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## Complete Summary

#### GUIDELINE TITLE

American Association of Clinical Endocrinologists medical guidelines for
clinical practice for the prevention and treatment of postmenopausal
osteoporosis: 2001 edition, with selected updates for 2003.

#### BIBLIOGRAPHIC SOURCE(S)

Hodgson SF, Watts NB, Bilezikian JP, Clarke BL, Gray TK, Harris DW,
Johnston CC Jr, Kleerekoper M, Lindsay R, Luckey MM, McClung MR, Nankin
HR, Petak SM, Recker RR, Anderson RJ, Bergman DA, Bloomgarden ZT, Dickey
RA, Palumbo PJ, Peters AL, Rettinger HI, Rodbard HW, Rubenstein HA.
.American Association of Clinical Endocrinologists medical guidelines
for clinical practice for the prevention and treatment of postmenopausal
osteoporosis: 2001 edition, with selected updates for 2003. Endocr
Pract 2003 Nov-Dec;9(6):544-64.
[PubMed](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14715483)

#### GUIDELINE STATUS

These guidelines will be continually updated to reflect the latest
advances in the prevention, diagnosis, and treatment of postmenopausal
osteoporosis. Because these changes often exceed the capability of the
American Association of Clinical Endocrinologists (AACE) printed medium,
these guidelines will be updated first on the [AACE Web
site](http://www.aace.com/).

### \*\* REGULATORY ALERT \*\*

#### FDA WARNING/REGULATORY ALERT

**Note from the National Guideline Clearinghouse**: This guideline
references a drug(s) for which important revised regulatory information
has been released.

-   On April 7, 2005, after concluding that the overall risk versus
    benefit profile is unfavorable, the FDA requested that Pfizer, Inc
    voluntarily withdraw Bextra (valdecoxib) from the market. The FDA
    also asked manufacturers of all marketed prescription nonsteroidal
    anti-inflammatory drugs (NSAIDs), including Celebrex (celecoxib), a
    COX-2 selective NSAID, to revise the labeling (package insert) for
    their products to include a boxed warning and a Medication Guide.
    Finally, FDA asked manufacturers of non-prescription (over the
    counter \[OTC\]) NSAIDs to revise their labeling to include more
    specific information about the potential gastrointestinal (GI) and
    cardiovascular (CV) risks, and information to assist consumers in
    the safe use of the drug. See the [FDA Web
    site](http://www.fda.gov/medwatch/SAFETY/2005/safety05.htm#Bextra)
    for more information.

> Subsequently, on June 15, 2005, the FDA requested that sponsors of all
> non-steroidal anti-inflammatory drugs (NSAID) make labeling changes to
> their products. FDA recommended proposed labeling for both the
> prescription and over-the-counter (OTC) NSAIDs and a medication guide
> for the entire class of prescription products. All sponsors of
> marketed prescription NSAIDs, including Celebrex (celecoxib), a COX-2
> selective NSAID, have been asked to revise the labeling (package
> insert) for their products to include a boxed warning, highlighting
> the potential for increased risk of cardiovascular (CV) events and the
> well described, serious, potential life-threatening gastrointestinal
> (GI) bleeding associated with their use. FDA regulation 21CFR 208
> requires a Medication Guide to be provided with each prescription that
> is dispensed for products that FDA determines pose a serious and
> significant public health concern. See the [FDA Web
> site](http://www.fda.gov/medwatch/SAFETY/2005/safety05.htm#NSAID) for
> more information.

**Additional Notice**

-   On May 18, 2005, Novartis and the U.S. Food and Drug Administration
    (FDA) notified dental healthcare professionals of revisions to the
    prescribing information to describe the occurrence of osteonecrosis
    of the jaw (ONJ) observed in cancer patients receiving treatment
    with intravenous bisphosphonates, Aredia (pamidronate disodium) and
    Zometa (zoledronic acid). The prescribing information recommends
    that cancer patients receive a dental examination prior to
    initiating therapy with intravenous bisphosphonates (Aredia and
    Zometa), and avoid invasive dental procedures while receiving
    bisphosphonate treatment. For patients who develop ONJ while on
    bisphosphonate therapy, dental surgery may exacerbate the condition.
    See the [FDA Web
    site](http://www.fda.gov/medwatch/SAFETY/2005/safety05.htm#zometa2)
    for more information.

### COMPLETE SUMMARY CONTENT

 \*\* REGULATORY ALERT \*\*\
 SCOPE\
 METHODOLOGY - including Rating Scheme and Cost Analysis\
 RECOMMENDATIONS\
 EVIDENCE SUPPORTING THE RECOMMENDATIONS\
 BENEFITS/HARMS OF IMPLEMENTING THE GUIDELINE RECOMMENDATIONS\
 CONTRAINDICATIONS\
 QUALIFYING STATEMENTS\
 IMPLEMENTATION OF THE GUIDELINE\
 INSTITUTE OF MEDICINE (IOM) NATIONAL HEALTHCARE QUALITY REPORT
CATEGORIES\
 IDENTIFYING INFORMATION AND AVAILABILITY\
 DISCLAIMER

### SCOPE

#### DISEASE/CONDITION(S)

Postmenopausal osteoporosis

#### GUIDELINE CATEGORY

Management\
Prevention\
Treatment

#### CLINICAL SPECIALTY

Endocrinology\
Internal Medicine

#### INTENDED USERS

Physicians

#### GUIDELINE OBJECTIVE(S)

**Overall Objective**

To help physicians and their patients make good decisions about skeletal
health and postmenopausal osteoporosis

**Specific Objectives**

-   To reduce the incidence of fractures related to osteoporosis

-   To achieve the highest quality of life possible for individual
    patients by using the most effective and efficient methods of
    diagnosis and management

#### TARGET POPULATION

Postmenopausal women

#### INTERVENTIONS AND PRACTICES CONSIDERED

**Diagnosis/Risk Assessment**

1.  Comprehensive medical evaluation including a complete history and
    physical examination and laboratory work-up in order to identify
    coexisting medical conditions that cause or contribute to bone loss

2.  Assessment of risk factors for fractures and falling

3.  Bone mineral density measurements, including a variety of
    measurement techniques and measurement sites

4.  Biochemical markers of bone turnover

5.  Assessment of patient\'s reliability, understanding, and willingness
    to accept available interventions

**Note**: Standard radiography is considered as a technique to diagnose
osteoporosis but not recommended.

**Prevention and Treatment**

1.  Prevention of osteoporosis through promoting diets with adequate
    calcium content throughout the lifespan, encouraging good general
    nutrition, promoting adequate vitamin D intake, advocating regular
    weight-bearing exercise, and strongly discouraging the use of
    tobacco

2.  Measures to reduce the risk of falls and injuries

3.  Pharmacologic agents: bisphosphonates (alendronate, risedronate,
    etidronate, pamidronate), calcitonin, estrogen, teriparatide, and
    raloxifene; calcium and vitamin D supplementation

#### MAJOR OUTCOMES CONSIDERED

-   Morbidity and mortality due to postmenopausal osteoporosis,
    including bone fracture and its attendant clinical complications:
    pain, deformity, postural changes (spinal fractures), disability,
    physical deconditioning due to inactivity, changes in self-image,
    and death.

-   Efficacy of treatment in preventing bone loss and reducing the risk
    and incidence of fractures

-   Bone mineral density measurements or bone turnover markers

-   Side effects and cost effectiveness of treatment

### METHODOLOGY

#### METHODS USED TO COLLECT/SELECT EVIDENCE

Hand-searches of Published Literature (Primary Sources)\
Searches of Electronic Databases

#### DESCRIPTION OF METHODS USED TO COLLECT/SELECT THE EVIDENCE

Reports in the peer-reviewed literature dealing with prevention,
diagnosis, and treatment of postmenopausal osteoporosis that were
published and indexed between 1996 and 2003 were identified by computer
search.

The literature collected for the selected updates included articles
published in 2002 (such as the Women\'s Health Initiative \[WHI\] paper)
and 2003.

#### NUMBER OF SOURCE DOCUMENTS

Not stated

#### METHODS USED TO ASSESS THE QUALITY AND STRENGTH OF THE EVIDENCE

Weighting According to a Rating Scheme (Scheme Given)

#### RATING SCHEME FOR THE STRENGTH OF THE EVIDENCE

**Levels of Evidence**

**Level 1 Evidence**: Recommendations were based on randomized,
prospective, double-blind studies of well-defined patient populations,
using the most relevant clinical endpoint, fracturing.

**Level 2 Evidence**: Recommendations were based on cross-sectional
studies, investigations that tested smaller or nonrandomized patient
populations, or studies that tested secondary or surrogate clinical
endpoints for fracture, such as bone mineral density (BMD) or bone
turnover markers, in treated populations.

**Level 3 Evidence**: Recommendations were based on reviews, editorials,
and expert opinions.

#### METHODS USED TO ANALYZE THE EVIDENCE

Review of Published Meta-Analyses\
Systematic Review

#### DESCRIPTION OF THE METHODS USED TO ANALYZE THE EVIDENCE

Not stated

#### METHODS USED TO FORMULATE THE RECOMMENDATIONS

Not stated

#### RATING SCHEME FOR THE STRENGTH OF THE RECOMMENDATIONS

Not applicable

#### COST ANALYSIS

A formal cost analysis was not performed and published cost analyses
were not reviewed.

#### METHOD OF GUIDELINE VALIDATION

Internal Peer Review

#### DESCRIPTION OF METHOD OF GUIDELINE VALIDATION

Nine physicians are acknowledged as reviewers in the guideline document
(see \"Group Composition\" field).

### RECOMMENDATIONS

#### MAJOR RECOMMENDATIONS

The levels of evidence (1 through 3) are defined at the end of the
\"Major Recommendations\" field.

**[Evaluation]{.underline}**

The following patients should undergo an assessment for postmenopausal
osteoporosis:

-   All women 65 years old or older

-   All adult women with a history of a fracture (or fractures) not
    caused by severe trauma (such as a motor vehicle accident)

-   Younger postmenopausal women who have clinical risk factors for
    fractures (who have low body weight, that is, less than 57.6 kg
    \[127 lb\], or a family history of spine or hip fracturing)

The evaluation should include the following items:

-   A comprehensive medical examination

-   Assessment of risk factors for fractures (refer to the guideline
    document for a list of risk factors for fractures)

-   Bone mineral density (BMD) measurements in younger postmenopausal
    women who have risk factors and in all women 65 years old or older

-   Assessment of the patient\'s reliability, understanding, and
    willingness to accept available interventions

**Medical Evaluation**

A comprehensive medical evaluation, including a complete history and
physical examination, is indicated in all women with postmenopausal
osteoporosis in order to identify coexisting medical conditions that
cause or contribute to bone loss.

The following laboratory tests should be considered for any woman who
has osteoporosis. These tests will establish baseline conditions or
definitively exclude secondary causes of osteoporosis, even in the
absence of other clinical indications:

-   Complete blood cell count

-   Serum chemistry studies (especially calcium, phosphorus, total
    protein, albumin, liver enzymes, alkaline phosphatase, creatinine,
    and electrolytes)

-   Urinary calcium excretion

If the medical history or physical findings suggest secondary causes of
bone loss, additional laboratory evaluations are warranted and may
include (but are not limited to) the following tests:

-   Serum thyrotropin

-   Erythrocyte sedimentation rate

-   Serum parathyroid hormone concentration (for possible primary or
    secondary hyperparathyroidism)

-   Serum 25-hydroxyvitamin D concentration

-   Urinary free cortisol and other tests for suspected adrenal
    hypersecretion

-   Acid-base studies

-   Biochemical markers of bone turnover (for example, bone-specific
    alkaline phosphatase and urine or serum collagen cross-links)

-   Serum tryptase, urine N-methylhistamine, or other tests for
    mastocytosis

-   Serum or urine protein electrophoresis (or both)

-   Bone marrow aspiration and biopsy to look for marrow-based diseases

-   Undecalcified iliac bone biopsy with double tetracycline labeling
    (consider only when osteoporosis is diagnosed and the patient has no
    apparent cause for the condition, no response to therapy, or
    suspected osteomalacia or mastocytosis)

The causes of secondary osteoporosis in adults are listed in the
original guideline document (see Table 2 titled \"Causes of Generalized
Secondary Osteoporosis in Adults\").

**Standard Radiography**

In patients with known or suspected vertebral fractures or with
unexplained loss of height, radiography of the thoracic and lumbar spine
is indicated to identify and confirm the presence of those fractures.
Radiographic studies are usually indicated to confirm the presence of
fractures at other sites as well. The sensitivity and reliability of
standard radiography to assess bone mineral density are poor, and in the
absence of vertebral fractures, this technique cannot be used to
diagnose osteoporosis.

**Biochemical Markers of Bone Turnover**

Biochemical markers of bone turnover may be useful for the following
specific situations:

-   Assessing fracture risk in elderly patients

-   Assessing therapeutic responses to antiresorptive agents, such as
    estrogen and bisphosphonates

-   Identifying patients with high bone turnover (to predict rapid bone
    loss)

**Bone Mineral Density Measurement**

In women who are at risk for postmenopausal osteoporosis, bone mineral
density (BMD) measurement can accomplish the following:

-   Establish the diagnosis of postmenopausal osteoporosis

-   Determine fracture risk (for every 1-standard deviation decrease in
    age-adjusted BMD, the relative risk \[RR\] of fracture increases
    1.5- to 2.5-fold)

-   Identify candidates for intervention

-   Assess changes in bone mass over time in treated and untreated
    patients

-   Enhance acceptance of and adherence to treatment

***Measurement Techniques***

Dual x-ray absorptiometry of the lumbar spine and proximal femur
provides reproducible values at important sites of
osteoporosis-associated fracture. These central sites are also more
likely than peripheral sites to show a response to treatment and are
preferred for baseline and serial measurements. The most reliable
comparative results for serial measurements are obtained when the same
instrument and, ideally, the same technologist are used.

For bone mass measurement, several other techniques (listed
alphabetically) are available:

-   Quantitative computed tomography for measurement of both central and
    peripheral sites

-   Quantitative ultrasonometry

-   Radiographic absorptiometry

-   Single-energy x-ray absorptiometry

The various BMD measurement techniques are outlined in the original
guideline document (see Table 3 titled \"Bone Mineral Density
Measurement Techniques\").

***Measurement Sites***

Peripheral measurements can identify patients with low bone mass.
*T*-scores from peripheral devices, however, are not as sensitive or
specific as those from central devices, and the risk of future fracture
depends on the skeletal site even when *T*-scores from different
skeletal sites are identical. Work is currently under way to redefine
the thresholds for peripheral devices and resolve these discrepancies.
In the meantime, peripheral measurements should be limited to the
assessment of fracture risk.

***Bone Density Reports***

Bone density data are reported as *T*-scores and *Z*-scores. *T*-scores
represent the number of standard deviations from the normal young adult
mean bone density values, whereas *Z*-scores represent the number of
standard deviations from the normal mean value for age- and sex-matched
control subjects. Results showing *Z*-scores of -2.0 or lower may
suggest a secondary cause of osteoporosis.

Bone density reports also include values for specific subregions within
the proximal femur and for specific vertebrae. Diagnostic and
therapeutic studies, cost analyses, and cost-effectiveness data,
however, are based on total hip, femoral neck, or total lumbar spine
measurements (or some combination of these measurements).

***Role in Clinical Decision-Making***

A clinical diagnosis of osteoporosis can be made without BMD testing in
women who have fragility fractures. Nevertheless, BMD measurement is
advisable in these patients to establish a baseline for assessing the
response to treatment and for quantifying fracture risk.

For women with no history of fragility fracture, the World Health
Organization (WHO) definitions of osteopenia and osteoporosis (please
refer to Table 1 titled \"World Health Organization Diagnostic Criteria
for Women without Fragility Fractures\" in the original guideline
document) represent BMD levels associated with a high risk of fracture,
as determined from prospective trials. Cutoff values, however, cannot
define a true \"fracture threshold\" or the naturally occurring limits
of a disease process because osteoporosis exerts its pathologic effects
over a continuum of bone density values.

It must also be recognized that factors other than bone density have an
important role in the pathogenesis of fractures. The increases in bone
density that result from therapeutic interventions are modest and
explain less than 50% of the observed reductions in fracture rates. When
BMD is used as a surrogate endpoint in therapeutic trials, the
relationship between bone mass and fracture rate is highly variable and
depends on the specific agent used. For example, the relationship is
reasonably strong in bisphosphonate trials, weak in raloxifene trials,
and absent in trials that have used high-dose sodium fluoride or
calcitonin. Clearly factors other than bone mass also contribute to
fracturing.

Therefore, treatment decisions for individual patients with low BMD
should be made after consideration of non-bone mass factors as well,
including the following:

-   Patient acceptance and understanding of the risks and benefits of
    the proposed treatment

-   Age (fracture risk increases with advancing age independent of bone
    density)

-   The patient\'s usual activity level and its historical effect on
    skeletal injury

-   Patient expectations and functional needs

-   Health status (for example, menopausal status and comorbidities)

-   Lifestyle (such as use of tobacco and alcohol or risk-taking
    behavior)

-   Medications (for example, postmenopausal women taking more than 7.5
    mg of prednisone or its equivalent for more than 3 months should be
    considered for a preventive strategy with use of a bisphosphonate;
    women taking levothyroxine require periodic thyrotropin
    determinations and modification of thyroid hormone dose to normalize
    serum thyrotropin, if necessary)

***Indications***

The following are recommendations intended to reflect the most effective
and efficient use of BMD measurement within the context of the endocrine
specialty practice.

BMD measurements should be performed in the following settings:

-   For risk assessment in perimenopausal or postmenopausal women who
    have risk factors for fractures and are willing to consider
    available interventions

-   In women who have x-ray findings that suggest osteoporosis

-   In women beginning or receiving long-term glucocorticoid therapy or
    other drugs associated with bone loss

-   In all adult women with symptomatic hyperparathyroidism or other
    diseases or nutritional conditions associated with bone loss in whom
    evidence of bone loss would result in adjustment of management

-   For establishing skeletal stability and monitoring therapeutic
    response in women receiving treatment for osteoporosis (baseline
    measurements should be made before intervention)

-   In all women 40 years old or older who have sustained a fracture

-   In all women beyond 65 years of age

**[Prevention of Osteoporosis]{.underline}**

Effective preventive strategies that can be implemented during skeletal
development (infancy and childhood) and in later life are needed to
minimize the physical, social, and economic consequences of
osteoporosis. The following are goals of prevention programs:

-   Optimize skeletal development and maximize peak bone mass at
    skeletal maturity

-   Prevent age-related and secondary causes of bone loss

-   Preserve the structural integrity of the skeleton

-   Prevent fractures

**General Principles**

The following general principles are applicable to all individuals,
particularly children and adolescents:

-   Promote a diet with adequate calcium content.

> Adequate calcium intake is a fundamental element of any osteoporosis
> prevention or treatment program. The recommended daily calcium intake
> for various populations is outlined in the original guideline document
> (see Table 4 titled \"Recommended Daily Calcium Intake for Various
> Populations,\" as is a guide to calcium-rich foods (see Table 5 titled
> \"Calcium Content of Various Calcium-Rich Foods\" in the original
> guideline document). Calcium supplementation should be prescribed
> whenever it is needed to achieve the recommended daily intake levels
> (see the section titled \"Pharmacologic Agents,\" below). Although
> many of the effects of supplemental calcium on the developing skeleton
> are incompletely understood, it is well recognized that supplemental
> calcium substantially increases bone mass in physically active
> children.

-   Encourage good general nutrition.

-   Promote adequate vitamin D intake (at least 400 IU/day; as much as
    800 IU per day in the elderly).

> Vitamin D is not widely available in natural food sources. It is
> primarily found in fish oils (including cod liver oil), some
> vegetables, and fortified milk, cereals, and breads. Supplements of
> 400 IU daily should be prescribed for younger adults. Supplements of
> 800 IU daily should be prescribed for elderly patients (in whom
> vitamin D absorption may be reduced), malnourished patients, patients
> with intestinal malabsorption, and patients receiving long-term
> anticonvulsant or glucocorticoid therapy.

-   Advocate regular weight-bearing exercise.

> Weight-bearing exercise enhances bone development in children and
> adolescents and may slow bone loss attributable to disuse in elderly
> persons. In addition, regular exercise promotes mobility, agility, and
> muscle strength, all of which may help prevent falls.

-   Strongly discourage use of tobacco.

> Cigarette smokers tend to be thinner, undergo earlier menopause, have
> increased catabolism of endogenous estrogen, and experience more
> fractures.

**Additional Measures**

Consider the following additional measures in specific circumstances:

-   Pharmacologic agents (in addition to calcium and vitamin D) to
    prevent bone loss in perimenopausal and postmenopausal women at high
    risk of developing osteoporosis

-   A bisphosphonate (alendronate or risedronate) for all adult women
    who will require more than 7.5 mg of prednisone or its equivalent
    for more than 3 weeks (see the section titled \"Pharmacologic
    Agents,\" below).

-   Periodic monitoring of thyroid function, and adjustment of the dose
    of thyroid hormone to normalize serum thyrotropin concentrations in
    all women receiving thyroid hormone replacement therapy for
    nonmalignant conditions

-   Identification and treatment of children and adolescents with
    constitutional delay of growth and puberty and other states or
    conditions that predispose to low peak bone mass and osteoporosis in
    later life

-   Identification of patients who have fallen or are predisposed to
    falling. Some measures to reduce the risk of falling are listed in
    Table 6 in the original guideline document. Hip protectors do not
    reduce the risk of falling. Intuitively, hip protectors should
    reduce the risk of fracture. Positive results have been seen in some
    trials, but not in all. Hip protectors should be considered for
    patients who have sustained a prior hip fracture, for slender or
    frail patients who have fallen in the past, and for patients who
    have significant risk factors for falling, such as postural
    hypotension or difficulty with balance, whether they have
    osteoporosis or not.

Additional measures, listed below, should be personalized to the needs
of each patient:

**Preventive Measures for Decreasing the Risk of Osteoporosis in
High-Risk Women**

*All Women*

Identify and remedy secondary causes (refer to Table 2 titled \"Causes
of Generalized Secondary Osteoporosis in Adults\" in the original
guideline document).

*Perimenopausal and Postmenopausal Women*

Identify and treat women with osteoporosis-related fractures and women
with low bone mass.\
Identify and treat sensory defects, neurologic disease, and arthritis,
which can contribute to frequency of falls.\
Adjust dosage of drugs with sedative effects, which could slow reflexes
or decrease coordination and impair patient\'s ability to break impact
of a fall.\
Recommend appropriate lifestyle changes, including smoking cessation,
increase in weight-bearing activities, and dietary improvements.\
Minimize risk of falls and injuries with gait and balance training.

*Elderly Women*

Same as perimenopausal and postmenopausal group plus:

Anchor rugs.\
Minimize clutter.\
Remove loose wires.\
Use nonskid mats.\
Install handrails in bathrooms and halls and along stairways.\
Light hallways, stairwells, and entrances.\
Encourage patient to wear sturdy, low-heeled shoes.

*Patients who are predisposed to falling*

Recommend hip protectors.

**[Treatment of Osteoporosis]{.underline}**

**Goals**

The following are goals of treatment of osteoporosis:

-   Prevent fractures

-   Stabilize or achieve a moderate increase in bone mass

-   Relieve symptoms of fractures and skeletal deformity

-   Maximize physical function (for example, halt progressive deformity)

The ability to achieve these goals depends on the patient\'s and the
physician\'s commitment to therapy and the potential for the chosen
therapeutic program to yield results.

**Candidates for Treatment**

The following women may benefit from pharmacologic treatment of
osteoporosis:

1.  Women with postmenopausal osteoporosis:

    -   Women with low-trauma fractures and low BMD

    -   Women with BMD *T*-scores of -2.5 and below

2.  Women with borderline-low BMD (e.g., *T*-scores of -1.5 and below)
    if risk factors are present

3.  Women in whom nonpharmacologic preventive measures are ineffective
    (bone loss continues or low-trauma fractures occur)

**Nonpharmacologic Measures**

Refer to the information provided on preventive strategies (see the
section titled \"General Principles,\" above).

**Pharmacologic Agents**

The American Association of Clinical Endocrinologists and the American
College of Endocrinology recommend the following pharmacologic agents
when pharmacotherapy is indicated:

-   **First priority**; agents approved by the U.S. Food and Drug
    Administration (FDA) for the prevention or treatment (or both) of
    osteoporosis

-   **Second priority**: agents that are not approved by the FDA but for
    which level 1 or level 2 evidence of efficacy and safety is
    available (these agents are appropriate for patients who are unable
    to take approved agents or who have complex and extenuating medical
    problems that preclude the effective use of approved agents)

Agents approved by the FDA for osteoporosis prevention and/or treatment
include (in alphabetical order) bisphosphonates (alendronate,
risedronate), salmon calcitonin, estrogen, raloxifene, and teriparatide.
All act by reducing bone resorption, except for teriparatide, which has
anabolic effects on bone. Although estrogen is not approved for
treatment of osteoporosis, there is level 1 evidence for its efficacy in
reducing vertebral fractures, non-vertebral fractures, and hip
fractures. Level 1 evidence of efficacy in reducing the risk of
vertebral fractures is available for all the agents approved for
treatment of osteoporosis (bisphosphonates, calcitonin, raloxifene, and
teriparatide). Prospective trials have demonstrated the effectiveness of
bisphosphonates and teriparatide in reducing the risk of nonvertebral
fractures (level 1), but only bisphosphonates have been shown to reduce
the risk of hip fractures in prospective controlled trials (level 1).

***Calcium and Vitamin D Supplementation***

***Role in Clinical Practice***. Adequate calcium and vitamin D intake
are fundamental to all prevention and treatment programs for
postmenopausal osteoporosis.

***Available Forms and Recommended Dosing***. The available forms and
recommended dosages of calcium supplements are outlined in the original
guideline document (see Table 7 titled \"Some Commercially Available
Calcium Preparations\"). To minimize gastrointestinal side effects and
enhance absorption, patients should take calcium in conjunction with
food (with meals or a bedtime snack).

***Duration of Treatment***. Calcium and vitamin D supplementation can
be administered safely to most women indefinitely.

***Bisphosphonates: Alendronate***

***Role in Clinical Practice***. Alendronate, a nitrogen-containing
bisphosphonate, is approved by the FDA for prevention of bone loss in
recently menopausal women, treatment of established postmenopausal
osteoporosis, and treatment of glucocorticoid-induced osteoporosis.

***Available Forms and Recommended Dosing***. The approved dosage of
alendronate for prevention of bone loss in recently menopausal women and
for treatment of corticosteroid-induced osteoporosis in men and
estrogen-replete women is 5 mg daily (or 35 mg once weekly). For
treatment of established postmenopausal osteoporosis and for treatment
of corticosteroid-induced osteoporosis in estrogen-deficient women, 10
mg of alendronate daily (or 70 mg once weekly) is the approved dosage.
Once-weekly dosing (that is, 70 mg once weekly) has been shown to be
equivalent to daily dosing (10 mg/day), as reflected by changes BMD and
biochemical markers (**Level 2 evidence**), but no fracture data are
available.

Alendronate is supplied in 5- and 10-mg tablets for daily
administration. It is also available in 35- and 70-mg tablets for
once-weekly administration for prevention and treatment of
postmenopausal osteoporosis, respectively. Alendronate should be taken
with plain water on an empty stomach, at least 1/2 hour before the first
food, beverage, or orally administered medication of the day. Taking
alendronate in conjunction with food, any beverage other than plain
water, or certain medications, or ingesting it within 2 hours after a
meal, may substantially reduce or abolish the absorption of alendronate.
In order to avoid irritation of the esophagus, alendronate should be
taken with approximately 8 ounces of water, and the patient should
remain upright (seated or standing) until food has been eaten.

***Duration of Treatment***. The therapeutic efficacy of alendronate has
been demonstrated for 7 years. Efficacy and safety beyond 7 years have
not yet been established. When alendronate therapy is discontinued, no
acceleration of bone loss relative to placebo has been noted, although
slow bone loss may occur.

***Bisphosphonates: Risedronate***

***Role in Clinical Practice***. Risedronate, a nitrogen-containing
bisphosphonate, is approved by the FDA for prevention of bone loss in
recently menopausal women, treatment of established osteoporosis, and
prevention and treatment of glucocorticoid-induced osteoporosis in men
and women.

***Available Forms and Recommended Dosing***. Risedronate is supplied as
5-mg tablets for daily administration. It is also available in 35-mg
tablets for once-weekly administration. Risedronate should be taken with
plain water on an empty stomach, at least 1/2 hour before the first
food, beverage, or orally administered medication of the day. After
taking risedronate, the patient should remain upright (seated or
standing) until food has been eaten.

***Duration of Treatment***. The therapeutic efficacy of risedronate has
been demonstrated for a 3-year period. The efficacy and safety beyond 3
years have not yet been established, and the effect of termination of
treatment on the rate of bone loss has not been assessed.

***Other Bisphosphonates***

Etidronate and pamidronate are available but have not been approved for
prevention or treatment of osteoporosis. These agents are used \"off
label\" for patients with osteoporosis.

-   ***Etidronate*** has antifracture efficacy (**Level 1 evidence**)
    and has been approved for treatment of osteoporosis in several
    countries. It is an alternative for patients who have
    gastrointestinal intolerance of approved orally administered
    bisphosphonates. Etidronate for treatment of osteoporosis is given
    in an intermittent cyclic regimen, 400 mg daily for 14 days, with
    cycles repeated every 3 months.

-   ***Pamidronate***, given by intravenous infusion, may be used for
    patients who cannot tolerate orally administered bisphosphonates or
    who may not absorb orally taken bisphosphonates because of
    gastrointestinal disease (**Level 2 evidence**). A typical treatment
    schedule for pamidronate is a loading dose of 90 mg followed by 30
    mg every third month given by intravenous infusion in dextrose or
    saline during a 2-hour period.

***Calcitonin***

***Role in Clinical Practice***. Injectable salmon calcitonin was
approved by the U.S. Food and Drug Administration for treating
osteoporosis in 1984. Its use was limited by the need for subcutaneous
injection and side effects such as nausea and flushing that occurred in
approximately 20% of subjects. Nasal spray salmon calcitonin has been
available since 1995.

***Available Forms and Recommended Dosing***. Injectable calcitonin is
available in sterile solution. For maximal effect, 100 IU/day is
administered subcutaneously or intramuscularly. Nasally administered
calcitonin is available in a spray bottle that delivers 200 IU per puff.
The recommended dosage is one spray (200 IU) daily.

***Duration of Treatment***. The optimal duration of treatment with
calcitonin (either the parenterally or the nasally administered form) is
unknown.

***Estrogen and Menopausal Hormone Therapy***

***Role in Clinical Practice***. In the United States, oral and
transdermal forms of estrogen and combined estrogen-progestin
(menopausal hormone therapy \[MHT\]) are approved for prevention of bone
loss in recently menopausal women.

***Available Forms and Recommended Dosing***. A continuous daily
estrogen regimen is recommended to prevent estrogen-deficiency symptoms
and promote compliance. A progestin should be administered
concomitantly, either cyclically or daily, in women who have not
undergone hysterectomy. A partial list of estrogens and combination
menopausal hormone therapy approved for prevention of bone loss in
recently menopausal women are shown in Table 8 of the guideline
document. Although oral estrogen is most commonly prescribed,
transdermal administration has beneficial effects on bone mineral
density (**Level 1 evidence**) and may have different effects on lipids
and coagulation factors. The usual dose of conjugated estrogens
prescribed for bone benefits has been 0.625 mg daily, but lower doses
may be of benefit.

***Duration of Treatment***. Estrogen is often prescribed for relief of
symptoms of estrogen deficiency (e.g., hot flashes, night sweats, and
vaginal dryness), symptoms that may be mild and self-limited. The risks
and benefits of estrogen in this context were not evaluated in the
Women\'s Health Initiative Menopausal Hormone Therapy study. In absolute
terms, the risks seen in the Women\'s Health Initiative are small, and
do not preclude the use of MHT for symptom relief. Women who take
estrogen or MHT for symptom relief should use the lowest dose necessary
for relief of symptoms and periodically reconsider whether or not they
need to continue MHT. Women who are currently taking estrogen or MHT
should reconsider whether or not they should continue. Women who decide
to stop estrogen or MHT should have bone mineral density testing done to
determine if adding a pharmacologic agent for prevention of bone loss or
treatment of osteoporosis is appropriate.

***Selective Estrogen Receptor Modulators***

Selective estrogen receptor modulators activate estrogen receptors in
target organs selectively to produce quantitatively variable estrogenic
effects on estrogen-responsive tissues. Raloxifene has been approved by
the FDA for prevention and treatment of postmenopausal osteoporosis.
Raloxifene has agonistic effects on bone and lipoprotein production but
has antagonistic effects on breast tissue and neutral effects on uterine
mucosa.

***Role in Clinical Practice***. Raloxifene is FDA approved for the
treatment of postmenopausal osteoporosis and the prevention of bone loss
in recently menopausal women.

***Available Forms and Recommended Dosing***. Raloxifene is available as
a 60 mg tablet. The dosage of raloxifene for prevention of bone loss in
recently menopausal women and for treatment of established osteoporosis
is 60 mg daily.

***Duration of Treatment***. Efficacy and safety have been determined
for up to 40 months.

***Teriparatide (recombinant human parathyroid hormone \[PTH\] 1-34)***

***Role in clinical practice***. The FDA has approved teriparatide for
the treatment of postmenopausal osteoporosis and in men with idiopathic
or hypogonadal osteoporosis who are at high risk for fracture or who
have failed or are intolerant to previous osteoporosis therapy.

***Available forms and recommended dosing***. The dose is 20 micrograms
daily and is injected subcutaneously. It is dispensed in a glass
cartridge, which is pre-assembled into a disposable multiple dose pen
device designed to provide 28 doses.

***Duration of treatment***. The efficacy and safety of teriparatide
have been assessed for a period of two years and are presently unknown
thereafter.

***Concomitant Use of Therapeutic Agents***

No data firmly establish that the combined use of two antiresorptive
agents (for example, bisphosphonates plus estrogen replacement therapy
or raloxifene; estrogen plus calcitonin) has an additive effect on
fracture reduction. Additive effects on bone mass and bone turnover have
been observed. Until the effect of combined therapy on fracture risk is
understood, however, the American Association of Clinical
Endocrinologists does not recommend concomitant use of these agents for
prevention or treatment of post-menopausal osteoporosis.

***Unapproved and Adjuvant Pharmaceutical Therapies***

The unapproved and adjuvant therapies for post-menopausal osteoporosis
are summarized in the original guideline document (see Table 9 titled
\"Unapproved and Adjuvant Pharmacotherapies for Postmenopausal
Osteoporosis\").

**[Follow-Up]{.underline}**

The efficacy and safety of preventive and therapeutic strategies should
periodically be reassessed, reinforced, and revised as needed. The
American Association of Clinical Endocrinologists recommends annual
reassessment, which should include the following:

-   Interim history

-   Complete medical examination, including breast and pelvic
    examinations, mammography, and Papanicolaou smear if indicated

-   Assessment of adherence to recommended program, including calcium,
    vitamin D, exercise, and any pharmacologic therapy

-   Assessment of stature and skeletal integrity, including radiographic
    assessment of new deformities or newly symptomatic osseous
    deformities

-   Reinforcement of the therapeutic program and evaluation of the
    patient\'s level of understanding and concern

-   Periodic assessment of BMD

**Bone Mineral Density for Monitoring Treatment**

Serial BMD measurements are useful for monitoring changes in bone mass.
Each technique for evaluation of bone density has an inherent
variability (i.e., precision error) that must be considered when the
clinical significance of BMD changes is assessed. With dual x-ray
absorptiometry, for example, a BMD difference between measurements must
be in the range of 3 to 5% to be clinically significant. Patients
treated with bisphosphonates often demonstrate changes of this magnitude
at the spine within a year and at the hip after 2 or more years. No
change or even a slight reduction of BMD, however, is not evidence of
treatment failure and does not warrant alteration of therapy.

Until specific data about the most efficient use of BMD for monitoring
become available, the following general guidelines for performing
follow-up BMD measurements may be used:

-   ***For patients with \"normal\" baseline BMD*** (*T*-score more than
    -1.0), consider a follow-up measurement every 3 to 5 years. Patients
    whose bone density is well above the minimal acceptable level may
    not need further bone density testing.

-   ***For patients in an osteoporosis prevention program***, perform a
    follow-up measurement every 1 to 2 years until bone mass stability
    is documented. After BMD has stabilized, perform follow-up
    measurements every 2 to 3 years.

-   ***For patients on a therapeutic program***, perform a follow-up
    measurement yearly for 2 years. If bone mass has stabilized after 2
    years, perform a follow-up measurement every 2 years. Otherwise,
    continue with annual follow-up measurements until stability of bone
    mass is achieved.

**[Definitions]{.underline}**:

**Levels of Evidence**

**Level 1 Evidence**: Recommendations were based on randomized,
prospective, double-blind studies of well-defined patient populations,
using the most relevant clinical endpoint, fracturing.

**Level 2 Evidence**: Recommendations were based on cross-sectional
studies, investigations that tested smaller or nonrandomized patient
populations, or studies that tested secondary or surrogate clinical
endpoints for fracture, such as bone mineral density (BMD) or bone
turnover markers, in treated populations.

**Level 3 Evidence**: Recommendations were based on reviews, editorials,
and expert opinions.

#### CLINICAL ALGORITHM(S)

None provided

### EVIDENCE SUPPORTING THE RECOMMENDATIONS

#### TYPE OF EVIDENCE SUPPORTING THE RECOMMENDATIONS

The type of supporting evidence is identified and graded for the
selected recommendation (see \"Major Recommendations\").

### BENEFITS/HARMS OF IMPLEMENTING THE GUIDELINE RECOMMENDATIONS

#### POTENTIAL BENEFITS

**Calcium and Vitamin D Supplementation**

Calcium (500 to 1,000 mg/day) and vitamin D (400 to 800 IU/day)
supplementation can reduce the rate of bone loss in women who are more
than 5 years postmenopausal. Fracture reduction efficacy of calcium and
vitamin D supplementation has been demonstrated in women beyond 75 years
of age.

**Alendronate Sodium**

Alendronate therapy has been shown in prospective, randomized,
double-blind, placebo-controlled trials (**Level 2 evidence**) to
prevent bone loss and increase bone mineral density (BMD) at the spine
and hip by 5 to 10%. Alendronate therapy has also been shown to prevent
bone loss at the forearm and reduce the risk of fractures of the spine
and nonvertebral sites such as the hip and wrist by 40 to 50% (**Level 1
evidence**). The effects of alendronate on BMD at the spine and hip are
maintained for at least 2 years after use of the drug is discontinued in
older, but not in younger, patients (**Level 2 evidence**). Alendronate
has also been shown to be effective for the treatment of
glucocorticoid-associated osteoporosis.

**Risedronate**

Controlled clinical trial data show that risedronate increases BMD at
the spine and hip, prevents bone loss at the forearm, and reduces the
risk of fractures of the spine, hip, and other nonvertebral sites by 30
to 50% (**Level 1 evidence**). Risedronate also preserves bone mass and
reduces the incidence of vertebral fractures in glucocorticoid-treated
patients.

**Etidronate**

Etidronate has antifracture efficacy (**Level 1 evidence**).

**Calcitonin**

Several prospective, randomized, double-blind, placebo-controlled trials
have shown modest increases in spinal BMD (**Level 2 evidence**) with
injectable calcitonin, but adequate trials to evaluate the effects of
injectable calcitonin on fracture have not been conducted.

Nasal spray salmon calcitonin was approved by the U.S. Food and Drug
Administration in 1995 for the treatment of postmenopausal osteoporosis,
on the basis of preliminary data showing effects on BMD and an ongoing
fracture trial. This 5-year trial, now completed, showed a 36% reduction
in the incidence of new vertebral fractures with use of 200 IU of
nasally administered calcitonin daily. Studies to assess the effect of
calcitonin nasal spray on hip fractures or other nonvertebral fractures
(**Level 1 evidence**) have not been conducted.

**Estrogen and Menopausal Hormone Therapy**

Prospective studies (**Level 2 evidence**) have demonstrated increases
in bone mass with estrogen and menopausal hormone therapy (MHT).
Epidemiologic evidence and meta-analyses of pooled data (**Level 2
evidence**) indicate that women exposed to estrogen therapy for more
than 7 years have a 50% lower incidence of osteoporotic fractures than
non-users. The Women\'s Health Initiative (WHI), a prospective,
randomized, placebo- controlled, double-blind trial involving over
16,000 postmenopausal women, showed a 33% reduction in vertebral
fractures, a 33% reduction in hip fractures, and a 24% overall reduction
in fractures with MHT (specifically, conjugated equine estrogen \[CEE\],
0.625 mg, plus medroxyprogesterone acetate \[MPA\], 2.5 mg daily)
compared with placebo over 5.2 years (**Level 1 evidence**). However,
even long-term estrogen users may still experience age-related bone
loss.

*Nonskeletal Effects*. A large prospective secondary prevention trial
(the Heart and Estrogen/progestin Replacement Study \[HERS\]) showed
that MHT was not associated with any significant reductions in
cardiovascular events in women with established coronary artery disease
(secondary prevention). Further, women in this study who received MHT
had more cardiovascular events during the first year of therapy. The
Women\'s Health Initiative Menopausal Hormone Therapy Trial that
demonstrated the anti-fracture benefit of MHT also showed increases in
the risks of heart attack (primary prevention), stroke, pulmonary
emboli, and breast cancer and concluded that the overall balance of
risks and benefits of MHT were unfavorable. The American Association of
Clinical Endocrinologists (AACE) recommends against prescribing MHT to
asymptomatic women to prevent or treat osteoporosis or for prevention of
heart disease or other chronic medical problems. Although the findings
of the Women\'s Health Initiative Menopausal Hormone Therapy study may
not apply to other forms and doses of MHT or estrogen without a
progestin, AACE does not recommend the use of estrogen in asymptomatic
women for skeletal or other possible benefits unless such benefits have
been established in prospective controlled studies.

**Raloxifene**

Among postmenopausal women with osteoporosis studied for 36 months,
raloxifene (60 and 120 mg daily) reduced the risk of vertebral fractures
by 30 to 50% (**Level 1 evidence**). Raloxifene did not reduce
nonvertebral fractures, but this study had insufficient statistical
power for full assessment of the effects of this agent on nonvertebral
fractures. Raloxifene increased BMD in the spine by 2.7% and in the
femoral neck by 2.4% over placebo, and it reduced bone turnover to
premenopausal levels.

*Nonskeletal Effects*. Raloxifene reduces total cholesterol and
low-density lipoprotein cholesterol fractions by about 7% and 11%,
respectively, but it has no observable effect on concentrations of
high-density lipoprotein cholesterol. The potential cardiovascular risks
or benefits of raloxifene have not been studied.

In the Multiple Outcomes of Raloxifene Evaluation (MORE) Study of 5,129
postmenopausal women with osteoporosis treated with raloxifene, a 76%
overall reduction of breast cancer and a 90% reduction in estrogen
receptor-positive breast cancer were noted in comparison with placebo. A
large study in patients at high risk for breast cancer is currently
being conducted.

**Teriparatide (Recombinant Human Parathyroid Hormone \[PTH\] I-34)**

The approved dose of teriparatide has been shown to decrease the risk of
vertebral and nonvertebral fractures in postmenopausal women by 65% and
54%, respectively, over a 19-month treatment period (**Level 1
evidence**) and to increase bone density in lumbar spine and the femoral
neck in men with idiopathic or hypogonadal osteoporosis over 11 months
(**Level 2 evidence**).

#### POTENTIAL HARMS

**Calcium and Vitamin D Supplementation**

*Side Effects*. The most common side effects of calcium and vitamin D
supplementation are gas and constipation. Hypercalciuria is unusual at
dosages of \<2 g/day.

**Alendronate Sodium**

*Side Effects*. Side effects of alendronate are generally mild and may
include gastrointestinal discomfort and headache. Safety data for longer
than 7 years of treatment are not yet available.

**Calcitonin**

*Side Effects*. Common side effects of parenterally administered
calcitonin, which occur in up to 20% of patients, include nausea, local
inflammatory reactions at the injection site, and vascular symptoms,
including flushing and tingling of the hands.

The gastrointestinal side effects noted with the parenteral form are
much less common with the nasal spray form. The major side effect of the
nasal spray is nasal discomfort, including rhinitis, irritation of the
nasal mucosa, and occasional epistaxis.

**Estrogen and Menopausal Hormone Therapy**

*Side Effects*. Women who have not undergone hysterectomy who receive
unopposed estrogen have an increased chance of developing endometrial
hyperplasia and carcinoma. When appropriate dosages of progestin are
added to the regimen, this risk diminishes and is comparable to that of
women who are not taking hormone therapy. Irregular vaginal bleeding can
occur in women who have not undergone hysterectomy and who are taking a
combined estrogen-progestin regimen. This risk may diminish with time.
Estrogen therapy increases the risk of cholelithiasis twofold. Moreover,
fluid retention, mastalgia, abdominal pain, and headache may occur but
may be ameliorated with a lower dose. There is an approximate threefold
increased risk of venous thromboembolism in women who use estrogen
compared with nonusers. The absolute risk is small (\~3 in 1,000 to 3 in
10,000). There is a small but significant increase in the risk of breast
cancer associated with menopausal hormone therapy. In the menopausal
hormone therapy arm of the Women\'s Health Initiative, combined
conjugated equine estrogen (CEE) + medroxyprogesterone acetate (MPA) was
associated with a statistically significant 26% increase in the risk of
invasive breast cancer over 5.2 years. It is not clear if unopposed
estrogen is associated with an increased risk of breast cancer.

**Raloxifene**

*Side Effects*. As with estrogen, raloxifene is associated with an
approximate threefold increase in venous thromboembolic diseases in
comparison with placebo (relative risk \[RR\] 3.1), although the
absolute risk is low. Other side effects include hot flashes, leg
cramps, peripheral edema, and accumulation of endometrial fluid in the
absence of endometrial disease.

**Teriparatide (recombinant human parathyroid hormone \[PHT\] 1-34)**

*Side Effects*. Observed side effects have been mild and transient, and
include nausea and orthostatic hypotension (which usually does not
require discontinuation, occurs within the first few doses, and responds
to assuming a recumbent posture). Transient and asymptomatic
hypercalcemia has been observed.

*Use in clinical practice*. Experience with teriparatide is limited. Its
effects in other skeletal and nonskeletal conditions and its use in
combination with most other medications is unknown. Therefore, exclusion
of coexisting conditions which might be adversely affected by this agent
should be undertaken, and pretreatment measurement of serum levels of
parathyroid hormone, 25 hydroxyvitamin D, creatinine, calcium, and
phosphorous is recommended. Monitoring patients on treatment for
hypercalcemia and hypercalciuria should be considered.

### CONTRAINDICATIONS

#### CONTRAINDICATIONS

**Calcium and Vitamin D Supplementation**

*Contraindications*. Contraindications to use of calcium supplements
include hypercalciuria (urinary calcium excretion of more than 300 mg/24
h) that cannot be controlled with a thiazide.

**Alendronate Sodium**

*Contraindications*. Contraindications to alendronate therapy include
hypersensitivity to alendronate, hypocalcemia, inability to follow the
dosing regimen (that is, inability to remain upright for at least 1/2
hour), and presence of esophageal abnormalities that might delay transit
of the tablet (e.g., achalasia or stricture). Use of alendronate is
relatively contraindicated in patients with active upper
gastrointestinal disease. Hypocalcemia and other disturbances of mineral
metabolism must be corrected before any bisphosphonate therapy is
initiated. No dose adjustment of alendronate is necessary for patients
who have mild to moderate renal insufficiency (creatinine clearance of
35 to 60 mL/min). Alendronate should be used with caution in patients
who have more severe renal insufficiency.

**Risedronate**

*Contraindications*. Contraindications to risedronate therapy include
hypocalcemia and hypersensitivity to risedronate. Hypocalcemia and other
disturbances of mineral metabolism must be corrected before initiation
of bisphosphonate therapy.

**Estrogen and Menopausal Hormone Therapy**

*Contraindications*. The following factors are contraindications to
estrogen or combination estrogen-progestin therapy:

-   Known or suspected pregnancy

-   Known or suspected cancer of the breast

-   Known or suspected estrogen-dependent neoplasia

-   Undiagnosed abnormal genital bleeding

-   Active thrombophlebitis or thromboembolic disorders or a history of
    thromboembolic disease

-   Hypersensitivity to the hormones

Side effects not tolerated by the patient, as well as a substantial and
uncontrollable increase in serum triglycerides, are valid reasons for
discontinuing estrogen or menopausal hormone therapy.

**Raloxifene**

*Contraindications*. Raloxifene is contraindicated in women who are or
are capable of becoming pregnant, who have had venous thromboembolic
disease, or who are known to be hypersensitive to any component of
raloxifene tablets.

**Teriparatide (recombinant human parathyroid hormone \[PHT\] 1-34)**

*Contraindications*. Because teriparatide caused an increased incidence
of osteosarcomas in male and female rats (but not in humans), it is
contraindicated for use in patients with Paget\'s disease, patients with
open epiphyses, patients with a history of irradiation involving the
skeleton, or patients with an undefined elevation of alkaline
phosphatase of skeletal origin.

### QUALIFYING STATEMENTS

#### QUALIFYING STATEMENTS

-   The guideline developers recognize that the process of developing
    clinical guidelines necessarily results in a narrowing and
    codification of clinical choices, which can be inappropriate in some
    clinical situations. Because the application of objective
    information to the specific needs of patients is the ultimate
    responsibility of the practicing physician, clinical practice
    guidelines are not intended to be rigid or restrictive, nor should
    they be used for the formation of public policy.

-   As a basic principle of medical decision making, The American
    Association of Clinical Endocrinologists (AACE) recognizes a
    physician\'s prerogative to refer the patient for consultation to
    qualified experts. Osteoporosis is a complex endocrinologic disorder
    of bone and mineral metabolism. Formal training in the science and
    clinical management of metabolic bone disease is a basic element of
    the endocrinologist\'s academic preparation. Therefore, the clinical
    endocrinologist is a reliable resource for primary physicians who
    seek consultation for their patients with osteoporosis and other
    metabolic bone diseases and for patients who desire subspecialty
    care. There are many circumstances where referral to an osteoporosis
    specialist would be appropriate (please refer to the original
    guideline document).

-   ***Biochemical Markers of Bone Turnover***. Currently, the precise
    role of biochemical markers in the clinical management of
    osteoporosis has not been established. Several confounding issues
    must be resolved before a clear role for these measurements can be
    determined. Age, gender, menopausal status, meals, diurnal
    variation, and certain medications all influence resorption marker
    levels and can cause extreme variability. Moreover, a relationship
    has not been demonstrated between changes in bone marker levels
    after treatment and reduced fracture risk. In addition, the
    relationship between changes in bone marker levels and bone balance
    is unclear.

-   ***Measurement Sites for Bone Mineral Density***. Peripheral
    measurements can identify patients with low bone mass. *T*-scores
    from peripheral devices, however, are not as sensitive or specific
    as those from central devices, and the risk of future fracture
    depends on the skeletal site even when *T*-scores from different
    skeletal sites are identical. Work is currently under way to
    redefine the thresholds for peripheral devices and resolve these
    discrepancies. In the meantime, peripheral measurements should be
    limited to the assessment of fracture risk.

-   ***Indications for Bone Mineral Density Testing***. The
    cost-effectiveness of bone mineral density testing and the benefits
    to society are controversial. Clinicians, politicians, patients,
    industrial interests, and third-party payers all have different
    perspectives on the indications for and timing of bone mineral
    density measurements.

### IMPLEMENTATION OF THE GUIDELINE

#### DESCRIPTION OF IMPLEMENTATION STRATEGY

An implementation strategy was not provided.

### INSTITUTE OF MEDICINE (IOM) NATIONAL HEALTHCARE QUALITY REPORT CATEGORIES

#### IOM CARE NEED

Living with Illness\
Staying Healthy

#### IOM DOMAIN

Effectiveness

### IDENTIFYING INFORMATION AND AVAILABILITY

#### BIBLIOGRAPHIC SOURCE(S)

Hodgson SF, Watts NB, Bilezikian JP, Clarke BL, Gray TK, Harris DW,
Johnston CC Jr, Kleerekoper M, Lindsay R, Luckey MM, McClung MR, Nankin
HR, Petak SM, Recker RR, Anderson RJ, Bergman DA, Bloomgarden ZT, Dickey
RA, Palumbo PJ, Peters AL, Rettinger HI, Rodbard HW, Rubenstein HA.
.American Association of Clinical Endocrinologists medical guidelines
for clinical practice for the prevention and treatment of postmenopausal
osteoporosis: 2001 edition, with selected updates for 2003. Endocr
Pract 2003 Nov-Dec;9(6):544-64.
[PubMed](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14715483)

#### ADAPTATION

Not applicable: The guideline was not adapted from another source.

#### DATE RELEASED

1996 Mar-Apr (updated 2003 Nov-Dec)

#### GUIDELINE DEVELOPER(S)

American Association of Clinical Endocrinologists - Medical Specialty
Society\
American College of Endocrinology - Medical Specialty Society

#### SOURCE(S) OF FUNDING

Financial support for this guideline was provided by Wyeth-Ayerst
Pharmaceuticals, Merck & Co., Inc., Proctor & Gamble Pharmaceuticals,
Inc., Novartis Pharmaceuticals Corp., and Eli Lilly and Company.

#### GUIDELINE COMMITTEE

Osteoporosis Task Force

#### COMPOSITION OF GROUP THAT AUTHORED THE GUIDELINE

*Osteoporosis Task Force Members*: Stephen F. Hodgson, MD, MACE
(Co-chairperson); Nelson B.Watts, MD, FACE (Co-chairperson); John P.
Bilezikian, MD, FACE; Bart L. Clarke, MD, FACE; T. Kenney Gray, MD,
FACE; David W. Harris, MD, FACE; C. Conrad Johnston, Jr., MD, FACE;
Michael Kleerekoper, MD, FACE; Robert Lindsay, MD, FACE; Marjorie M.
Luckey, MD, FACE; Michael R. McClung, MD, FACE; Howard R. Nankin, MD,
FACE; Steven M. Petak, MD, JD, FACE; Robert R. Recker, MD, FACP, FACE

*Reviewers*: Robert J. Anderson, MD, FACP, FACE; Donald A. Bergman, MD,
FACE; Zachary T. Bloomgarden, MD, FACE; Richard A. Dickey, MD, FACP,
FACE; Pasquale J. Palumbo, MD, MACE; Anne L. Peters, MD; Herbert I.
Rettinger, MD, FACE; Helena W. Rodbard, MD, FACE; Harvey A. Rubenstein,
MD, FACE

#### FINANCIAL DISCLOSURES/CONFLICTS OF INTEREST

Not stated

#### GUIDELINE STATUS

These guidelines will be continually updated to reflect the latest
advances in the prevention, diagnosis, and treatment of postmenopausal
osteoporosis. Because these changes often exceed the capability of the
American Association of Clinical Endocrinologists (AACE) printed medium,
these guidelines will be updated first on the [AACE Web
site](http://www.aace.com/).

#### GUIDELINE AVAILABILITY

Electronic copies: Available in Portable Document Format (PDF) from the
[American Association of Clinical Endocrinologists (AACE) Web
site](http://www.aace.com/pub/pdf/guidelines/osteoporosis2001Revised.pdf).

Print copies: Available from the American Association of Clinical
Endocrinologists (AACE), 245 Riverside Avenue, Suite 200, Jacksonville,
FL 32202.

#### AVAILABILITY OF COMPANION DOCUMENTS

The following is available:

-   American Association of Clinical Endocrinologists protocol for
    standardized production of clinical practice guidelines. Endocrine
    Pract 2004 Jul/Aug; 10(4):353-61.

Electronic copies: Available in Portable Document Format (PDF) from the
[American Association of Clinical Endocrinologists (AACE) Web
site](http://www.aace.com/pub/pdf/guidelines/GLStandards.pdf).

Print copies: Available from the American Association of Clinical
Endocrinologists (AACE), 245 Riverside Avenue, Suite 200, Jacksonville,
FL 32202.

#### PATIENT RESOURCES

The following is available:

-   Will your bones stand the test of time? A women\'s guide to
    osteoporosis. Jacksonville (FL): American Association of Clinical
    Endocrinologists; 2003. 2 p.

Print copies: Available from the American Association of Clinical
Endocrinologists (AACE), 245 Riverside Avenue, Suite 200, Jacksonville,
FL 32202.

Please note: This patient information is intended to provide health
professionals with information to share with their patients to help them
better understand their health and their diagnosed disorders. By
providing access to this patient information, it is not the intention of
NGC to provide specific medical advice for particular patients. Rather
we urge patients and their representatives to review this material and
then to consult with a licensed health professional for evaluation of
treatment options suitable for them as well as for diagnosis and answers
to their personal medical questions. This patient information has been
derived and prepared from a guideline for health care professionals
included on NGC by the authors or publishers of that original guideline.
The patient information is not reviewed by NGC to establish whether or
not it accurately reflects the original guideline\'s content.

#### NGC STATUS

This summary was completed by ECRI on August 28, 2001, and updated on
February 13, 2004. The updated information was verified by the guideline
developer on March 29, 2004. This summary was updated by ECRI on May 20,
2005, following the U.S. Food and Drug Administration advisory on Aredia
(pamidronate disodium) and Zometa (zoledronic acid). This summary was
updated by ECRI on June 16, 2005, following the latest U.S. Food and
Drug Administration advisory on COX-2 selective and non-selective
non-steroidal anti-inflammatory drugs (NSAIDs).

#### COPYRIGHT STATEMENT

This NGC summary is based on the original guideline, which is subject to
the guideline developer\'s copyright restrictions, as follows:

All rights reserved. No part of these materials may be reproduced or
retransmitted in any manner without the prior written permission of the
American Association of Clinical Endocrinologists/American College of
Endocrinologists.

### DISCLAIMER

#### NGC DISCLAIMER

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