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Back to Endocrine Diseases
Osteoporosis
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 Dual Energy
X-ray Absorptiometry. A BMD of 2.5 standard deviations below the 20
year old person standard is considered osteoporosis.
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 national direct
expenditures (hospitals and nursing homes) for osteoporotic and
associated fractures was $17 billion in 2001.
Causes
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.
Risk Factors
Risk Factors for Osteoporosis Fracture
Nonmodifiable
- Personal history of fracture as an adult
- History of fracture in first-degree relative
- Female sex
- Advanced age
- Caucasian race
- Dementia
Potentially modifiable
- Current cigarette smoking
- 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
- Poor health/frailty
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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.
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%.
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.
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.
Diagnosis
Dual Energy X-ray Absorptiometry is considered diagnostic for
osteoporosis when bone mineral density (BMD) is under 2.5.
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 the
other causes mentioned above.
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 alendronate (Fosamax?)
10 mg a day or 70 mg once a week.
Recently, recombinant parathyroid hormone (teriparatide) has been
shown to be effective in osteoporosis, either alone or together with
alendronate.
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