POSTMENOPAUSAL OSTEOPOROSIS

Overview: Prevalence and Impact
Osteoporosis is defined as a "skeletal disorder characterized by compromised bone strength predisposing to an increased risk of fracture."[1] The bone-thinning disease has been referred to as the "silent thief" for its covert way of stealing bone mass and depleting bone strength with no symptoms until a bone fracture occurs. [2]

This most common among bone diseases affects some 8 million American women aged 50 and older (and about 2 million men in the same age group). Another 22 million 50-and-older women are at high risk for developing osteoporosis because they have low bone mass, a condition known as osteopenia. [3]

Non-Hispanic Caucasian women are disproportionately affected by osteoporosis; half of all Caucasian women have osteoporosis or osteopenia within a decade after menopause. [4] Osteoporosis is more prevalent in Asians, and Hispanics, too, than in African Americans. But despite their higher bone mineral density (BMD) throughout life compared to non-Hispanic Caucasian women, significant numbers of African American women also have the disease. [4,5]

Osteoporosis can result in diminished quality of life, disability, and death. Hip and other fractures are a destructive consequence of osteoporosis. Each year in the United States, 1.5 million osteoporotic fractures occur, 300,000 of which are hip fractures. Other typical fractures are those of the vertebrae (spine) and forearm (wrist). [5] Osteoporotic fractures are linked with significant increases in mortality; [6] a year after a hip fracture, for example, one in five patients is no longer alive. Various studies have shown the negative impact of osteoporotic fracture on survival, [7,8] and on quality of life as measured by the ability to carry out day-to-day activities such as bending, lifting, reaching, and walking.[ 9,10,11]  According to morbidity data, only 33 to 40 percent of people who suffer a hip fracture regain their prior ability to perform basic activities of daily living; 20 percent remain nonambulatory; and 10 to 60 percent cannot return home. [12]

Vertebral fractures can cause adverse effects such as acute and chronic back pain, height loss, kyphosis (outward curvature of the spinal column's thoracic region, also known as dowager's hump), crowding of internal organs, and generally prolonged disability and increased mortality. [4] Also negatively impacting overall health and quality of life of those with osteoporosis: psychosocial consequences, such as a negative self-perception, social withdrawal, anxiety, and depression.[13]

The estimated health care costs related to osteoporotic fractures in the United States are $17 billion (2001 dollars) per year. Total medical costs associated with each hip fracture amount to approximately $40,000 (2001 dollars). [14]

Etiology
Osteoporosis is caused when the body's process of bone remodeling-the process that maintains a healthy skeleton by continually removing and replacing older bone-gets out of balance. When bone removal, or resorption, outpaces bone formation, the result is bone loss. As people age, and particularly at menopause, the rate of bone remodeling increases; in turn, any imbalance is magnified, bone mass is reduced, and bones become fragile and increasingly vulnerable to fracture. [5]

The state of a person's bone mass depends on two factors: peak bone mass (the maximum level of bone density a person attains in his or her lifetime, usually achieved by age 25 or 30) and the amount of bone subsequently lost. [5]

Peak bone mass is mainly determined by genetics, but may be modified by additional factors such as extent of physical activity, dietary choices, and concomitant diseases. The higher the peak bone mass, the better, because it will take greater deterioration to weaken bone to the level of fracture susceptibility. [4]

Bone loss, like peak bone mass, is affected by both genetic and environmental factors. During the average lifetime, a woman will experience a decline in BMD of about 50 percent. [15]  At menopause, bone remodeling becomes imbalanced and causes bone loss throughout the skeleton, and an increase in the number of bone turnover sites accelerates this process of bone depletion. Declining estrogen concentration is one contributor to hastened bone loss post-menopause, and some nutritional factors, lifestyle choices, and concurrent diseases may also exacerbate bone loss. [4]

Most cases of osteoporosis are primary (related to age or menopause), [16] but many medical conditions (such as hyperthyroidism, Cushing's syndrome, hyperparathyroidism, gastrointestinal conditions such as celiac sprue, kidney disease, rheumatoid arthritis, and organ transplantation) have also been associated with bone loss and so-called "secondary" osteoporosis. [17] Medications that have been linked with a negative impact on bone include glucocorticoids, anticonvulsant medicines, heparin, excessive thyroid hormone, luteinizing hormone-releasing hormone agonists, neuroleptic agents, lithium, and aluminum. [17,18]

The National Osteoporosis Foundation's lists of medical conditions associated with osteoporosis. Medical conditions that may increase the risk of osteoporosis:

• AIDS/HIV
• Amyloidosis
• Ankylosing spondylitis
• Chronic obstructive pulmonary disease
• Congenital porphyria
• Cushing's syndrome
• Eating disorders
• Female athlete triad
• Gastrectomy
• Gaucher's Disease
• Hemochromatosis
• Hemophilia
• Hyperparathyroidism
• Hypogonadism
• Hypophosphatasia
• Idiopathic scoliosis
• Inadequate diet
• Inflammatory bowel disease
• Insulin-dependent diabetes mellitus
• Lymphoma
• Leukemia
• Malabsorption syndromes
• Mastocytosis
• Multiple myeloma
• Multiple sclerosis
• Pernicious anemia
• Rheumatoid arthritis
• Severe liver disease
• Spinal cord transection
• Sprue
• Stroke
• Thalassemia
• Thyrotoxicosis
• Tumor secretion of parathyroid hormone-related peptide
• Weight loss

While low bone density and micro-architectural damage set the stage for possible osteoporotic fractures, nonskeletal factors such as falls are also etiologic mechanisms that contribute to fracture risk. Falls are involved in about 90 percent of nonspinal fractures in the elderly. [15]

With aging, the rate of falls increases, with an estimated 20 percent of Caucasian women 60 and older falling at least once a year and 30 percent of those 85 and older falling with this frequency. [15] Meanwhile, the ability to respond so as to prevent injury is impaired by declines in muscle strength, balance, and other measures of physical performance. Specifically, the following factors are among those that contribute to the increased risk of falls and resulting fracture: impaired vision; reduced muscle strength and agility; slowed reaction time; increased use of medications; and cognition- and balance-affecting conditions.

Evaluating Risk for Osteoporosis and Fracture
All postmenopausal women should be evaluated for osteoporosis risk to establish a need for BMD testing. Assessment tools for osteoporosis risk include medical history, physical examination, and laboratory tests.

Medical History to Identify Risk Factors
The most significant osteoporosis risk factors are: [4]

• A personal history of fragility fracture-also called low-trauma fracture-as an adult (at least 40 to 45 years of age) 
• Low BMD

Bone mineral density is the most useful predictor of fracture risk by far, accounting for 70 percent of variance in bone strength.[19,20,21] Some factors have been identified as predictors of low bone density-among them, female sex, increased age, estrogen deficiency, low weight and body mass index (BMI), family history of osteoporosis, smoking, and Caucasian race. Other clinical risk factors that have been identified as contributing to fracture risk include premature menopause, family history of hip fracture, and the use of oral corticosteroids. [5,22]

The National Osteoporosis Foundation's list of risk factors for osteoporosis and fracture. Risk factors for osteoporosis and osteoporotic fractures in Caucasian postmenopausal women:

• Personal history of fracture during adulthood
• History of fragility fracture in a first-degree relative
• Low body weight (<127 lbs.)
• Current smoking
• Use of oral corticosteroid treatment
• Impaired vision
• Early estrogen deficiency (<45 years of age)
• Dementia
• Poor health/frailty
• Recent falls
• Low calcium intake (throughout life)
• Physical inactivity
• Alcohol consumption >2 drinks per day

*Until more data become available regarding non-Caucasian populations, the National Osteoporosis Foundation recommends that the same risk factors be used for other groups in evaluating the need for osteoporosis testing and treatment.

Physical Examination to Identify Fracture Signs and Symptoms. Physical findings that may suggest a vertebral fracture has occurred include loss of height and change in posture. [1]

Laboratory Tests for Secondary Causes
Routine laboratory tests, such as a complete blood count and measurement of serum levels of creatinine, urea nitrogen, calcium, phosphorus, alkaline phosphatase, and albumin, can rule out most secondary causes of osteoporosis. In women diagnosed with osteoporosis, the following should also be routinely measured: thyroid-stimulating hormone, 25-hydroxy vitamin D, and urine concentrations of calcium and phosphorus. Follow-up testing should be undertaken as necessary based on initial test results.[4]

Proteins and enzymes produced during bone resorption and formation can be measured in the serum or urine and interpreted as indicators of turnover. These biochemical markers of bone turnover may help identify at-risk women, but should not be used to diagnose osteoporosis. [23]

Diagnosis
A diagnosis of osteoporosis is established or confirmed by a measurement of bone mineral density. BMD has an inverse relationship to the risk of fracture-lower BMD translates into greater fracture risk. [5]

The World Health Organization's (WHO) osteoporosis definition is based on a comparison of the patient's BMD (measured at the spine, hip, or wrist) with the mean BMD for a "young normal" adult of the same sex, called the T-score. (Others compare the patient's BMD to a Z-score, which is the expected BMD for the patient's age and sex.) The difference between the patient's BMD score and the norm is reported as a number of standard deviations (SD) from the mean. Following are the WHO definitions: [24]

• Normal: T-score at -1 and above, meaning BMD is within 1 SD of a "young normal" adult 
• Low bone mass (osteopenia): T-score between -1 and -2.5, meaning that BMD is between 1 and 2.5 SD below that of a "young normal" adult 
• Osteoporosis: T-score at or below -2.5, meaning BMD is at least 2.5 SD below that of a "young normal" adult. Patients in this group who have already experienced at least one fracture are deemed to have severe, or established, osteoporosis. [5]

Bone mineral density, measured by one of several technologies, can support a diagnosis of osteoporosis. Central devices measure BMD at the vertebrae and hips, while peripheral devices measure at the heel, fingers, and forearms. To predict the risk of hip or spine fracture, it is best to measure BMD at these sites, respectively. [25,26]

To establish a diagnosis of osteoporosis, the preferred measurement is taken by dual x-ray absorptiometry (DXA) of the hip or spine. The technique is precise and quick, and emits radiation at a dose much lower than even a standard chest x-ray. Other BMD testing techniques, which are also good predictors of fracture, are called peripheral dual x-ray absorptiometry (pDXA) and single-energy x-ray absorptiometry (SXA) (measure bone density in the forearm, finger, or heel); quantitative computed tomography (QCT) (can measure trabecular and cortical bone density at several skeletal sites, but is usually used to measure the trabecular bone density in the spine); and ultrasound densitometry (assesses bone in the heel, tibia, patella, or other peripheral sites with relatively superficial bones). [5]

The question remains: Who should get tested? The possibility of osteoporosis and fracture risk exists in all postmenopausal women, and various guidelines exist that go to this issue of who is a candidate for testing.

The National Institutes of Health (NIH) consensus statement does not recommend routine screening, preferring instead that decision-making be based on an individualized system with consideration to age and risk factors. [1]

The National Osteoporosis Foundation and the North American Menopause Society urge testing for all women aged 65 and older, as well as postmenopausal women younger than 65 with other independent risk factors for fractures; all women with secondary causes of bone loss; women with fractures; and women considering osteoporosis therapy. [5,27] .And the American Association of Colleges of Endocrinology recommends testing in the above groups, plus perimenopausal women with risk factors for fractures. [4]

Recommendations for Patients
To promote peak bone mass, minimize bone loss, and prevent fractures, the following lifestyle choices should be encouraged throughout a person's life: thoughtful dietary decisions, physical activity, not smoking, and not drinking excessive amounts of alcohol. Also, steps should be encouraged to minimize the risk of falls.

Consuming Adequate Amounts of Calcium and Vitamin D
Sufficient intake of these two nutrients is critical to optimize peak bone mass and preserve bone mass throughout life. [1] Calcium decreases bone turnover and slows the rate of bone loss, [22] while vitamin D positively impacts bone resorption by increasing calcium absorption in the gastrointestinal tract. [28] Studies have shown that calcium and vitamin D can reduce the rate of bone loss and also substantially reduce fracture risk. [29,30,31]

For postmenopausal women who wish to reduce their risk of osteoporosis, the NIH recommends a daily consumption of 1000 mg (for women on estrogen replacement therapy) to 1500 mg (absent estrogen replacement) of elemental calcium. [32] The recommended vitamin D intake for women over age 50 is 400 to 600 IU (10 to 15 mcg). Daily supplementation with 800 IU (20 mcg) of vitamin D may reduce the risk of fracture in individuals with low blood levels of vitamin D. [33]

A well-balanced diet, supplemented as necessary with a daily multivitamin, may supply sufficient amounts of these vitamins, but additional supplementation with one of both nutrients may be required for those falling short of the recommended dietary intake. [1]

The most common sources of dietary calcium are dairy products such as milk, cheese, and yogurt. Other foods, such as orange juice, cereals, breads, and nutrition bars, may be fortified with calcium [4,28]. People can determine the calcium content in a food by reading its nutrition label, which shows the content of elemental calcium as a percentage of the recommended daily allowance (RDA) of 1000 mg per day.

While women can benefit from calcium at any age, they need additional calcium as they reach menopause because the body's declining estrogen production means a decreased ability to use dietary calcium efficiently [28]. For those who do not take in enough calcium from their food-and it has been shown that most postmenopausal women consume less than 600 mg of elemental calcium daily [34] — calcium supplements should be considered. Calcium supplement labels can be used to determine the amount of elemental calcium in a dose.

Exceeding the recommended intake of calcium may be harmful to health. Because of the risk of hypercalcemia and hypercalciuria, the National Academy of Sciences does not recommend intakes higher than 2500 mg per day. [35]

As for vitamin D, deficiency is common with aging for a variety of reasons, such as the body's reduced ability to convert 7-dehydrocholesterol to vitamin D3, inadequate exposure to sunlight, and reduced absorption of vitamin D from the gastrointestinal tract. [36] The body can get the nutrient from sunlight exposure, as well as from dietary consumption of vitamin D-fortified milk and cereals, egg yolks, salt-water fish, and liver. Multivitamins and vitamin D supplements offer additional alternatives. [5] The safe upper limit for vitamin D is currently the subject of debate, but believed to be between 2000 to 4000 IU per day.[*, **] The principal risks associated with excess vitamin D intake are hypercalcemia and hypercalciuria. [35]

Engaging In Weight-Bearing and Muscle-Strengthening Exercise
Regular weight-bearing and muscle-strengthening exercise can reduce the risk of falls and fractures[5] (though optimum levels of exercise for risk reduction are unknown[37]). Many studies point to benefits from exercise, such as substantially reduced risk of hip fractures, as well as improved BMD, in the context of osteoporosis management.[37,38,39,40,41] Weight-bearing exercises include walking, jogging, tennis, dancing, and Tai-Chi. Muscle-strengthening activities include weight-lifting and other resistance exercises. In older women, some back-strengthening exercises may reduce pain and increase functioning. [41] Patients should be medically cleared to undertake an exercise program.

Avoiding Tobacco and Excessive Alcohol
Cigarette smoking has been linked with several osteoporosis-associated factors in postmenopausal women, including reduced BMD, lower body weight, increased bone-turnover markers, decreased estrogen levels, and impaired calcium absorption, as well as a substantial increase in the risk of hip fractures. [37,42,43,44,45,46,47]

Excessive alcohol consumption (more than two drinks per day) negatively affects bone health and can increase the risk of falls. (Moderate alcohol intake, however, has no known detrimental effects on bone and in fact may be associated with slightly improved bone density and reduced risk of fracture in postmenopausal women.) [5]

Taking Steps to Prevent Falls
Methods for improving safety in the home and outside should be reviewed with at-risk patients. [48] Consideration should be given to the following steps: [4,5]

• Make sure that home lighting is sufficient and switches are easily accessible
• Keep the home tidy to avoid tripping 
• Use nonskid rugs and pads beneath rugs 
• Install grab bars in the bathtub or shower 
• Place nonskid decals on the bathroom floor and on the floor of the bathtub or shower 
• Apply nonskid treads to steps 
• Keep frequently used items in easy-to-reach locations 
• Pay attention for pets or children in the home and outside 
• Use handrails when ascending and descending stairs 
• Wear shoes with nonskid rubber soles 
• Be careful on uneven or icy sidewalks 
• Clean up spills immediately 
• Get regular eye check-ups 
• Rise slowly from the seated position

Some medications have been associated with a heightened risk of falls and fractures in elderly people, and should be discontinued if not medically necessary. The classes of medications at issue include antidepressants (for which there is the most compelling evidence of an increased risk), benzodiazepines, and digoxin. [49]

Studies of the anti-fracture protective effect of external hip protectors have come to conflicting conclusions.[50,51] The devices should be considered for some patients who have had a prior hip fracture or have other significant risk factors for falling. [4]

Pharmacologic Treatment
The main treatment goal of pharmacologic treatment for osteoporosis is fracture prevention. [1] Currently, only a small proportion of Caucasian women with osteoporosis are treated for the disease, and a smaller proportion yet of minority women (as well as men) get needed osteoporosis treatment. [13] By one overall estimate, only one-seventh of American women with osteoporosis get treated. [4]

Pharmacologic therapy should be initiated, along with counseling on lifestyle modification for risk reduction, for women at high risk of osteoporotic fracture, defined by the National Osteoporosis Foundation as: [5]

• BMD T-scores below -2.0 by central DXA, with or without risk factors
• BMD T-scores below -1.5 by central DXA, with at least one risk factor
• A prior vertebral or hip fracture

Effective options for treating and preventing postmenopausal osteoporosis include antiresorptive agents, which increase BMD by inhibiting bone resorption, but not stimulating new bone formation; and an anabolic agent, which stimulates bone formation.

The Food and Drug Administration (FDA) has approved four antiresorptive agents for osteoporosis prevention and treatment: the bisphosphonates alendronate, risedronate, and ibandronate (approved but currently not marketed) and the selective estrogen-receptor modulator (SERM) raloxifene. The anabolic agent teriparatide is also approved to prevent and treat the disease. Calcitonin is approved for the treatment, but not prevention of osteoporosis, whereas Estrogens are approved for the prevention, but not the treatment of osteoporosis.

Alendronate (brand name Fosamax®) [52,53,54]
Alendronate is a nitrogen-containing bisphosphonate approved by FDA for the prevention (tablets) and treatment (tablets and oral solution) of osteoporosis in postmenopausal women, among other osteoporosis-related indications. Alendronate can reduce the chance of osteoporotic fracture by reducing the activity of osteoclasts that draw calcium from the bones; slowing postmenopausal bone loss; and increasing bone mass.

For treatment of postmenopausal osteoporosis, the medication is generally taken as a 10-mg tablet once a day, or a 70-mg tablet or 70-mg bottle of oral solution once a week. For prevention, the usual dose for women is one 5-mg tablet once a day or one 35-mg tablet once a week.

To achieve optimal absorption and avoid irritation of the esophagus, the medication should be taken as follows:

• Tablet: Whether it is according to the once-daily or once-weekly regimen, the tablet should be taken whole with 6 to 8 ounces of plain water
• Solution: After drinking the entire bottle of solution, the patient should drink at least 2 ounces (one-quarter cup) of plain water
  In either form, the drug should be taken at least 30 minutes before the day's first food, drink, or other medication, and the patient should stay fully upright (sitting, standing, or walking) for at least 30 minutes, and should not lie down until after the first food of the day.

Patients on alendronate may develop severe digestive reactions such as irritation, inflammation, or ulceration of the esophagus. The most commonly reported side effect is abdominal pain, and other, less common side effects are nausea; heartburn; esophageal pain or irritation; vomiting; difficulty swallowing; a bloated feeling in the stomach; constipation, diarrhea or black and/or bloody stools; stomach or other peptic ulcers; gas; bone, muscle, or joint pain; headache; an altered sense of taste; and, rarely, a rash, itching, eye pain, or severe skin reactions. Allergic reactions such as hives or, rarely, swelling of the face, lips, tongue, and/or throat also have occurred, as have mouth ulcers when the tablet was chewed or dissolved in the mouth.

People should not take alendronate if they have certain esophageal disorders; are unable to stand or sit upright for at least 30 minutes; have hypocalcemia, severe kidney disease, or allergy to the drug; or are pregnant or nursing.

Risedronate (brand name Actonel®) [55,56]
Risedronate, like alendronate, is a nitrogen-containing bisphosphonate approved by FDA for indications including the prevention and treatment of osteoporosis in postmenopausal women. Risedronate reduces the activity of cells that cause bone loss and increases BMD, thus reducing the risk of fracture.

For treatment or prevention, risedronate is available in a 5-mg tablet for daily use and a 35-mg tablet for weekly dosing.

The medication should be swallowed whole with 6 to 8 ounces of plain water, at least 30 minutes before the day's first food, drink, or other medication. The patient should remain in an upright position for at least 30 minutes.

The most common side effects associated with risedronate are back and joint pain, upset stomach, abdominal pain, constipation, diarrhea, gas, and headache. Like alendronate, Risedronate may cause dysphagia, esophagitis, or stomach or esophageal ulcers. The drug is contraindicated in those with hypocalcemia, the inability to remain upright for 30 minutes, allergy to risedronate, or kidney disease, as well as in those who are pregnant or nursing.

Calcitonin-Salmon (nasal spray brand name Miacalcin®) [57,58]
Calcitonin, a synthetic form of a naturally occurring hormone produced by the body's thyroid gland, is approved for the treatment of osteoporosis in women who are at least 5 years beyond menopause and who cannot tolerate estrogens or for whom estrogens are not an option.

Like the previously approved injectable form of calcitonin, the more commonly used nasal spray form slows the rate of bone loss and increases spinal bone mineral density in most patients. The usual dose is one 200 IU spray each day into alternate nostrils-one nostril one day, the other the next. Nasal exams should precede treatments and should be undertaken, too, if nasal complaints arise during treatment.

Possible side effects of calcitonin include nasal symptoms such as runny nose and nosebleed, back pain, headache, and joint pain. Calcitonin-salmon should not be used by those who are allergic to the protein.

Raloxifene (brand name Evista®) [59,60]
Raloxifene is FDA-approved for the prevention and treatment of osteoporosis in postmenopausal women. The medication reduces bone loss and increases bone density like, but to a lesser extent, than estrogen. Studies are underway to examine whether raloxifene reduces the risk for cardiovascular disease and breast cancer.

The 60-mg tablet is taken once a day, at any time of day, with or without food. An infrequent but serious side effect of the drug is development of blood clots in the veins, which can cause disability or death. The most common side effects of raloxifene are hot flashes and leg cramps.

Women who are, or could become, pregnant should avoid raloxifene, as should those who have an allergic reaction to the drug. Because raloxifene increases the risk of blood clots, patients should avoid raloxifene if they have a history of blood clot formation, such as deep vein thrombosis, pulmonary embolism, or retinal vein thrombosis. Also, patients should be aware that immobility can add to the risk of blood clots. Patients should not take raloxifene while they are taking estrogen therapy in the form of a pill, patch, or injection, or with cholestyramine or colestipol. The dose of warfarin or other coumarin blood thinner may have to be adjusted in patients also taking raloxifene.

Estrogen and Estrogen with Progestin Therapies for Postmenopausal Women
Oral and transdermal forms of both estrogen and estrogen-progestin combinations are FDA-approved for prevention of osteoporosis in menopausal women.[4] Because estrogen can increase a woman's risk of developing endometrial cancer, progesterone is necessary for its protective effect on the uterine lining except in women who have had their uterus removed by hysterectomy.

Studies have shown that various forms of estrogen, including estrogen in combination with progestin, can improve bone density or prevent bone loss in postmenopausal women. Recently, the NIH-sponsored Women's Health Initiative (WHI) clinical trial provided the first definitive evidence that postmenopausal hormone therapy can reduce the risk for osteoporotic hip fractures as well as fractures at other sites. In the trial, daily estrogen plus progestin (0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate) reduced the relative risk of hip and spine fractures by 34 percent and reduced the relative risk of other osteoporosis-related fractures by 23 percent. (Another ongoing part of the WHI trial is studying the effects of estrogen alone on osteoporosis and other conditions. [61,62]

Other important findings from the WHI relate to the risks of estrogen-progestin combinations-specifically, the study revealed an increased risk of breast cancer in women taking the estrogen-progestin combination compared to women taking placebo pills, and increased risks, too, for heart attacks, strokes, and blood clots in the lungs and legs. [61] The study's investigators concluded that, in selecting among the available agents for osteoporosis prevention, the substantial risks for cardiovascular disease and breast cancer must be weighed against the benefit in terms of fracture risk reduction. [62]

Based on FDA's analysis of these risks, the agency recently made safety changes to the labeling of Prempro, Premphase, and Premarin. The new labeling specifies that when prescribing solely for the prevention of postmenopausal osteoporosis, therapy should only be considered for women at significant risk of osteoporosis and non-estrogen medications should be carefully considered.

FDA believes that in the absence of data to the contrary, the risks from all estrogen-progestin products are similar to those from the studied drugs, and has asked all manufacturers of these products to update their labeling to reflect the WHI findings. Along with the labeling changes, FDA has advised women that estrogens and progestins should be used at the lowest dose and for the shortest time to achieve the goals of treatment. [63]

Side effects from estrogen and estrogen with progestin therapies may include vaginal bleeding, breast tenderness, mood disturbance, and gallbladder disease. Side effects, as well as doses and other directions for use, contraindications, and other drug-related information, vary from medication to medication and should be reviewed thoroughly in the individual drug's labeling.

Teriparatide (brand name Forteo®) [64,65]
FDA approved teriparatide in late 2002 for the treatment of osteoporosis in postmenopausal women with a high risk for fracture. Teriparatide is a portion of human parathyroid hormone (PTH), the primary regulator of calcium and phosphate metabolism in bones. The medication, which is injected once daily into the thigh or abdomen in a 20 mcg dose, is the first approved osteoporosis treatment to increase BMD by stimulating new bone formation.

Common side effects reported with use of teriparatide include nausea, dizziness, and leg cramps. Because an increased rate of osteosarcoma in rats was observed in preclinical studies the drug's labeling highlights the possibility that humans treated with teriparatide may face an increased risk of developing this rare but serious bone cancer.

People should not take teriparatide if they have an increased baseline risk for osteosarcoma. Conditions associated with an increased risk for osteosarcoma include Paget's disease of the bone (unexplained high levels of alkaline phosphatase in the blood should raise suspicion of Paget's disease), and a history of radiation therapy involving the skeleton, Because osteosarcoma tends to occur more frequently in growing adolescents with open epiphyses, teriparatide should generally not be used in pediatric patients. Others who should not receive teriparatide include patients with metabolic bone disease other than osteoporosis, patients with hypercalcemia; women who are pregnant or nursing; or those who have had an allergic reaction to teriparatide or one of its ingredients.

Conclusion: The Pharmacist's Role
Though osteoporosis is preventable and treatable, the disease is often not diagnosed in its early phase because of a lack of warning signs until a fracture occurs. Considering the prevalence of osteoporosis in the United States, everyone should take steps to reduce the risk of brittle bones and fracture susceptibility, with or without evidence of low bone mineral density.

Pharmacists and other health professionals are in a position to educate postmenopausal women, as well as others, about the seriousness of osteoporosis and about protective steps that can be taken to lower risk for the potentially life-threatening condition. As if osteoporosis risk reduction isn't reason enough to counsel patients on modifying their lifestyle, the steps that will serve to reduce patients' risk for osteoporosis-such as ensuring adequate calcium and vitamin D intake, incorporating physical activity into the day, ceasing to smoke, not drinking to excess, and taking care not to experience an avoidable fall-are all lifestyle improvements that can have far-reaching health benefits.

By informing patients about risk factors for osteoporosis, the pharmacist can encourage appropriate candidates to inquire further about bone mineral density testing. And finally, if the opportunity to discuss osteoporosis comes at a time when a woman has already been diagnosed with the condition, the pharmacist's role is equally critical: to help guide her consideration of all of her treatment options based on the risks and benefits of each in her particular medical circumstances.

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Source
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2. National Osteoporosis Foundation