Information about Osteoporosis*
What is Osteoporosis?
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Osteoporosis is a disease of bone in which bone mineral density (BMD) is reduced and bone microarchitecture is disrupted. Osteoporotic bones are susceptible to fracture. It is defined according to the bone mineral density as measured by DEXA: a BMD of 2.5 standard deviations below the peak bone mass (20-year-old person standard) is indicative of osteoporosis. While treatment modalities are becoming available, prevention is still the most important way to reduce fracture. Due to its hormonal component, more women suffer from osteoporosis than men.
Signs and symptoms
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 vertebrae
("compression fracture") leads to chronic pain, characteristic bent stature, and
decreased pulmonary function (ability to breathe) 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
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, European ancestry, high risk of falls and dementia
Potentially modifiable: prolonged intake of the prescription drug prednisone, 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 and vitamin D intake, alcoholism, impaired eyesight despite adequate correction, recurrent falls, inadequate physical activity (i.e. too little but also far too excessive), poor health/frailty.
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Diagnosis
Dual energy X-ray absorptiometry (DEXA) is considered the gold standard for
diagnosis of osteoporosis. Diagnosis is made when the bone mineral density is
greater than 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. A low trauma or osteoporotic fracture, defined as one
that occurs as a result of a fall from a standing height, is also diagnostic of
osteoporosis regardless of the T-score.
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.
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 million 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 presently sodium alendronate (Fosamax®)
10 mg a day or 70 mg once a week. Other commonly used treatments include the
other oral bisphosphonates: risedronate (Actonel®) and ibandronate (Boniva®),
and raloxifene (Evista®), a selective estrogen receptor modulator (SERM).
Estrogen replacement remains a good treatment for osteoporosis but, at this
time, is not recommended unless there are other indications for its use as well.
Recently, teriparatide (Forteo®, recombinant parathyroid hormone 1-34) has been
shown to be effective in osteoporosis. It is used mostly for patients who have
already fractured, have particularly low BMD or several risk factors for
fracture or cannot tolerate the oral bisphosphonates. It is given as a daily
injection with the use of a pen-type injection device. Oral Strontium ranelate
has also become available; this agent may also increase bone, rather than simply
halting its breakdown. Both teriparatide and strontium are registered only for
treatment if bisphosphonates have failed or are contraindicated.
Changes to lifestyle factors and diet are also recommended; the "at-risk"
patient should include 1500mg of calcium daily either via dietary means (for
instance, an 8 oz glass of milk contains approximately 300 mg of calcium) or via
supplementation. The body will absorb only about 500 mg of calcium at one time
and so intake should be spread throughout the day. 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 nutritionists 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.
Increasing vitamin D intake has been shown to reduce fractures up to twenty-five
percent in older people, according to recent studies.
There is some evidence to suggest bone density benefits from taking the
following supplements (in addition to calcium and vitamin D): boron, magnesium,
zinc, copper, manganese, silicon, strontium, folic acid, and vitamins B6, C, and
K.
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.
The source of this article is
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