Osteoporosis
in Juvenile Rheumatic Diseases
Egla Rabinovich,
M.D., M.P.H.
From Lupus News Fall 2002,
Vol. 22. No. 3
Background about
normal bone growth
What is osteoporosis and how can
we diagnose it?
Measuring bone health
What are risk factors for osteoporosis?
Corticosteroids and bone loss
Prevention and treatment of
osteoporosis
Summary
About the Author
Background
about normal bone growth
When one thinks of bones, what often comes to mind
are the hard, dead bones of skeletons. However, bones
are living, changing connective tissues that are always
undergoing change, even as you sit reading this! Childhood
is a unique time in bone biology-not only is there
the same constant turnover of cells that occurs in
adult bones, but you also have to add growth to the
picture.
There are three important functions
of bone. First, there is a structural function: bones
give support to our body, allow our legs and arms
to function, and protect organs such as heart and
lungs. Second, the essential elements of blood are
made in the center, or marrow, of bones. Third, bones
act as a reservoir for essential minerals, most importantly
calcium, magnesium, and phosphorus. In fact, 99 percent
of the calcium found in the human body is found in
bone.
Bone is therefore dynamic, living tissue.
The cells that are important in determining the strength
of bone are called osteoblasts and osteoclasts. Osteoblasts
are cells that build bone; they secrete collagen,
which is later calcified to form bone as we know it.
Osteoclasts are cells that "eat up," or
reabsorb bone; they lie on the inner bone surface,
and secrete acids and enzymes that break up bone.
The usual sequence of events in normal
bones (called "remodeling") is that there
is activation of the process causing osteoclasts to
eat up bone, and then osteoblasts come along and lay
down new bone. The two cells have very complex regulatory
mechanisms that are usually tightly linked.
Regulation of bone turnover (i.e.: the
building and breakup of bone) is complex and not totally
understood. But we do know that there is regulation
by hormones secreted elsewhere in the body, including
parathyroid hormone, insulin, growth hormone, vitamin
D, thyroid hormones, and steroids-both corticosteroids
(i.e., the type of prednisone usually made in the
body) and sex steroids (estrogen, progesterone). In
addition, proteins secreted by cells in the bone regulate
bone turnover locally. How all these regulators interact
is not totally understood, and is an area of active
research.
As mentioned above, childhood is a unique
time for bone because not only do bones have to constantly
turn over, but they also have to grow in length. They
have to "eat up" bone while laying down
bone in a way to allow for gain in vertical height.
This occurs at the ends of bones at a special area
called, quite appropriately, the growth plate.
During childhood, the bone growth process
is under control by hormones such as the growth hormone.
During adolescence, however, the sex hormones are
the most important regulators of bone growth.
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What is osteoporosis
and how can we diagnose it?
Osteoporosis is a disease of abnormally weak bones,
and causes an increased risk of broken bones (fractures).
The World Health Organization has defined osteoporosis
for adults, but there is no specific definition for
children. In order to understand the definition of
osteoporosis, we first need to understand how we look
at bones to measure their strength.
The only way to directly measure bone
strength is to cut out a piece of bone (a bone biopsy)
and test its strength by placing increasing pressure
on the bone until it breaks. As you might imagine,
this is not popular with patients! Therefore, we look
instead at indirect measures of bone strength.
An X-ray of a bone will give some information
about whether bones are normal or thin. The problem
with regular X-rays is that they are not very good
at telling the difference between normal and abnormal
bone. So, specialized types of X-ray machines have
been developed for the specific purpose of measuring
bone thickness, or density, as an indirect measure
of bone strength. One of the most common machines
used for diagnosis of osteoporosis is called a DEXA
machine. DEXA stands for "dual energy radiographic
absorptiometry" which is a specialized type of
X-ray. Besides being more accurate, DEXA scans have
several advantages: the machine works fast (usually
a scan takes less than 30 minutes); results are accurate
and precise; and a minimal dose of radiation is used.
The DEXA scan works by running its sensor
over a certain part or parts of the body. The lower
spine and the hip are the most common body parts measured.
As rays are passed over the body, they "see"
how much mineral is in the skeleton and also measure
the area of the skeleton. The result is called the
bone density. The bone density is a measure of the
mineral content in bones divided by the bone area
measured. It is expressed in grams per centimeter
squared (gm/cm2).
Other machines used to measure bone
density include other (older) absorptiometry machines
(single photon and dual photon absorptiometry); a
computer tomography or CT scan; and, newest in development,
the use of ultrasound.
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Measuring
bone health
Now that you know what a bone density is, we can now
explore the World Health Organization's definition
of osteoporosis. The WHO has defined osteoporosis
as "a bone density that is 2.5 standard deviations
below that seen in a healthy normal adult." A
standard deviation is a statistical measure of the
distribution of values on a test or measurement for
a population of subjects.
If the values are evenly distributed
in a way that represents the usual values in a population,
then the values fit a "bell curve" distribution.
If you include all those who are within 2.5 standard
deviations, this will includes 97 percent of all measures
in a population. So, if a bone density is greater
than 2.5 standard deviations below normal, it corresponds
to the lowest 1.5 percent of the population.
Another weak bone condition is "osteopenia"
(bones that are weaker than normal, but not as weak
as osteoporotic bones), which the WHO defines as "a
bone density greater than 1 standard deviation below
a healthy normal adult, but less than 2.5 standard
deviations below normal." The cutoff of 2.5 standard
deviations below normal was chosen because, at this
level of decreased bone density, there is an associated
significant risk for bone fracture with even normal
daily activities. Again, it is important to note that
these definitions have been developed and evaluated
for use in adults, not in children.
As children grow, their bones grow and
the corresponding bone density rises continually during
each year of growth. During the teenage years the
bone density takes a big jump; this rapid increase
corresponds to the growth spurt and is under hormonal
control. In the late teenage years, the bone density
hits a maximum, called "the peak bone mass".
Once peak bone mass is achieved, it
never can increase further. Thus, if peak bone mass
is adversely affected during childhood, the potential
for osteoporosis increases-even though we may not
see fractures until 20 to 40 years later! This is
why osteoporosis during childhood is often called
a "silent" disease: osteoporosis with resultant
fractures remains quiescent until much later in life.
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What are risk
factors for osteoporosis?
There are plenty of well recognized risk factors for
osteoporosis in the elderly:
The family history of osteoporosis is
very important since heredity is thought to account
for 60-80 percent of bone density.
In children, however, the risk factors
are not firmly established. It appears that children
who are more physically active have increased bone
densities; a greater calcium intake has also been
linked to higher bone densities. Yet teenage girls
who exercise so much that their menstrual periods
go away, or who are anorexic, are at risk for osteoporosis.
Children with other hormone-related
disorders, such as Turner's syndrome, are at risk
for osteoporosis. In addition, having certain chronic
diseases, such as juvenile rheumatoid arthritis (JRA)
or juvenile diabetes, can increase the risk of osteoporosis
for young people.
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Corticosteroids
and bone loss
Investigators around the world have been looking at
bone health in children who have rheumatic diseases,
including JRA and lupus. They now know that children
who have to take corticosteroids to treat their disease
are at increased risk for osteoporosis with resultant
fractures. Besides prednisone, other forms of corticosteroids
you may be familiar with are Prelone, prednisolone,
Sterapred, Pediapred and intravenous Solumedrol.
Fractures have been seen during the
childhood years in patients who have been on long-term
steroids. Besides the usual broken bones, there also
can be compression fractures of the spine in children
who were taking prednisone every day, and these types
of fractures also are linked to higher doses of corticosteroids.
Corticosteroids are essential for controlling
disease activity in lupus, and patients should always
follow the doctor's advice about taking this, or any
other, medication. In fact, it can actually be dangerous
to stop steroids suddenly if your body is used to
taking steroids regularly. We do know, however, that
steroids work negatively on bone health.
Corticosteroids decrease the body's ability to absorb
calcium through the intestines; they also increase
calcium loss through the kidney. In addition, corticosteroids
have a direct negative effect on the bone cells, especially
a suppressive effect on the osteoblasts (as you remember,
these are the cells that build bone). The effect of
corticosteroids on bone is most pronounced in the
type of bone found in the spine, in the ribs, and
at the ends of the long bones of the skeleton.
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Table 1 - Calcium Intake Recommendations
by Age Group
Age Group Calcium Goal (mg/day)
1-3 years 500
4-8 years 800
9-18 years 1,300
Pregnant or lactating < 18 years 1,300
19-50 years 1,000
"Dietary Reference
Intakes for Calcium, Phosphorus, Magnesium, Vitamin
D and Fluoride." Washington, DC: National Academy
Press, 2101 Constitution Avenue NW, Washington DC
20418; 1997.
Other important sources of calcium include
yogurt and cheese, sardines, canned salmon with bones,
broccoli, leafy greens, all kinds of meat, and calcium-fortified
foods, such as orange juice. Vitamin D is found in
supplemented milk, but is also made by the body when
skin is exposed to sunlight. Calcium supplements are
available by prescription, but are also found in some
antacids (for example, Tums and Rolaids). Ask your
doctor if your child might benefit from calcium supplementation.
* If you have a strong family history of osteoporosis,
or if your child is taking steroids, ask your doctor
about the possibility of getting a DEXA scan done.
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Summary
One of the problems with childhood osteoporosis is
that treatments have been geared towards adults. Treatment
for osteoporosis in childhood has not been established
and should be considered experimental. There is more
research needed on the bone health in children with
lupus and prevention or treatment of osteoporosis.
About the Author
Dr. Egla Rabinovich is an Assistant Clinical Professor
in the Department of Pediatric Rheumatology at Duke
University Medical Center in Durham, NC. She received
her medical degree from Southern Illinois University
School of Medicine in Springfield, IL, and her Master's
degree in Public Health in Epidemiology from the School
of Public Health, University of North Carolina-Chapel
Hill.
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7-29-2003
