MGUS is a relatively stable condition afflicting 3% of people aged 50 and 5% of people aged 70; it progresses to multiple myeloma at a rate of 0.5–1% cases per year; smoldering multiple myeloma does so at a rate of 10% per year for the first 5 years, but then falls off sharply to 3% per year for the next 5 years and thereafter to 1% per year.Overall, some 2–4% of multiple myeloma cases eventually progress to plasma cell leukemia. Diagnosis
Blood tests
The globulin level may be normal in established disease. A doctor may request protein electrophoresis of the blood and urine, which might show the presence of a paraprotein (monoclonal protein, or M protein) band, with or without reduction of the other (normal) immunoglobulins (known as immune paresis). One type of paraprotein is the Bence Jones protein, which is a urinary paraprotein composed of free light chains. Quantitative measurements of the paraprotein are necessary to establish a diagnosis and to monitor the disease. The paraprotein is an abnormal immunoglobulin produced by the tumor clone. In theory, multiple myeloma can produce all classes of immunoglobulin, but IgG paraproteins are most common, followed by IgA and IgM. IgD and IgE myeloma are very rare. In addition, light and or heavy chains (the building blocks of antibodies) may be secreted in isolation: κ- or λ-light chains or any of the five types of heavy chains (α-, γ-, δ-, ε- or μ-heavy chains).
This was confirmed by another meta-analysis involving 945 286 patients in 8 retrospective cohort studies, most in the US.In 2012, the U.S. Justice Department announced GlaxoSmithKline had agreed to plead guilty and pay a $3 billion fine, in part for withholding the results of two studies of the cardiovascular safety of Avandia between 2001 and 2007. Death
There was no difference in all cause and vascular death in a meta-analysis of 4 trials against controls. Two meta-analyses of cohort studies found excess deaths against pioglitazone. Stroke
An retrospective observational study performed using Medicare data found that patients treated with rosiglitazone had a 27% higher risk of stroke compared to those treated with pioglitazone. Bone fractures
GlaxoSmithKline reported a greater incidence of fractures of the upper arms, hands and feet in female diabetics given rosiglitazone compared with those given metformin or glyburide. The information was based on data from the ADOPT trial The same increase has been found with pioglitazone (Actos), another thiazolidinedione. A meta-analysis of 10 RCTs, involving 13,715 patients and including both rosiglitazone- and pioglitazone-treated patients, showed an overall 45% increased risk of fracture with thiazolidone use compared with placebo or active comparator. It doubled the risk of fractures among women with type 2 diabetes, without a significant increase in risk of fractures among men with type 2 diabetes. Hypoglycaemia
The risk of hypoglycaemia is reduced with thiazolidinediones when compared with sulfonylureas; the risk is similar to the risk with metformin (high strength of evidence).