The hematological etiology of osteoporosis.

In this article we present a new working hypothesis, suggesting that overexertion of the hematopoietic system resulting from constant excessive need for blood cell production, plays an important role in the etiology of osteoporosis. It is generally accepted that the development of osteoporosis in postmenopausal women is due to the reduction of estrogen level. However a most striking observation is the fact that in the male organism, which has never been protected by high levels of estrogen, osteoporosis in senescence is significantly less frequent then in the female organism, which has been protected by estrogens for at least 35 years. Healthy women loose about 70 ml of blood every month, which adds up to some 850 ml per year and approximately 30 l over the 35 years of their reproductive life. Blood loss intensifies hematopoiesis by increasing the level of hematopoietic growth factors while, at the same time, stimulating proliferation of osteogenic progenitor cells. Osteogenic activity has, indeed, been detected in the blood of bled animals. The chain of events that converts continuous requiremental pressure on hematopoiesis into development of osteoporosis may be formulated as follows: on the one hand, blood loss creates developmental pressure on the hematopoietic system, augments production of hematopoietic growth factors with subsequent intensified proliferation of hematopoietic progenitor cells, increases the number of hematopoietic cells including osteoclasts, thus intensifying resorption of bone tissue and extension of hematopoietic territories. On the other hand, blood loss leads to stimulation of bone development, extensive proliferation of osteogenic progenitor cells resulting in increased numbers of osteoblasts, followed by new bone formation and, at the same time, increased production and maturation of osteoclasts which then enter the cycle of bone resorption. The bone resorption process itself is characterized by the release of bone morphogenic proteins that induce proliferation of osteogenic cells and subsequent production of osteoclasts that in their turn enter the cycle of bone resorption. Important evidence supporting the substantial role of hematopoietic insufficiency in the development of osteoporosis comes from the field of clinical hematology: hematological diseases accompanied by chronic anemia, such as beta thalassemia major, sickle cell anemia, chronic hemolytic anemia, pernicious anemia, etc., are also characterized by the concomitant development of osteoporosis. Patients suffering from hemophilia tend to develop osteoporosis as well. The possible role of functional interaction between hematopoietic and bone tissues in the development of age related osteoporosis is also discussed.