Osteoporosis

Osteo- refers to bones and -porosis means pores. So, osteoporosis is when there’s a higher breakdown of bone in comparison to the formation of new bone which results in porous bones, meaning a decrease in bone density to the point of potential fracture.

Looking at a cross-section of a bone, there’s a hard-external layer known as the cortical bone and a softer internal layer of spongy bone or trabecular bone that is composed of trabeculae. The trabeculae are like a framework of beams that give structural support to the spongy bone. The cortical bone, in turn, is made up of many functional, pipe-like units called osteons, which run through the length of the bone. In the center of these osteons, there are hollow spaces called Haversian canals, which contain the blood supply and innervation for the bone cells. Around the Haversian canals, there are concentric lamellae, which look a bit like tree rings. The lamellae have an organic part, which is mostly collagen, and an inorganic part called hydroxyapatite, which is mostly calcium phosphate. In between neighboring lamellae, there are spaces called lacunae, which contain bone cells called osteocytes.

At first glance, bone may appear inert and unchanging, but it’s actually a very dynamic tissue. In fact, spongy bone is replaced every 3 to 4 years and compact bone is replaced every 10 years, in a process called bone remodeling, which has two steps: bone resorption, when specialized cells called osteoclasts break down bone, and bone formation, which is when another type of cells called osteoblasts form new bone.

Bone remodeling as a whole is highly dependent on serum calcium levels, which, in turn, are kept in the normal range by a balance between parathyroid hormone, or PTH, calcitonin and vitamin D.

Parathyroid hormone is produced by the parathyroid glands in response to low serum calcium, and it increases bone resorption to release calcium into the bloodstream. On the other hand, calcitonin is produced by the thyroid gland in response to high serum calcium, so it opposes the action of PTH - therefore promoting bone formation and decreasing bone resorption. Finally, vitamin D promotes calcium absorption in the gut, so it increases serum calcium, promoting bone formation and decreasing bone resorption.

The balance between these regulatory factors results in a peak bone mass, usually by age 20 to 29 - and this usually occurs earlier in females than in males. Factors that determine the peak bone mass are genetics and nutrition (meaning adequate vitamin D intake increases bone peak mass). Finally, strength training increases peak bone mass, as well as hormones like estrogens and androgens that inhibit bone resorption.

Ok, now, when osteoclasts break down bone faster than the osteoblasts can rebuild, it results in the lowering of the bone mass and eventually in osteoporosis.

If we zoom into a cross-section of an osteoporotic bone, it will show normal cells with normal mineralization, which differentiates it from osteomalacia where there's lack of mineralization. So with osteoporosis, abnormal findings include fewer trabeculae in the spongy bone and thinning of the cortical bone, as well as the widening of the Haversian canals. These bone changes increase the risk of fracture, and they are known as fragility or pathologic fractures. Some bones like the vertebrae, shoulder blades, and ribs consist mainly of spongy bone, so they are at great risk of fragility fractures.

Factors that accelerate bone mass loss and increase the risk of osteoporosis are low estrogen levels, like after menopause, and low serum calcium. Additional factors include alcohol consumption, smoking, drugs like glucocorticoids, which decrease calcium absorption from the gut through antagonism of vitamin D, and drugs like heparin and L-thyroxine. Another factor is physical inactivity, as seen in astronauts in a zero-gravity environment where they just don't use their musculoskeletal system as hard as when they’re on earth. As a result, bone deposition decreases due to a lack of stress, while resorption increases. There are also diseases that can cause osteoporosis like Turner syndrome, hyperprolactinemia, Klinefelter syndrome, Cushing syndrome, and diabetes mellitus.