Pathophysiology of Osteoporosis

It is observed that bone fractures increase with age. Another observation is that children have much more proteins and water in their bones as elderly people which have more mineral components in their bones. With increasing the age both components are decreasing and thus come osteoporosis.

Very controversial studies prove that in societies with high milk products consummation is osteoporosis much wider spread as in societies which do not consume milk products. Perplexing, isn`t it?

Bone maintenance is a delicate business. In adults, the daily removal of small amounts of bone mineral, a process called resorption, must be balanced by an equal deposition of new mineral if bone strength is to be preserved. When this balance tips toward excessive resorption, bones weaken (osteopenia) and over time can become brittle and prone to fracture (osteoporosis).

This continual resorption and redeposition of bone mineral, or bone remodeling, is intimately tied to the pathophysiology of osteoporosis. Understanding how bone remodeling is regulated is the key to the effective prevention and treatment of osteoporosis.

Bones, like the framework of an aircraft, have evolved to be light yet strong. These properties are conferred to a large degree by architecture. The long bones are tubular in shape, with a strong outer shell, or cortical layer, surrounding a softer, spongier core called trabecular bone. The combination makes these bones strong and light, but flexible enough to absorb the stress – from high impact exercises – without breaking. The vertebrae are similarly constructed, with a thick cortical layer surrounding sheets of trabecular bone. As a unit, each vertebra can compress when temporarily loaded and then return to their original size.

But unlike an aircraft frame, a skeleton is alive and must be able to grow, heal, and respond to its environment. This is where bone remodeling plays a crucial role. However, there is a downside. As we age, daily remodeling leads to a gradual restructuring of the bone. Resorption of the minerals on the inside of the cortical layer and in the bone cavity itself leads to an inexorable loss of trabecular bone and a widening of the bone cavity. This is partly compensated for by the gradual addition of extra layers of mineral to the outside of the cortical layer.

The upshot is that overall the bones get slightly thicker. But the danger is that they are not getting any denser. In fact, peak bone mass, reached in early adulthood, gradually declines as people get older.

Bone architecture and continual remodeling combine to have a huge impact on the pathophysiology of osteoporosis. For example, young adults with wider femurs might be at higher risk for hip fractures late in life because, on average, wider bones tend to have thinner cortical layers. The thinner this layer is, the more susceptible it will be to resorption later in life.

The balance between bone resorption and bone deposition is determined by the activities of two principle cell types, osteoclasts and osteoblasts, which are from two different origins. Osteoclasts are endowed with highly active ion channels in the cell membrane that pump protons into the extracellular space, thus lowering the pH in their own microenvironment.

This drop in pH dissolves the bone mineral. Osteoblasts, through an as yet poorly characterized mechanism, lay down new bone mineral. The balance between the activities of these two cell types governs whether bone is made, maintained, or lost. The activities of these cells are also intimately intertwined. In a typical bone remodeling cycle, osteoclasts are activated first, leading to bone resorption.

Then, after a brief “reversal” phase, during which the resorption “pit” is occupied by osteoblasts precursors, bone formation begins as progressive waves of osteoblasts form and lay down fresh bone matrix. Because the bone formation phase typically takes much longer than the resorption phase, any increase in remodeling activity tends to result in a net loss of bone. At various stages throughout this process, the precursors, osteoclasts, and osteoblasts communicate with each other through the release of various “signaling” molecules. How these signaling molecules and various other endogenous (such as hormones) or external (such as diet and exercise) factors influence the cells involved in bone physiology is a topic of intense research activity.