Osteoporosis

Pathogenesis

The underlying mechanism in all cases of osteoporosis is an imbalance between bone resorption and bone formation. Either bone resorption is excessive, and/or bone formation is diminished. Bone matrix is manufactured by the osteoblast cells, whereas bone resorption is accomplished by osteoclast cells. The mechanisms influencing the formation of the disease are complex. Most cases do not result from inadequate calcium intake, but include other factors affecting bone matrix formation and reabsorption. These include: (1) cigarette smoking, which inhibits the activity of osteoblasts; (2) sedentary lifestyle with little weight bearing exercise, such as walking; (3) a family history of osteoporosis; and being age 30 or older. Trabecular bone is the sponge-like bone in the center of long bones and vertebrae. Cortical bone is the hard outer shell of bones. Because osteoblasts and osteoclasts inhabit the surface of bones, trabecular bone is more active, more subject to bone turnover, to remodeling. Long before any overt fractures occur, the small spicules of trabecular bone break and are reformed in the process known as remodeling. Bone will grow and change shape in response to physical stress. The bony prominences and attachments in runners are different in shape and size than those in weightlifters. It is an accumulation of fractures in trabecular bone that are incompletely repaired that leads to the manifestation of osteoporosis. Common osteoporotic fracture sites, the wrist, the hip and the spine, have a relatively high trabecular bone to cortical bone ratio. These areas rely on trabecular bone for strength.

Low peak bone mass is important in the development of osteoporosis. Bone mass peaks in both men and women between the ages of 25 and 35, thereafter diminishing. Achieving a higher peak bone mass through exercise and proper nutrition during adolescence is important for the prevention of osteoporosis.

Bone remodeling is heavily influenced by nutritional and hormonal factors. Calcium and vitamin D are nutrients required for normal bone growth. Parathyroid hormone regulates the mineral composition of bone, with higher levels causing resorption of calcium and bone. Glucocorticoid hormones cause osteoclast activity to increase, causing bone resorption. Calcitonin, estrogen and testosterone increase osteoblast activity, causing bone growth. The loss of estrogen following menopause causes a phase of rapid bone loss. Similarly, testosterone levels in men diminish with advancing age and are related to male osteoporosis. In addition to estrogen, follicle-stimulating hormone (FSH) affects BMD. In mice, lower levels of FSH mean less resorption by osteoclasts.[5]

Those who suffer certain auto-immune and inflammatory disorders are prone to have a higher level of cytokines in the body. The presence of these proteins increase the body's inflammatory response which may upset the process of the osteoblast and osteoclast cycle.

Physical activity causes bone remodeling. People who remain physically active throughout life have a lower risk of osteoporosis. Conversely, people who are bedridden are at a significantly increased risk. Physical activity has its greatest impact during adolescence, affecting peak bone mass most. In adults, physical activity helps maintain bone mass, and can increase it by 1 or 2%. However, excessive exercise can lead to constant damages to the bones which can cause exhaustion of the structures as described above. There are numerous examples of marathon runners who developed severe osteoporosis later in life.

Lastly, osteoporosis on its own would not be a significant disease, were it not for the falls which precipitate fractures. Age-related sarcopenia, or loss of muscle mass, loss of balance and dementia contribute greatly to the increased fracture risk in patients with osteoporosis. Physical fitness in later life is associated more with a decreased risk of falling than with an increased bone mineral density.

[edit] Epidemiology

[edit] Disease burden

It is estimated that 1 in 3 women and 1 in 12 men over the age of 50 worldwide have osteoporosis. It is responsible for millions of fractures annually, mostly involving the lumbar vertebrae, hip, and wrist. Fragility fractures of ribs are also common in men.

[edit] Natural history

Today, many cases of osteoporosis in developed countries are diagnosed before symptoms develop. This is due to widespread screening for osteoporosis using the DXA scan. With treatment, bone mineral density increases, and fracture risk decreases.

In the absence of treatment, overt osteoporosis is heralded by a fracture. Some fractures, like vertebral compression fractures or sacral insufficiency fractures, may not be apparent at first, appearing to patient and physician as a very bad back ache or completely without symptoms. Hip fractures and wrist fractures are more obvious.

Hip fractures are responsible for the most serious consequences of osteoporosis. In the United States, osteoporosis causes a predisposition to more than 250,000 hip fractures yearly. It is estimated that a 50-year-old white woman has a 17.5% lifetime risk of fracture of the proximal femur. The incidence of hip fractures increases each decade from the sixth through the ninth for both women and men for all populations. The highest incidence is found among those men and women ages 80 or older.

An estimated 700,000 women have a first vertebral fracture each year. The lifetime risk of a clinically detected symptomatic vertebral fracture is about 15% in a 50-year-old white woman. However, because symptoms are often overlooked or thought to be a normal part of getting older, it is believed that only about one-third of vertebral compression fractures are actually diagnosed.

Distal radius fractures, usually of the Colles type, are the third most common type of osteoporotic fractures. In the United States, the total annual number of Colles' fractures is about 250,000. The lifetime risk of sustaining a Colles' fracture is about 16% for white women. By the time women reach age 70, about 20% have had at least one wrist fracture.
source:en.wikipedia.org