Diffuse Idiopathic Skeletal Hyperostosis of Cervical Spine with Dysphagia-Molecular and Clinical Aspects.

Diffuse idiopathic skeletal hyperostosis (DISH) is a condition characterized by the calcification and ossification of the ligaments of the cervical spine; in some cases, it may result in dysphagia. The condition is more common in men over 50 years of age with metabolic disorders, and it is often asymptomatic and not a major issue for patients. The etiology of DISH is poorly understood, and known genetic factors indicate multiple signal pathways and multigene inheritance. In this review, we discuss the epidemiological, clinical, and etiological aspects of DISH with a special focus on dysphagia.

Heterotopic ossification in a patient with diffuse idiopathic skeletal hyperostosis: Input from histological findings.

A high incidence of heterotopic ossification (HO) has been reported in patients with diffuse idiopathic skeletal hyperostosis (DISH), a metabolic disease characterized by calcifications of entheses at spine and peripheral sites. We performed histological and immunohistochemical analyses in five different HO sites in a patient with DISH to study a possible mutual interaction of bone morphogenetic protein 2 (BMP-2), transforming growth factor beta (TGF-ß), and decorin, crucial for bone mass increasing, matrix calcification, and endochondral bone formation. We speculated that the surgical trauma triggered HO, inducing TGF-ß release at the lesion site. TGF-ß recruits osteoblast precursor cells and determines the overexpression of BMP-2 in the surrounding skeletal muscle, inducing a further osteogenic differentiation, contributing to HO onset.

Differences in Bone Mineral Density and Bone Turnover Markers Between Subjects With and Without Diffuse Idiopathic Skeletal Hyperostosis.

STUDY DESIGN: Japanese resident cohort study based on a municipal registry. OBJECTIVE: This study of a community-dwelling elderly Japanese population employed random sampling from the basic resident registry of a rural town for subject selection to investigate the differences in bone mineral density (BMD) and bone turnover markers between subjects with and without diffuse idiopathic skeletal hyperostosis (DISH). SUMMARY OF BACKGROUND DATA: DISH is a condition characterized by the calcification and ossification of soft tissues. Although some reports have addressed BMD in DISH, the precise status of BMD and bone metabolism in individuals with DISH remains unclear. METHODS: Eight groups based on age (50s, 60s, 70s, and 80s) and sex after random sampling from the resident registry of Obuse town were established. A total of 411 participants (202 males and 209 females) were enrolled for the evaluation of BMD and bone turnover markers. All subjects underwent a single whole-spine lateral radiographic examination for the existence of DISH. The BMD and bone turnover markers of subjects with and without DISH were analyzed for associations with the disorder using multivariate analysis. RESULTS: DISH was detected in 66 (16.1%) participants in our population cohort. According to multivariate analysis, increased lumbar and hip BMD were significantly related to DISH (odds ratio: 7.47 and 22.8, respectively). CONCLUSION: This study clarified the differences in BMD and bone turnover markers between subjects with and without DISH on a general population basis. Multivariate analysis revealed increased lumbar and hip BMD to be significantly associated with DISH, with no remarkable findings for bone turnover markers. LEVEL OF EVIDENCE: 4.

Impaired insulin secretion and uptake in patients with diffuse idiopathic skeletal hyperostosis.

OBJECTIVE: So far, high prevalence of metabolic symptoms accompanying diffuse idiopathic skeletal hyperostosis (DISH) appears not definitely elucidated because of their possible origin from other disorders such as diabetes and/or body mass differences. From such reasons this study was aimed to compare non-diabetic DISH patients to a group of age and BMI matched controls in order to distinguish the influence of DISH proper on metabolic parameters free of additional metabolic effects caused by diabetes and/or body weight differences. METHODS: Both groups of patients were subjected to oral glucose tolerance test (OGTT) and fasting serum levels of glucose, insulin, C-peptide, growth hormone, insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGF-BP3) were assayed. Fasting serum total cholesterol, HDL cholesterol, triglycerides, non-esterified fatty acids (NEFA) and uric acid were determined as well. The indices of insulin sensitivity and insulin secretion were calculated. RESULTS: With the exception of decreased NEFA serum level and decreased insulinogenic index and insulin/C-peptide ratio in DISH patients any other significant differences in serum parameters and indices of insulin sensitivity were not found. CONCLUSIONS: The data obtained suggest impaired beta-cell pancreatic stimulation and increased insulin hepatic extraction in DISH. It is assumed that the above mentioned conditions, if persisting for a long time, might lead to decreased ability of insulin to maintain normal serum glucose level and consequently to insulin resistance which is highly prevalent in symptomatic DISH patients.

[The new bone formation and bone metabolism in Forestier disease]. / Stopien nowotworzenia kosci oraz metabolizm kostny w przebiegu zespolu Forestiera.

The study was performed on 36 male patients between 65 and 83 years who were either hospitalised or treated in the out-patients clinic due to Forestier's disease. The aim of the study was to evaluate the advance of ectopic bone formation process in cervical spine and bony metabolic changes in treated patients. The study showed reverse corelation between the degree of advance of cervical hyperostosis and the prevalence of osteoporosis and metabolic disorders in the tested group. The authors have emphasized the need of precise evaluation and differentiation of Forestier's disease and degenerative spine disease.

[Diffuse idiopathic skeletal hyperostosis and its relation to metabolic parameters]. / Difuzní idiopatická skeletální hyperostóza a souvislost s metabolickými parametry.

Diffuse idiopathic skeletal hyperostosis (DISH) is a non-inflammatory disease of skeleton characterized by hyperostosis of axial and peripheral skeleton. The association of DISH with type 2 diabetes mellitus and other metabolic alterations (e.g. impaired lipid metabolism) has been known for many years. However, it has not been explained satisfactorily yet. It seems that this pathological process is significantly influenced by hyperglycemia and insulin resistance. Also, it is affected by growth hormone (GH) and its action mediated by insulin-like growth factor (IGF) and its binding proteins (IGFBP2, IGFBP3). From the point of symptomatic therapy, patients should not be given medicaments that aggravate hyperinsulinemia.

Calcium deposition and associated chronic diseases (atherosclerosis, diffuse idiopathic skeletal hyperostosis, and others).

Extracellular matrix mineralization or calcification occurs in many pathologic conditions, including atherosclerosis, medial wall calcification, diffuse idiopathic skeletal hyperostosis, and chondrocalcinosis. Vascular wall calcification is the most common and involves two mechanisms: passive calcification resulting from breakdown of the protection system and active calcification resulting from transdifferentiation of mesenchymal cells in the vascular wall to bone. Although reports are conflicting, several matrix proteins are identified as protective factors against dystrophic calcification in nonosseous tissues. Serum matrix Gla protein may be a marker of osteometabolic syndromes that cause hyperostosis and plays a role in Milwaukee shoulder syndrome.

Study of peripheral bone mineral density in patients with diffuse idiopathic skeletal hyperostosis.

Diffuse idiopathic skeletal hyperostosis (DISH) is an ossifying systemic enthesopathy which involves not only the spine but which may also appear in other sites. Degenerative, inflammatory and metabolic factors have been reported for a possible pathogenic role in the new bone growth that characterises DISH. In the present study peripheral bone mineral density (BMD) has been measured in patients affected by DISH and the results compared to those of a control group. Forty-two patients (33 females and 9 males) affected by DISH and 84 controls (66 females and 18 males) were examined. All subjects underwent radiological study of the lumbar and dorsal spine and the pelvis. BMD was evaluated using dual-energy X-ray absorptiometry and the examination was performed in the distal radius. In DISH patients the mean value of BMD was significantly higher than in controls (P<0.002), even when it was referred to sex subgroups. Statistical analysis showed significant differences between both the two male groups (P<0.002) and the two female groups (P<0.01). In the two female subgroups (DISH patients and controls) BMD was significantly inversely related to age and to the duration of the postmenopausal period. The present study showed higher BMD in DISH patients than in the control group.

Retinoid and bone metabolic marker in ossification of the posterior longitudinal ligament.

The pathogenesis of ossification of the posterior longitudinal ligament (OPLL) remains to be elucidated, though etiologic factors for OPLL have been identified. High levels of serum retinol and retinol binding protein (RBP) have been observed in patients with diffuse idiopathic skeletal hyperostosis (DISH). OPLL is often associated with DISH. In this study, the levels of serum retinol and RBP were determined in 70 patients with OPLL in the cervical spine, and compared with those in normal subjects. Bone metabolic markers of serum intact osteocalcin, urinary pyridinoline and deoxypyridinoline were examined as well. Among female patients, level of serum RBP was significantly higher in those in their 60's, and those with mixed type OPLL. Level of serum RBP was significantly higher in both sexes, and retinol was exhibited higher in female patients, if they were associated with DISH. Patients with OPLL exhibited no abnormal bone metabolic marker levels. These findings suggest that vitamin A may play a role in the development of OPLL.

Growth factors, insulin-like growth factor-1 and growth hormone, in synovial fluid and serum of patients with rheumatic disorders.

OBJECTIVE: Synovial fluid (SF) plays an important role in joint function. We evaluated the growth factors, insulin-like growth factor-1 (IGF-1) and growth hormone (GH) in SF and serum from patients with osteoarthritis (OA), rheumatoid arthritis (RA), gout, pseudogout and diffuse idiopathic skeletal hyperostosis (DISH). DESIGN: Standard radioimmunoassay techniques were used to measure concurrent levels of IGF-1 and GH. SF samples and serum samples were obtained concomitantly from 27 patients with OA, 22 patients with RA, nine men with gout, 14 patients with pseudogout and eight men with DISH. RESULTS: In the case of IGF-1, a comparison of serum and SF levels shows that SF levels of IGF-1 are lower than serum levels in all groups. Men and women gave similar values. In contrast, in the case of GH, all groups, except males with RA, had higher GH values in SF when compared with serum values. Individual patients with other forms of arthritis demonstrated similar relationships. CONCLUSION: The finding that IGF-1 is present in levels about one-half as great in SF as compared with serum suggests that IGF-1 may be produced in lesser amounts or is utilized by the patient in customary joint function. The finding that GH is present in SF at values twice as high, or more, of serum levels in inflammatory arthritides suggests that GH may play a role in the pathophysiology of arthritic disorders.

Vertebral hyperostosis and diabetes mellitus: a case-control study.

OBJECTIVE: To compare glucose metabolism in patients with vertebral hyperostosis (VH), with that in control patients. METHODS: We studied 50 patients aged 60 years or more who had VH according to Resnick's criteria, and 50 control patients without VH, matched for sex, age, weight and height. Plasma glucose was evaluated before and 120 minutes after ingestion of 75 g glucose. World Health Organisation criteria for diabetes mellitus (DM) were used. Radiographs of the pelvis and thoracic and lumbar spine were performed and read blind by two physicians. RESULTS: Statistical analysis showed no difference between cases and control patients for prevalence of DM, and plasma glucose at 0 and 120 minutes. CONCLUSION: These data suggest that glucoregulation in patients with VH does not differ from that in matched controls.

Metabolic arthropathies.

In this article, recent advances in the understanding of some of the metabolic arthropathies are reviewed. Among hemoglobinopathies, sickle-cell disease is frequently the source of rheumatic syndromes, as emphasized in recent epidemiologic studies. Avascular necrosis is one of the most common features and may be disabling, leading to total joint replacement of the hip or knee. Joint effusions more rarely are observed and have been associated with subchondral bone infarctions. The clinical and radiologic presentations of the arthropathy of hemochromatosis have been extensively reviewed. Screening for the disease appears important, because it is the only way to prevent progressive worsening of organ involvement and arthropathy in particular. The rheumatic involvement in type IIa and type III hyperlipoproteinemias recently was confirmed in a case-control study. Magnetic resonance imaging appears to be useful in assessing the extent and activity of bone marrow involvement in Gaucher's disease. Replacement therapy is developing. Dialysis-associated amyloidosis remains the target of active research, which recently led to the identification of several newly recognized components, including alpha 2-macroglobulin and hyaluronan. The main component of this amyloid, beta 2-microglobulin, has been shown to be modified by advanced glycosylation products, and these changes appear to confer inflammatory properties on the molecule.

[Metabolism of vitamin A in Forestier-Rotès-Quérol hyperostosis]. / Etude du métabolisme de la vitamine A au cours de la maladie hyperostosique de Forestier et Rotès-Quérol.

High doses of retinol produce hyperostotic lesions in animals and humans. In this study we measured in fasting subjects and 5 hours after administering 50,000 IU of retinol, levels in the serum of retinol, retinol-binding protein (RBP) and prealbumin in 35 hyperostotic subjects (HVA) and 22 control subjects. Retinol levels were equally high after fasting and after consumption of vitamin A (p 0.01). The levels of retinol-binding protein and prealbumin increase in parallel, such that the molar ratios of retinol to retinol-binding protein or to prealbumin are not changed. Taken with literature data, those of the present study indicate that vitamin A is responsible for the production of hyperostotic lesions.