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Osteoporosis is a condition of low bone mass and deterioration of bone
tissue leading to bone fragility and potentially fracture with many
preventable and inherent risk factors.
Prevention and treatment of osteoporosis focus on modifying preventable
risk, providing adequate dietary supplementation of calcium and vitamin
D, increasing bone mineral density, and reducing fracture rates.
Pharmacologic therapy is reserved for those patients with a hip or
vertebral fracture, individuals with a T-score less than or equal to −2.5
at the femoral neck or spine once secondary causes have been
excluded, and individuals with low bone mass with a 10-year probability
of greater than or equal to 3% risk of hip fracture or greater than or
equal to 20% risk of major osteoporotic fracture.
Initial therapy with oral bisphosphonates is recommended unless patients
are unable to take or have relative contraindications to oral
Estrogen/progesterone therapy, selective estrogen receptor modulators,
parathyroid hormone, denosumab, and calcitonin are alternative
therapies for prevention and/or treatment of postmenopausal
Duration of treatment with antiresorptive and/or anabolic therapy has
remained controversial, secondary to concerns for oversuppression of
bone turnover markers and the potential for the development of
Prevention and treatment of osteoporosis secondary to prolonged
glucocorticoid therapy should be incorporated into a patient’s treatment
plan with considerations for dosage and duration of glucocorticoid
therapy, the patient’s individual risk factors, sex, and age.
Pharmacologic therapies to be considered for osteoporosis treatment in
men include oral and intravenous bisphosphonates and parathyroid
Osteoporosis is a well-recognized disorder of reduced bone strength leading to an
increased risk of fractures. It is the most common bone disease in humans,
characterized by low bone mass and a deterioration of bone tissue.
Osteoporosis is considered a silent disease and can progress without symptoms
1 Fractures and their complications make osteoporosis a major
2 Fractures of the spine, hip, and wrist are the most common
and may be followed by a complete recovery, considerable pain and disability, or
1 Consequences of an osteoporosis fracture are physical, financial, and
psychological. The considerable morbidity and mortality from these fractures create
Osteoporosis can be classified as primary or secondary. Primary osteoporosis is
the deterioration of bone mass that is not associated with other chronic conditions
and is associated with natural aging and decreased gonadal function.
women experience osteoporosis. Age-related bone loss begins in the sixth decade of
life. Bone loss is accelerated in women in the late perimenopausal period and first
4 Conditions that contribute to primary osteoporosis are
prolonged periods of inadequate calcium intake, sedentary lifestyle, and tobacco and
alcohol abuse. Secondary osteoporosis is the deterioration of bone mass that is
associated with chronic conditions or from the use of various medications.
Secondary causes of osteoporosis are listed in Table 110-1 and include nutritional
deficiencies, endocrine disorders such as hyperparathyroidism and diabetes mellitus,
malignancies, gastrointestinal diseases, renal failure, connective tissue diseases, and
medications, which include anticonvulsant therapy, long-term glucocorticoid therapy,
or long-term proton pump inhibitors.
Risk Factors Associated with the Development of Osteoporosis
Predisposing medical problems (e.g., chronic liver disease, chronic
renal failure, hyperthyroidism, primary hyperparathyroidism,
Cushing syndrome, diabetes mellitus, anorexia nervosa,
gastrointestinal resection, malabsorption, vitamin D deficiency,
irritable bowel disease, chronic obstructive pulmonary disease,
spinal cord injury, Parkinson disease, and human immunodeficiency
Early menopause or oophorectomy
Drugs (e.g., corticosteroids, long-term anticonvulsant therapy
[phenytoin or phenobarbital], aromatase inhibitors, gonadotropin-
releasing hormone [GnRH] analogs, depot medroxyprogesterone,
therapy, proton pump inhibitors, H2
receptor antagonists, excessive
use of aluminum-containing antacids)
The standard method of identifying osteoporosis is the measurement of bone
mineral density (BMD) at either the femur neck region of the proximal femur (hip) or
2,6 The World Health Organization (WHO) uses a defined criteria to
diagnose osteoporosis that has been widely accepted.
deviations or more below the average value for young healthy women, a T-score of
less than −2.5 SD, is considered osteoporosis and an effective method to identify
patients at increased risk for fracture. As the T-score decreases, the risk for fracture
increases. A T-score between −2.5 and −1 is defined as osteopenia, but is better
referred to as low bone mass or low bone density. A T-score greater than or equal to
−1 is considered normal. The National Osteoporosis Foundation (NOF) clinician
guidelines include this measurement of BMD in the diagnosis of osteoporosis, but
also states that the occurrence of adulthood hip or vertebral fracture in the absence of
major trauma can be considered osteoporosis without the measurement of BMD.
Although the fracture rate is lower than in osteoporosis, the majority of fractures
occur in patients with low bone mass. The prevalence of low bone mass is higher
than osteoporosis, and therefore, it is important to monitor for clinical risk factors to
Osteoporosis is a global concern estimated to affect more than 200 million people
8 The prevalence of osteoporosis and the risk of fracture increase with
age and vary by race and ethnicity. The risk of hip fracture is greatest in Northern
Europe, Australia, and North America.
9 According to data from the United States
National Health and Nutrition Examination Survey (NHANES), 2005 to 2008, 9% of
adults aged 50 years and over had osteoporosis, as defined above, at either the
10 Forty-nine percent had low bone mass at either the
femur neck or lumbar spine and 48% had normal bone mass at both sites. In 2010,
using data from NHANES 2005 to 2010 and the 2010 US Census, it was estimated
that 10.3% or 10.2 million adults in the same age range had osteoporosis and 43.9%
or 43.4 million adults had low bone mass.
11 Almost 80% of the affected population
are women. Osteoporosis at either the femur neck or lumbar spine ranged from 7% to
35% in women and 3% to 10% in men. Prevalence increased with each decade after
the age of 50 years in women, but not until the age of 80 years in men.
prevalence of low bone mass at either the femur neck or lumbar spine in adults aged
50 years and over ranged from 54% to 67% in women and 32% to 60% in men. The
prevalence of low bone mass in women increased with age until age 70 years and
then remained stable. In men, the prevalence of low bone mass did not increase with
age until aged 70 years and increased progressively thereafter.
The National Health and Nutrition Examination Survey, 2005 to 2008, provides a
separate estimate of osteoporosis and low bone mass by race and ethnicity in three
10 The number of individuals with osteoporosis or low bone mass
was highest among non-Hispanic white women and men. The prevalence or rate,
however, was highest among Mexican Americans compared to non-Hispanic white
persons and non-Hispanic black persons. Non-Hispanic black persons had the lowest
rate of either osteoporosis or low bone mass at the femur neck or lumbar spine.
Approximately 50% of Caucasian women and 20% of men will sustain an
osteoporosis-related fracture in their lifetime.
1 The risk of fracture is highest in
Caucasian women, followed by Asian, African American, and Hispanic women.
clinical impact of osteoporosis is reflected in the impact of these fractures. More
than 1.5 million fractures per year occur in the United States that are attributed to
12 Estimated costs range from 14 to 20 billion dollars each year and
include more than 432,000 hospital admissions, 180,000 nursing home admissions,
and almost 2.5 million medical office visits.
1,12 Hip fractures account for almost
three-fourths of the total cost of osteoporosis-related care, yet represent only 14% of
the incident fractures. Hip fractures have a profound impact on the quality of life and
a considerable associated mortality. The mortality during the first year after hip
fracture is as high as 36% with a higher mortality in men than women.
2.5-fold increased risk of future fractures relative to persons of the same sex and
similar age without fractures. In addition, hip fractures result in a multitude of
complications for the elderly, including prolonged hospitalization, decreased
independent living, depression, fear of future falls, and lifelong disability. An
estimated 20% require long-term nursing home placement and approximately 60%
are unable to regain their prefracture level of independence. Vertebral fractures may
be painless or result in pain that usually lasts less than 3 months. The initiating injury
may be as minor as a cough or turning over in bed. The risk of additional vertebral
fractures is high. Vertebral collapse or deformity can result in loss of height,
kyphosis, abdominal protuberance, or decreased pulmonary function as the
abdominal cavity is shortened, chronic back pain, decreased mobility, or mortality.
The rates of osteoporosis and low bone mass have recently declined, but the total
numbers of men and women with osteoporosis and low bone mass remain high.
total number of 53.6 million adults over the age of 50 years with osteoporosis or low
bone mass could potentially increase by 30% in the year 2030 based on the trends
from 2005 to 2010. The impact of osteoporosis on the healthcare system, rising
healthcare costs, in an aging population is potentially staggering.
Eighty percent of bone that makes up the adult human skeleton is cortical bone, a
13 Twenty percent is trabecular bone which is less dense than
cortical bone and often referred to as spongy or cancellous bone. Cortical bone forms
the outer shell as a protector of the marrow space and trabecular bone forms the
interior structures in the bone marrow compartment, forming in a honeycombed
fashion. Depending on location, bone consists of varied ratios of cortical to
cancellous bone leading to differences in hardness and porosity.
The bones of the skeleton help to support and protect the body and undergo cycles
of modeling (reshaping) and remodeling (renewal) to remove older bone and to
replace it with stronger newly formed bone.
In young healthy bone, a balance
between osteoblast and osteoclast activity results in a continuous remodeling
process. Osteoclasts resorb old bone by increasing enzymes that dissolve bone
proteins and mineral, and osteoblasts help reform bony surfaces and fill bony
cavities by synthesizing a bony matrix that is made up of collagen and other
13,14 Bone minerals deposit into the bony matrix and calcify strengthening
newly formed bone. When the rate of resorption or removal exceeds the rate of
replacement, the resulting bone loss decreases bone strength and increases the risk of
Bone mass peaks between ages 18 and 25 and begins to gradually decrease
beginning at approximately age 30.
15 This slow, age-related bone loss phase leads to
a 20% to 30% loss of cortical bone and a loss of 20% to 30% of cancellous bone in
both men and women over a lifetime.
During menopause, women undergo an additional phase of bone mineral density
(BMD) loss. Unlike the slow age-related phase, this phase is rapid and leads to a
loss of 20% to 30% of cancellous and 5% to 10% of cortical bone due to the decline
in 17β-estradiol concentrations. Early cancellous bone loss in conjunction with
postmenopausal decreases in cortical and cancellous bone may lead to increased
vertebral and distal forearm fractures, which may be seen early after
In addition, women may have an increased risk for osteoporosis because
throughout life they have 30% less bone mass than men of similar age.
Hormone-related, accelerated bone loss can also occur after surgical
In males, androgens and estrogens play a role in the growth and development of
19,20 Serum testosterone concentrations have been evaluated in many studies and
its effects on bone metabolism have been controversial. Data suggest that testosterone
has a direct beneficial effect on bone, but to a lesser extent than estrogen, and
decreases in bioavailable estrogen due to age-related changes may be responsible for
Other hormones regulated by the hypothalamic–pituitary–gonadal axis (e.g.,
progesterone, follicle-stimulating hormone, inhibins, oxytocin, and prolactin) have
been studied for their effects on the skeletal system.
Bone remodeling in humans occurs constantly, replacing the adult human skeleton
22 This is a complex process that involves a balance of
local and systemic regulators to form discrete skeletal foci or bone remodeling
The receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin
are local regulators that determine the formation, activation, and resorption of
Osteoblast-derived RANKL binds to the osteoclast RANK receptor and facilitates
osteoclast differentiation and resorptive activity. The B cells produce a decoy
receptor osteoprotegerin (OPG) that competitively antagonizes RANKLby binding to
it and preventing osteoclast stimulation. This process begins with bone resorption
that is initiated by osteoclasts excavating lacuna found on the surface of cancellous
bone, or it occurs when cavities are formed in cortical bone (Fig. 110-1).
Figure 110-1 The bone remodeling cycle at the cellular level.
Enzymes, specifically transforming growth factor-β (TGF-β), produced in this
process dissolve bone mineral and proteins serving as a chemoattractant for
osteoblast precursors to the sites where resorption has occurred.
in the bones, have growth factors that display direct and indirect effects on bone
turnover. This occurs as collagen fills in bone cavities, which then are calcified.
Calcium and vitamin D are important nutrients required for bone growth.
Parathyroid hormone (PTH), glucocorticoid hormones, calcitonin, estrogen, and
testosterone are all factors involved in bone remodeling.
glucocorticoid hormones have been associated with bone resorption, whereas
calcitonin, estrogen, and testosterone have been associated with bone formation.
Dietary calcium is absorbed in the gastrointestinal tract. The kidneys reabsorb
calcium in the tubular system, and the skeletal system serves as a reservoir for
calcium. Calcium is primarily regulated by the actions of PTH, vitamin D, and
calcitonin. The parathyroid gland releases PTH in response to low serum calcium
levels, which in turn facilitates the mobilization of calcium and phosphate from bone
and stimulates reabsorption of calcium through the tubular system in the kidneys.
Vitamin D aids in intestinal absorption of calcium, phosphorus, and magnesium.
Increases in vitamin D levels decrease PTH levels. Vitamin D also increases bone
resorption to prevent symptomatic hypocalcemia. Calcitonin is released in response
to high serum calcium levels. Calcitonin decreases intestinal absorption of calcium
and phosphorus, enhances calcium excretion in the kidneys, and prevents bone
Osteoporosis is a condition of low bone mass and deterioration of bone tissue with a
high-risk factor for fracture. Prevention, identification, and treatment of osteoporosis
should all be incorporated into primary health care. Preventive measures to reduce
fracture risk include adequate intake of daily calcium and vitamin D. Lifestyle
modifications that are universally recommended are weight-bearing exercise,
reduced alcohol consumption, and smoking cessation. Fall prevention strategies are
also universal suggestions. These recommendations apply to both men and women.
Pharmacologic treatment should be considered in patients with low-trauma hip or
vertebral fracture, patients with a T-score of ≤ −2.5, and patients with low bone
mass who are at increased risk for fracture. Medications include selective estrogen
receptor modulators (SERMs; e.g., raloxifene) and calcitonin in women,
bisphosphonates (e.g., alendronate), RANKL inhibitors (e.g., denosumab), and
parathyroid hormone for both men and women. Testosterone therapy is recommended
for men at high risk for fracture with low testosterone levels (<200 ng/dL or 6.9
nmol/L) who cannot tolerate the approved pharmacologic agents for osteoporosis.
smoke and occasionally drinks alcohol. Does T.J. have an increased risk for developing osteoporosis?
Table 110-1 lists risk factors associated with the development of osteoporosis.
T.J. has several risk factors that could increase her risk for osteoporosis. She is a
white woman of small stature and low weight (body mass index; BMI = 19.8 kg/m2
has a positive family history, and has a low calcium intake.
Prevalence of osteoporosis worldwide varies with gender, race, and ethnicity.
the United States, Mexican American women have the highest prevalence of low
bone mass and osteoporosis, but non-Hispanic white women are at greatest risk for
9,11,25 When prevalence is adjusted for risk factors such as age, body
mass index, previous fracture, current smoking, alcohol intake, and glucocorticoid
use, more non-Hispanic white women meet the NOF criteria for osteoporosis
treatment compared to non-Hispanic black or Mexican American women.
T.J. has a small stature, and a BMI just under 20 kg/m2 and on the low side of normal
). Low body mass index (BMI less than 20) is an established
independent risk factor for osteoporosis and fracture.
cohorts including 60,000 men and women, a BMI of 20 kg/m2 was associated with
almost twice the risk of hip fracture compared to a BMI of 25 kg/m2
kg/m2 was associated with a 17% reduction in the risk of hip fracture compared to 25
. Nevertheless, obesity should not be considered a protective factor. When
adjusted for BMD, there was still a 42% increase in hip fracture in patients with a
, but no difference in the patients with a BMI of 30 kg/m2
FAMILY HISTORY AND GENETIC FACTORS
Osteoporosis is a multifactorial disorder that results from the effects of genetic and
environmental factors. A family history of osteoporotic fracture is believed to be an
underlying genetic predisposition.
7 Small stature or height is inherited. Smaller bone
size can influence the risk of fracture, as bigger bones may be more resistant to
breaking. The significance of heredity as a risk factor for osteoporosis has been
studied. Certain disease states are genetic and have an associated risk of
osteoporosis (e.g., celiac disease—a disorder associated with malabsorption).
Genetic factors associated with osteoporosis may be related to peak bone mass,
polymorphisms in the vitamin D receptor, genes associated with estrogen deficiency
or estrogen resistance, bone morphogenetic proteins, signaling pathways, and various
other bone-related proteins and receptors.
7,28,29 Women with a positive family history
of osteoporosis or osteoporotic fracture typically have lower BMD than those with a
MOBILITY AND PHYSICAL ACTIVITY
Bone mass is dependent on physical activity.
7 Prolonged immobility of a limb or
prolonged bed rest can result in a loss of skeletal tissue and bone mass. A number of
studies have looked at the effect of exercise on bone mass. Cochrane Database
published a meta-analysis of randomized controlled trials that included different
types of exercise interventions in the prevention and treatment of osteoporosis in
31 The effect of all exercise types versus control was a small;
there was significant improvement in BMD at the spine and trochanter, but not at the
femoral neck or total hip and there was no difference in risk of fracture. Significant
effects of low force weight-bearing exercise, such as walking or Tai Chi, were found
at the spine and wrist. A significant effect on BMD from high force weight-bearing
exercise, such as jogging, jumping, running, dancing, and vibration platform, was
found at the hip. Significant effects of non-weight-bearing exercise, such as
progressive resistive strengthening, were seen at the spine and the neck of the femur.
Combinations of exercise types had a significant effect on BMD at the neck of the
femur, spine, and trochanter and reduced the risk of fractures. BMD at the hip,
however, favored control. Limitations reported by the authors include small sample
size, loss of follow-up, lack of reported exercise characteristics, and heterogeneity.
Though the evidence for exercise has limitations and the lasting value of exercise
when stopped is not known, there is good evidence that physical activity is
associated with improved health, reduced mortality, and should be encouraged.
These include walking, jogging, Tai Chi, stair climbing, dancing, tennis, weight
training, and other resistive exercises. The Institute for Clinical Systems
Improvement (ICSI) guidelines also recommend a combination of exercise to
maintain and improve bone health; impact exercise such as jogging, brisk walking,
stair climbing; strengthening exercise with weights; and balance training such as Tai
26 Exercise can decrease the risk of falls by about 25%.
CIGARETTE SMOKING AND ALCOHOL INGESTION
Although T.J. does not smoke and only occasionally ingests alcohol, it is important to
include questions concerning cigarette and alcohol use when obtaining a medical
history from a person at risk for osteoporosis. Women and men who smoke have an
increased risk for fractures, including hip fractures, compared with nonsmokers.
Smoking impairs the absorption of dietary and supplemental calcium, lowers body
weight, influences estrogen metabolism, and may be directly toxic to bone cells.
Excessive alcohol use by both women and men is associated with decreased
BMD. Moderate alcohol consumption has been associated with increased BMD in
32 however, conflicting evidence exists. The effect of alcohol
on bone is dose dependent; consuming more than two alcoholic drinks daily
significantly increases the fracture risk.
7 The proposed mechanism may be a direct
effect of alcohol on osteoblasts, or it may be secondary to nutritional compromise
that could result in impaired calcium and vitamin D intake with subsequent decrease
in bone formation. The effect on bone formation has been seen even at no more than
one drink per day for women and two drinks per day for men.
that alcohol be limited to this amount to protect bone health and reduce the risk of
Dietary Reference Intakes for Calcium and Vitamin D33
Life Stage Group RDA Calcium RDA Vitamin D
19–50 years 1,000 mg 600 IU (15 mcg)
51–70 years 1,000 mg 600 IU (15 mcg)
>70 years 1,200 mg 600 IU (15 mcg)
19–50 years 1,000 mg 600 IU (15 mcg)
51–70 years 1,200 mg 600 IU (15 mcg)
>70 years 1,200 mg 800 IU (20 mcg)
aNOF recommends vitamin D 800 to 1,000 IU in patients ≥ 50 years.
IU, International Unit; RDA, Recommended Dietary Allowance.
Dietary calcium and vitamin D are critical to bone health and needed to strengthen
bones and increase bone mass. Peak bone mass is achieved in early adulthood and
afterward bone constantly undergoes remodeling.
33 Maintaining normal bone mass
reduces the risk of osteoporosis and fracture. Women and men need adequate calcium
and vitamin D intake to achieve and help maintain optimal bone mass. The Institute of
Medicine of the National Academies published recommendations for both calcium
and vitamin D intake that would promote bone maintenance along with a neutral
33 For men and nonpregnant women 19 to 50 years of
age, intake of 1,000 mg of elemental calcium per day and 600 international units (IU)
of vitamin D per day is recommended (Table 110-2). The National Institutes of
Health (NIH) base their recommendations on the same published report.
National Osteoporosis Foundation (NOF) has similar recommendations for calcium
and, however, differs in their recommendations for vitamin D intake.
to 1,000 international units (IU) per day is recommended for individuals 50 years of
Calcium is best ingested from the diet. Significant sources of calcium include dairy
products, tofu, and canned fish (Table 110-3). Calcium absorption from foods is
approximately 30%, but will vary depending on the food.
decreases with age. Absorption from dairy products or fortified juice is about 30%,
but for certain green vegetables such as broccoli and kale, the absorption can be
twice as high. Oxalate or oxalic acid-containing foods can impair calcium
absorption. Kale and broccoli are foods low in oxalate as are mustard or turnip
22 Examples of foods that contain high levels of oxalic acid are spinach, sweet
potatoes, beans, or collard greens. Even if high in calcium, oxalate impairs the
absorption of calcium. Some foods high in fiber can interfere with calcium
absorption; thus, intake of a variety of foods with calcium is recommended. Alcohol,
caffeine from coffee or tea, a low protein diet, a high intake of sodium, and excess
dietary phosphorous, all negatively affect calcium balance.
Vitamin D is considered a nutrient and a regulatory hormone. It is a fat-soluble
vitamin that is found naturally in very few foods, but is added to certain foods and is
available in supplement form. Vitamin D is a nutrient that can be synthesized in the
skin through the action of sunlight, but exposure to sunlight should be limited due to
33 Sunlight may also not produce enough vitamin D due to
differences in skin pigmentation, latitude, or use of sunscreen. Vitamin D regulates
calcium and phosphate, which make it important in the development and maintenance
Calcium Content of Selected Foods
Food Serving Size Calcium (mg)
Milk, dry nonfat 1 cup 350–450
Ice cream or ice milk 1/2 cup 50–150
Salmon, canned (pink) 3 oz. 167
Calcium-fortified juices 1 cup 100–350
Spinach, fresh cooked 1/2 cup 245
Collards, turnip greens 1/2 cup 175
It directly stimulates calcium and phosphate absorption from the intestinal tract
and, with the help of parathyroid hormone (PTH), can mobilize calcium from bone or
stimulate calcium reabsorption at the renal distal tubule (see also Chapter 28,
Chronic Kidney Diseases). Vitamin D that is found in the diet or that is synthesized
from the sun must be converted to its active form, calcitriol. Two major forms of
vitamin D are available. Vitamin D3
, cholecalciferol, is synthesized in the skin of
humans from 7-dehydrocholesterol, is synthesized commercially, and can also be
found in fatty fish, beef liver, egg yolks, and cheese. Vitamin D2
plant-based and largely synthesized commercially. Both forms can be found in
dietary supplements or fortified foods. Cholecalciferol and ergocalciferol are
inactive until they are converted to active vitamin D first by the liver to 25-
hydroxyvitamin D (25OHD) and then by the kidneys to 1,25-dihydroxyvitamin D,
calcitriol. The serum level of 25OHD is considered the marker for adequate intake.
The National Osteoporosis Foundation recommends vitamin D intake to maintain
serum 25OHD levels > 30 ng/mL (75 nmol/L).
1 Aging, chronic renal insufficiency,
intestinal disease, malabsorption, very dark skin, obesity, certain medications, and
reduced sun exposure are associated with reduce serum levels of vitamin D.
When vitamin D is taken in conjunction with calcium in postmenopausal women,
the risk of fracture and bone loss is slightly reduced; however, the same effect from
vitamin D alone is not established.
26,35,36 The combination of vitamin D and calcium
results in small increases in BMD of the spine, the total body, femoral neck, and total
There are few adverse effects from vitamin D supplementation. Vitamin D3
combined with calcium can increase the chance of forming kidney stones and
supplementation with the active form of vitamin D can increase the risks of
Calcium Content in Various Supplements
Tricalcium phosphate (calcium phosphate, tribasic) 39
Dibasic calcium phosphate dehydrate 23
T.J. is typical of the average American and has a diet low in calcium. If the
calcium or vitamin D in her diet does not achieve the recommendations, supplements
should be added. (Table 110-4; see Case 110-1, Questions 2, 3)
Various medications and medical conditions that have been associated with the
development of secondary osteoporosis are listed in Table 110-1.
CASE 110-1, QUESTION 2: Although T.J. is premenopausal, what recommendations could be made to
decrease her future risk of developing osteoporosis?
Universal recommendations for the prevention of osteoporosis are adequate intake
of daily calcium and vitamin D, weight-bearing and strengthening exercise, reduced
alcohol consumption, and smoking cessation. T.J.’s course of action should be to
maximize her peak bone mass and prevent or decrease bone loss. Her diet should
consist of adequate calcium of 1,000 mg and adequate vitamin D of 600 IU. T.J.
should continue to exercise, developing a lifelong exercise program, and continue to
refrain from smoking. T.J. should also maintain her BMI between 20 and 25 kg/m2
T.J. should be encouraged to participate regularly in weight-bearing and
strengthening exercises such as jogging, walking, running, biking, tennis, or weight
lifting and to continue appropriate exercise for her age throughout life. Physical
activity has numerous benefits in addition to promoting bone health. Exercise
enhances overall health and well-being, helps to control blood pressure, and lowers
risk factors for cardiovascular disease, colon cancer, and type 2 diabetes.
women such as T.J. should be made aware that it is important to maintain regular
menstrual periods. Amenorrhea due to strenuous exercise or extremely low body
weight can increase the long-term risk of osteoporosis and fractures.
T.J. should eat a well-balanced diet rich in fruits and vegetables, low-fat dairy
products, whole grains, fish, and nuts. This will provide calcium as well as other
nutrients needed for bone health. She should ensure her diet contains 1,000 mg of
elemental calcium and 600 IU vitamin D, optimally from dietary sources.
products are the major source of dietary calcium in the United States. Low-fat or
nonfat versions have the full amount of calcium. Fortified juices or fortified cereals
are also good sources of calcium. Although nondairy sources may contain lower
amounts of calcium, they can be an important source for men or women with dietary
preferences, those who cannot tolerate dairy, or who have food allergies (Table 110-
ingestion of foods rich in phytates and oxalates (e.g., cereal grains, legumes, and
nuts) may decrease calcium absorption.
If T.J. cannot meet her daily calcium requirement from dietary sources, she can use
a calcium supplement. Table 110-4 lists the percentage of elemental calcium
available from selected calcium salts. (see Case 110-1, Question 3, for further
information on calcium supplements.)
Vitamin D is found in few foods naturally (e.g., beef liver, egg yolk, salmon, tuna),
but can be found in fortified juice or milk. It is difficult to quantify the amount of
vitamin D obtained from sunlight. Genetic factors, skin pigment, latitude, and the use
of sunscreen are all factors that affect sun exposure.
33 T.J. should be able to obtain
adequate vitamin D intake from her diet. She could also add a supplement to her diet
to achieve 600 IU of vitamin D daily.
Other bone-related nutrients include magnesium, phosphorous, vitamin K, and
protein. Magnesium affects the concentration of parathyroid hormone, is involved in
the formation of bone, and is widely available in foods and fortified cereals.
dietary intake of magnesium has been associated with lower bone mineral density,
but not an increase in the incidence of hip fracture or total fractures.
magnesium intake was estimated in 73,684 postmenopausal women enrolled in the
Women’s Health Initiative Observational Study. Women who consumed magnesium
in the highest quintile had a 3% higher total hip BMD and a 2% higher whole-body
BMD than those in the lowest quintile. The incidence of hip fracture or total fracture
was not statistically different across quintiles of magnesium intake. Calcium as well
as phosphorous is stored in the bone. A complex balance of both is necessary for
22 Low dietary intake of phosphorous as well as excessive intake has
adverse effects on bone. Vitamin K is also important to maintain healthy bone.
Patients who are on long-term vitamin K antagonists or who have a diet low in
vitamin K are at increased risk for fracture and osteoporosis, but this risk is
39 Currently, there is no strong evidence and no recommendations for
Isoflavones are a class of phytoestrogens found in soybeans and
red clover, have estrogen-like activity, and have been shown to increase bone
density. There is conflicting and insufficient information on phytoestrogens to support
the use of isoflavones for osteoporosis prevention.
22 Soy, however, is a good source
of protein, which is also important for bone health. Calcium absorption is decreased
in diets that are low in protein.
Smoking cessation should be encouraged in men or women who smoke. Rates of
bone loss are greater in smokers than for nonsmokers and calcium absorption may be
26 T.J. occasionally drinks alcohol and should be educated on the risk of
alcohol and decreased bone mineral density. Recommended alcohol intake should be
limited to no more than one drink per day for women and two drinks per day for men.
CASE 110-1, QUESTION 3: If T.J. needs a calcium supplement, which calcium salt should be
The amount of elemental calcium in supplements varies. Two common forms of
calcium supplements are calcium carbonate and calcium citrate.
calcium carbonate tends to be lower and it contains the highest percentage of
elemental calcium (40%), allowing fewer tablets per day to meet daily calcium
requirements. Calcium absorption from supplements depends on the total amount of
elemental calcium consumed at one time. The percentage of calcium absorbed
decreases as the dose increases. Maximal absorption occurs at doses ≤ 500 mg at
If T.J. needs a calcium supplement, calcium carbonate is a reasonable
choice. She should be advised to take it in divided doses up to 500 mg/dose to
maximize absorption. Calcium carbonate absorption is dependent on stomach acid
and should be taken with food. Calcium citrate contains less elemental calcium, 21%,
is less dependent on stomach acid for absorption, and can be taken with or without
food. Calcium citrate is beneficial in patients with achlorhydria, inflammatory bowel
disease, or in patients taking proton pump inhibitors or histamine 2 receptor
blockers. Supplements should be taken with plenty of fluids. Calcium can compete or
interfere with the absorption of iron, zinc, and magnesium. Significant drug
interactions can also occur, such as impaired absorption of medications including
tetracyclines, thyroid products, and quinolones (Table 110-5). T.J. should be
informed that the most common adverse effects of calcium are constipation, GI
irritation, bloating, and flatulence. Caution should be used in patients with renal
insufficiency, hypoparathyroid disease, hypercalcemia, and a history of kidney
stones. If T.J. or any family member has a history of urinary stones, her clinician
should be aware of supplementation. T.J. should drink plenty of water throughout the
day and take calcium carbonate with food to ensure absorption or switch to calcium
Examples of Drug–Calcium Supplement Interactions
Allopurinol Protease inhibitors
Bisphosphonate derivatives Tetracycline derivatives
Calcium-channel blockers Protease inhibitors
Certain cephalosporin antibiotics Quinidine
Corticosteroids (oral) Quinolone antibiotics
HMG-CoA reductase inhibitors Sucralfate
Itraconazole, ketoconazole Thyroid products
Magnesium salts Tetracycline derivatives
Multivitamins/fluoride (with ADE) Vitamin D analogs
Multivitamins/minerals (with ADEK, folate, iron) Zinc
aDoes not include all calcium–drug interactions
Source: Facts & Comparisons eAnswers. Accessed February 15, 2015 from
http://online.factsandcomparisons.com/index.aspx. Accessed June 18, 2015.
which noted her T-score to be −2.0 and a Z-score of −1.0.
developing osteoporosis or has already developed osteoporosis?
In addition to M.J.’s DXA, a detailed medical history including medication history
(prescription and over-the-counter medications), diet, social history (smoking,
alcohol), and a physical examination, which includes height, are needed along with a
risk factor analysis. Diagnostic tests are indicated when there are multiple risk
1 The goals of a comprehensive evaluation are to identify modifiable
risk factors, rule out potential causes of osteoporosis, and to treat if indicated.
From her history and risk factor analysis, it is determined that M.J. shares similar
risk factors for osteoporosis with her daughter. In addition, she is early in the
postmenopausal phase, has GERD, and was a previous smoker. M.J. has no loss of
height, does not complain of back pain, and does not have signs of kyphosis, all of
which may be signs of osteoporosis. As part of the aging process, women may lose 1
to 1.5 inches in height due to degenerative arthritis and shrinking of intervertebral
It is important to monitor height as a loss of height may indicate that the
patient has a vertebral fracture.
Biochemical markers of bone turnover are not needed for M.J. at this time (e.g.,
alkaline phosphatase, calcium levels, phosphorus levels, bone-specific alkaline
phosphatase, osteocalcin, cross-linked C-terminal telopeptide, and N-telopeptide).
They are not used to diagnose osteoporosis but may be used to evaluate drug
The North American Menopause Society (NAMS) recommends a BMD
measurement in women such as M.J. who are older than 50 years of age if one or
more risk factors for fracture are present.
32 These risk factors include weight <127
, fracture other than skull, facial bone, ankle, finger or toe
after menopause, first-degree relative with a history of hip fracture, smoking,
rheumatoid arthritis, or alcohol consumption of two drinks per day (1 drink = 12 oz
of beer, 4 oz of wine, or 1 oz of liquor).
NAMS also recommends BMD testing in postmenopausal women with bone loss
due to medical conditions such as hyperparathyroidism, medications such as steroids,
postmenopausal women who have had a fragility fracture, and all women over the
32 The NOF recommends BMD testing for women age 65 years and older;
men age 70 years and older; menopausal women or women in menopausal transition
who are younger than age 65 and at increased risk of osteoporosis or who suffered a
low impact fracture; nonmenopausal women over age 50 and men ages 50 to 70 who
have suffered a low impact fracture or who are at risk for fracture; and adults with a
condition or who take medication that is associated with low bone mass.
evidence-based recommendations, insurance reimbursement plays a role in BMD
Bone mineral density refers to the amount or weight of bone mass per area and is
. BMD is reported as T-score (Table 110.6) and also as Z-score.
As T-score is a comparison of BMD to what is expected in a young healthy adult
population of the same gender, Z-score is a comparison of BMD to what is expected
in a healthy adult population of a similar age, gender, and ethnicity.
Dual-energy X-ray absorptiometry (DXA) is a two-dimensional X-ray considered
the standard for measuring BMD to diagnose or assess therapy.
spine, and femoral neck remain the preferred measurement for definitive diagnosis
Other methods can be used for screening but should not be used for diagnosis or to
follow a patient’s response to therapy.
For postmenopausal women who are not receiving medications for osteoporosis
prevention, a DXA may be useful no more frequently than every 2 to 5 years because
the rate of bone loss is approximately 1% to 1.5% per year.
supported by both the NAMS and NOF for diagnosis. The International Society for
Clinical Densitometry (ISCD) recommends using Z-scores when screening low BMD
in children, premenopausal women, and men less than age 50. A Z-score of −2.0 or
less is below the expected range and a Z-score greater than −2.0 is considered within
Definitions of Bone Mineral Density
Osteopenia (Low bone mass) −2.5 to −1.0 SD
translated into a 1.5-fold to 3-fold change in risk for fractures (Table 110-7).
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