Effect of fibromyalgia on bone mineral density in patients with fibromylagia and rheumatoid arthritisMA Buyukbese1, ON Pamuk2, OA Yurekli3, N Yesil4
1 Department of Internal Medicine, KSU School of Medicine, Kahramanmaras, Turkey
2 Division of Rheumatology, Trakya University Medical Faculty, Edirne, Turkey
3 Department of Internal Medicine, Sema Hospital, Istanbul, Turkey
4 Department of Internal Medicine, Trakya University Medical Faculty, Edirne, Turkey
Objectives: Fibromyalgia (FM) may t cause a decrease in bone mineral density (BMD) because of decreased mobility. The condition is relatively frequent in rheumatoid arthritis (RA) and RA patients with FM have more disability than those without FM. We evaluated the effect of FM on BMD and investigated the effect of FM on BMD in RA patients. Materials and Methods: We included age-matched 56 FM, 52 RA patients, and 37 healthy females as controls. Twenty three of all RA subjects met 1990 ACR FM criteria. Patients using the antiresorptive drugs, those on hormone replacement therapy, patients with thyroid or parathyroid dysfunction were excluded. Self-reported pain and fatigue severity, functional items of FM impact questionnaire were questioned in FM and RA patients. In all subjects, BMD of the lumbar spine and femur neck were determined by dual X-ray absorptiometry, and T-scores were recorded. Results: Self-reported pain and fatigue scores in FM subjects were significantly higher than in RA patients (P0<0.001). The mean lumbar spine and femur neck BMD and their T-scores in RA patients were significantly lower than in FM and control groups ( P values<0.01). There was no difference in BMD between FM subjects and the control group. BMD in RA patients with and without FM were similar ( P>0.05). There was a significant negative correlation between self-reported pain score and lumbar spine BMD in FM subjects (r=–0.41, P=0.006). Conclusions: In spite of functional disability, FM does not cause a decrease in BMD. The presence of FM in RA patients does not result in a change in BMD.
Keywords: Bone mineral density, fibromyalgia, fibromyalgia impact questionnaire, osteoporosis, rheumatoid arthritis
Fibromyalgia (FM) is a chronic musculoskeletal disorder characterized by widespread pain, asthenia, fatigue, and sleep disturbance. Females with FM have impaired mobility because of fatigue and aggravation of pain with exercise. , It was reported that impaired mobility resulted in osteopenia. , Data on the incidence of osteoporosis in FM patients are contradictory. ,,,, While some studies reported low bone mineral density (BMD) in FM, , others could not find such an association. , Many FM patients are admitted to internal medicine and rheumatology clinics with widespread pain; and there is a general belief that the reason for the pain might be osteoporosis. Therefore, FM patients should be evaluated for the presence of osteoporosis and their management should be planned accordingly.
Rheumatoid arthritis (RA) is a chronic inflammatory disease and it is known that both periarticular and systemic osteoporosis might develop during the course of the disease. FM is seen frequently in RA patients and its presence is associated with a worse prognosis because of functional disability. , Nevertheless, it is not known whether the coexistence of FM in RA patients has any influence on the development of osteoporosis. We carried out the present study to evaluate the effect of FM on BMD in female patients and them with healthy controls. In addition, we evaluated the influence of FM on BMD in RA patients.
We included 56 FM and 52 RA patients diagnosed at the Rheumatology Division of Trakya University Medical Faculty. The 1987 ACR criteria for RA was used and the 1990 criteria for FM. , Twenty three RA subjects defined chronic widespread pain, which met ACR 1990 criteria. Thirty seven apparently healthy females who came to our Internal Medicine Out-patient Clinic for check-up were taken as our control group. None of these subjects had RA or FM. The demographic features, medical history, drug intake (including disease modifying antirheumatic drugs (DMARD) and steroids), smoking, alcohol consumption, menopausal status in all subjects were recorded down; body mass indexes were calculated. Subjects using antiresorptive drugs for osteoporosis, those on oral contraceptives or hormone replacement therapy, patients with known thyroid or parathyroid dysfunction were excluded. All patients gave written, informed consent. The study design was in accordance witarefulh the guidelines issued by the Ethics Committee of our institution.
All subjects underwent joint examination and tender points were determined. Erythrocyte sedimentation rate, C-reactive protein, and rheumatoid factor were available in all subjects. FM and RA patients were requested to assess the severity of self-reported pain and fatigue by means of a visual analogue scale (VAS) that ranged from 0 cm to 10 cm indicating the greatest. The duration of morning stiffness was also interrogated.
All FM and RA patients were administered the physical function items of the fibromyalgia impact questionnaire (FIQ) scale.  Sarmer et al.  performed the Turkish validation and reliability of the FIQ score. Disease activity score (DAS) was calculated in RA patients. 
Lumbar spine (L2-4), femoral neck BMD was determined with Norland scanner. All measurements were obtained by dual X-ray absorptiometry technique. BMD was expressed as T-score, i.e., the number of standard deviations from the mean values of healthy young adults.
For statistical analysis of the data, Chi-square, one-way variance analysis (ANOVA) and unpaired t-test were used. The relationship between lumbar-femoral neck BMD and pain, FIQ and fatigue scores were evaluated via Pearson's correlation test. All analyses were done at 5% significance.
The groups were similar in age and menopausal status. Self-reported pain and fatigue scores on VAS were significantly higher in FM group than in RA group (P0<0.001). While, the mean lumbar spine and femur neck BMD in RA patients were lower than other groups; the mean lumbar spine and femur neck T-scores were significantly lower ( P<0.01). When pre- and post-menopausal patients were considered as separate groups, comparison of data yielded similar results (data not shown). Lumbar spine and femur neck BMD were similar in FM patients using and not using antidepressant and/or neuropathic pain drugs ( P>0.05). Data about RA, FM, and control groups are seen in [Table 1].
The demographic features, drug intake and DAS scores in RA patients with and without FM were similar. RA patients with FM had significantly higher self-reported pain and fatigue scores on VAS and higher FIQ functional score than RA patients without FM ( P<0.05). There were no differences in the lumbar spine and femur neck BMD between RA patients with and without FM ( P>0.05). The features of both groups are seen in [Table 2].
There was a significant negative correlation between lumbar spine BMD and VAS self-reported pain score ( r=−0.41, P=0.006) and duration of self-reported pain ( r=−0.42, P=0.005) in FM patients. The correlation between BMD and pain scores is seen in [Figure 1]. There was a trend toward a lower BMD in RA patients using steroids although it did not reach statistical significance (P=0.1).
In our study, females with FM had lumbar spine and hip BMD results similar to controls who were matched with them for age, menopausal status and osteoporosis risk factors. The BMD of age-matched RA patients, on the other hand, was significantly lower when compared to FM and control groups.
The inflammatory process in RA provokes intense resorption of the bone.  It has been shown with prospective data that when there is optimal control of inflammation in RA, there is a decrease in structural damage and bone loss.  Cross-sectional DEXA studies in RA have conflicting results about steroids.  Another factor accused for RA-related osteoporosis is reduced mobility; however, it probably has less importance because we found a negative association between low BMD in RA patients and FM. This is a surprising and interesting observation. The explanation might be that patients with FM are more ambulant than often reported or patients with RA have longer periods of immobility. FM patients very frequently use antidepressant neuropathic medications with positive effect on BMD: This might be another reason for RA patients with FM not having more osteoporosis. Nevertheless, literature data reveal that tricyclic and selective serotonin reuptake inhibitor antidepressants increase the tendency to osteoporosis.  A recent study showed that neuropathic pain drugs like gabapentin had no risk for or protection against osteoporosis.  In our study, BMD were not significantly different between FM patients using or not using antidepressants and/or neuropathic pain drugs.
Studies about the increased frequency of osteoporosis in FM yielded contradictory results. FM patients and controls had similar BMD of the lumbar spine and hip in the study of Jacobsen et al.  and of the calcaneus in the study of Zerahn et al.  Reduced BMD was detected by only Zerahn et al.  when they corrected for a slight overweight among FM patients. A study later performed by Swezey and Adams  in a small group of FM patients stated that BMD of the lumbar spine was decreased, and BMD of the hip was decreased in only post-menopausal patients. A recent study by Jensen et al.  reported that there was a tendency towards a lower BMD of the hip-and not of the lumbar spine-in pre-menopousal FM subjects. Al-Allaf et al.  detected decreased BMD of the middistal radius, which correlated with cortical bone; however, they observed no differences in BMD of the other regions. One interesting result of this study was finding vitamin D subnutrition in FM patients. As mentioned above, some studies detected decreased BMD in FM subjects. , Nevertheless, it is difficult to reach a certain conclusion because the number of patients in these studies was few, BMD was decreased in only some subgroups of patients and in certain bone regions.
An important proportion of RA patients have secondary FM; it was reported that RA patients with FM had more abnormal measures of function, pain, disease activity. , Since, FM is diagnosed when patients have widespread pain thus finding that patients with FM had more pain as compared to RA without FM is a circular argument. As reduced physical activity has been defined as an important risk factor for osteoporosis, , we evaluated the effect of the presence of FM on osteoporosis in RA, which is a disease with an increased incidence of osteoporosis. We found that self-reported pain, fatigue, and FIQ functional item scores were higher in RA patients with FM. In spite of this, BMD in this group was not different from RA patients without FM. In addition, there was no relation between FIQ score and BMD. As a result, the presence of FM is associated with more pain and more disability in RA patients; however, it does not seem to be associated with osteoporosis.
Although, it did not reach statistical significance, it was noteworthy that RA patients with FM had much less DMARD usage - including, methotrexate - than the RA group without FM. This situation raised the question of whether their FM symptoms could possibly be related to less aggressive treatment of their RA. Nevertheless, since almost all of our patients were using DMARD with or without methotrexate, we assume that giving non-methotrexate DMARD to RA patients was not related with the presence of FM. Another probability is that the frequent problem of drug intolerance in FM might result in RA patients with FM using less methotrexate. Less intense DMARD treatment in RA might be responsible for the higher frequency of FM; however, the contrary might also be true. FM patients might have high tender joint scores, which could cause artifactual elevations in DAS28 scores; thereby leading to the usage of higher dose DMARDs and earlier introduction of biologic therapies, which have a positive effect on BMD.
One interesting result of our study was that there was a negative correlation between self-reported pain score and lumbar spine BMD in FM patients. Similarly, Jensen et al.  detected a negative correlation between pain score and BMD of the hip. In the above-mentioned study, BMD of the hip tended to be lower in the FM group; but, the difference was non-significant. The results of our and Jensen et al. studies suggest that pain, which is a major symptom in FM might affect BMD negatively. It is probable that the pain felt by patients with FM leads to immobilization; thus, further deteriorating lumbar BMD in the long term. Since, FIQ score is multidimensional includes pain together with many other parameters; and as a correlation between FM activity and FIQ score could not be demonstrated, the factor, which is most effective on BMD is the severity of the pain felt by the patients.
Recent studies demonstrated that vitamin D modulated the immune system and had anti-inflammatory properties.  In addition, vitamin D levels in autoimmune diseases like RA were low and symptoms improved with supplementation.  Studies about FM evaluated the association with vitamin D deficiency. However, study results are inconclusive and in general, supplementation with vitamin D does not lead to any improvement in pain.  In our study, we did not evaluate vitamin D levels.
In our study, we observed that BMD was not decreased in FM patients; and although the presence of FM is associated with functional disability in RA subjects, BMD was not negatively affected. Nevertheless, there was a negative correlation between self-reported pain score and lumbar spine BMD, which suggests that the severity of FM might have a negative influence on spine bone mass.
[Table 1], [Table 2]