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    Complementary and Alternative Medical Lab Testing Part 15: Musculoskeletal
    Complementary and Alternative Medical Lab Testing Part 15: Musculoskeletal
    Complementary and Alternative Medical Lab Testing Part 15: Musculoskeletal
    Ebook326 pages4 hours

    Complementary and Alternative Medical Lab Testing Part 15: Musculoskeletal

    By Ronald Steriti

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    About this ebook

    Complementary and Alternative Medical Lab Testing (CAM Labs) contains summaries of the published research on lab tests, primarily from PubMed trials on humans. Each chapter (disease) begins with a brief summary of conventional lab tests, followed by additional lab tests, including diabetes, insulin resistance, metabolic syndrome, inflammation, etc. There are sections on endocrine hormones (thyroid, adrenal, sex steroids) and environmental medicine (toxic heavy metals). The nutritional assessments section includes minerals, vitamins and amino acids.

    CAM Labs 15 – Musculoskeletal

    1. Ankylosing Spondylitis
    2. Back Pain
    3. Bursitis
    4. Carpal Tunnel Syndrome
    5. Diffuse Idiopathic Skeletal Hyperostosis (DISH)
    6. Fibromyalgia
    7. Frozen Shoulder
    8. Gout
    9. Herniated Disc
    10. Osteoarthritis
    11. Osteomalacia
    12. Osteoporosis
    13. Overtraining Syndrome
    14. Polymyositis
    15. Psoriatic Arthritis
    16. Restless Legs Syndrome
    17. Rheumatoid Arthritis
    18. Sarcopenia
    19. Sciatica
    20. Sjögren Syndrome
    21. Tendinitis

    LanguageEnglish
    PublisherRonald Steriti
    Release dateMay 30, 2016
    ISBN9781311116239
    Complementary and Alternative Medical Lab Testing Part 15: Musculoskeletal
    Author

    Ronald Steriti

    Dr. Ronald Steriti is a graduate of Southwest College of Naturopathic Medicine and currently is researcher for Jonathan V. Wright at the Tahoma Clinic.

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      Complementary and Alternative Medical Lab Testing Part 15 - Ronald Steriti

      Chapter 1. Ankylosing Spondylitis

      Ankylosing spondylitis is a chronic, usually progressive, condition in which inflammatory changes and new bone formation occurs at the attachment of tendons and ligaments to bone (enthesopathy). Sacroiliac joint involvement that limits lumbar flexion is the hallmark of ankylosing spondylitis, although 20-30% of patients also have larger peripheral joint involvement.

      Conventional Lab Tests

      None to diagnose

      Normochromic normocytic anemia of chronic disease in 15%

      ESR or CRP is elevated in 75% (Spoorenberg et al., 1999)

      Alkaline phosphatase (ALP) is elevated in 50%

      HLA-B27

      Klebsiella pneumoniae titers (Rashid et al., 2013) (Rashid and Ebringer, 2007)

      Additional Lab Tests

      Fasting Glucose, Hemoglobin A1C

      A study used a sub-dataset of the National Health Insurance Research Database from 1996 to 2010 to established a AS cohort consisting new patients with AS or spondyloarthritis (N = 7,778) and a non-AS cohort without the diseases (N = 31,112). Incidences of T2DM in the two cohorts, hazard ratios (HRs) of risk of T2DM in association with AS, and cumulative probability of having T2DM were estimated by the end of 2010. The incidence of T2DM was 1.17-fold higher in the AS cohort than in the non-AS cohort (13.5 vs. 11.5, per 1,000 person-years), with an adjusted HR of 1.16 (95 % CI = 1.05-1.29). The T2DM incidence was higher for women than for men; while the Cox model measured sex-specific adjusted HR of T2DM was higher for men than for women. The incidence rate of T2DM increased with age in both cohorts, while the age-specific measures showed that the adjusted HR of T2DM was higher in young AS patients (

      Insulin Resistance, Metabolic Syndrome

      Twenty-four consecutive AS patients (men, 87.5%; median age, 50.5 years; median disease duration, 16.5 years) and 19 age- and sex-matched controls were investigated. Systolic blood pressure (p=0.04), triglyceride to HDL cholesterol ratio (p=0.002), and LDL cholesterol (p=0.03) were found significantly higher in AS patients than in controls; on the contrary, HDL cholesterol was pointed out as significantly lower (p<0.001). MetS was found in 11/24 (45.8%) of AS patients and in 2/19 (10.5%) of controls (p=0.019). (Malesci et al., 2007)

      This was a cross-sectional study of 63 men with AS, median age 40 (19-69) years, and 126 age-matched controls. Patients were on anti-TNFalpha treatment because of considerable disease activity at some time during the course of the disease. Patients had lower high-density lipoprotein cholesterol (HDL-C) (p<0.001), higher systolic (p=0.001) and diastolic (p<0.01) blood pressure compared with controls. The prevalence of the MetS was higher in patients compared to controls (34.9% vs. 19.0%; p<0.05). AS patients with MetS were older (p<0.01), with higher Framingham risk score (p=0.001), had longer disease duration (p<0.05) and higher BASDAI (5.1 vs. 3.7; p<0.05) than those without MetS, while both BASFI and CRP had an inverse correlation with HDL-C levels. Men with AS have a higher prevalence of cardiovascular risk factors and MetS compared with controls. The presence of MetS was associated with increased 10 year CVD risk in these patients. The association of AS disease activity with MetS suggests that CVD in AS patients may, at least in part, be attributed to the inflammatory burden of the disease. (Papadakis et al., 2009)

      Fourteen nonobese male patients with AS and 14 matched healthy controls underwent frequent-sampling intravenous glucose tolerance test (FSIVGTT). Fasting glucose, insulin, cholesterol, high-density lipoprotein and low-density lipoprotein cholesterol, triglyceride levels, HOMA2, glucose effectiveness, insulin sensitivity and insulin response to FSIVGTT did not differ between patients and controls. Tumor necrosis factor-alpha and interleukin (IL)-6 concentrations tended to be higher in AS patients than in controls. Second-phase beta-cell responsiveness was 37% lower (p = 0.05) in AS patients than in controls. A negative correlation was found between the percentage of beta-cell secretion and IL-6 in all subjects (r = -0.54, p = 0.006). We found normal insulin sensitivity but attenuated glucose utilization in the second phase of FSIVGTT in AS patients. These results indicate that elevated IL-6 levels may play a pathophysiological role in attenuating beta-cell responsiveness, which may explain the association between elevated IL-6 levels and increased risk for type 2 diabetes. (Penesova et al., 2005)

      C-Reactive Protein (CRP)

      A total of 269 patients (153 with AS and 116 with nrSpA) were included. In the whole group of patients with AS, hsCRP showed a better than routine CRP correlation with clinical parameters. In the whole group of patients with nrSpA, hsCRP correlated with the level of enthesitis-related tenderness only. In the AS subgroup with a negative routine CRP (<6 mg/litre) there was a clear trend for an increased level of pain, stiffness and functional impairment in patients with higher hsCRP concentration. Such a trend was less pronounced in patients with nrSpA. hsCRP correlates better than routine CRP with clinical disease activity parameters in patients with axial SpA, especially in AS. Therefore, hsCRP could be superior to standard CRP in assessing disease activity in axial SpA. (Poddubnyy et al., 2010)

      Data of 851 patients with painful axial AS participating in two randomized controlled trials evaluating coxibs (celecoxib) and NSAIDs (naproxen/ketoprofen) were used. The 851 enrolled patients (73% of whom were men) had an active disease, as assessed through functional impairment. Mean (s.d.) baseline CRP was 14 (19) (median 7.2) mg/l; 61% of patients had an increased CRP. The CRP levels were correlated positively with male sex, BASDAI and BASFI and negatively with age (multivariate analysis). There was a significant difference in the changes of CRP between placebo and NSAIDs/coxibs group (P = 0.003; SRM over placebo: 0.25). Such a treatment effect was of higher magnitude in the subgroup of patients with increased CRP and usually of lower magnitude than the treatment effect of other outcome variables such as BASDAI and BASFI. Increased CRP was frequently observed in patients with painful axial AS and was correlated both with activity and functional severity of the disease. The treatment effect of NSAIDs/coxibs was relevant in the subgroup of patients with increased CRP at baseline. (Benhamou et al., 2010)

      IL-27 and VEGF

      One hundred and forty AS patients and 90 healthy controls were included in the current study. The levels of IL-27 and VEGF in serum and synovial fluid (SF) samples were measured. The serum levels of IL-27 were remarkably higher in AS patients than healthy groups and significantly correlated with serum levels of VEGF. Furthermore, the serum levels of IL-27 were correlated with BASDAI independent of other markers of inflammation. Elevated serum levels of IL-27 and VEGF were detected in AS patients with peripheral arthritis and HLA-B27 positive. The SF levels of IL-27 and VEGF were significantly higher than serum levels in AS patients with peripheral arthritis. By contrast, levels of IL-27 and VEGF were not increased in AS patients with hip involvement and eye involvement. IL-27 may regulate the immunological or inflammatory process of AS. (Lin et al., 2014)

      RDW

      Laboratory parameters including RDW tests were conducted consecutively on the entire cohort of AS patients and healthy individuals. AS patients with increased RDW showed significant difference compared to healthy individuals (13.66+/-0.77 vs. 12.77+/-0.47, P<0.01), similarly, difference of AS patients and heathy individuals stratified by sex was almost the same as that in two groups. Some significantly positive correlation were observed between RDW and CRP, ESR, IgG, BASDAI score in patients with AS (r=0.356, P=0.018; r=0.481, P=0.001; r=0.385, P=0.010; r=0.586, P<0.01), almost identical results were showed when AS patients was stratified by gender. Finally, receiver operating characteristic (ROC) curves of RDW levels to identify AS patients exhibited a statistically significant level (area under the curve of 0.853; sensitivity of 72.7%, specificity of 81.4%). The results suggested that increased RDW was associated with AS and may be used as a potential marker estimating disease activity of AS. (Peng et al., 2014)

      Nitrites and Nitrates (NOx)

      Thirty five patients with RA, 32 patients with AS, and 36 patients with OA were entered into this study. In addition, 30 healthy volunteers acted as a control group. Serum nitrate and nitrite levels were found to be higher in patients with AS and RA than in the OA group (p<0.01). In addition, serum nitrate and nitrite levels were higher in all three groups than in the control group (p<0.01). Moreover, serum nitrate and nitrite levels were higher in patients who had SAD than in those who had not in the RA and AS groups (p<0.01 and p<0.05, respectively), and there was a correlation between serum nitrate and nitrite concentrations and SAD variables in patients with RA (Spearman's r(s)=0.414, p<0.05 and r(s)=0.408, p<0.05, respectively) and AS (r(s)=0.421, p<0.05 and r(s)=0.412, p<0.05, respectively). The findings suggest that nitrate and nitrite production is enhanced in patients with inflammatory arthritis compared with OA. In addition, serum nitrate and nitrite levels are enhanced in patients with RA, AS, and OA compared with healthy subjects. Furthermore, there is a correlation between the SAD variables and serum nitrate and nitrite levels in patients with RA and AS. (Ersoy et al., 2002)

      Digestive Assessments

      Celiac Disease

      30 AS patients and 19 age- and sex-matched controls were analysed for human leucocyte antigen (HLA)-B27, AGA and endomysial antibodies (EMA). Eleven (36.7%) of AS patients were AGA positive (compared with none of the control subjects) and three (10.0%) of these AS patients were also EMA-positive. The presence of AGA was not associated with more severe AS. Mild-to-severe villous atrophy and hyperplasia of crypts with increased chronic inflammatory cells in the lamina propria, which is typical of CD, was only observed in one AGA/EMA positive AS patient; CD was subsequently diagnosed by histology. AGA positivity might contribute to the pathogenesis of AS by increasing intestinal permeability to micro-organisms or by modifying intestinal immune mechanisms. (Togrol et al., 2009)

      Intestinal Permeability

      A study examined the intestinal permeability to 51Cr-EDTA in 20 patients with AS, 65 of their healthy relatives, and 25 normal volunteers. Gut permeability was found to have increased in the patients and their healthy relatives compared to the control group. No difference in gut permeability was found between patients and relatives regardless of whether they had the HLA B27 antigen or not. The increased intestinal permeability in the patients had no relation to the disease activity, to the presence of peripheral arthritis or to the intake of NSAIDs. Gut permeability was shown to bear no relation to IgA levels, ESR or CRP. Our findings suggest that the increase in gut permeability in AS patients and their relatives is a primary defect and may be an aetiologic factor in this disease. (Martinez-Gonzalez et al., 1994)

      A study found increased small intestinal permeability to 51Cr- EDTA in patients with ankylosing spondylitis compared with controls. There is no significant difference between patients with ankylosing spondylitis and patients with rheumatoid arthritis taking non-steroidal anti-inflammatory drugs (NSAID). The increased intestinal permeability in ankylosing spondylitis is independent of disease activity. These findings suggest that the increased permeability is caused by NSAID treatment and is probably not a primary lesion of small bowel mucosa. (Morris et al., 1991) (Mielants et al., 1992)

      Intestinal permeability was measured using a low molecular weight polyethylene glycol as a permeability marker in patients with osteoarthritis, ankylosing spondylitis (AS) and rheumatoid arthritis (RA). Patients with AS showed a significant increase in bowel permeability when compared to controls. Intestinal permeability was also increased in patients with active RA but was less than the control group in RA patients who did not have active joint disease. (Smith et al., 1985)

      Calprotectin

      Consecutive AS patients were recruited from a long-term prospectively collected longitudinal AS cohort at Cedars-Sinai Medical Center. Controls were recruited from Cedars-Sinai Medical Center employees or spouses of patients with AS. A total of 81 subjects (39 AS patients and 42 controls) were included for analysis. The average age of AS patients was 47 years and the average disease duration was 22 years. AS patients were predominantly male; 76% were HLA-B27-positive. Median fCAL levels were 42 mug/g and 17 mug/g in the AS group and controls, respectively (P < 0.001). When using the manufacturer's recommended cutoff value for positivity of 50 mug/g, stool samples of 41% of AS patients and 10% of controls were positive for fCAL (P = 0.0016). With the exception of ANCA, there were no significant differences in antibody levels between patients and controls. Median ANCA was 6.9 ELISA units in AS patients and 4.3 ELISA units in the controls. Among AS patients stratified by fCAL level, there were statistically significant differences between patients and controls for multiple IBD-associated antibodies. Calprotectin levels were elevated in 41% of patients with AS with a cutoff value for positivity of 50 mug/g. fCAL-positive AS patients displayed higher medians of most IBD-specific antibodies when compared with healthy controls or fCAL-negative AS patients. (Matzkies et al., 2012)

      A study found elevated levels of fecal calprotectin (>50 mg/kg) in 140 of 205 AS patients (68%). Levels of fecal calprotectin were associated with increasing age, disease duration, ESR, CRP, and serum calprotectin, but not with gastrointestinal symptoms. Fecal calprotectin was higher in patients using NSAIDs, salicylates, and proton pump inhibitors, but lower in patients using methotrexate and infliximab. Serum calprotectin levels were normal or low in 98% of AS patients and not different from the levels in healthy blood donors. Serum calprotectin levels were positively associated with ESR, CRP, WBC, and PLT. Two-thirds of AS patients had elevated levels of fecal calprotectin, without associated gastrointestinal symptoms. Serum calprotectin was mostly normal in AS, in contrast to various other inflammatory rheumatic diseases. Fecal calprotectin may be a marker for subclinical intestinal inflammation in AS and should be measured after stopping NSAIDs. (Klingberg et al., 2012)

      A total of 124 of 213 (58%) available first-degree relatives of 47 patients with AS in Iceland underwent investigation for intestinal inflammation (fecal calprotectin concentration), HLA-B27 genotyping, and computerized tomography of the sacroiliac joints. A total of 41% of the first-degree relatives had subclinical intestinal inflammation, whereas 15 of 17 spouses were normal. Variance components analyses suggest that the inheritance pattern of this inflammation is affected by a major additive gene. Some sacroiliac changes, suggestive of early AS, differed significantly between subjects with and without subclinical intestinal inflammation (mean diameter of subchondral cysts [2.9 vs. 1.2 mm; P = 0.026] and blurring of joint margins [9 of 44 (20%) vs. 1 of 41 (2%); P = 0.02]). Intestinal inflammation and sacroiliac changes did not relate to the subjects' HLA-B27 status. Many first-degree relatives of patients with AS appear to have an inherited abnormality that leads to subclinical intestinal inflammation. The association between the presence of this inflammation and the sacroiliac changes suggests that it may play a pathogenic role in the spondylarthropathy of AS. (Bjarnason et al., 2003)

      Comprehensive Thyroid Panel

      In this cross sectional study, 80 patients with AS fulfilling the 1984 Modified New York Criteria and 80 healthy subjects, age and sex-matched with AS patients, were included. As the positive control group, 62 female patients with primary SjS were also studied. The frequencies of parenchymal heterogeneity with thyroid ultrasonography (USG) (30 vs 11.3 %, p = 0.045), thyroid autoantibody positivity (13.8 vs 2.5 %, p = 0.017), and concomitant diagnosis of Hashimoto's thyroiditis (HT) (10 vs 1.3 %, p = 0.034) were significantly higher in AS group compared to healthy controls. Among AS patients having HT, subclinical hypothyroidism was detected only in a single patient. Frequency of autoimmune thyroid disease was significantly higher in AS group, compared to healthy controls. (Emmungil et al., 2014)

      Data of 108 patients (female/male (F/M) 27/81) were analyzed. 44 (F/M 15/29) patients were receiving anti-TNF alpha, while 64 (F/M 12/52) were receiving other drugs [(sulfasalazine, anti-inflammatory drug (NSAIDs)]. Among those not receiving anti-TNF alpha therapy, TPO level was high in 23 patients (mean TPO value 86.69 +/- 65.28 U/ml), while it was high only in nine receiving anti-TNF alpha (mean TPO 36.61 +/- 14.02 U/ml) (p < 0.05). Investigating the data regarding gender in both populations, autoimmune thyroid disease frequency was found to be lower in the patient group receiving anti-TNF alpha treatment. Subclinical hyperthyroidism was discovered in three patients (one female two male), and subclinical hypothyroidism in two (two male). Thyroid nodule was detected in 29 patients. It was concluded that the frequency of thyroid autoimmune disease was higher in our study than that reported in the literature, and the frequency of thyroid disorder in patients with AS was lower in those receiving anti-TNF alpha compared to those not. This may arise from the role of TNF alpha on pathogenesis of thyroid disorders. (Tarhan et al., 2013)

      In 22 female patients with AS and 22 healthy age-matched control subjects parameters of thyroid gland function, rheumatic activity, as well as a subtle drug anamnesis of the rheumatic medication, and an ultrasonographic examination of the thyroid gland were determined. Thyroid function was tested by intravenous injection of 400 microg thyrotropin-releasing hormone (TRH). In parallel basal levels of reverse-T3 (rT3), calcium and anti-thyroid antibodies were estimated. In the AS-group an enlarged thyroid volume was seen in 10 cases, basal FT4, FT3 and TT3 were significantly lower, TSH and TT4 were found to be in the normal range and rT3 was significantly increased. The prevalence of anti-thyroid antibodies was significantly higher in the AS-group. The AS-patients responded as well as the controls with thyroid hormone secretion to TRH, within an observation period of 2 hours. No differences were observed in TSH response. Free serum calcium showed in both groups no significant difference. (Lange et al., 1999)

      Comprehensive Sex Steroid Panel

      Estradiol and Progesterone

      Ovarian function was studied in 17 women with active ankylosing spondylitis (AS). Levels of FSH, LH, prolactin and androstenedione were normal in menstruating patients and FSH and LH were elevated in menopausal patients. In menstruating patients with active AS the estradiol levels were lower than in patients with inactive AS and significantly (p less than 0.05) lower than controls. Progesterone levels in menstruating patients were lower (P = NS) than controls. In menopausal patients estrogen levels were lower than their controls (P = NS). There was a significant (p less than 0.05) inverse correlation between the sedimentation rate and the estrogen level. Seven patients accepted oral estrogen therapy (average duration 4 months) and peripheral arthritis subsided within one month, all variables of clinical activity of AS improved and at the end of the study all patients were in functional class I. (Jimenez-Balderas et al., 1990)

      Estradiol/Testosterone Ratio

      Testicular function was studied in 22 patients with ankylosing spondylitis (AS) with serum measurements of hormone levels, seminal fluid analysis and testicular reserve test. Results were correlated with disease activity. The abnormal findings were elevated luteinizing hormone (LH), inversion of estradiol/testosterone ratio (E2:T) and diminished testicular reserve for testosterone (T) and slightly increased for estradiol (E2). Nine patients with severe active AS received biweekly 2,500 IU of human chorionic gonadotrophin injections with a resulting increase in E2 serum levels. When the values of E2 reached 40 pg/ml or higher, there was a decrease of the sedimentation rate (p less than 0.05) and a reversal to normal of the E2:T ratio. This was accompanied by an improvement in AS at the 10th week that lasted up to 9 weeks after discontinuation of treatment. These findings suggest a possible role of sex hormones in the physiopathogenesis of AS. (Tapia-Serrano et al., 1991)

      SHBG in Men

      Fifty-six male patients with mild AS were studied. There was a small, not significant reduction in serum total testosterone in patients with AS compared to controls [16.02 (5.0) vs 21.0 (6.2) nmol/l]. Serum SHBG was significantly lower in patients with AS [27.29 (10.6) vs 35.0 (13.0) nmol/l; p < 0.001] compared to controls. There was no significant difference in the mean TFI between patients and controls [58.7 (21.2) vs 60 (22.2) nmol/l; p > 0.05] or in the levels of LH and FSH. No significant correlation was found between sex hormones, BMD, and vertebral fractures in patients with AS. Sex hormones are not altered significantly in patients with mild AS and do not appear to be related to BMD or vertebral fractures. Osteopenia in men with mild AS is therefore unlikely to be secondary to hypogonadism. (Mitra et al., 1999)

      DHEA in Men

      A cross-sectional study included 58 male patients with primary AS. The mean age was 38.2 years (range 18-59 years). Bone loss was observed in 54.5% of cases at the femoral neck and in 52.3% of cases at the trochanter and total hip. Bone loss was found in 40 (69%) cases in at least one of these three regions. Serum DHEAS was low in 12 (30.8%) of the cases with bone loss, and one (5.9%) of those without (P = 0.043). The ratio of serum T/DHEAS was higher in those with bone loss (5.24 +/- 3.70) than in those without (3.58 +/- 3.16) (P = 0.026). The results showed that bone loss might be related to low serum DHEAS levels in males with AS. (Aydin et al., 2005)

      Nutritional Assessments

      Iron, Ferritin

      One hundred and thirty patients diagnosed with AS according to modified New York criteria and 91 age- and sex-matched healthy control subjects were included in this study. RLS was significantly more common in patients with AS (30.8%) than in healthy controls (13.2%). When AS patients with RLS were compared with AS patients without RLS, it was seen that peripheral arthritis, uveitis, anemia, smoking and polyneuropathy were significantly higher in the former group. RLS is common in patients with AS and iron deficiency, smoking and small fiber neuropathy seem

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