High prevalence of morphometric vertebral deformities in patients with inflammatory bowel disease.

BACKGROUND: Earlier studies have documented that the prevalence of decreased bone mineral density (BMD) is elevated in patients with inflammatory bowel disease. The objective of this study was to investigate the prevalence of vertebral deformities in inflammatory bowel disease patients and their relation with BMD and bone turnover. METHODS: One hundred and nine patients with Crohn's disease (CD) and 72 with ulcerative colitis (UC) (age 44.5+/-14.2 years) were studied. BMD of the hip (by dual X-ray absorptiometry) was measured and a lateral single energy densitometry of the spine for assessment of vertebral deformities was performed. Serum markers of bone resorption (carboxy-terminal cross-linked telopeptide of type I collagen) and formation (procollagen type I amino-terminal propeptide) were measured, and determinants of prevalent vertebral deformities were assessed using logistic regression analysis. RESULTS: Vertebral deformities were found in 25% of both CD and UC patients. Comparing patients with and without vertebral deformities, no significant difference was found between Z-scores and T-scores of BMD, or levels of serum carboxy-terminal cross-linked telopeptide of type I collagen and serum procollagen type I amino-terminal propeptide. Using logistic regression analysis the only determinant of any morphometric vertebral deformity was sex. The presence of multiple vertebral deformities was associated with older age and glucocorticoid use. CONCLUSION: The prevalence of morphometric vertebral deformities is high in CD and UC. Male sex, but neither disease activity, bone turnover markers, clinical risk factors, nor BMD predicted their presence. The determinants for having more than one vertebral deformity were age and glucocorticoid use. This implies that in addition to screening for low BMD, morphometric assessment of vertebral deformities is warranted in CD and UC.

Quantitative ultrasound does not identify patients with an inflammatory disease at risk of vertebral deformities.

BACKGROUND: Previous studies from our group have shown that a high prevalence of vertebral deformities suggestive of fracture can be found in patients with an inflammatory disease, despite a near normal bone mineral density (BMD). As quantitative ultrasound (QUS) of the heel can be used for refined assessment of bone strength, we evaluated whether QUS can be used to identify subjects with an inflammatory disease with an increased chance of having a vertebral fracture. METHODS: 246 patients (mean age: 44 +/- 12.4 years) with an inflammatory disease (sarcoidosis or inflammatory bowel disease (IBD)) were studied. QUS of the heel and BMD of the hip (by dual X-ray absorptiometry (DXA)) were measured. Furthermore lateral single energy densitometry of the spine for assessment of vertebral deformities was done. Logistic regression analysis was performed to assess the strength of association between the prevalence of a vertebral deformity and BMD and QUS parameters, adjusted for gender and age. RESULTS: Vertebral deformities (ratio of <0.80) were found in 72 vertebrae of 54 subjects (22%). In contrast to the QUS parameters BUA (broadband ultrasound attenuation) and SOS (speed of sound), T-score of QUS and T-scores of the femoral neck and trochanter (DXA) were lower in the group of patients with vertebral deformities. Logistic regression analysis showed that the vertebral deformity risk increases by about 60 to 90% per 1 SD reduction of BMD (T-score) determined with DXA but not with QUS. CONCLUSION: Our findings imply that QUS measurements of the calcaneus in patients with an inflammatory condition, such as sarcoidosis and IBD, are likely of limited value to identify patients with a vertebral fracture.

Bone turnover and hip bone mineral density in patients with sarcoidosis.

BACKGROUND AND AIM OF THE WORK: Sarcoidosis is a chronic inflammatory T-cell-driven disease that can also affect bone. We evaluated bone remodelling and bone mineral density (BMD) in patients with sarcoidosis and their dependency of disease-related and treatment-related factors. METHODS: In 124 patients BMD of the hip (DXA) and markers of bone resorption (ICTP) and formation (PINP) were evaluated. Furthermore a lateral DXA of the spine for morphometric assessment of vertebral deformities was performed in 87 patients. Potential predictors of bone markers, BMD and determinants of prevalent vertebral deformities were assessed using multiple and logistic regression analysis. RESULTS: The population studied comprised untreated patients (n=51), patients that previously used glucocorticoids (n=31) and patients currently using glucocorticoids (n=42). In all these groups the age- and gender corrected Z-scores of the hip were normal, except in untreated patients, which revealed an increased Z-score at the trochanter (p = 0.004). In all but the patients currently on glucocorticoids the Z-scores for PINP and ICTP were increased (p < 0.05). In patients currently on glucocorticoids the Z-ICTP was also increased (p < 0.05), but the Z-PINP decreased (p < 0.01 compared to untreated patients). In 20.6% of patients one or more morphometric vertebral deformities were found. CONCLUSIONS: Hip BMD is normal in patients with sarcoidosis, despite an increased bone turnover. This may imply that in sarcoidosis mechanisms are involved that compensate for the well-known effects of cytokines in inflammatory diseases on osteoclastogenesis and bone resorption. Nonetheless, vertebral deformities suggestive of fracture were found in a significant number of patients which indicates that patients with sarcoidosis still have a relevant fracture risk.

Total contact casting of the diabetic foot in daily practice: a prospective follow-up study.

OBJECTIVE: A limited number of clinical trials have shown that the total contact cast (TCC) is an effective treatment in neuropathic, noninfected, and nonischemic foot ulcers. In this prospective data collection study, we assessed outcome and complications of TCC treatment in neuropathic patients with and without peripheral arterial disease (PAD) or (superficial) infection. RESEARCH DESIGN AND METHODS: Ninety-eight consecutive patients selected for casting were followed until healing; all had polyneuropathy, 44% had PAD, and 29% had infection. Primary outcomes were percentage healed with a cast, time to heal, and number of complications. RESULTS: Ninety percent of all nonischemic ulcers without infection and 87% with infection healed in the cast (NS). In patients with PAD but without critical limb ischemia, 69% of the ulcers without infection and 36% with infection healed (P < 0.01). In multivariate analyses, PAD, infection, and heel ulcers were associated with a lower percentage healed (all P < 0.05). Median duration of cast treatment was 34 days. New ulcers, all superficial, developed in 9% and preulcerative lesions in 28% of the patients; these skin lesions healed in the cast within a maximum of 13 days. CONCLUSIONS: In comparison to pure neuropathic ulcers, ulcers with moderate ischemia or infection can be treated effectively with casting. However, when both PAD and infection are present or the patient has a heel ulcer, outcome is poor and alternative strategies should be sought. The high rate of preulcerative lesions stresses the importance of close monitoring during TCC treatment.

Hip bone mineral density, bone turnover and risk of fracture in patients on long-term suppressive L-thyroxine therapy for differentiated thyroid carcinoma.

OBJECTIVE: Untreated hyperthyroidism and treatment with high doses of thyroid hormone are associated with osteoporosis. However, their effect on bone turnover, their contribution to bone mineral density (BMD) in the context of other clinical risk factors for osteoporosis and the prevalence of vertebral fractures is not well documented. DESIGN: Cross-sectional study. METHODS: We studied 59 patients receiving L-thyroxine suppressive therapy for differentiated thyroid carcinoma (DTC). BMD of the hip was measured by dual X-ray absorptiometry (DXA) and lateral DXA pictures of the lumbar and thoracic vertebrae were performed. Bone resorption was measured by C-telopeptides of type I collagen (ICTP) and bone formation by procollagen type I N-propeptide (PINP). Clinical risk factors for osteoporosis were evaluated using a questionnaire. RESULTS: Z-scores of BMD were similar as the NHANES (National Health and Nutrition Examination Survey) III reference group in women and men, also after long-term (> 10 years) suppression therapy. Patients in the lowest and highest quartile of BMD showed significant differences in the presence of clinical risk factors. ICTP levels were significantly higher than in age-matched controls, PINP levels were not different. We found four patients with a prevalent vertebral fracture. CONCLUSIONS: We conclude that patients with well-differentiated thyroid carcinoma are not at increased risk of developing low bone mass nor have a higher prevalence of vertebral fracture at least when treated with relatively low doses of L-thyroxine.

An integrated medical treatment for type-2 diabetes.

This paper tries to emphasize two relevant concepts: the first is that type 2 diabetes is a chronic diseases characterized by both a dysmetabolism and a chronic oxidative stress. A variety of orthodox drugs are somewhat able to correct the metabolic alterations, but do not deal with the chronic inflammation. Consequently, as the validity of precisely treating blood with therapeutic ozone concentrations in restoring a redox homeostasis has been now demonstrated, the integration of ozone therapy appears essential for a rational treatment of type 2 diabetes. Such a combination may be able to reduce the diabetic epidemic.

Diabetes and chronic oxidative stress. A perspective based on the possible usefulness of ozone therapy.

It is now well established that hyperglycemia, present in both type 1 and type 2 diabetes, causes a variety of biochemical derangements leading to a diffused vascular damage responsible for several pathologic manifestations. Although preclinical and clinical studies have been performed by an unreliable administration route, the correct approach of oxygen-ozonetherapy may break a vicious circle. Messengers, released by a precise interaction ex vivo of the patient's blood with an equivalent calculated dose of ozone (0.42-0.84 mM), react with a variety of cells after blood infusion and restore a number of functions went astray. This paper aims to open a debate on this new therapy for improving the prognosis of diabetes.

Advanced glycation end products and diabetic foot disease.

Diabetic foot disease is an important complication of diabetes. The development and outcome of foot ulcers are related to the interplay between numerous diabetes-related factors such as nerve dysfunction, impaired wound healing and microvascular and/or macrovascular disease.The formation of advanced glycation end products (AGEs) has been recognized as an important pathophysiological mechanism in the development of diabetic complications. Several mechanisms have been proposed by which AGEs lead to diabetic complications such as the accumulation of AGEs in the extracellular matrix causing aberrant cross-linking, the binding of circulating AGEs to the receptor of AGEs (RAGE) on different cell types and activation of key cell signalling pathways with subsequent modulation of gene expression, and intracellular AGE formation leading to quenching of nitric oxide and impaired function of growth factors. In the last decade, many experimental studies have shown that these effects of AGE formation may play a role in the pathogenesis of micro- and macrovascular complications of diabetes, diabetic neuropathy and impaired wound healing. In recent years also, several clinical studies have shown that glycation is an important pathway in the pathophysiology of those complications that predispose to the development of foot ulcers. Currently, there are a number of ways to prevent or decrease glycation and glycation-induced tissue damage. Although not in the area of neuropathy or wound healing, recent clinical studies have shown that the AGE-breakers may be able to decrease adverse vascular effects of glycation with few side effects.

Homocysteine and vascular disease in diabetes: a double hit?

Cardiovascular disease is a major problem in diabetes, and risk factors presumably unrelated to diabetes, such as hyperhomocysteinaemia, may be related to the development of cardiovascular complications in diabetic individuals. Plasma homocysteine levels are usually normal in diabetes, although both lower and higher levels have been reported. Homocysteine levels in diabetes are modulated by hyperfiltration and renal dysfunction, as well as low folate status. Insulin resistance does not appear to be a major determinant of plasma homocysteine level. Hyperhomocysteinaemia has been associated with microalbuminuria and retinopathy in type 1 and type 2 diabetes. In patients with type 2 diabetes, plasma homocysteine concentration is a significant predictor of cardiovascular events and death. This relation seems to be stronger in subjects with diabetes than without. The underlying pathophysiological mechanism of this increased vascular risk remains unexplained, but may be related to worsening of endothelial dysfunction and/or structural vessel properties induced by oxidative stress. Because homocysteine and diabetes have apparent synergistic detrimental vascular effects, patients with diabetes are candidates for screening and treatment with folic acid until the results of ongoing clinical trials are available.