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Osteoporosis
Last Updated: December 16, 2005
Synonyms and related keywords: osteoporosis, soft bones, broken hip, dowager hump, thin bones, fragile
bones, hormone replacement therapy, HRT, calcium, bone aging, brittle bones, bone loss, bone mass,
postmenopausal osteoporosis, type 1 osteoporosis, estrogen deficiency, testosterone deficiency, type 2
osteoporosis, senile osteoporosis, osteopenia, low bone mass, secondary osteoporosis, primary osteoporosis,
hypogonadism, heparin, anticonvulsants, phenytoin, barbiturates, carbamazepine, treatment-induced vitamin D
deficiency, decreased intestinal calcium absorption, secondary hyperparathyroidism, corticosteroids, decreased
calcium absorption, chemotherapeutic agents, cyclosporine A, antacids, aluminum-containing antacids, Cushing
syndrome, chronic thyrotoxicosis, prolonged immobilization, multiple myeloma, calcium deficiency, beta
thalassemia, type 3 osteoporosis
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Author: Coburn Hobar, MD, Clinician in Rheumatology, Hobar Health and Wellness, and Anti-Aging & Wellness
Center of Sarasota
Coburn Hobar, MD, is a member of the following medical societies: American Academy of Anti-Aging Medicine, and
American College of Rheumatology
Editor(s): Anne Davidson, MBBS, FRACP, Assistant Professor, Departments of Medicine and Microbiology,
Director, Rheumatology Training Program, Columbia University; Consulting Staff, Department of Medicine,
Columbia Presbyterian Medical Center; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine;
Herbert S Diamond, MD, Professor of Medicine, Temple University School of Medicine; Chairman, Department of
Internal Medicine, Western Pennsylvania Hospital; Alex J Mechaber, MD, FACP, Associate Professor, Department
of Internal Medicine, Division of General Internal Medicine, University of Miami School of Medicine; and Arthur
Weinstein, MD, Professor of Medicine, Georgetown University Medical Center; Associate Chairman, Department of
Medicine, Director, Section of Rheumatology, Washington Hospital Center

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Background: Osteoporosis is a systemic skeletal disorder characterized by decreased bone mass and deterioration
of bony microarchitecture. The result is fragile bones and an increased risk for fracture with even minimal trauma.
Osteoporosis is a chronic condition of multifactorial etiology and is usually clinically silent until a fracture occurs.
Osteoporosis is a significant health problem in the United States and around the world.
Pathophysiology: Osteoporosis results from a combination of genetic and environmental factors that affect both
peak bone mass and the rate of bone loss. These factors include medications, diet, race, sex, lifestyle, and physical
activity. Osteoporosis may be either primary or secondary. Primary osteoporosis is subdivided into types 1 and 2.
Secondary osteoporosis is also called type 3.
Type 1, or postmenopausal, osteoporosis is thought to result from gonadal (ie, estrogen, testosterone) deficiency.
Estrogen or testosterone deficiency, regardless of age of occurrence, results in accelerated bone loss. The exact
mechanisms of this bone loss potentially are numerous, but, ultimately, an increased recruitment and
responsiveness of osteoclast precursors and an increase in bone resorption, which outpaces bone formation,
occurs. After menopause, women experience an accelerated bone loss of 1-5% per year for the first 5-7 years. The
end result is a decrease in trabecular bone and an increased risk of Colles and vertebral fractures.
Evidence indicates that estrogen deficiency causes bone to become more sensitive to the effects of parathyroid
hormone (PTH), leading to an increase in calcium release from bone, a decrease in renal calcium excretion, and
increased production of 1,25-dihydroxyvitamin D (1,25[OH]2 D3). Increased production of 1,25(OH)2 D3, in turn,
causes increased calcium absorption from the gut, increased calcium resorption from bone, and increased renal
tubular calcium resorption. PTH secretion then decreases via a negative feedback effect, causing the opposite
effects. Osteoclasts are also influenced by cytokines, such as tumor necrosis factor-alpha and interleukins 1 and 6,
whose production by mononuclear cells may be increased in the presence of gonadal deficiency.
Type 2, or senile, osteoporosis occurs in women and men because of decreased formation of bone and decreased
renal production of 1,25(OH)2 D3 occurring late in life. The consequence is a loss of cortical and trabecular bone
and increased risk for fractures of the hip, long bones, and vertebrae.
Type 3 osteoporosis occurs secondary to medications, especially glucocorticoids, or other conditions that cause
increased bone loss by various mechanisms.
Frequency:
• In the US: Approximately 10 million people have osteoporosis. Another 14-18 million have osteopenia
(low bone mass).
• Internationally: According to the International Osteoporosis Foundation, osteoporosis affects
approximately 1 in 3 women and 1 in 8 men worldwide.
Mortality/Morbidity:
• In Europe, an estimated 1 in 8 persons older than 50 years experiences a spinal fracture, and 1 in 3
women and 1 in 9 men older than 80 years experiences a hip fracture due to osteoporosis.
• Approximately 1.5 million fractures per year in the United States are attributed to osteoporosis, and more
than 37,000 people die from subsequent fracture-related complications. Among women who sustain a hip
fracture, 50% spend time in a nursing home while recovering, and 14% of all patients with hip fractures
remain in nursing homes 1 year later.
• Only one third of patients return to their prefracture level of function. Patients incur a diminished quality
of life and decreased independence in daily living.
Race: Whites, especially of northern European descent, and Asians are at increased risk for osteoporosis.
Sex: In type 1 and type 2 osteoporosis, women are affected more often than men, with female-to-male ratios of
6:2 and 2:1, respectively. In type 3, both sexes are equally affected.
Age: The peak incidence of type 1 osteoporosis is in people aged 50-70 years, and the peak incidence for type 2 is
in people aged 70 years or older. Type 3 can occur in persons of any age.

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History: Osteoporosis is largely asymptomatic until a fracture occurs, although patients may note a loss of height
and gradually increasing kyphosis; therefore, prevention is a key aspect of management. Patients may present
with a fracture in a typical location, such as vertebra, proximal femur, or distal radius, after minimal trauma.
History should focus on a thorough review of risk factors, which include the following:
• Age, sex, and race
• Family history of osteoporotic fractures
• Reproductive factors, especially with regard to early menopause and estrogen replacement therapy
• Lifestyle factors associated with decreased bone density
o Strenuous exercise (such as occurs in marathon runners) that results in amenorrhea
o Smoking
o Alcohol consumption
o Low levels of physical activity
• Dietary factors, especially calcium and vitamin D intake (important because deficiencies of both increase
osteoporosis risk), and eating disorders such as anorexia nervosa
• Other medical conditions and medications, especially the use of corticosteroids
• Risk factors for falls in older patients
o Poor balance
o Orthostatic hypotension
o Weakness of the lower extremity muscles
o Diminished reaction time
o Medication use (eg, sedatives)
o Poor vision
o Cognitive impairments
Physical: Osteoporosis can occur in either a generalized or a regional form. The cardinal feature is a fracture, and
the clinical picture depends on the fracture site.
• Vertebral fracture often manifests as acute back pain after bending, lifting, or coughing or as
asymptomatic progressive kyphosis with loss of height.
o Most fractures occur in the mid-to-lower thoracic or upper lumbar spine. The pain is described
variably as sharp, nagging, or dull; movement may exacerbate pain; and, sometimes, pain
radiates to the abdomen.
o Acute pain usually resolves after 4-6 weeks. In the setting of multiple fractures with severe
kyphosis or dowager hump, the pain may become chronic. When kyphosis becomes severe, the
patient may develop a restrictive pattern of respiratory impairment.
• Forearm, hip, and proximal femoral fractures usually occur after falls, with forward falls often resulting in
Colles fractures and backward falls resulting in hip fractures.
 • Rib fractures are most often associated with osteoporosis secondary to corticosteroid use or Cushing
syndrome, but they can also be observed with other etiologies.
Causes:
• Estrogen deficiency
• In men, hypogonadism with low testosterone levels
• Impaired osteoblast function and impaired 1 alpha-hydroxylase activity in the kidneys, which result from
aging
• Medications
o Heparin (after long-term administration) - Due to an unknown mechanism
o Anticonvulsants (eg, phenytoin, barbiturates, carbamazepine) - Due to treatment-induced
vitamin D deficiency and resultant decreased intestinal calcium absorption and secondary
hyperparathyroidism
o Corticosteroids - Due to direct inhibition of bone formation, decreased intestinal absorption of
calcium, increased renal calcium excretion, secondary hyperparathyroidism, and decreased
gonadal hormone production.
o Chemotherapeutic agents (eg, cyclosporine A, which is also used in transplantation) - Have been
shown to increase bone turnover in rodent studies
o Antacids containing aluminum (after excessive use) - Due to inhibition of phosphate absorption
and disruption of bone mineralization
• Endocrinologic disorders such as Cushing syndrome (due to excessive endogenous corticosteroids) or
chronic thyrotoxicosis (due to increased resorption and increased excretion of calcium)
• Alcohol - Due to direct toxic effect on bone (Persons with alcoholism also often have poor nutritional
status.)
• Smoking - Due to increased hepatic metabolism of estrogen and direct toxic effect on bone (Persons who
smoke also may weigh less and have earlier menopause.)
• Prolonged immobilization - Such as after a stroke, resulting in bone loss
• Cancer, especially multiple myeloma (in which cytokines produced by the malignant cells activate
osteoclasts) and less often with leukemia (usually children or adolescents) or lymphoma (usually localized)
• Calcium deficiency - Resulting in increased PTH levels and increased bone resorption (Vitamin D deficiency
results in defective mineralization of bone matrix, ie, osteomalacia.)
• Gastrointestinal disorders, such as inflammatory bowel disease resulting in malabsorption, and eating
disorders, such as anorexia nervosa with resultant rapid weight loss, nutritional deficiencies, and
associated amenorrhea
• Beta-thalassemia - Due to marrow hyperplasia and thinning of the adjacent trabeculae (in addition to
secondary hypogonadism observed in these patients)
• Idiopathic
• Prolonged strenuous exercise resulting in amenorrhea

DIFFERENTIALS
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Hyperparathyroidism
Multiple Myeloma

Other Problems to be Considered:

Osteomalacia
Renal osteodystrophy
Metastases
Leukemia
Lymphoma
Osteogenesis imperfecta in children

WORKUP
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Lab Studies:
• Levels of serum calcium, phosphate, and alkaline phosphatase are usually normal in persons with primary
osteoporosis, although alkaline phosphatase levels may be elevated for several months after a fracture.
 • Checking thyroid function is prudent because abnormal values may indicate a cause of secondary
osteoporosis.
• In men, low testosterone levels can contribute to bone loss; therefore, checking testosterone levels is
important.
• Markers of bone turnover (both formation and resorption) may be elevated in high bone turnover states
(eg, early type 1 osteoporosis) and may be useful in some patients for monitoring early response to
therapy. However, further study is needed to determine their clinical utility in osteoporosis management.
Some of these biochemical measures include the following:
o Bone-specific alkaline phosphatase (bone formation)
o Osteocalcin (bone formation)
o Type I procollagen peptides (bone formation)
o Urinary deoxypyridinoline and cross-linked N- and C-telopeptide of type I collagen (bone
resorption)
Imaging Studies:
• Obtain radiographs of the affected area in patients who are symptomatic. Lateral spine radiographs are
obtained in patients who are asymptomatic and at risk for detection of vertebral fracture.
o Radiographs may show fractures or other conditions, such as osteoarthritis, disk disease, or
spondylolisthesis.
o Osteopenia (low bone density) may be apparent as radiographic lucency but is not always
noticeable until 30% of bone mineral is lost.
o Radiograph findings also depend somewhat on technique and exposure.
o Plain radiography is not as accurate as bone mineral density (BMD) testing.
• BMD testing is the best predictor of fracture risk. Although measurement at any site can be used to assess
overall fracture risk, measurement at a particular site is the best predictor of fracture risk at that site.
o According to guidelines from the National Osteoporosis Foundation, BMD should be measured in
the following people:
ƒ Postmenopausal women older than 65 years because, although preventive measures
may no longer be effective, these women are at risk and should be treated if they have
osteoporosis
ƒ Postmenopausal women younger than 65 years who have 1 or more risk factor
ƒ Postmenopausal women who present with fragility fractures
ƒ Women who are considering therapy in which BMD will affect that decision
ƒ Women who have been on hormone replacement therapy (HRT) for prolonged periods
ƒ Men who experience fractures after minimal trauma
ƒ People with evidence of osteopenia on radiographs or a disease known to place them at
risk for osteoporosis.
o BMD is reported as a T-score, which compares the patient's BMD to that of a healthy young adult.
Based on criteria proposed by the World Health Organization, a normal value is within 1 standard
deviation (SD) of a young adult, or greater than -1 SD.
ƒ T-score of -1 to -2.5 SD - By definition indicates osteopenia
ƒ T-score of less than -2.5 SD - By definition indicates osteoporosis
ƒ T-score of less than -2.5 SD with fragility fracture(s) - By definition indicates severe
osteoporosis
o Quantitative computed tomography measures BMD as a true volume density in g/cm3, which is
not influenced by bone size. This technique can be used for both adults and children. It has some
disadvantages in that (1) it only determines bone density at the spine, (2) osteophytes can
interfere with measurement, and (3) it is associated with significant radiation exposure and high
cost.
o Dual-energy x-ray absorptiometry (DEXA) requires less radiation, is less expensive, and has
better reproducibility than quantitative computed tomography. It can also measure bone density
at the spine and the hip. It has become the standard method for determining bone density.
However, differences in calibration have been noted. Whenever possible, the same technologist
should perform subsequent measurements on the same patient using the same machine. This
method can be used in both adults and children. Confounding factors in DEXA results
interpretation (falsely high bone density) include spinal fractures, osteophytosis, and extraspinal
(eg, aortic) calcification.
o Peripheral DEXA can measure BMD at the wrist.
o Quantitative ultrasonography of the calcaneus can be used for general screening; however, this is
not as accurate as other methods and thus is less useful in following response to treatment. Its
advantages include low cost, portability, and lack of ionizing radiation.
o Radiogrammetry, used to measure cortical dimensions, is usually performed on the hand,
specifically the second metacarpal. It is useful in assessing BMD in children and is the simplest
and least expensive method. It is not as precise as DEXA and, therefore, is less sensitive for
detecting changes over time.
TREATMENT
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Medical Care: Osteoporosis is largely asymptomatic until a fracture occurs. Taking steps to identify patients at risk
and implementing preventive measures, such as changes in diet and activity levels, are important.
Preventive measures should begin in childhood and adolescence, with adequate calcium intake and exercise. In
patients who must take glucocorticoids for other medical conditions, some protective measures can be
implemented. These include using the lowest dose possible, using inhaled (rather than oral) forms of
glucocorticoids, instituting alternate-day dosing of steroids, and performing muscle-strengthening exercises.
Effective medical therapy is available to help prevent and treat osteoporosis, including gonadal hormone
replacement, calcitonin, selective estrogen-receptor modulators, and bisphosphonates. However, these agents
reduce bone resorption with little, if any, effect on bone formation. Experimental evidence indicates that slow-
release sodium fluoride and low-dose PTH are capable of increasing bone formation and thus preventing bone loss
in women who are estrogen deficient. The former has also been used to decrease vertebral fracture rates. These
are not yet approved for the treatment of osteoporosis. A newer medication approved by the US Food and Drug
Administration (FDA) for the treatment of osteoporosis is an anabolic agent, recombinant human PTH (rhPTH) (1-
34), which has been shown to stimulate the formation of new bone. The newest medication to receive FDA
approval is ibandronate, a once daily oral bisphosphonate.
Surgical Care: The goals of surgical treatment of fractures are rapid mobilization and return to normal function
and activities.
Consultations:
• Orthopedist - For fixation and stabilization of hip or wrist fracture
• Rheumatologist - To assist with management and determination of underlying etiologies in complex cases
• Endocrinologist - To assist with management and determination of underlying etiologies in complex cases
Diet:
• Adequate calcium and vitamin D intake are important for persons of any age, particularly in childhood as
the bones are maturing. If dietary intake is inadequate, add supplements.
• For women who are postmenopausal, men who are older than 50 years, and other persons at risk for
osteoporosis, the recommendation is 1500 mg of calcium daily.
• For women who are premenopausal and men who are younger than 50 years without osteoporosis risk
factors, the recommendation is 1000 mg/d.
• Vitamin D intake should be 400-800 IU/d.
Activity:
• Weight-bearing exercise has been shown to have a positive effect on BMD, although the exact mechanism
is not known. Regular exercise should be encouraged in all patients, including children and adolescents in
order to strengthen the skeleton during the maturation process.
• Exercise also improves agility and balance, thereby reducing the risk of falls.
• Encourage patients to be as active as possible.
• Physical therapists can assist in developing exercise regimens, instructing patients in proper techniques,
and monitoring progress and consistency.
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Several classes of medications have been studied to prevent and treat osteoporosis. Most studies have been
conducted in women. Most of these medications are postulated to have a similar effect in men, with the exception
of estrogen replacement therapy and selective estrogen-receptor modulators.
Several studies have demonstrated a beneficial effect on BMD, or at least maintenance of bone mass, with
testosterone treatment in osteoporotic men with hypogonadism.
Calcium and vitamin D supplementation are important preventive measures.
Drug Category: Hormone replacement therapy -- These agents have been considered effective treatment and were
once considered the treatment of choice for the prevention and treatment of postmenopausal osteoporosis.
However, some controversy exists as to their effects on other systems; HRT must be avoided in women with a
history of breast cancer or blood clots and in those who are intolerant of adverse effects. Some evidence indicates
that bioidentical hormones may be safer than synthetic hormones, and this may be an option for some women,
especially if they develop symptoms of menopause such as hot flashes. In the remaining patients, other therapies
are available and effective.
Drug Name
Estrogen, conjugated (Premarin) -- Reduces bone resorption and may increase osteoblast activity.
Multiple studies have shown bone loss prevention at the spine and hip when started within 10 y of menopause (but
initiate as soon as possible) and continued for life if tolerated. Although due to safety concerns, many now
advocate stopping hormones when menopausal symptoms abate and then using other treatments.
 Adult Dose
0.625 mg PO qd
In those patients with an intact uterus, cyclical administration of 3 wk of daily estrogen and 1 wk off recommended
Pediatric Dose
Not established
Contraindications
Documented hypersensitivity; known or suspected pregnancy; breast cancer; undiagnosed abnormal genital
bleeding; active thrombophlebitis or thromboembolic disorders; history of thrombophlebitis, thrombosis, or
thromboembolic disorders associated with previous estrogen use (except when used in treatment of breast or
prostatic malignancy)
Interactions
May reduce hypoprothrombinemic effect of anticoagulants; coadministration of barbiturates, rifampin, and other
agents that induce hepatic microsomal enzymes may reduce levels; pharmacologic and toxicologic effects of
corticosteroids may occur as a result of estrogen-induced inactivation of hepatic P-450 enzyme; loss of seizure
control has been noted when administered concurrently with hydantoins
Pregnancy
X - Contraindicated in pregnancy
Precautions
Certain patients may develop undesirable manifestations of excessive estrogenic stimulation (eg, abnormal or
excessive uterine bleeding, mastodynia); may cause some degree of fluid retention (exercise caution); prolonged
unopposed estrogen therapy may increase risk of endometrial hyperplasia (combine with progesterone in women
with uterus); caution in hepatic dysfunction, women who breastfeed, gallbladder disease, bone disease associated
with hypercalcemia, and uterine leiomyomata; perform initial complete physical examination with blood pressure,
PAP smear, and mammogram and repeat annually; discontinue if jaundice or severe uncontrollable hypertension
develops; discontinue 2 wk before surgery associated with thromboembolism
Drug Name
Estradiol (Estrace, Vivelle, Climara, Estraderm, Esclim, Alora) -- Reduces bone resorption and may increase
osteoblast activity.
Multiple studies have shown it prevents bone loss at spine and hip when started within 10 y of menopause (initiate
as soon as possible after start of menopause) and continued for life if tolerated.
Adult Dose
0.1 mg PO qd in cyclic regimen of 3 wk on and 1 wk off
Transdermal: Initiate with patch that releases at least 0.05 mg/d, adjust dosage prn to control concurrent
menopausal symptoms
Pediatric Dose
Not established
Contraindications
Documented hypersensitivity; pregnancy; breast cancer; thrombophlebitis; undiagnosed vaginal bleeding
Interactions
May reduce hypoprothrombinemic effects of anticoagulants; levels may be reduced with coadministration of
barbiturates, rifampin, and other agents that induce hepatic microsomal enzymes; an increase in corticosteroid
levels may occur when administered concurrently with ethinyl estradiol; use of ethinyl estradiol with hydantoins
may cause spotting, breakthrough bleeding, and pregnancy; increase in fluid retention caused by estrogen intake
may reduce seizure control
Pregnancy
X - Contraindicated in pregnancy
Precautions
Unopposed estrogen is associated with endometrial hyperplasia and endometrial carcinoma in women with a uterus
(combine estrogen with progesterone in these patients); hepatic dysfunction; conditions aggravated by fluid
retention; gallbladder disease; bone disease associated with hypercalcemia; uterine leiomyomata; perform initial
complete physical examination with blood pressure, PAP smear, and mammogram (repeat annually); discontinue if
jaundice or severe, uncontrollable hypertension develops; discontinue 2 wk before surgery associated with
thromboembolism; caution in women who breastfeed
Drug Name
Ethinyl estradiol and norethindrone (FemHrt) -- Used to treat moderate-to-severe vasomotor symptoms associated
with menopause.
Adult Dose
1 tab PO qd
Pediatric Dose
Not established
Contraindications
Documented hypersensitivity, endometrial and hepatic cancer; thromboembolic disorders; undiagnosed vaginal
bleeding; smoking in those >35 y; cardiovascular disease
Interactions
Phenobarbital, phenytoin, paramethadione, carbamazepine, troglitazone, rifampicin, and griseofulvin induce
enzymes that reduce levels of contraceptive steroids; oral anticoagulants may increase thromboembolic potential
 Pregnancy
X - Contraindicated in pregnancy
Precautions
Caution in patients diagnosed with hepatic impairment, migraine, seizure disorders, cerebrovascular disorders,
breast cancer, or thromboembolic disease
Drug Category: Bisphosphonates -- These agents inhibit bone resorption and increase BMD. Their mechanism is not
fully understood, but they are speculated to alter function and activation of osteoclasts. They should be avoided in
patients who are pregnant or planning to become pregnant because long-term effects are unknown.
Drug Name
Alendronate (Fosamax) -- Has been shown to reduce bone resorption and prevalence of fracture at spine, hip, and
wrist by approximately 50%. Is treatment of choice for prevention of glucocorticoid-induced osteoporosis in
premenopausal women.
Adult Dose
Prevention: 5 mg PO qd
Treatment: 10 mg PO qd or 70 mg PO qwk
Pediatric Dose
Not recommended
Contraindications
Documented hypersensitivity; inability to stand or sit upright for at least 30 min; hypocalcemia; esophageal
abnormalities (eg, stricture, achalasia) that might delay esophageal emptying
Interactions
Coadministration with calcium-containing products and other multivalent cations decreases absorption (separate
dosing by 30 min); increased GI distress with aspirin, NSAIDs, or other GI irritants
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Upper GI disease; renal insufficiency (CrCl <35 mL/min); treat disturbances of mineral metabolism; ensure
adequate vitamin D and calcium intake; discontinue if esophageal reaction (eg, dysphagia, odynophagia,
retrosternal pain, worsening heartburn) occurs; not for use in women who breastfeed
Drug Name
Risedronate (Actonel) -- Shown to reduce bone resorption and increase BMD of spine by 5% and femoral neck by
1.6%. Also shown to reduce prevalence of vertebral fracture by 41% and nonvertebral fracture by 39% over 3-y
period in postmenopausal women.
Adult Dose
5 mg PO qd
Pediatric Dose
Not recommended
Contraindications
Documented hypersensitivity; hypocalcemia; inability to stand or sit upright for at least 30 min
Interactions
Coadministration with calcium-containing products and other multivalent cations decreases absorption (separate
dosing by 30 min); caution with aspirin, NSAIDs, or other GI irritants
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Upper GI disease; renal insufficiency (CrCl <30 mL/min); correct any preexisting hypocalcemia or other mineral or
bone disturbances prior to starting therapy; ensure adequate vitamin D and calcium intake; discontinue if
esophageal reaction (eg, dysphagia, odynophagia, retrosternal pain, worsening heartburn) occurs; not for use in
women who breastfeed
Drug Name
Etidronate (Didronel) -- Reduces bone resorption and does not alter renal tubular reabsorption of calcium. First-
generation bisphosphonate that has been shown to increase bone density at spine and femoral neck, although
studies have failed to demonstrate a decrease in fractures.
Approved for treatment of osteoporosis in several countries, including Canada, but not in United States.
Adult Dose
400 mg PO qd for 14 d q3mo (hold calcium during 14-d course)
Pediatric Dose
Not established
Contraindications
Documented hypersensitivity; hypocalcemia; renal impairment; osteomalacia
Interactions
Coadministration with calcium-containing products and other multivalent cations decreases absorption (separate
dosing by 2 h)
Pregnancy
B - Usually safe but benefits must outweigh the risks.
Precautions
Monitor hypercalcemia-related parameters (eg, serum levels of calcium, phosphate, magnesium, potassium);
maintain adequate intake of calcium and vitamin D to prevent severe hypocalcemia; caution in active upper GI
problems; do not administer with alendronate for osteoporosis in postmenopausal women; not for use in women
who breastfeed
Drug Name
Ibandronate (BONIVA) -- Inhibits osteoclast-mediated bone resorption. In postmenopausal women, reduces bone
turnover rate, leading to net gain in bone mass.
Adult Dose
2.5 mg PO qd; administer with water at least 1 h prior to first food or beverages (other than water) of day
Pediatric Dose
Not established
Contraindications
Documented hypersensitivity; uncorrected hypocalcemia; inability to stand or sit upright for at least 60 min
following drug administration
Interactions
Multivalent cations (eg, calcium, aluminum, magnesium, iron) decrease absorption, administer at least 1 h prior to
vitamin and mineral supplements; NSAIDs may aggravate GI irritation
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
May cause upper GI disorders (eg, dysphagia, esophagitis, ulceration), minimize GI risk by standing or sitting
upright 1 h following dose; calcium and vitamin D supplementation required; not recommended with severe renal
impairment (ie, CrCl <30 mL/min)
Drug Category: Androgens -- Studies have shown that testosterone replacement in men with severe deficiency
increases spinal, but not hip, BMD. These agents are presumed to act as an antiresorptive agent.
Drug Name
Testosterone injection (Andro LA 200, Depotest 200) -- Indicated for treatment of hypogonadism with low BMD.
Adult Dose
200 mg IM q2-4wk
Pediatric Dose
Not recommended
Contraindications
Documented hypersensitivity; women with breast cancer; men with breast or prostate cancer
Interactions
None reported
Pregnancy
X - Contraindicated in pregnancy
Precautions
Caution in renal impairment and elderly patients; may increase risk of prostatic hyperplasia; monitor PSA; may
increase growth of subclinical prostate carcinoma; discontinue if edema or jaundice occurs; monitor liver function,
hemoglobin, hematocrit, and cholesterol; ensure adequate calcium and vitamin D intake
Drug Name
Testosterone topical (Androderm) -- Indicated for treatment of hypogonadism with low BMD.
Adult Dose
5-7.5 mg/d topically, rotate application sites
Pediatric Dose
Not recommended
Contraindications
Documented hypersensitivity; women with breast cancer; men with breast or prostate cancer
Interactions
May potentiate oral anticoagulants and oxyphenbutazone; may alter insulin effects
Pregnancy
X - Contraindicated in pregnancy
Precautions
Caution in renal impairment and elderly patients; may increase risk of prostatic hyperplasia; monitor PSA; may
increase growth of subclinical prostate carcinoma; discontinue if edema or jaundice occurs; monitor liver function,
hemoglobin, hematocrit, and cholesterol; ensure adequate calcium and vitamin D intake
Drug Category: Parathyroid hormone -- This agent promotes new bone formation, leading to increased BMD.
Teriparatide is a biological product containing a portion of human PTH, which primarily regulates calcium and
phosphate metabolism in bones. Teriparatide is approved for men or women at high risk of fracture due to primary
or hypogonadal osteoporosis or postmenopausal osteoporosis, respectively.
Drug Name
Teriparatide (Forteo) -- rhPTH (1-34) that has identical sequence to 34 N-terminal amino acids (biologically active
region) of 84-amino acid human PTH. Acts as endogenous PTH, thus regulating calcium and phosphate metabolism
in bone and kidney. Works primarily to stimulate new bone by increasing number and activity of osteoblasts (bone-
forming cells). Additional physiological actions include regulation of bone metabolism, renal tubular reabsorption of
calcium and phosphate, and intestinal calcium absorption. When administered with calcium and vitamin D,
increases BMD and decreases risk of fractures in patients with osteoporosis.
Adult Dose
20 mcg SC qd
Pediatric Dose
Not established
Contraindications
Documented hypersensitivity; increased risk for osteosarcoma (including those with Paget disease of bone or
unexplained elevations of alkaline phosphatase, open epiphyses, or prior radiation therapy involving skeleton);
children or growing adults; patients with bone metastases or history of skeletal malignancies and those with
metabolic bone diseases other than osteoporosis
Interactions
None reported
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Monitor for hypercalcemia; may cause orthostatic hypotension (particularly following first several doses), dizziness,
or leg cramps
Drug Category: Selective estrogen-receptor modulators -- These agents act as weak estrogens in some organ
systems, while acting as estrogen antagonists in others. Provide protection against osteoporosis, coronary artery
disease, and breast and endometrial cancer.
Drug Name
Raloxifene (Evista) -- Nonsteroidal benzothiophene that acts as estrogen agonist on bone, decreasing bone
resorption. Shown to increase BMD at spine and hip but to a lesser extent than estrogen therapy.
Recommended for use in women at moderate risk for osteoporosis who are unwilling or unable to take estrogen,
who have infrequent vasomotor symptoms of menopause (eg, hot flashes), and who are at low risk for
cardiovascular disease and moderate-to-high risk for breast cancer.
Studies demonstrate 40-50% risk reduction in vertebral fracture.
Adult Dose
60 mg PO qd
Pediatric Dose
Not recommended
Contraindications
Documented hypersensitivity; thrombophlebitis; pregnancy
Interactions
May antagonize warfarin; avoid with anion exchange resins (eg, cholestyramine); caution with other drugs that are
highly protein bound (eg, diazepam, diazoxide, lidocaine)
Pregnancy
X - Contraindicated in pregnancy
Precautions
Not for use in premenopausal women; not recommended for use with concomitant estrogen replacement therapy;
discontinue 72 h before prolonged immobilization or surgery associated with thromboembolism and resume once
fully ambulatory; hepatic dysfunction; not recommended for use in women who breastfeed
Drug Category: Calcitonin-salmon -- This agent is a peptide hormone used to treat and prevent osteoporosis in
patients in whom bisphosphonates and estrogen are contraindicated or not tolerated. Also has an analgesic effect
in fractures.
Drug Name
Calcitonin (Miacalcin, Calcimar, Cibacalcin) -- Inhibits osteoclast activity, thereby slowing bone loss. Available in
parenteral and intranasal forms; however, intranasal form is more convenient and better tolerated. Diminution of
benefit may occur after 20 mo with parenteral form.
Adult Dose
200 IU (1 puff) qd in alternating nostrils
100 IU IM/SC qod
Pediatric Dose
Not established
Contraindications
Documented hypersensitivity
Interactions
May potentiate oral anticoagulants and oxyphenbutazone; may alter insulin effects
Pregnancy
B - Usually safe but benefits must outweigh the risks.
Precautions
Perform periodic nasal examinations and discontinue if severe ulceration occurs with nasal spray use; monitor for
hypocalcemic tetany initially and urine sediments over long term with injectable use; hypocalcemia may occur
(supplement with calcium and vitamin D); examine urine sediment during prolonged therapy; caution in women
who breastfeed
FOLLOW-UP
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Further Outpatient Care:

• Follow-up BMD (ie, DEXA) studies should be performed approximately every 1-2 years in patients being
treated for osteopenia or osteoporosis.
• In some patients with high bone turnover, markers of bone formation or resorption indicate a reduction
from previously high levels within a few months of successful therapy.
Deterrence/Prevention:
• Prolonged prevention of bone loss has been shown to occur when women are administered estrogen
replacement therapy beginning soon after menopause and continuing it for at least 5 years. However,
because of recent concerns about the effects of other bodily systems, including the cardiovascular system,
the use of HRT in postmenopausal women is controversial.
• To prevent bone loss, immediately start patients with diseases known to cause osteoporosis or patients
who take medications known to cause osteoporosis on preventive therapies, such as calcium, vitamin D,
and bisphosphonates or calcitonin.
Complications:
• The most serious consequences of osteoporosis are fractures and, in some patients, death resulting from
postfracture complications.
• Respiratory compromise can occur in patients with multiple vertebral fractures resulting in severe
kyphosis.
Prognosis:
• Every year, an estimated 37,500 patients die from osteoporotic fracture-related complications.
• Half the women who sustain a hip fracture in a given year spend time in a nursing home while recovering,
and 14% of all patients with hip fractures remain in nursing homes 1 year after the fracture.
• Only one third of patients return to their prefracture level of function. Patients incur a diminished quality
of life and decreased independence in daily living.
Patient Education:
• Educate patients about osteoporosis and encourage them to follow preventive measures, including
adequate calcium and vitamin D intake, exercise, cessation of smoking, and moderation of alcohol
consumption.
• For excellent patient education resources, visit eMedicine's Bone Health Center; Eating Disorders Center;
Esophagus, Stomach, and Intestine Center; and Women's Health Center.
Also, see eMedicine's patient education articles Osteoporosis, Understanding Osteoporosis Medications,
Anorexia Nervosa, Inflammatory Bowel Disease, Menopause, and Hormone Replacement and
Osteoporosis.

MISCELLANEOUS
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Medical/Legal Pitfalls:
• Osteoporosis is a preventable disease with potentially devastating consequences. Failure to identify
patients at risk, to educate them, and to implement preventive measures may cause legal pitfalls.
Special Concerns:
• Identify the underlying etiology whenever possible, and treat the underlying cause in addition to the
osteoporosis.
• In pediatric patients, the treatment of osteoporosis consists of ensuring adequate calcium intake, vitamin
D supplementation when needed, and supportive care.
• Institute screening and preventive measures immediately in patients who will be taking medications
known to induce osteoporosis, including glucocorticoids, and in patients with diseases known to put them
at risk. Preventive measures include adequate calcium, vitamin D, and exercise. Also, consider starting
bisphosphonates or other medications early if BMD is noted to be decreasing, even if the patient does not
yet meet the criteria for osteoporosis.

BIBLIOGRAPHY
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Bibliography
 • Finkelstein JS, Klibanski A, Arnold AL, et al: Prevention of estrogen deficiency-related bone loss with
human parathyroid hormone-(1-34): a randomized controlled trial. JAMA 1998 Sep 23-30; 280(12):
1067-73[Medline].
• Gambacciani M, Ciaponi M: Postmenopausal osteoporosis management. Curr Opin Obstet Gynecol 2000
Jun; 12(3): 189-97[Medline].
• Gregg EW, Pereira MA, Caspersen CJ: Physical activity, falls, and fractures among older adults: a review of
the epidemiologic evidence. J Am Geriatr Soc 2000 Aug; 48(8): 883-93[Medline].
• Heinemann DF: Osteoporosis. An overview of the National Osteoporosis Foundation clinical practice guide.
Geriatrics 2000 May; 55(5): 31-6; quiz 39[Medline].
• Iqbal MM: Osteoporosis: epidemiology, diagnosis, and treatment. South Med J 2000 Jan; 93(1): 2-
18[Medline].
• Kenny AM, Prestwood KM: Osteoporosis. Pathogenesis, diagnosis, and treatment in older adults. Rheum
Dis Clin North Am 2000 Aug; 26(3): 569-91[Medline].
• Lane NE: An update on glucocorticoid-induced osteoporosis. Rheum Dis Clin North Am 2001 Feb; 27(1):
235-53[Medline].
• Lim PA, Brander VA, Kaelin DL, Oh TH: Rehabilitation of orthopedic and rheumatologic disorders. 1.
Osteoporosis. Arch Phys Med Rehabil 2000 Mar; 81(3 Suppl 1): S55-9; quiz S78-86[Medline].
• Sambrook PN, Dequeker J, Rasp HH: Osteoporosis. In: Klipper JH, Dieppe PA, eds. Rheumatology. 2nd ed.
London, UK: Mosby-Year Book; 1998: 8.
• Watts NB: Treatment of osteoporosis with bisphosphonates. Rheum Dis Clin North Am 2001 Feb; 27(1):
197-214[Medline].
NOTE:
Medicine is a constantly changing science and not all therapies are clearly established. New research changes drug
and treatment therapies daily. The authors, editors, and publisher of this journal have used their best efforts to
provide information that is up-to-date and accurate and is generally accepted within medical standards at the time
of publication. However, as medical science is constantly changing and human error is always possible, the
authors, editors, and publisher or any other party involved with the publication of this article do not warrant the
information in this article is accurate or complete, nor are they responsible for omissions or errors in the article or
for the results of using this information. The reader should confirm the information in this article from other
sources prior to use. In particular, all drug doses, indications, and contraindications should be confirmed in the
package insert. FULL DISCLAIMER
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