Author: Simon Kipersztok, M.D., University of Florida

Pathophysiology of Osteoporosis

Bone is a metabolically active organ where constant architectural changes take place. As a result of physical stresses experienced during activities of daily living micro fractures can occur. If left unattended, these micro fractures can become clinically evident as fractures. Osteoclasts and osteoblasts are in charge of repairing the micro fractures. These two cells originate in the bone marrow from a common precursor. As a result of endocrine signals that are poorly understood and in the presence of a number of growth factors and cytokines the osteoclasts are recruited and create a "resorption pit" where bone is digested (see Figure 1). Thereafter, the osteoclasts abandon the pit while osteoblasts settle within it to deposit new bone. When resorption and deposition are coupled there is no net change in the amount of bone present. Following menopause and after some pathological processes the coupling is altered in favor of increased resorption and as a result there is a loss in bone mass.

Many conditions that affect different organ systems can cause osteoporosis. One of the more common etiologies is hypogonadism. In women, menopause signals the end point of the perimenopause, a process that started 10-12 years earlier, where the number of follicular units capable of producing estradiol within the ovary starts to decline until it is completely exhausted. Amenorrhea and systemic hypoestrogenism follows. As a result of low levels of estrogen there is an accelerated rate of bone loss particularly in the spine. A similar clinical picture can be observed when both ovaries are surgically removed or when the ovaries are not appropriately stimulated by gonadotropins to produce estradiol. This can occur in younger women as a result of excessive exercise, low body fat or as a sequelae to eating disorders such as anorexia nervosa. Many other conditions, besides hypogonadism, can cause osteoporosis.