curan, & Finch, 2007; Badsha, Daher, & Ooi Kong, 2009; Bhatty, Shaikh, Irfan, Kashif, Vaswani, Sumbhai, & Gunpat, 2010; Block, 2004; de Rezende Pena, Grillo, & das Chagas Medeiros, 2010; Heidari, Shirvani, Firouziahi, Heidari, & Hajian-Tilaki, 2010; Plotnikoff & Quigley, 2003; Tandeter, Grynbaum, Zuili, Shany, & Shyartzman, 2009; Ulusoy, Sarica, Arslan, Ozyurt, Cetin, Bırgul, & Yıldırım, 2010; Warner & Arnspiger, 2008). Some studies have reported a positive association between vitamin D and FM symptoms (Armstrong et al., 2007; Badsha et al., 2009; Bhatty et al., 2010; Plotnikoff & Quigley, 2003) and others no association (Block, 2004; de Rezende Pena, Grillo, & das Chagas Medeiros, 2010; Heidari et al.,2010; Tandeter et al., 2009; Ulusoy et al., 2010; Warner & Arnspiger, 2008). The aim of the present study was to comparatively determine vitamin D deficiency in FM patients and control subjects with localized pain. We also aimed to assess the relationship between serum vitamin D levels and the common symptoms of FM.
MATERIALS AND METHODS Forty premenopausal female patients who fulfilled the American College of Rheumatology (ACR) criteria for FM syndrome (Wolfe, Smythe, Yunus, Bennett, Bombardier, Goldenberg, Tugwell, Campbell, Abeles, Clark, et al., 1990) were recruited from the Rheumatology unit outpatient clinics. Physical Medicine and Rehabilitation Clinic, Ankara Training and Research Hospital, between November and March 2009. The inclusion criteria for the FM group were generalized pain in both upper and lower extremities and both left and right sides of the body. Seventy-eight female patients with widespread pain were assessed for eligibility during the study period, and 68 patients fulfilled the ACR criteria for FM; 14 patients were excluded owing to postmenopausal status, ten were excluded owing to comorbid conditions, and four refused to participate in the study. Forty age-similar (2 years) premenopausal control subjects who were admitted for mechanical localized low back pain or tendinitis, and who had volunteered to participate in the study, were also included. We obtained informed consent from each of the patients The inclusion criterion for the control group was localized pain either in the low back or in one of the shoulders, elbows, wrists, knees, or ankles due to tendinitis. Exclusion criteria for both patient and control groups were having concomitant inflammatory rheumatic diseases, inflammatory bowel disease, liver and kidney diseases, osteoporosis, thyroid or parathyroid diseases, or cancer. All of the subjects previously or currently treated with systemic steroids or other demineralizing agents were also excluded, and the study was approved by the Ethics Committee of the hospital. The demographic characteristics of FM patients and control subjects, including age, sex, and body mass index (BMI), were recorded. Height and weight were measured and BMI calculated in kg/m2 as an index of body fat in both patients and control subjects. All subjects completed a questionnaire including questions on menarche age, number of pregnancies, lactation duration, and FM-related symptoms, including muscle weakness, sleep disturbance, fatigue, and tingling. All of the participants underwent a complete physical examination comprising tender point evaluation. All the tender points were algometrically measured by
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using a Fischer tissue compliance meter, a manually operated mechanical device that can also be used a pressure algometer (Fischer, 1987). The apparatus has a force pressure handle connected to a rubber disc and is calibrated in kg/cm2. Pressure was applied vertically on the 18 tender points and increased at a rate of 1 kg/s. Subjects were asked to say ‘ yes’’ when pain was experienced. Self-reported pain of the subjects during the last week was measured using a visual analog scale (VAS) that ranged from 0 to 10. The activities of daily living component of the Fibromyalgia Impact Questionnaire (FIQ-ADL) was used to assess the physical functional capacity in all subjects (Burckhardt, Clark, & Bennett, 1991). The responses to the FIQ-ADL were scaled from 0 (‘‘always able to do’’) to 3 (‘‘never able to do’’). The items were added together and divided by the number of valid scores to yield one physical functioning score (Jensen, Wittrup, Bliddal, DanneskioldSamsoe, & Faber, 2003). Laboratory tests for measurement of serum calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), and parathyroid hormone were determined by routine methods for subjects in both groups. Serum vitamin D (25-hydroxy vitamin D) was measured in both groups by a radioimmunoassay method (Gamma-C12; Berthold, Wilberg, Germany). All samples for vitamin D level measurements were collected between November and March, which corresponds to the winter season in our country. Serum samples were tested in duplicate and the results expressed in nmol/L. Vitamin D levels
