New Study Provides In-Depth Look at How Osteoporosis Treatments Function Within Bone
August 08 2005 - 6:00PM
PR Newswire (US)
Demonstration of different mechanisms of action is important step
in defining how best to use FORTEO(R) and Fosamax(R) in treating
postmenopausal osteoporosis patients INDIANAPOLIS, Ind., Aug. 8
/PRNewswire-FirstCall/ -- A new study comparing the head-to-head
effects of teriparatide [rDNA origin] injection, (20 mcg), marketed
in the US as FORTEO, the first and only FDA approved bone formation
agent that actually forms new bone in postmenopausal women with
osteoporosis at high risk for fracture, and Fosamax (10 mg
alendronate sodium(1)), an inhibitor of bone resorption, gives new
information on how the two osteoporosis therapies affect bone cell
activity. These data were published in the August 2005 issue of
Archives of Internal Medicine. The study, which provides more
in-depth information than previously available about these two
treatments, found that both therapies increase bone mineral density
(BMD), but to different degrees and through different means. While
FORTEO builds new bone by increasing the rate of bone formation,
Fosamax increases bone density by preventing bone loss -- different
mechanisms of action on bone remodeling. "This is the first
head-to-head study to give us important information about how two
osteoporosis therapies can work through diametrically opposite
mechanisms of action," said Dr. Michael McClung, M.D., founding
director of the Oregon Osteoporosis Center and lead investigator of
the study. "Both treatments cause bone density to increase, but the
skeleton responds differently to each. By gaining knowledge about
how different therapies work, we can understand the nature of
changes in bone density and make more informed treatment decisions
based on the individual patient's needs." What is bone cell
activity? In addition to preventing fractures, understanding how
therapies impact the body's natural bone cell activity is an
emerging but important focus for determining how to treat
osteoporosis. Bone is a living tissue that continually breaks down
(resorption) and replenishes (formation) itself in order to
maintain strength and fracture resistance. This process is called
bone turnover or remodeling, and is the foundation for bone health.
When bone turnover is thrown out of balance, which is often seen in
women of menopausal age due to the decrease in estrogen, the
resorption process surpasses the formation process. If not
corrected, this can lead to osteoporosis or low bone mass. "The
main goal of a physician who treats a patient with osteoporosis is
to reduce the patient's risk for suffering an osteoporotic
fracture. Increasing BMD is an important part of the process, but
so is the method by which it's improved," said Dr. McClung. "This
study assesses these skeletal changes through several measurements
-- BMD and markers of bone turnover -- to give us a better
understanding of how those skeletal changes occur." The Study Two
hundred and three postmenopausal women between 45 and 84 years of
age participated in this 18-month randomized, parallel,
double-blind study. Women included in the study were 5 or more
years past menopause and had a bone mineral density T-score between
-2.5 and -4.0 at either the lumbar spine or femoral neck. Patients
were randomized to receive once-daily injections of FORTEO(R) 20
mcg/day and oral placebo or oral Fosamax(R) 10 mg/day and once-
daily injectable placebo. Each woman was given daily calcium
supplements and vitamin D (1000 milligrams and 400-800 IU,
respectively). Markers of bone turnover and areal BMD were assessed
for all 203 women. Areal BMD was assessed using a dual energy x-ray
absorptiometry (DXA) of the lumbar spine at baseline and 3,6,12 and
18 months and femoral neck at baseline, 12 and 18 months.
Volumetric BMD of the lumbar spine and the femoral neck was
assessed in a subset of 56 patients by quantitative computed
tomography (QTC) at baseline and 6 and 18 months. Results This
study shows the following effects on BMD and bone turnover: * At 18
months, FORTEO(R) increased volumetric spine BMD by 19.0 percent,
while Fosamax increased volumetric spine BMD by 3.8 percent) * At
18 months, FORTEO increased areal spine BMD by 10.3 percent, while
FOSAMAX increased areal spine BMD by 5.5 percent * At 18 months,
FORTEO increased areal BMD at the femoral neck 3.9 percent, while
Fosamax increased areal BMD at the femoral neck by 3.5 percent * At
18 months, femoral neck trabecular BMD increased 4.9 percent in
patients taking FORTEO while femoral neck trabecular BMD increased
2.2 percent in patients taking Fosamax * At 18 months, cortical
bone density at the femoral neck increased 7.7 percent in patients
receiving Fosamax, while in those receiving FORTEO, cortical bone
density at the femoral neck decreased 1.2 percent * After 6 months
of treatment, PINP serum procollagen type I N-terminal propeptide,
a marker of bone formation, peaked at 6 months with teriparatide by
218%; while Fosamax decreased PINP by 67% * Fosamax significantly
decreased NTx, urinary N - telopeptide, a marker of bone resorption
at 6 months by 72 percent while FORTEO increased NTx by 58 percent
at 6 months * 26 patients receiving FORTEO reported new or
worsening back pain as an adverse event after 18 months of
treatment while 39 patients receiving Fosamax reported new or
worsening back pain as an adverse event during treatment * After 18
months, eight patients taking Fosamax experienced fractures while
nine patients taking FORTEO experienced clinical fractures
Important Safety Information about FORTEO In two-year studies in
rats, FORTEO(R) caused an increase in the incidence of
osteosarcoma, a malignant bone tumor, which was dependent on dose
and duration of treatment. Although no case of osteosarcoma has
been reported in the patients who received FORTEO in clinical
trials, it is not known if humans treated with FORTEO are at
increased risk for this cancer. FORTEO should be prescribed only to
patients for whom the potential benefits are considered to outweigh
the potential risk. The drug should not be prescribed for patients
at increased baseline risk for osteosarcoma, including patients
with Paget's disease of bone or unexplained elevations of alkaline
phosphatase, children or growing adults, or those who have had
prior external beam or implant radiation therapy involving the
skeleton. Additionally, patients with bone metastases or a history
of skeletal malignancies, and those with metabolic bone diseases
other than osteoporosis, should not receive FORTEO. Patients with
high levels of calcium in their blood should not receive FORTEO due
to the possibility of increasing their blood levels of calcium. In
clinical trials, the most frequent treatment- related adverse
events reported at the 20-microgram (mcg) dose approved for
marketing were mild, similar to placebo and generally did not
require discontinuation of therapy. Reported adverse events that
appeared to be increased by FORTEO treatment were leg cramps and
dizziness (2.6 and 8 percent, respectively), compared with placebo
(1.3 percent and 5.4 percent, respectively). FORTEO is supplied in
a disposable pen device that can be used for up to 28 days to give
once-daily self-administered injections. FORTEO is available in a
20-mcg dose and should be taken for a period of up to 24 months.
Lilly has implemented a risk management program that includes
comprehensive measures regarding the appropriate use of FORTEO in
the target patient population. A Medication Guide explaining the
details of the drug to the patient also accompanies the product.
FORTEO also has a black box warning in its package insert about the
osteosarcoma findings in rats during preclinical testing. For full
prescribing information, please visit http://www.forteo.com/. About
Osteoporosis More than 50 percent of all women over the age of 75
are estimated to have osteoporosis, and due to their advanced age,
have a high risk of fracture. In fact, most American women over the
age of 50 will experience one or more osteoporosis-related
fractures during their lifetimes, and women with osteoporosis who
have two or more previous fractures have up to a nine times greater
risk of future fracture compared with women who have not suffered a
previous fracture. About Lilly Lilly, a leading innovation-driven
corporation, is developing a growing portfolio of first-in-class
and best-in-class pharmaceutical products by applying the latest
research from its own worldwide laboratories and from
collaborations with eminent scientific organizations. Headquartered
in Indianapolis, Ind., Lilly provides answers -- through medicines
and information -- for some of the world's most urgent medical
needs. Additional information about Lilly is available at
http://www.lilly.com/. P-LLY (1) Fosamax(R) is a prescription
medication manufactured by Merck & Co. (Logo:
http://www.newscom.com/cgi-bin/prnh/20031219/LLYLOGO )
http://www.newscom.com/cgi-bin/prnh/20031219/LLYLOGO DATASOURCE:
Eli Lilly and Company CONTACT: Keri S. McGrath of Eli Lilly and
Company, +1-317-651-6001, Email:
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