Paget's disease of bone: osteitis deformans or osteodystrophia deformans?

Sir, We read with interest the review of Paget's disease byLangston and Ralston [1]. We are pleased that, unlike many authors,they resisted the urge to refer to this     

Fibrinogen--marker or mediator of vascular disease?

Fibrinogen plays a key role in platelet aggregation, the final step of the coagulation cascade, i.e. the formation of fibrin, and it is a major determinant of plasma viscosity and erythrocyte aggregation. It is both constitutively expressed and inducible during an acute phase reaction. Increased plasma fibrinogen levels are associated with an increased risk of coronary heart disease and myocardial infarction. The question as to whether fibrinogen is only a marker of the inflammatory process involved in atherosclerosis or a mediator, i.e. a pathogenic factor, has not yet been answered. Human in vivo studies do not permit a conclusive answer to this question. If it is a pathogenic factor, fibrinogen lowering would be a therapeutic option. Selective fibrinogen-lowering agents do not exist however. All agents that lower fibrinogen also have other cardiovascular effects such as a decrease in cholesterol or inflammation. Newer information stems from molecular biology. Polymorphisms in the human fibrinogen gene with higher fibrinogen levels do not increase the risk for myocardial infarction. Fibrinogen knockout mice crossed with an atherosclerosis-susceptible strain (apoprotein E null mice) did not show a decreased extent of atherosclerosis despite the absence of fibrinogen, and a mouse strain over-expressing fibrinogen did not show an increased degree of atherosclerosis. Thus, fibrinogen seems to be a marker rather than a mediator of vascular disease, which would make selective fibrinogen lowering a useless preventive or therapeutic strategy.     

Mechanisms of disease: is osteoporosis the obesity of bone?

Osteoporosis and obesity, two disorders of body composition, are growing in prevalence. Interestingly, these diseases share several features including a genetic predisposition and a common progenitor cell. With aging, the composition of bone marrow shifts to favor the presence of adipocytes, osteoclast activity increases, and osteoblast function declines, resulting in osteoporosis. Secondary causes of osteoporosis, including diabetes mellitus, glucocorticoids and immobility, are associated with bone-marrow adiposity. In this review, we ask a provocative question: does fat infiltration in the bone marrow cause low bone mass or is it a result of bone loss? Unraveling the interface between bone and fat at a molecular and cellular level is likely to lead to a better understanding of several diseases, and to the development of drugs for both osteoporosis and obesity.