Osteoporosis is a disease of bone in which the amount of bone is decreased and the strength of trabecular bone is reduced, cortical bone becomes thin and bones are susceptible to fracture. It is defined according to the bone mineral density (BMD) as measured by DEXA: a BMD of 2.5 standard deviations below the peak bone mass (20 year old person standard) is considered osteoporosis. While treatment modalities are becoming available, prevention is still the most important way to reduce fracture.

Signs and symptoms

Osteoporotic fractures are those that occur in situations that would not lead to fractures in nonosteoporotic people. Typical fractures are vertebral fractures, hip fractures and those of the distal forearm. Collapse of vertebrae leads to chronic pain and characteristic bent statue, while the fractures of the long bones acutely impair mobility and may require surgery. Hip fracture, in particular, carries a poor prognosis.

While osteoporosis may occur in men, the problem is overwhelmingly one of postmenopausal women.

Risk factors for osteoporotic fracture can be split between modifiable and non-modifiable:

• Nonmodifiable: history of fracture as an adult, family history of fracture, female sex, advanced age, Caucasian race, dementia
• Potentially modifiable: tobacco smoking, intake of soft drinks (containing phosphoric acid), low body weight <58 kg (127 lb), estrogen deficiency, early menopause (<45 years) or bilateral oophorectomy, prolonged premenstrual amenorrhea (>1 year), low calcium intake, alcoholism, impaired eyesight despite adequate correction, recurrent falls, inadequate physical activity (i.e. too less but also far too excessive), poor health/frailty

Diagnosis

Dual energy X-ray absorptiometry (DEXA) is considered the diagnostic standard for osteoporosis when bone mineral density (BMD) is over 2.5 standard deviations under the peak bone mass (bone mass of a healthy 20-year old, or T-score).

In order to differentiate between the possible causes of osteoporosis, blood tests and X-rays are usually done to rule out cancer with metastasis to the bone, multiple myeloma, Cushing's disease and other causes mentioned above.

Etiology

Estrogen deficiency following menopause causes a rapid reduction in BMD. This, plus the increased risk of falling associated with aging, leads to fractures of the wrist, spine and hip. Other hormone deficiency states can lead to osteoporosis, such as testosterone deficiency. Glucocorticoid or thyroxine excess states also lead to osteoporosis. Lastly, calcium and/or vitamin D deficiency from malnutrition increases the risk of osteoporosis.

List of disorders associated with osteoporosis:

• Hypogonadal states - Turner syndrome, Klinefelter syndrome, anorexia nervosa, hypothalamic amenorrhea, hyperprolactinemia.
• Endocrine disorders - Cushing's syndrome, hyperparathyroidism, thyrotoxicosis, insulin-dependent diabetes mellitus, acromegaly, adrenal insufficiency
• Nutritional and gastrointestinal disorders - malnutrition, parenteral nutrition, malabsorption syndromes, gastrectomy, severe liver disease (especially biliary cirrhosis), pernicious anemia.
• Rheumatologic disorders - rheumatoid arthritis, ankylosing spondylitis
• Hematologic disorders/malignancy - multiple myeloma, lymphoma and leukemia, mastocytosis, hemophilia,thalassemia.
• Inherited disorders - osteogenesis imperfecta, Marfan syndrome, hemochromatosis, hypophosphatasia, glycogen storage diseases, homocystinuria, Ehlers-Danlos syndrome, porphyria, Menkes' syndrome, epidermolysis bullosa.
• Iatrogenic osteoporosis, caused by the therapeutic use of glucocorticoids.
• Other disorders - immobilization, chronic obstructive pulmonary disease, pregnancy and lactation, scoliosis, multiple sclerosis, sarcoidosis, amyloidosis

Pathogenesis

The underlying mechanism in all cases of osteoporosis is an imbalance between bone resorption and bone formation. Either bone resorption is excessive, or bone formation is diminished. Bone matrix is manufactured by the osteoblast cells, whereas bone resorption is accomplished by osteoclast cells. Trabecular bone is the sponge-like bone in the center of long bones and vertabrae. 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. The common osteoporotic fracture sited, 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.

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.

Epidemiology

It is estimated that 10 million Americans have established osteoporosis and another 34 million have osteopenia, or low bone mass, which leads to osteoporosis. It is responsible for 1.5 millions fractures annually, mostly involving the lumbar vertebrae, hip, and wrist. About 50% of women and 25% of men are expected to have osteoporosis in their lifetime. The estimated US(?) national direct expenditures (hospitals and nursing homes) for osteoporotic and associated fractures was $17 billion in 2001.

Natural history

Today, most cases of osteoporosis are diagnosed before symptoms develop. This is due to widespread screening for osteoporosis using the DEXA 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.

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.

Treatment

Patients at risk for osteoporosis (e.g. steroid use) are generally treated with vitamin D and calcium supplements. In renal disease, a different form of Vitamin D (D₃) is used, as the kidney cannot adequately synthesise D3 from precursors.

In osteoporosis (or a very high risk), bisphosphonate drugs are prescribed. The most often prescribed bisphosphonate is sodium alendronate (Fosamax®) 10 mg a day or 70 mg once a week. Other commonly used treatments include risedronate (Actonel) and raloxifene (Evista).

Recently, teriparatide (Forsteo®, recombinant parathyroid hormone) has been shown to be effective in osteoporosis, either alone or together with alendronate. Oral Strontium ranelate has also become available; this agent may also increase bone, rather than simply halting its breakdown.

Changes to lifestyle factors and diet are also recommended; the "at-risk" patient should include up to 1000mg of calcium in their diet (1500mg for a post-menopausal woman), which is roughly 3 servings of foodstuffs high in calcium daily. However, the benefit of supplementation of calcium alone remains to a degree controversial, since several nations with high calcium intakes through milk-products (e.g. the USA, Sweden) have some of the highest rates of osteoporosis worldwide. A few studies even suggested an adverse affect of calcium excess on bone density and blamed the milk-industry for misleading customers. Some nutrionalists assert that excess consumption of dairy products causes acification, which leaches calcium from the system, and argue that vegetables and nuts are a better source of calcium and that in fact milk products should be avoided. In any case, thirty minutes of weight-bearing exercise such as walking or jogging, three times a week, has been shown to increase bone mineral density, and reduce the risk of falls by strengthening the major muscle groups in the legs and back.

Prognosis

Patients with osteoporosis are at a high risk for additional fractures (the best predictor of fracture is a previous fracture). Treatment can improve fracture risk considerably.

Fractures can lead to decreased mobility and an additional risk of deep venous thrombosis and/or pulmonary embolism. Vertebral fractures can lead to severe chronic pain of neurogenic origin, which can be hard to control.

Although osteoporosis patients have an increased mortality rate due to the complications of fracture, most patients die with the disease rather than of it.

External Links

• Dr. Susan Ott's great site on osteoporosis (http://courses.washington.edu/bonephys/opop/opop.html)
• Osteoporosis Pictures (http://health.allrefer.com/health/osteoporosis-info.html)