Is there a place for bone turnover markers in the assessment of osteoporosis and its treatment?

As populations age, the number of osteoporotic fractures will increase. Bone mineral density (BMD) measurement remains the major way to diagnose osteoporosis and to indicate therapy. The FRAX tool, based on clinical risk factors, estimates the 10-year risk of hip and major osteoporotic fractures. The association of BMD and FRAX measurements has improved the identification of patients who are most at risk. However, some patients can still be overlooked and denied therapy. It is sound that adding the measure of bone turnover markers to the former risk factors and their follow-up during therapy could best address the efficacy of treatment of osteoporosis. Whether this behavior is cost-effective remains to be settled.     

Is there a synergy between physical exercise and drug therapies for osteoporosis?

Combining physical exercise with drug therapies for osteoporosis has been attempted with the aim to maximize osteogenic stimulus. Potential synergetic effects may prevent post-menopausal bone loss, or maximise gains during peak bone mass acquisition. However, research studies yielded mixed results, impeding the emergence of a consensus on the effects of exercise and drug therapies for osteoporosis on bone tissue. Independent, additive or synergetic effects of exercise and drug therapies have been reported, but while animal studies offer promising results, human studies are less clear. The aim of this work was to critically review existing data on the subject in an attempt to clarify existing knowledge and to encourage further investigations with a 2 x 2 factorial design, as elucidation of these questions will benefit osteoporosis prevention.     

Is there a role for bronchial thermoplasty in the treatment of asthma?

Bronchial thermoplasty is a new technique proposed to improve control of moderate to severe asthma. It delivers thermal energy to the large airways during a bronchoscopy to decrease the amount of bronchial smooth muscle. This intervention has been shown to reduce asthma exacerbations, and improve asthma control and quality of life over a three-year period without significant complications up to a five-year period. It could be considered as another option in the treatment of selected patients requiring oral and/or high doses of inhaled corticosteroids to control asthma. It should, however, be performed in specialized centres in patients who understand the potential benefits and side-effects of this technique. The response to this treatment varies from one patient to another. Consequently, further studies are required to better define the role of this option in the treatment of asthma.     

Is there a direct effect of antithymocyte globulin on hematopoiesis?

The efficacy of immunosuppressive therapy in aplastic anemia (AA) provides the strongest argument to support its immune-mediated pathophysiology. While several immunosuppressive effects of antithymocyte globulin (ATG) can be demonstrated in vitro, some reports have implied that the activity of ATG in AA may be rather due to a variety of positive hematopoietic effects. We studied the effects of horse (h) and rabbit (r) ATG on marrow progenitors in vitro. Both types of ATG bound to CD34 cells and, in colony assays performed with total marrow cells, hATG had a dose-dependent, triphasic effect, with maximal increase in colony formation between 1 and 10 microg/ml and inhibition between 100 and 1000 microg/ml. As determined using CD34 cells, these effects did not require accessory cells. rATG showed similar activity, but was about 10-fold more potent than hATG. In the presence of complement, no increased cytotoxicity was observed. At concentrations equivalent to those measured in patients immediately after infusion, ATG showed moderate suppression of colony formation, while the stimulatory concentrations in vitro correspond to those seen in vivo within the first weeks after ATG administration. In control experiments, the patterns of the biologic effects of preimmune rIgG or hIgG preparations were similar to those of rATG and hATG, indicating a nonspecific nature of the effects of ATG on progenitor cells. Biological activity in methylcellulose cultures was observed with the F(ab)(2) fragments but was not found in purified Fc IgG. In summary, the spectrum of effects of ATG on hematopoietic progenitors is dependent upon the concentrations of ATG and may not be related to its antigenic specificity.     

Is there a role of free oxygen radicals in primary male osteoporosis?

OBJECTIVE: There is not enough evidence about the relationship between free radicals and male osteoporosis. In this study we investigated the role of free oxygen radicals and antioxidants on male osteoporosis in 31 male patients with primary osteoporosis and 21 subjects as controls. METHODS: Bone mineral densities (BMD) of the lumbar and femoral neck region were evaluated using dual energy X-ray absorbsiometry. Serum malondialdehyde (MDA) and nitric oxide (NO) levels and superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were measured by analytical methods. In addition, serum osteocalcine and C telopeptide levels were determined to evaluate bone turnover MDA and NO levels and SOD activity were significantly increased (p < 0.05) in osteoporotic males. RESULTS: There was a negative correlation between SOD and lumbar BMD levels (r= -0.328; p = 0.021). The same trend was observed between NO and lumbar BMD (r = -0.473; p = 0.001) and femoral neck BMD values (r = -0.540; p = 0.000). There was no significant correlation between free radical levels and bone turnover markers. CONCLUSION: The data indicate an increase in free oxygen radical levels. As a result, antioxidant defenses would compromise in primary male osteoporotic patients. Therefore, it may be suggested that oxidative stress plays an important role in the pathophysiology of primary male osteoporosis.     

Mechanisms and clinical implications of the placebo effect: is there a potential for the elderly? A mini-review

In recent years, the placebo effect has been a topic of considerable interest both in the scientific and the clinical community. In this time, the placebo effect has evolved from being considered a nuisance in clinical and pharmacological research to becoming a neurobiological phenomenon worthy of scientific investigation in its own right. Recent research shows that placebo effects are genuine psychobiological events attributable to the overall therapeutic context, and that these effects can be robust in both laboratory and clinical settings. These psychosocially induced biochemical changes in a patient's brain and body may in turn affect the course of a disease and the response to a therapy. Here we summarize and discuss the current insights into placebo mechanisms and discuss the potentially widespread implications for research and clinical practice. Even though a systematic knowledge of placebo effects across the lifespan is lacking, we aim at highlighting specific aspects related to the care of elderly patients and those suffering from neurodegenerative diseases.     

Of mice and men: Is there a future for metformin in the treatment of hepatic steatosis?

Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver diseases, of which the first stage is steatosis. It is one of the most common liver diseases in developed countries and there is a clear association between type 2 diabetes (T2DM) and NAFLD. It is estimated that 70% of people with T2DM have NAFLD and yet there is currently no licensed pharmacological agent to treat it. Whilst lifestyle modification may ameliorate liver fat, it is often difficult to achieve or sustain; thus, there is great interest in pharmacological treatments for NAFLD. Metformin is the first-line medication in the management of T2DM and evidence from animal and human studies has suggested that it may be useful in reducing liver fat via inhibition of lipogenesis and increased fatty acid oxidation. Findings from the majority of studies undertaken in rodent models clearly suggest that metformin may be a powerful therapeutic agent specifically to reduce liver fat accumulation; data from human studies are less convincing. In the present review we discuss the evidence for the specific effects of metformin treatment on liver fat accumulation in animal and human studies, as well as the underlying proposed mechanisms, to try and understand and reconcile the difference in findings between rodent and human work in this area.     

Is there a place for interferon-alpha in the treatment strategy of multicentric Castleman's disease?

INTRODUCTION: Castleman's disease is an unusual condition of unknown cause, consisting of massive proliferation of lymphoid tissue. Two forms (localized and multicentric) have been described. Interleukin-6 (IL-6) is at the core of the disease, being responsible for most of the clinical and biological signs that may be observed. Despite the benignancy of this pre-lymphoma condition, its course is usually aggressive and of poor prognosis in regard to the multicentric form. No consensus regarding treatment has been defined. Available data on the multicentric form of the disease are to scarce to allow any conclusion about the treatment timing and type of chemotherapy best suited to this condition. We report the case of a patient in whom interferon alpha (IFN-alpha) was used as first line treatment. EXEGESIS: The case of a 52-year-old man with multicentric Castleman's disease combined with high IL-6, in whom, however, testing for human herpes virus-8 proved to be negative, is described. Interferon alpha (4.5 MU/m2 three times per week during 18 months) administered as first line treatment induced dramatic improvement in the patient's general condition and normalization of the tumoral syndrome. Moreover, biological parameters and IL-6 returned to normal. Two years after interferon disruption, complete remission is still present. CONCLUSION: On the basis of the present data and those of two previous observations, anti-IL-6 and anti-infective properties of IFN-alpha are discussed. Treatment of multicentric Castleman's disease is based on corticosteroids and drugs derived from those pertaining to treatment of malignant lymphomas. Our results indicate that IFN-alpha is truly directed against Castleman's disease and has less toxicity than drugs usually prescribed. This argues for early use of IFN-alpha in Castleman's disease, in association or not with corticosteroids.