Serum adiponectin levels in patients with diffuse idiopathic skeletal hyperostosis (DISH).

To evaluate the relationship between serum adiponectin ADP (sADP) levels and the risk of metabolic syndrome (MS) and cardiovascular disease (CVD) in patients with DISH and to assess the relationship between sADP levels, and the tendency for new bone formation in these patients. sADP levels were measured in DISH and non-DISH (NDISH) patients. sADP levels were compared between the two groups and were also correlated with weight circumference, BMI, serum lipid profile, concomitant diseases, use of medications, the presence of MS, the risk of developing CVD, and the extent of bony bridges. Eighty-seven patients with DISH and 65 in NDISH were examined. A negative significant correlation between sADP and insulin resistance, and serum insulin levels in the DISH group (r = - 0.375, p = 0.0004; r = -0.386, p = 0.0002, respectively) was observed. sADP levels positively correlated with serum cholesterol and LDL levels in the DISH group. Higher sADP levels positively correlated with the extent of bony bridges (r = 0.245, p = 0.02). It appears that at least in patients with DISH, sADP has an osteogenic effect. Increasing sADP levels might reduce insulin resistance and hyperinsulinemia and reduce the CV risk and the osteogenic effect exerted by insulin. However, increasing sADP levels might directly increase new bone formation aggravating the already enhanced osteogenesis. Studies of larger populations with earlier disease might shed light on the enigmatic role played by ADP in patients with DISH and the eventual effect of manipulating its levels.

Simultaneous occurrence of ankylosing spondylitis and diffuse idiopathic skeletal hyperostosis: a systematic review.

Objectives: AS and DISH are both spinal ankylosing conditions with a 4-fold increased risk of spinal fractures. The most commonly used criteria for DISH were designed to exclude radiographic signs of spondyloarthritis. However, case reports describing the presence of both conditions exist. In this study, the co-occurrence of AS and DISH were reviewed in the literature to explore the potential need to revise the criteria for DISH. Methods: A search was conducted in Pubmed, Embase, Web of Science and the Cochrane library using the terms 'spondyloarthritis' and 'DISH' and their matching synonyms. Full-text articles describing the coexistence of both conditions in the same patient were included. A quality assessment was performed, and the case descriptions were extracted. Results: Twenty articles describing simultaneous occurrence of AS and DISH in 39 cases were retrieved. All articles were case reports or series of moderate quality. Back or neck pain was present in 97% of the patients (mean age 61.2 years, 90% male) and HLA-B27 was positive in 9/27 documented measurements. Radiographic abnormalities were described in the SI joint (82% AS, 13% DISH) and in the spine (49% AS, 100% DISH). Conclusion: Simultaneous occurrence of AS and DISH has been reported in the literature in at least 39 cases. AS and DISH should not be seen as mutually exclusive. If the results of the current study are confirmed in a large observational study, revision of the current criteria to include the co-existence of both conditions should be considered.

Correlation of blood bone turnover biomarkers and Wnt signaling antagonists with AS, DISH, OPLL, and OYL.

BACKGROUND: Wnt signaling plays an important role in development and maintenance of many organs and tissues. The most-studied secreted Wnt inhibitors are sclerostin (SOST), Dickkopf-related protein 1 (DKK-1), and secreted frizzled related protein 1 (SFRP-1) which play important roles in bone turnover. The present study investigated the relationship between serum Wnt inhibitors and diseases with excessive ossification structures, such as ossification of posterior longitudinal ligament (OPLL), ankylosing spondylitis (AS), diffuse idiopathic skeletal hyperostosis (DISH), and ossification of yellow ligament (OYL). METHODS: Twenty-five patients with AS, DISH, OPLL, or OYL were recruited in this study. Fasting peripheral blood samples were collected from all patients and nine controls. Various biomarkers of bone turnover including osteocalcin (OSC), osteoprotegerin (OPG), SFRP-1, DKK-1, and SOST were investigated. RESULTS: Our data showed that serum levels of OSC were higher, but Dkk-1 levels were lower in AS, DISH, OPLL, and OYL patients than those in the controls. Serum levels of SFRP-1 were significantly higher in DISH patients than those in the controls. Serum levels of SOST were significantly higher in DISH and OPLL patients than both levels in the controls. Serum levels of OPG were lower in AS patients than those in the controls. Serum levels of OSC were higher in the OPLL patients than those in the AS patients. Serum levels of DKK-1, SFRP-1, SOST, and OPG were not significantly different between the different disease groups. CONCLUSIONS: In this exploratory study, both OSC and DKK-1 levels are correlated with the clinical conditions associated with excessive ossification, indicating that blood OSC and DKK-1 levels may serve as diagnostic biomarkers for AS, DISH, OPLL, and OYL. These findings may also help discover potential drug therapies for management of these diseases in the future.

Low circulating Dickkopf-1 and its link with severity of spinal involvement in diffuse idiopathic skeletal hyperostosis.

OBJECTIVE: Dickkopf-1 (DKK-1) is an inhibitor of osteoblastogenesis, and its lower levels are linked to new bone formation. The aim of this study was therefore to explore serum levels of DKK-1 and to evaluate DKK-1's association with the severity of spinal involvement in diffuse idiopathic skeletal hyperostosis (DISH). METHODS: Serum levels of total and functional DKK-1 and C-reactive protein (CRP) were measured in 37 patients with DISH and 22 healthy age and sex-matched controls. Plain radiographs of the cervical and thoracic spine were performed, and the diagnosis of DISH was defined using the Resnick criteria. Patients were divided into three groups based on spinal involvement. Bone mineral density (BMD) and bone turnover markers were evaluated in patients with DISH. RESULTS: The levels of total serum DKK-1 were significantly lower in patients with DISH than in healthy controls (p<0.0001). Importantly, low serum levels of DKK-1 were associated with more severe spinal involvement in DISH, independent of age, sex, disease duration, CRP, bone turnover markers or BMD. However, these findings were less significant for functional DKK-1. CONCLUSION: These observations indicate that DKK-1 may play a significant role in bone formation during DISH.

A case of psoriasis vulgaris with diffuse idiopathic skeletal hyperostosis involved with ossifications of posterior and anterior longitudinal ligament.

Diffuse idiopathic skeletal hyperostosis (DISH) is difficult to distinguish from various forms of inflammatory arthritis, including psoriatic arthritis (PsA), rheumatoid arthritis, and ankylosing spondylitis. A 67-year-old Japanese male had been treated for psoriasis vulgaris for 13 years. Numbness of his right arm and lower limbs and spinal stiffening had developed 7 years prior to his initial evaluation at our facility. He noticed pain mainly while exercising. There were symmetrical marginal syndesmophytes in the spine, from the thoracic vertebrae to the upper lumbar vertebrae, on radiological examinations. We therefore suspected DISH. Furthermore, ossifications of the posterior and anterior longitudinal ligaments were noted in the cervical spine. Laboratory examinations revealed a normal peripheral white blood cell count, serum C-reactive protein, and erythrocyte sedimentation rate, and he was negative for rheumatoid factor. We detected human leukocyte antigen B39 but not B27. All distal interphalangeal joints were swollen but without pain. X-ray imaging showed narrowing of the joint space, and the consolidation of the joint was recognized, but there was no new juxta-articular bone formation. Based on clinical and radiological findings, we concluded that he had DISH and not PsA. DISH was indicated by marked radiological features of the axial skeleton, particularly the thoracic spine, but may also have involved the peripheral joints. DISH is one of the entheseal disorders, and 10% of Japanese middle-aged and elderly men have DISH. Therefore, the differentiation of DISH from PsA is necessary in psoriasis patients with spinal involvement.

Body mass index and blood glucose: correlations with serum insulin, growth hormone, and insulin-like growth factor-1 levels in patients with diffuse idiopathic skeletal hyperostosis (DISH).

Obesity is a frequent co-morbid condition associated with diffuse idiopathic skeletal hyperostosis (DISH). Serum growth hormone (GH), insulin-like growth factor (IGF-1) and insulin are significantly elevated in patients with DISH. In this study, we examined the relationship between body mass index (BMI) and basal serum GH, IGF-1, and insulin concentration in a group of 36 DISH patients. Basal serum insulin levels were significantly elevated (P<0.001) in DISH patients with a BMI>28 kg m(-2), classified as obese, compared with DISH patients with BMI ranging from 23 to 28 kg m(-2). In addition, BMI strongly positively correlated with serum insulin concentration in DISH patients (adjusted r2 = 0.348, P<0.001). However, BMI did not correlate with either basal serum GH (adjusted r2 = -0.013) or IGF-1 levels (adjusted r2 = -0.010) in DISH. We conclude that BMI does not seem to contribute to elevated serum GH and IGF-1 levels in symptomatic DISH.

Current therapeutic options in the management of diffuse idiopathic skeletal hyperostosis.

Diffuse idiopathic skeletal hyperostosis (DISH) is a condition characterised by calcification and ossification of soft tissues, mainly ligaments and enthesis. Although DISH often coexists with osteoarthritis, this disorder differs from primary osteoarthritis by a dissimilar prevalence within the general population, gender distribution, anatomical site of primary involvement and magnitude and distribution in the spine and the peripheral joints. Little is known about the pathogenesis of the disease and possible therapeutic interventions. Treatment should be aimed at the symptomatic relief of pain and stiffness; the prevention, retardation or arrest of progression; the treatment of associated metabolic disorders and the prevention of spontaneous or induced complications. Change of lifestyle, nutrition and therapeutic options to alleviate pain and stiffness are measures that might improve quality of life in patients affected by DISH. Control of associated metabolic disorders such as hypertension, hyperinsulinaemia with or without hyperglycaemia, hyperlipidaemia and hyperuricaemia may reduce the morbidities associated with these disorders and prevent further progression of the condition. Recent developments in our understanding of the molecular basis of the ligamentous and entheseal changes that lead to the development of DISH might pave the way to future, more targeted and effective therapies.

Intra-erythrocyte deposition of growth hormone in rheumatic diseases.

Standard radioimmunoassay was employed to quantify matched basal intra-erythrocyte growth hormone (GH) and serum GH levels from patients with osteoarthritis, diffuse idiopathic skeletal hyperostosis (DISH), gout, and Sjögren's syndrome and in a group of normal volunteers (control group). Basal intra-erythrocyte GH concentration was significantly higher ( P<0.05) than serum GH concentration in blood samples from patients with osteoarthritis and DISH but not from those with gout or Sjögren's syndrome. Regression analysis determined that basal serum GH levels did not correlate with age. While intra-erythrocyte GH levels exceeded serum GH levels in osteoarthritis and DISH, intra-erythrocyte GH was not a strong predictor of serum GH levels in osteoarthritis, DISH, or in the control group.

Growth hormone and insulin-like growth factor-I in symptomatic and asymptomatic patients with diffuse idiopathic skeletal hyperostosis (DISH).

Basal serum growth hormone (GH) and insulin-like growth factor-I (IGF-I) concentration was measured by radioimmunoassay in patients with diffuse idiopathic skeletal hyperostosis (DISH) with muscle and joint pain and stiffness (symptomatic group) and in DISH patients without these constitutional clinical symptoms (asymptomatic group), but with persistent radiographic evidence of DISH. Serum GH and IGF-I was also measured in normal volunteers (control group) matched for gender and age to patients with DISH. Symptomatic male and female DISH patients had elevated serum GH and IGF-I concentration when compared to the control group. Asymptomatic DISH patients had serum GH levels that were significantly lower than their symptomatic counterparts. Clinical improvement did not alter serum IGF-I concentration. We conclude that serum GH concentration could be employed to monitor clinical remission in DISH.

Hyperleptinemia in female patients with ossification of spinal ligaments.

In order to examine the involvement of leptin in the ossification of spinal ligaments (OSL), the present study examined (i) serum levels of leptin and insulin in OSL patients and controls, (ii) serum leptin levels in children of OSL females with severe obesity, (iii) the expression of leptin receptor mRNA in human spinal ligaments, and (iv) effects of leptin on cultured human ligament cells. In the OSL females, serum leptin levels were significantly higher than those of the control females, and the levels were positively correlated to the serum insulin levels, while in the control females, there was a tendency of inverse correlation. The daughters of OSL females with severe obesity also had high serum leptin levels, although they had not developed OSL. The expression of leptin receptor mRNA was confirmed in the ligaments, but leptin did not influence the alkaline phosphatase activity nor procollagen type I carboxyl-terminal peptide content of the ligament cells. These findings suggest that leptin is involved genetically and indirectly with the pathogenesis of OSL in female patients.

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.

Ossification of the posterior longitudinal ligament, diffuse, idiopathic skeletal hyperostosis, abnormal retinol and retinol binding protein: a familial observation.

We describe a 52-year-old man who presented with diffuse idiopathic skeletal hyperostosis, ossification of the posterior longitudinal ligament, and abnormal levels of retinol and retinol binding protein (RBP). The molar retinol/retinol binding protein ratio was high, suggesting congenital functional RBP deficiency. His two sons, aged 23 and 27 years, shared the same biological abnormality without clinical symptoms. To our knowledge, this is the first case report of such a familial association.

Growth promoting peptides in osteoarthritis and diffuse idiopathic skeletal hyperostosis--insulin, insulin-like growth factor-I, growth hormone.

OBJECTIVE: To investigate growth factors influencing bone and cartilage in patients with diffuse idiopathic skeletal hyperostosis (DISH). METHODS: Standard radioimmunoassays (INCSTAR, Stillwater, MN) quantified serum levels of insulin, insulin-like growth factor-I (IGF-I) and growth hormone (GH) in patients with DISH, in patients with osteoarthritis (OA) and in controls. Patients with DISH with comorbidity with obesity, hypertension, diabetes and coronary artery disease, also were studied. RESULTS: Patients with DISH demonstrated normal IGF-I levels; patients with OA had reduced IGF-I levels. Subjects with DISH or OA had elevated insulin and GH values. Patients with DISH with comorbidity had changes in growth factors similar to those found in patients with DISH only. There is frequent association of DISH with obesity, hypertension, coronary artery disease and diabetes mellitus suggesting that these associations are not random. CONCLUSION: Specific associations of skeletal abnormalities with clinical features in which skeletal change and clinical features combine with disturbances of insulin, IGF-I and GH exist in DISH that are distinct from OA. DISH is considered a multisystemic hormonal disorder with protean presentations.

Growth hormone secretion in diffuse idiopathic skeletal hyperostosis.

Serum insulin and C-peptide response to an oral glucose tolerance test (OGTT) and serum growth hormone (GH) response to an intravenous insulin tolerance test (IVITT) were investigated in six non-obese patients, with normal glucose tolerance, affected by diffuse idiopathic skeletal hyperostosis (DISH). Basal serum insulin, C-peptide and GH values were similar in DISH patients and in controls. After OGTT, insulin and C-peptide values were not significantly different in the two groups at any time interval. In contrast, after IVITT, a significant increase in GH concentrations was noted at 30 and 45 minutes in DISH patients when compared to controls. Growth hormone either acting alone or through somatomedin intermediaries results in new bone growth in acromegaly, and the same may be true for DISH. Recent reports suggest that GH promotes tissue growth by stimulating precursor cells in various tissues including cartilage and bone. The increased GH response to IVITT corroborates the hypothesis that GH may act as a bone growth-promoting factor in DISH.

Increased concentrations of endogenous 13-cis- and all-trans-retinoic acids in diffuse idiopathic skeletal hyperostosis, as demonstrated by HPLC.

Endogenous 13-cis- and all-trans-retinoic acids have been quantitated in human serum using a solvent extraction procedure followed by isocratic reversed phase high performance liquid chromatography and UV detection. In healthy adults, after an overnight fasting period, the concentrations of 13-cis- and all-trans-retinoic acids yielded 5.3 +/- 2.43 nmol/l and 11.8 +/- 3.3 nmol/l, respectively (mean +/- SD). The method has been successfully applied to the analysis of both isomers in serum from patients with idiopathic skeletal hyperostosis in whom, the 13-cis- as well as all-trans-retinoic acid levels were raised as compared to the control group.

[Transient idiopathic periosteal hyperostosis with hyperproteinemia (Goldbloom syndrome)]. / Hiperostosis perióstica idiopática transitoria con disproteinemia (síndrome de Goldbloom).

The case of a 13 year old girl is presented, who developed intense pain in extremities and experienced marked weight loss after an acute upper respiratory tract infection. Roentgenograms revealed a diffuse periosteal reaction, most intensely affecting long bones. Principal laboratory findings were a slight normocytic, normochromic anemia; high erythrocyte sedimentation rate; medullar plasmocytosis and dysproteinemia, with a large increase in plasma gammaglobulin concentration. Clinical recovery and normalization of roentgenograms and laboratory parameters were observed eleven months after the acute episode, with no intervening therapeutic measures. This case matches Goldbloom's syndrome, described originally in two children in 1966. Only 3 other cases have been reported in the literature.

[Plasma levels of vitamins A and E in hyperostosis, ankylosing spondylarthritis and rheumatoid polyarthritis]. / Taux plasmatiques des vitamines A et E au cours de la maladie hyperostosique, la spondylarthrite ankylosante et la polyarthrite rheumatoïde.

In animal and man, chronic intoxication with vitamin A or retinoids may be responsible for vertebral hyperostosis and periosteal appositions. Vertebral hyperostosis is found in hyperostotic disease but also in the course of ankylosing spondylarthritis. Therefore, we felt it would be interesting to study blood retinol levels in 22 patients with hyperostotic disease, 29 patients with ankylosing spondylarthritis, 18 patients with rheumatoid polyarthritis and 21 reference patients. The Kurskal-Wallis test has demonstrated a significant difference of blood retinol levels between these four groups (p less than 0.0001). The blood retinol level was more elevated during hyperostotic disease (3.63 +/- 1.13 mumol/l) than in the reference group (2.94 +/- 0.76) and was, on the contrary, lower during ankylosing spondylarthritis (2.57 +/- 0.66) and rheumatoid polyarthritis (2.32 +/- 0.64). This study confirms the elevation of blood retinol during the course of hyperostotic disease; such a abnormality was not demonstrated in the course of ankylosing spondylarthritis, and on the contrary, suggest that a decreased blood retinol level may be observed during chronic inflammatory rheumatic diseases such as rheumatoid polyarthritis or ankylosing spondylarthritis.