Bone mineral density is highly correlated with bone strength and with fracture risk. Skeletal weakness, which develops in osteoporosis, results in part from structural and quantitative abnormal connections or alterations in bone quality. These include changes in bone turnover and in rate of repair, as well as loss of connectivity of the trabecular elements that comprise cancellous bone. Such changes contribute to skeletal weakness; however, some of these changes in bone quality are the direct result of bone loss.

Bone is a living tissue in a constant state of turnover and renewal. Bone remodeling maintains healthy bone with an ability to store calcium essential for bone density, bone strength, and other vital body functions. Bone responds to physiologic demands and repairs microstructural defects. Two major multinucleated, monocyte/macrophage lineage cell types, osteoclasts and osteoblasts, are involved with bone remodeling. Osteoclasts resorb bone and osteoblasts synthesize new bone matrix. Osteoid (the organic matrix of bone) subsequently calcifies to fill in defects resulting from osteoclast activity. Overall bone turnover is determined by the skeletal summation of metabolic activity generated by osteoclastic/osteoblastic coupling During growth and development, net bone formation exceeds resorption. The critical years for building bone mass begin in preadolescence. Peak bone mass occurs at about age 20 for the hip and during the early thirties for the spine. During the fourth decade in both genders, skeletal bone loss begins. At menopause, the rate of bone loss accelerates sharply. Estrogen receptors, present in bone, directly affect bone cell function by inhibiting osteoclastic bone resorption. With the decline in estrogen levels, osteoclastic and osteoblastic activity increase, but excess osteoclastic resorption occurs, causing a net bone loss of up to 2 to 3 percent per year for approximately 5 years. Total lifetime losses may equal 30 to 40 percent of peak mass for women and 20 to 30 percent for men.

Bone loss may occur in either trabecular or cor. tical bone from an imbalance of skeletal remodeling that favors bone resorption. Trabecular bone is spongy or cancellous and comprises 80 percent of the adult skeleton while cortical bone is com. pact or tubular and comprises 20 percent of the adult skeleton. Cortical bone predominates in the shafts of long bones, whereas trabecular bone is concentrated in the vertebrae, ends of long bones, pelvis, and other flat bones. Trabecular bone has a greater surface area than cortical bone and is therefore metabolically more active. Bone remod. eling is a dynamic process necessary to provide calcium for extracellular function, for repair and removal of old bone, and to maintain skeletal elasticity. Bone remodeling occurs at about one million bone sites at any given time and within a given year, remodeling occurs in 25 percent of trabecular and 3 percent of cortical bone. The complete bone remodeling cycle (bone resorption followed by formation of bone matrix and then mineralization of the matrix) takes up to 8 months to occur.