Estradiol falls at menopause and when it drops below a threshold a series of events take place that result in increased bone remodeling. With each remodeling cycle more bone is removed than replaced and the faster the rate of these cycles the more true this becomes.

Normative bone densitometry data from white women not on hormones or other drug therapy known to affect bone or mineral metabolism between age 50 and 60 years of age revealed a bone loss rate of 12% or 1.2% per annum.

Some of the key actors in the events that cause bone loss at menopause have now been identified and their roles and scripts recorded. Menopause unfolds the same for all women leading to an increase in bone remodeling for the same reasons. Interestingly though the outcomes in terms of osteoporosis and fracture rates are very different for some women compared to others.

The osteocytes direct the play by production of a number of proteins one of which is called RANK-L. This protein controls the fate of the bone absorbing osteoclast cells and stimulates them to begin a bone remodeling cycle. An increase in RANK-L causes the formation of many new osteoclasts from the pool of hematologic stem cells. Osteoclasts are charged with removing old dead bone from the skeleton. RANK-L also stimulates the activity of osteoclasts meaning how actively they approach their task. When estrogen is absent and remodeling becomes unmodulated by estradiol, the result is excessive and rapid bone absorption.

Bone formation by osteoblasts is coupled to absorption of bone by osteoclasts, which must precede it. The two activities are tightly coupled. The bone that is absorbed by osteoclasts contains growth factors and chemotactic agents (chemical messages) placed there 7 years ago by the osteoblasts that made the bone.

The growth factors act like messages in a time capsule for the yet to be born great grand daughters of the osteoblasts that buried them in bone substance during the process of the bone formation long ago. The messages released from the bone time capsule tell the mesenchymal stem cells that are destined to become osteoblast cells to change into this cell type and then where to go to replace the bone absorbed by the osteoclasts.

Testosterone plays an important role at this point. The pre-osteoblast stem cell requires testosterone to be present within their nucleolus occupying the nuclear receptor in order to become osteocytes. If testosterone is absent, then the cell differentiates into a fat cell. Once they arrive in the bay absorbed by the osteoclasts the message also contains exactly the right combination of fertilizing growth factors to stimulate the stem cells to differentiation into osteoblasts and to proliferate into enough cells to do the job of filling up the hole left in the bone.

Normally bone remodeling is characterized by bone absorption being only a little greater in quantity to the following bone formation. Remodeling unmodulated by estradiol and testosterone results more rapid and prolonged absorption followed by a shorted period of formation. This is observed to some extent in all human females at menopause but not to the same extent as observed in those white women of Northern European ancestry that carry the genetic osteoporosis complex. What transpires in them is significantly more bone is removed than is put back and the cycle is speeded up. The osteoclasts are speeded up and the osteoblasts cannot keep up. After each remodeling cycle, less bone is in the skeleton than was present before hand. If this goes on long enough, the disease osteoporosis is the outcome.

Each basic structural unit that does the remodeling is made up of a few thousand cells and can easily fit on a pinpoint with room to spare. The BSU is tiny and there are millions of BSU active all at once all over the skeleton. There are enough active to completely breakdown and replace 1% of the bone in the skeleton each month or 14% annually. This is a continuous process all day long, every day of the year all the days of our life. It is resource and energy intensive.