The sacroiliac joint: an overview of its anatomy, function and potential clinical implications.

This article focuses on the (functional) anatomy and biomechanics of the pelvic girdle and specifically the sacroiliac joints (SIJs). The SIJs are essential for effective load transfer between the spine and legs. The sacrum, pelvis and spine, and the connections to the arms, legs and head, are functionally interrelated through muscular, fascial and ligamentous interconnections. A historical overview is presented on pelvic and especially SIJ research, followed by a general functional anatomical overview of the pelvis. In specific sections, the development and maturation of the SIJ is discussed, and a description of the bony anatomy and sexual morphism of the pelvis and SIJ is debated. The literature on the SIJ ligaments and innervation is discussed, followed by a section on the pathology of the SIJ. Pelvic movement studies are investigated and biomechanical models for SIJ stability analyzed, including examples of insufficient versus excessive sacroiliac force closure.

Adrenal plasma steroid relations in glucocorticoid-naïve premenopausal rheumatoid arthritis patients during insulin-induced hypoglycemia test compared to matched normal control females.

OBJECTIVE: Clinical and experimental data indicate the involvement of adrenal steroids in the complex of rheumatoid arthritis (RA) pathogenesis. A subtle adrenocortical hypocompetence has been suggested in a subset of glucocorticoid-naïve premenopausal females with RA. METHODS: The interrelations among adrenal steroids: cortisol (CORT), 17alpha-hydroxyprogesterone (17-OHP), androstenedione (ASD), dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulphate (DHEAS) were evaluated in 15 glucocorticoid-naïve premenopausal females with RA and in 14 age- and body mass index- matched healthy females at basal and during insulin-induced hypoglycemia states. Spearman's correlations were used to analyze baseline plasma concentrations as well as areas under response curves of these steroids levels as assayed during the basal and/or insulin-induced hypoglycemia status. RESULTS: Six among 15 RA patients, but none of 14 controls had combined "lower" quartile range of basal cortisol (< 431 nmol/l) and lower DHEAS (< 2.79 micromol/l) levels, i.e., concentrations within the lowest quartiles of the control group (p = 0.017). In all subjects combined, basal correlations were significantly positive between ASD and other steroids (CORT, 17OHP, DHEA, DHEAS). When patient and control groups were analyzed separately, the positive basal correlation between ASD and CORT was significant only in RA patients (p = 0.030). In contrast, a positive basal correlation between ASD and DHEA was significant only in controls (p = 0.004). When comparing the areas under response curves (AUCs), the correlation of ASD and CORT was significantly negative in RA (p = 0.009), but positive in controls (RA vs control difference in Spearman's correlations, p = 0.002). The correlation between AUCs of ASD and DHEA was strongly positive in controls (p = 0.006), but not in RA (RA vs. control difference p = 0.044). CONCLUSIONS: The results suggest relative hypocompetence of adrenocortical function in premenopausal RA females. Different patterns of correlations of the adrenal steroids during basal vs. stimulatory testing suggested certain alterations in adrenal synthetic pathways or deficiencies in the dynamics of steroidogenesis in RA.

Integrated neuroendocrine immune risk factors in relation to rheumatoid arthritis: should rheumatologists now adopt a model of a multiyear, presymptomatic phase?

An integrative perspective of neuroendocrine immune (NEI) and related risk factors for the onset of rheumatoid arthritis (RA) is presented, based upon studies of the long-term presymptomatic phase. Besides the recognized genetic markers and familial predisposition, multiple immunological precursors of RA have been identified many years before the clinical onset of inflammatory manifestations. Rheumatoid factors and related antibodies occur in approximately one-half of presymptomatic susceptibles. Cigarette smoking in sufficient amount and duration is a major risk factor for RA, particularly for postmenopausal-onset women and for men. In premenopausal-onset RA, subtle insufficiency of adrenal cortical function is less well recognized. In such women, cytokine imbalance may also precede inflammatory onset of RA. In males alone, multiple hormonal and cytokine correlations were found many years before the onset of RA, implying long-term activation or perturbation of this NEI system. The proposed physiopathogenetic model of RA requires further controlled, prospective studies for validation of the multiyear presymptomatic phase of RA. Such studies promise to clarify the currently unknown causal and sequential chains in this enigmatic disease.

Jacques Forestier's vanished bowstring sign in ankylosing spondylitis: a call to test its validity and possible relation to spinal myofascial hypertonicity.

Jacques Forestier's bowstring sign (signe de la "corde de l'arc") in ankylosing spondylitis (AS) was described by him in his 1951 book (French). In free lateral bending, the early AS patient has palpably firm, contracted dorsolumbar muscles on the concave side, opposite to the findings in normals. Forestier described this sign as a common and characteristic finding in AS. Perplexingly, the sign is essentially unknown in the rheumatologic field. A single report (Polish) on electromyographic (EMG) findings in AS and control subjects documented the electromotor component of the bowstring sign as well as its diagnostic utility in early AS patients. In this paper, the literature on EMG studies in series of AS patients is reviewed as well as kinesiologic EMG studies of normals in lateral bending. Paravertebral and other muscle pathology in AS was reviewed in relation to the EMG findings. Critical, controlled assessment of Forestier's bowstring sign and biomechanical investigations of the dorsolumbar muscles in AS promise to offer new insights into the early physiopathogenesis of this unique disease.

Are adolescent idiopathic scoliosis and ankylosing spondylitis counter-opposing conditions? A hypothesis on biomechanical contributions predisposing to these spinal disorders.

Human spinal biomechanics are profoundly complex and not well understood, especially in terms of the dynamic spine function. Translation of biomechanics to disease is difficult, particularly since cause must be separated from effect. Primary dynamics predisposing to the onset of chronic spinal disorders, e.g., adolescent idiopathic scoliosis (AIS) or ankylosing spondylitis (AS), must clearly be differentiated from secondary alterations. This commentary addresses primary biomechanics that may predispose to these idiopathic diseases. A novel hypothesis is proposed, based upon inferences regarding their contrasting muscular dynamics. The hypothesis postulates opposing inherent muscle tonicity in AIS versus AS. Converse degrees of spinal stability may predispose to the respective curvature deformities of AIS and the enthesopathy lesions of AS. One condition is suspected to counter-oppose the other, within a polymorphic spectrum of spinal stability.

Ankylosing spondylitis: integrated clinical and physiological perspectives.

This hypothesis paper draws upon clinical epidemiological and physiological perspectives of axial muscle tone relevant to ankylosing spondylitis (AS). Skeletal muscle tonus is the property of intrinsic tension or resistance to stretch with no additional muscle contraction. The interpretations call attention to novel concepts of the intrinsic axial muscular system contributions to enthesopathic lesions in AS. The axial kinematic chain extends from the entire spine to the posterior aspects of the lower extremities and is essential for postural and mobility functions. Muscles and articular cartilage derive from common embryological precursor cells and are complexly coordinated in the maintenance of postures and dynamic functions. A definitive link between axial muscular dysfunction and respective joint pathology has not yet been demonstrated in AS. However, the following clinical epidemiological and physiological observations raise the possibility of a relationship between axial muscular hypertonicity and AS, which will be reviewed sequentially.

Hormonal and immunologic risk factors for the development of rheumatoid arthritis: an integrative physiopathogenetic perspective.

Evidence indicates that women who are susceptible to premenopausal onset of RA and men each have identifiable risk factors or risk markers long before onset of the clinical disease. Accordingly, further definition of such predictive factors promises to identify persons who are susceptible to developing RA during preclinical phases. Like coronary artery disease, once risks for developing RA can be reliably quantitated, research in primary prevention should become a realistic objective. Disease prevention objectives are central to the public health strategy of the National Arthritis Action Plan and the US Public Health Service "Healthy People 2000" plan (2010 plan also proposed). The decade of arthritis and musculoskeletal diseases (2000-2010) offers an incentive to nurture a new paradigm of RA prevention. Further research in neuroendocrine, immunologic, and microvascular risk factors for the development of RA promises to unravel its complex physiopathogenetic mechanisms and permit identification of persons who are at high risk for developing this disease. Successful research in identifying reliable risk factors (or markers) can be expected to lead to prevention strategies. Effective programs in identifying persons susceptible to RA could lead to earlier control measures and significantly reduce the enormous burden of this common disease, which affects all segments of the population.

Neuroendocrine immune mechanisms in rheumatic diseases. An overview and future implications.

A new physiopathogenetic paradigm may be proposed for RA and possibly its related systemic rheumatic diseases (i.e., mechanisms whereby multiple risk factors initially perturb the homeostasis of core physiologic components over an extended premorbid phase, which may progress to clinical disease in later decompensated stages). These complex interactive processes are likely to be individualized according to genetic, nongenomic somatic, developmental, behavioral, and environmental influences. Future research promises to further elucidate the roles of neuroendocrine mechanisms in the rheumatic diseases and offers promise for enhanced therapies and possible avenues for disease modification if not eventual prevention.

Adrenal androgen and glucocorticoid dissociation in premenopausal rheumatoid arthritis: a significant correlate or precursor to onset?

Controlled studies of adrenal steroids in premenopausal women with rheumatoid arthritis (RA) have revealed subtle and inconsistent decreases in glucocorticosteroid (GCS) function, but prominent deficiencies of adrenal androgens (AA). Such findings have suggested that hypoandrogenicity may predispose to RA in younger women. However, recent prospective studies of serum cortisol and dehydroepiandrosterone sulfate (DHEAS) levels before (x = 12 yrs) the onset of the disease (pre-RA) offer an alternative perspective. Significant dissociation of serum cortisol and DHEAS levels was found only in the subgroup of premenopausal women who developed RA before age 50. This subgroup alone had significant deficiency in serum DHEAS levels. Aggregate data imply that the documented deficits of DHEAS (and other AA) in such young females are a correlate of relative adrenal insufficiency, and that subtle GCS dysfunction may either contribute to development of RA in such young women as well as pubertal girls or may predispose to earlier onset of disease.

Neuroendocrine, immunologic, and microvascular systems interactions in rheumatoid arthritis: physiopathogenetic and therapeutic perspectives.

OBJECTIVE: To review the "core" systems interactions in rheumatoid arthritis (RA): neuroendocrine, immunologic, and microvascular, and to interpret an integrated physiopathogenesis of the disease, beginning at a preclinical phase of risk factors to the later stages of manifest clinical inflammation. METHODS: Publications on stress reactions, serum hormonal levels, biological mediators of inflammation and vascular alterations in RA during its preclinical phase, course of active disease, including pregnancy, and hormonal therapy of active disease were retrieved. In addition, experimental reports on biological models of the disease were considered. Levels of adrenal and gonadal steroids (ie, glucocorticosteroids [GCS], dehydroepiandrosterone [DHEA], its sulfate [DHEAS], estradiol [E2], and testosterone [T]), as well as prolactin (PRL) and other hormones, biological mediators, vascular endothelial system (VES) interactions with hormones, and immunologic mediators of inflammation in RA, were reviewed and interpreted. RESULTS: Women with premenopausal onset of RA not previously treated with GCS had lower basal serum levels of adrenal androgens, that is, DHEA or DHEAS, both before and after onset of clinical disease, compared with controls. Risk factors, including hormonal, immunologic, and hereditary indicators, were found to be uniformly present many years before clinical onset in such younger women, as compared with a frequency of circa 15% in matched controls. Also, a history of heavy cigarette smoking significantly predicted the onset of RA in perimenopausal women, and in men, suggesting that vascular endothelial alterations predispose to the disease. In the same prospective study, 1 or more of 4 risk factors were present an average of 12 years before clinical onset of disease in 83% of male RA cases versus 26% in matched controls (ie, sensitivity of 83% and specificity of 74%). Early RA patients may have lower serum cortisol levels than normal controls, and less than expected for the degree of ongoing inflammation, as well as having upregulated PRL levels. CONCLUSION: Among persons genetically prone to RA, the "core" systems are hypothesized to become "remodeled" during a long preclinical phase as a result of chronic imbalances in their interactive homeostasis. This hypothesis needs to be critically assessed in further studies of such physiological precursors of disease as well as stressors in the development and course of RA. Optimal hormonal management of biological mediators of RA is also a priority challenge for disease control in the future. RELEVANCE: Evidence indicates that men and women who are susceptible to premenopausal onset of RA can each be identified long before their clinical onsets of disease, and that productive research in primary prevention is an achievable objective. Disease prevention objectives are central in the public health strategy of the National Arthritis Action Plan and of the US Public Health Service "Healthy People 2000" (and 2010 proposed). Success in such prevention goals can be expected to significantly reduce the enormous burden of this common disease, which affects all segments of the population.

Perturbations of hypothalamic-pituitary-gonadal axis and adrenal androgen functions in rheumatoid arthritis: an odyssey of hormonal relationships to the disease.

Rheumatoid arthritis (RA) is a heterogeneous disease with a diverse spectrum of manifestations and course of illness. Multiple factors are believed to contribute to its etiology. Nevertheless, consistent features are observed across populations, which include (1) increased familial or immunogenetic risk in younger-onset disease; (2) female predisposition, particularly during child-bearing ages; (3) predictable clinical improvement during pregnancy and worsening postpartum; and (4) increased incidence with aging, which suggest that hormonal factors influence the disease. In 1974, serum was prospectively obtained from pre-RA cases, 4 to 20 (mean = 12.0) years prior to onset of disease and concurrently from controls (CN) matched (4 CN per 1 RA) on age (+/- 2 years), race (all Caucasians), and entry menopausal status (EMS). CN have no known rheumatic disease. Pre-RA were divided into subgroups, according to EMS, i.e., premenopausal vs. non-premenopausal (peri- or post-menopausal), and either age at entry in 1974 or age at onset of RA. For example, one 3-way subgrouping includes: I. Entry premenopausal and RA onset < age 50 years; II. Entry premenopausal and RA onset age 50+ years, and III. Entry postmenopausal. The 11 youngest pre-RA (I) had a mean entry age of 29 years and RA onset of 41 years. An alternative 4-way subgrouping (a, b, c, d) divided the female subjects into premenopausal (last menstrual period [LMP], 0-31 days) and non-premenopausal major groups, as well as younger vs. older subgroups within the major EMS categories. The younger premenopausal women in each subgrouping system, that is, I or a, overlap almost entirely. Assays (RIA) of the major sex hormones were performed, e.g., luteinizing hormone (LH); follicle stimulating (FSH); estradiol (E2); progesterone (P4); and total testosterone (T); as well as adrenal hormones, including androstenendione (A4); dehydroepiandrosterone (DHEA); its sulfate (DHEAS); and cortisol (C). A significantly lower entry mean serum DHEAS level (mumol/L) was found in the pre-RA subgroup I, than in the 43 CN (2.14 +/- 0.47 vs. 3.62 +/- 0.37, respectively, (p = 0.033). The 25 older pre-RA and 100 CN (subgroups II and III) showed close mean DHEAS levels (1.89 +/- 0.30 and 1.94 +/- 0.14, respectively, p = 0.45). The serum DHEAS levels in pre-RA vs. CN subgroups were validated in a second reference laboratory. Also, the youngest pre-RA subgroup (I) showed a significant dissociation between entry serum DHEAS and cortisol levels (r = -0.660, p = 0.027), which differed (p = 0.017) from its matched CN, and from the older pre-RA (p = 0.004). Analyses of results based upon subgroupings by EMS and entry age (a, b, c, d) showed similar results. No significant differences were found between pre-RA and CN groups in levels of serum cortisol, other adrenal steroids, or the sex hormones assayed. In a sample of younger premenopausal women, significantly low serum DHEAS levels were found 4 to 20 years prior to onset of RA. Dissociation of serum cortisol and DHEAS levels was also found in the youngest, but not older, pre-RA subjects. The data suggest that subtle adrenal cortical dysfunction, manifested mainly by adrenal androgen (AA) deficiency, may either predispose to younger-onset RA or be a long-term marker in a minority subgroup of women.