Osteoporosis

From Wikipedia, the free encyclopedia

Osteoporosis is a disease of bone in which bone mineral density (BMD) is
reduced, bone microarchitecture is disrupted, and the amount and variety of noncollagenous proteins in bone is changed. Osteoporotic bones are more susceptible to
fracture. Osteoporosis is defined by the World Health Organization (WHO) as either a
bone mineral density 2.5 standard deviations below peak bone mass (20-year-old person
standard) as measured by DEXA or any fragility fracture. While treatment modalities are
becoming available, prevention is still the most important way to reduce fracture. Due to
its hormonal component, more women, particularly after menopause, suffer from
osteoporosis than men.
Osteoporosis can be thought of as analogous to "sarcopenia", which is the agerelated loss of skeletal muscle. The combination of sarcopenia and osteporosis results in
the significant frailty often seen in the elderly population.

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 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 and bedrest.
Fractures of the long bones acutely impair mobility and may require surgery. Hip
fracture, in particular, carries a poor prognosis.

While osteoporosis occurs in men and pre-menopausal women, the problem is

overwhelmingly prevalent in postmenopausal women.

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

Nonmodifiable: 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,

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, premature ovarian failure, 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 or also if done in excess), high risk of falls, poor health/frailty.

Diagnosis
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 equal to or 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, Kallmann

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 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.[1]
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 1 in 3 women and 1 in 5 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.

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. 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.

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 (1,25dihydroxycholecalciferol or calcitriol which is the main biologically active form of
vitamin D) is used, as the kidney cannot adequately generate calcitriol from calcidiol (25hydroxycholecalciferol) which is the storage form of vitamin D.
In osteoporosis (or a very high risk), bisphosphonate drugs are prescribed. The most often
prescribed bisphosphonates are presently sodium alendronate (Fosamax) 10 mg a day
or 70 mg once a week, risedronate (Actonel) 5mg a day or 35mg once a week or and
ibandronate (Boniva once a month).

Other medicines prescribed for prevention of osteoporosis include raloxifene (Evista), a

selective estrogen receptor modulator (SERM). Estrogen replacement remains a good
treatment for prevention of 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. Teriparatide is only licensed for treatment if bisphosphonates have failed or are
contraindicated (however, this differs by country).
Oral Strontium ranelate (Protelos - Servier) is the first in a new class of drugs called a
Dual Action Bone Agents (DABA's), and has proven efficacy in the prevention of
vertebral and non-vertebral fractures (including hip fracture). Strontium Ranelate works
by stimulating the proliferation of osteoblast (bone building) cells, and inhibiting the
proliferation of osteoclast (bone absorbing) cells. This means that strontium Ranelate
increases BMD by forming new bone, rather than just preserving existing bone. In
comparison to bisphosphonates which only act on one aspect of bone remodeling,
strontium ranelate also preserves bone turnover, allowing the microarchitecture of the
bone to be continuously repaired as it would in healthy bone. Strontium ranelate is taken
as a 2g oral suspension daily, and is licenced for the treatment of osteoporosis to prevent
vertebral and hip fracture (this may differ by country). Strontium ranelate has show
significant efficacy at reducing both vertebral, and non-vertebral fractures in patients over
the age of 80, who are the most at risk where osteoporosis is concerned. This is unique to
strontium ranelate as bisphosphonates can only show efficacy in vertebral fracture
reduction, not non-vertabral. Strontium ranelate has side effect benefits over the
bisphosphonates, as it does not cause any form of upper GI side effect, which is the most
common cause for medication withdrawal in osteoporosis.
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 milkproducts (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 nutrionists 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. [2] [3]

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 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, and though rare, multiple
vertebral fractures can put pressure on internal organs and 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.