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“New Advancements in Treating
Osteoporosis”
Michael D. Miller, MD
Unpublished Article - July 2003
Last month (June 19-22, 2003), at the Annual Meeting of the Endocrine
Society in Philadelphia, endocrinologists from around the world gathered
to present and attend sessions on the latest research in the field.
One topic in particular - the Women’s Heath Initiative early
study findings (WHI) – caused passionate discussion and debate in just
about every session. Released
last year, the WHI revealed the increased risks associated with long-term
use of hormone replacement therapy (HRT) in menopausal and post-menopausal
women. These findings startled
physicians and patients who had long assumed that HRT provided successful
management of menopausal symptoms including night-sweats, vaginal dryness,
heart disease and osteoporosis. As
a result, many are seeking alternative therapies.
This trend was quite notable at the Endocrine Society meeting’s sessions
on osteoporosis. The
discussions often centered on the WHI and the quest for alternatives to
HRT. Experts presented cutting
edge data and theories about new treatments for the disease.
Furthermore, two other events in the past year, besides the WHI,
elevated these sessions to among the most popular at the meeting.
First, the Surgeon General’s Workshop on Osteoporosis and Bone
Health met as the first step towards a report and broad education campaign
about osteoporosis for physicians and the public due for 2004.
Second, in November, the U.S. Food and Drug Administration (USFDA)
approved the first anabolic bone forming treatment for osteoporosis –
parathyroid hormone (PTH).
Along with Medicare’s coverage of osteoporosis screenings since 1998,
the increased attention in the area of osteoporosis indicates a growing
appreciation for the rising prevalence of the disease and for the need for
early intervention to prevent the rapid deterioration associated with it
after an initial fracture occurs.
How serious is osteoporosis for our aging society?
Consider a few facts: individuals over 50 years old are 29% of our
population. Their numbers are
increasing at a rate of 2.5% per year and 55% of these individuals are at
risk for osteoporosis.
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Risk
Factors for Osteoporosis
The
most prevalent risk factor for osteoporosis is age.
As we age, the rate of bone resorbed by osteoclasts remains
the same, but less new bone is formed by osteoblasts to replace
the resorbed bone. In
osteoporosis, the imbalance between these two processes is so
great over a long enough period of time that the bones lose their
mass and strength putting patients at greater risk for fractures,
even from normal stresses.
Inherent risk factors for osteoporosis include female
gender, postmenopausal, low testosterone levels in men, and family
history of osteoporosis. Additional
risk factors that can cause osteoporosis at an early age are
diverse and include hypogonadism in both men and women,
hyperthyroidism, some anti-seizure medications, long-term systemic
steroid use, Cushing’s syndrome, conditions that affect calcium
absorbtion – including alcoholism. |
These older Americans are more active and healthier than previous
generations. However, they
increasingly face osteoporosis, a silent illness that robs people of their
mobility and can lead to permanent dependence and even death.
Osteoporosis causes 1.5 million fractures each year in the United
States, and 300,000 of these individuals die from fracture-related
complications. Only a small
percentage of the estimated 10 million who suffer from osteoporosis, and
the 34 million who are at risk, even realize that they have these
conditions.
Further, once a woman has had a
single osteoporotic fracture, without treatment her risk of additional
fractures is estimated to increase 50 - 100% above women with similar bone
density who have not had a fracture.
Even without causing fractures, osteoporosis can dramatically alter an
older person’s life. A
Gallop survey in May 2000 for the National Osteoporosis Foundation found
that 73% of women with osteoporosis are concerned about losing their
independence and 67% are concerned about having to reduce activities with
family and friends – both very real possibilities.
This same survey found that only 31% of women had taken steps to
prevent osteoporosis before diagnosis.
In light of the WHI and as evidenced by the discussions at the Endocrine
Society meeting, physicians and patients alike are asking for more choices
and improved alternative therapies to treat the disease.
Traditionally, there have been three options, in addition to a diet
rich in vitamin D and calcium, for treating osteoporosis.
With the approval last year of PTH, there are now four.
The Selective Estrogen Receptor
Modulators (raloxifene) act by selectively targeting a subset of the
body’s estrogen receptors – activating some and blocking others.
Specific to osteoporosis, it activates estrogen receptors in the
bones to reduce resorbtion and has been found to reduce the rate of
vertebral factures by 30-50% after 3 years.1
Conversely, it appears to block estrogen receptors in the uterus
and breast and thus in one study of postmenopausal women with osteoporosis
showed a reduction in the rate of estrogen-receptor positive breast
cancer.
The bisphosphonate class of medicines, (alendronate and risedronate) act
by increasing the strength of new bone by physically integrating
themselves into the mineral matrix of the bone.
These oral medicines have been found to reduce the risk of
fractures by 30-50% over a 3-4 year period.
Calcitonin has been available as a nasal spray since 1984, and more
recently as a subcutaneous injection.
It acts by reducing the number of osteoclasts and their bone
resorbing activity, and has been found to reduce vertebral fractures by
36%.
The newest treatment option – and one that received a great deal of
attention at the meeting - is teriparatide.
As the first bone growth promoting medicine, it encourages
physicians to shift the way they think about treating osteoporosis.
Teriparatide is a portion of naturally occurring human parathyroid
hormone (PTH) that acts by stimulating osteoblasts.
This contrasts with the other treatments for osteoporosis that act
by reducing the activity of osteoclasts to slow bone resorbtion.
Teriparatide is administered as a subcutaneous injection with an
auto-injecting pen device, and it has been found to increase BMD in over
90% of men and women. In
women, it has been shown to lower the risk of vertebral factures by 65%
and other fractures by 53% when used for an average of 19 months.2
Adding to the utility of teriparatide treatment are new reports from the
recent meetings of the European Calcified Tissue Society (Rome, May 8-12,
2003) and the Endocrine Society. The first of these directly
demonstrated the effectiveness of teriparatide in forming new trabecular
and endosteal bone using bone biopsies. The second showed that the
effectiveness of teriparatide treatment could be evaluated by monitoring
changes in patients' bone specific alkaline phosphatase - a marker of bone
formation - as early as one month after initiating treatment. Thus,
in the future, it may be possible to assess the progress of patients' bone
using blood tests rather than the more expensive and time consuming dual
x-ray absorptiometry (DXA) scans.
Future treatment options for osteoporosis fall into two categories.
The first uses currently available medications (in addition to
vitamin D and calcium), either concurrently or sequentially.
Now that we have medicines that act via several mechanisms of
action, these combinations provide very exciting opportunities for
improving treatment regimens. The
second category encompasses a range of innovative experimental compounds
being developed to treat osteoporosis.
As these experimental medicines prove both safe and effective,
physicians will have additional and possibly more effective options for
individualizing their patients’ treatment plans towards the goal of
actually ending osteoporosis.
A number of factors put osteoporosis at the forefront of national health
concerns. Our aging population
continues a trend of remaining active later in the life.
The WHI raises troubling questions about the benefit/risk ratio of
HRT, once considered the primary treatment for osteoporosis.
The Surgeon General plans to launch an educational campaign about
osteoporosis for both physicians and patients in the next year.
All these factors not only create demand for improved treatment
options but also provide opportunities for new ways of thinking about
osteoporosis. As Dr. Henry
Kronenberg, of the Endocrine Unit at Massachusetts General Hospital,
Boston, explained at a plenary session at the Endocrine Society Meeting,
“It’s not enough to prevent and treat, we want to end the disease of
osteoporosis.”
1 Raloxifene
also appears to activate estrogen receptors related to lipid metabolism
and thus lowers LDL cholesterol levels.
2 These
results were in a clinical trial comparing teriparatide, plus vitamin D
and calcium versus vitamin D and calcium plus placebo.
As an anabolic agent adequate vitamin D and calcium intake should
support its bone forming properties.
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