Osteoporosis is a disease in which bones become fragile and more likely to break. It is a disease of bone in which the bone mineral density (BMD) is reduced, bone microarchitecture is disrupted, and the amount and variety of non-collagenous proteins in bone is altered. If not prevented or if left untreated, osteoporosis can progress painlessly until a bone breaks. These broken bones, also known as fractures, occur typically in the hip, spine, and wrist.
Any bone can be affected, but of special concern are fractures of the hip and spine. A hip fracture almost always requires hospitalization and major surgery. It can impair a person’s ability to walk unassisted and may cause prolonged or permanent disability or even death. Spinal or vertebral fractures also have serious consequences, including loss of height, severe back pain, and deformity.

Signs and symptoms of Osteoporosis

Clinical picture

Osteoporotic fractures are those that occur under slight amount of stresses that would not normally lead to fractures in nonosteoporotic people. Typical fractures occur in the vertebral column, hip and wrist. Collapse of a vertebra (”compression fracture”) can cause one or a combination of the following: acute onset of back pain; a hunched forward or bent stature; loss of height; limited mobility and possibly disability. Fractures of the long bones acutely impair mobility and may require surgery. Hip fracture, in particular, usually requires prompt surgery, as there are serious risks associated with a hip fracture, such as deep vein thrombosis and a pulmonary embolism.
While osteoporosis occurs in men, especially elderly men, and pre-menopausal women, the problem is overwhelmingly prevalent in postmenopausal women, and occasionally in calcium deficient adolescents.

Risk factors

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

  • Non modifiable: history of fracture as an adult, family history of fracture, female sex, advanced age, European or Asian ancestry, and dementia.
  • Potentially modifiable: prolonged intake of the prescription drug prednisone or any other glucocortioid, tobacco smoking, low body mass index, estrogen deficiency, early menopause (1 year), low calcium and vitamin D intake, alcoholism, impaired eyesight despite adequate correction, high risk of falls or recurrent falls, inappropriate physical activity (i.e. too little or also if done in excess), poor health/frailty. Coeliac disease can lead those with an otherwise adequate calcium intake to develop osteoporosis due to the inability to absorb calcium. Osteoporotic fracture may indeed be the event that leads to diagnosis that celiac disease (which affects around one in a hundred people in the West) has affected the patient for many years. The effects of soft drinks (containing phosphoric acid) are debatable; soft drinks may merely displace calcium-containing drinks from the diet.

A strong association between cadmium, lead and bone disease has also been established. Low level exposure to cadmium is associated with an increased loss of bone mineral density readily in both genders, leading to pain and increased risk of fractures, especially in elderly and in females. Higher cadmium exposure results in osteomalacia (softening of the bone). An association with proton pump inhibitors has also been found: it is thought that reducing the level of stomach acid interferes with calcium absorption.

Aetiology

Family history of fracture or low bone mass are probably the most important etiological factors of primary osteoporosis. The heritability of the fracture as well as low BMD are relatively high, ranging from 25 to 80 percent. Estrogen deficiency following menopause is correlated with 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.
Other significant factors leading to the onset of osteoporosis include smoking cigarettes, low levels of physical activity (weight bearing exercise), and family history. Osteoporosis can be thought of as analogous to sarcopenia, which is the age-related loss of skeletal muscle. The combination of sarcopenia and osteoporosis results in the significant frailty often seen in the elderly population.

List of disorders associated with osteoporosis:

  1. Hypogonadal states - Turner syndrome, Klinefelter syndrome, Kallmann syndrome, anorexia nervosa, hypothalamic amenorrhea, hyperprolactinemia.
  2. Other endocrine disorders - Cushing’s syndrome, hyperparathyroidism, thyrotoxicosis, insulin-dependent diabetes mellitus, acromegaly, adrenal insufficiency.
  3. Nutritional and gastrointestinal disorders - malnutrition, parenteral nutrition, malabsorption syndromes (e.g. coeliac disease, Crohn’s disease), gastrectomy, severe liver disease (especially primary biliary cirrhosis).
  4. Rheumatologic disorders - rheumatoid arthritis, ankylosing spondylitis.
  5. Hematologic disorders/malignancy - multiple myeloma, lymphoma and leukemia, mastocytosis, hemophilia, thalassemia.
  6. Inherited disorders - osteogenesis imperfecta, Marfan syndrome, hemochromatosis, hypophosphatasia, glycogen storage diseases, homocystinuria, Ehlers-Danlos syndrome, porphyria, Menkes’ syndrome, epidermolysis bullosa.
  7. Medication: Steroid-induced osteoporosis (SIOP) due to use of glucocorticoids - analogous to Cushing’s syndrome and involving mainly the axial skeleton.
    Barbiturates (due to accelerated metabolism of vitamin D) and some other antiepileptics.
  8. Other disorders - immobilization, scoliosis

Prevalence

Osteoporosis is a major public health threat for an estimated 44 million Americans, or 55 percent of the people 50 years of age and older. In the U.S., 10 million individuals are estimated to already have the disease and almost 34 million more are estimated to have low bone mass, placing them at increased risk for osteoporosis.
Of the 10 million Americans estimated to have osteoporosis, eight million are women and two million are men.
Significant risk has been reported in people of all ethnic backgrounds.
While osteoporosis is often thought of as an older person’s disease, it can strike at any age.

Women

Eighty percent of those affected by osteoporosis are women.
Twenty percent of non-Hispanic white and Asian women aged 50 and older are estimated to have osteoporosis, and 52 percent are estimated to have low bone mass.
Five percent of non-Hispanic black women over age 50 are estimated to have osteoporosis; an estimated additional 35 percent have low bone mass that puts them at risk of developing osteoporosis.
Ten percent of Hispanic women aged 50 and older are estimated to have osteoporosis, and 49 percent are estimated to have low bone mass.
Osteoporosis is under-recognized and under-treated not only in Caucasian women, but in African-American women as well.

Men

Twenty percent of those affected by osteoporosis are men.
Seven percent of non-Hispanic white and Asian men aged 50 and older are estimated to have osteoporosis, and 35 percent are estimated to have low bone mass.
Four percent of non-Hispanic black men aged 50 and older are estimated to have osteoporosis, and 19 percent are estimated to have low bone mass.
Three percent of Hispanic men aged 50 and older are estimated to have osteoporosis, and 23 percent are estimated to have low bone mass.

Fractures

One in two women and one in four men over age 50 will have an osteoporosis-related fracture in her/his remaining lifetime.
Osteoporosis is responsible for more than 1.5 million fractures annually, including:

  • over 300,000 hip fractures;
  • approximately 700,000 vertebral fractures;
  • 250,000 wrist fractures;
  • 300,000 fractures at other sites.

Hip fracture risk is increasing most rapidly among Hispanic women. Women with a hip fracture are at a four-fold greater risk of a second one, and the risk factors are similar to those for the first hip fracture. Osteoporotic fractures lower a patient’s quality of life.

Costs

The estimated national direct care expenditures (including hospitals, nursing homes, and outpatient services) for osteoporotic fractures is $18 billion per year in 2002 dollars, and costs are rising.

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.
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.

Diagnosis of Osteoporosis

Dual energy X-ray absorptiometry (DXA, formerly DEXA) is considered the gold standard for diagnosis of osteoporosis. Diagnosis is made when the bone mineral density is less than or equal to 2.5 standard deviations below that of a young adult reference population. This is translated as a T-score. The World Health Organization has established diagnostic guidelines as T-score -1.0 or greater is “normal”, T-score between -1.0 and -2.5 is “low bone mass” (or “osteopenia”) and -2.5 or below as osteoporosis. When there has also been a low trauma or osteoporotic fracture, defined as one that occurs as a result of a fall from a standing height, the term “severe or established” osteoporosis is used. This is very important, because a person who has already had a fracture is at least 4 times as likely to have another fracture as another person of the same age and bone density. The absolute risk of fracture depends strongly on age as well as bone density and factors which affect strength and falling.
The rate of bone turnover can be measured with urine NTx, a byproduct of bone cartilage breakdown. Urine NTx greater than 40 may indicate osteoporosis.
In order to differentiate between “primary” (post-menopausal, regardless of age, or senile - related to age) and “secondary” 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.

Screening

The U.S. Preventive Services Task Force (USPSTF) recommends that all women 65 years of age or older should be screened with bone densitometry. The Task Force recommends screening women 60 to 64 years of age who are at increased risk. The best risk factor for indicating increased risk is lower body weight (weight Osteoporosis Treatment

The primary goal of treatment of osteoporosis is to reduce the risk of pathologic fractures. The three mainstays of treatment are:

Weight-bearing exercise

Exercise is an important treatment for osteoporosis to maintain healthy bones. Activities that stress bones have been shown to have a positive effect in maintaining and increasing bone mass and preventing osteoporosis. Individuals who live a sedentary lifestyle have weaker bones and are subjected to a higher risk of sustaining pathologic fractures. While resistance forms of exercise (e.g. light weights) are excellent to stimulate bone production, even light aerobic exercise (e.g. aerobics, jogging, walking) can help strengthen bones and prevent osteoporosis.

Nutrition supplementation

Calcium supplementation is an important treatment to ensure oral intake is at least 1200 to 1500 mg every day. Comsuming this quantity of calcium is a difficult task considering that to do this you would have to eat or drink the equivalent of five glasses of milk each day. Because of this, many patients at-risk for osteoporosis should take an oral calcium supplement each day. This can be taken with Vitamin D (400-800 Units is recommended) to help increase the absorption. Also, caffeinated substances (e.g. coffee, soda, etc.) decrease calcium absorption, and should be avoided!

Medications

There are several available medications used for osteoporosis treatment. These include:

  • Bisphosphanates (Fosamax): Bisphosphanates (e.g. Fosamax, Actonel) are a type of medication that helps to regulate calcium and prevent bone breakdown. Bone turnover, or replacement of old bone with new bone, is a normal process within our body. In patients with osteoporosis, the replacement with new bone does not maintain pace with the breakdown of old bone. Bisphosphanates slow the rate of bone breakdown to help maintain bone mass by inhibiting the osteoclast, the cell responsible for bone breakdown.
  • Calcitonin (Miacalcin): Calcitonin is a naturally occurring hormone produced by the thyroid gland that can be given as an injection or taken as a nasal spray. Sold under the trade name Miacalcin, calcitonin also inhibits the function of the cells that breakdown bone, the osteoclasts. Calcitonin has long been known to be beneficial in patients with osteoporosis, but the injections were difficult to administer, and had unpleasant side-effects. The nasal spray has greatly improved the use of calcitonin, and it is much more commonly used today. Calcitonin has been shown to slow bone loss, and also decrease pain associated with osteoporosis fractures.
  • Raloxifene: Raloxifene is a newer medication that has been developed to provide some of the same advantages of estrogen (HRT), without the potential side-effects. Raloxifene is a type of medication called a Selective Estrogen Receptor Modulator, or SERM. The effects of Raloxifene have been shown to be similar to estrogen, including an increase in bone mass and lower cholesterol. However, the SERMs do not have the same effects on the uterine lining, and therefore do not need to be combined with a progesterone. Furthermore, there is evidence that Raloxifene may decrease the risk of breast cancer.
  • Estrogen: Hormonal replacement therapy, or HRT, not only helps maintain, but it can increase bone mass after menopause. Multiple studies have shown the benefits of estrogen therapy, including a lower risk of osteoporosis and fractured bones. In addition, other benefits of estrogen replacement in the postmenopausal patient include lower cholesterol, decreased risk of colon cancer, and fewer postmenopausal symptoms. HRT was shown to increase the risk of uterine cancer, but this risk is eliminated when the estrogen is combined with progesterone. There have been studies showing an increase risk of breast cancer in some study populations. Patients on HRT have also shown a slightly increased risk of developing blood clots and strokes.

Prognosis

Patients with osteoporosis are at a high risk for additional fractures (the best predictor of fracture is a previous fracture). Treatment for the underlying osteoporosis can reduce the risk of a subsequent fracture considerably.
Hip 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, as well as deformity. The one year mortality rate following hip fracture is approximately 20%. Though rare, multiple vertebral fractures can lead to such severe hunch back (kyphosis) that the resulting pressure on internal organs can impair one’s ability to breathe.
Although osteoporosis patients have an increased mortality rate due to the complications of fracture, most patients die with the disease rather than of it.

Sources: wikipedia, national osteoporosis foundation, about

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