Treating the epidemic
At the International Osteoporosis Foundation
World Congress in Rio De Janeiro, Brazil in May this
year, leading experts in the field reported on the
latest research in drug treatments.
During the next 50 years,
the number of osteoporotic fractures, already numbering
in the millions, is expected to more than double,
worldwide. Facing this anticipated epidemic, researchers
are putting considerable resources into finding
medications that will stop bone loss, or even rebuild
weakened bone, in order to reduce fracture risk.
Currently there are several classes of drugs that are
approved for treatment of osteoporosis, including
bisphosphonates or selective
estrogen receptor modulators (SERMs) and parathyroid
hormone. Valued at around $7 billion in 2002, and
forecast to double by 2011, the osteoporosis market is
expected to see a rush of new drugs in the next five to
Bisphosphonates ... and kidney function
Paul Miller, from Colorado Center for Bone Re s e a rch,
Lakewood, Colorado, USA, reported that the established
risedronate is well tolerated in patients with reduced
kidney function. Miller and colleagues analysed placebo
controlled, phase III clinical trial data from over
9,000 patients with varying degrees of renal
insufficiency. Even those patients with severe kidney
impairment achieved significantly reduced frac-Osteoporosis.
Treating the epidemic ture risk on risedronate, without
compromising renal function.
... and for Paget’s Disease
Miller, newly elected to the IOF international Board, and colleagues also
investigated the use of bisphosphonates to treat a rare
condition called Paget’s disease. In this disease the
bones become weak due to an accelerated bone
turnover-the continuing loss and replenishment of bone
minerals. Miller and colleagues reported that one dose
of zoledronic acid, a bisphosphonate
that is given intravenously, may be slightly more
effective than daily dosing with risedronate in patients
with Paget’s. Six months after receiving zoledronic
acid, bone turnover in volunteers was still much lower
than in those who received a placebo, or who had taken
risedronate for 60 days but then stopped.
Compliance has been a problem with many
patients prescribed bisphosphonates, particularly those
medications requiring daily or weekly dosing. “Only 50%
of patients prescribed bisphosphonates are still!
taking them a year later,” noted Dr David Kendler, from
the Providence Health Care Center, Vancouver, Canada.
Kendler and colleagues reported that when patients stop
taking risedronate the control of their bone remodelling
This means that within a few months of stopping
treatment, patients are back to where they started and
bone is being lost as fast as it was before treatment.
“People who are on risedronate need to know that the
therapeutic effect would be rapidly reversed once they
stop,” said Kendler. Doctors can play their part helping
patients maintain their medication regimens, stressed
IOF President Pierre Delmas, from the
INSERM Resarch Unit, Lyon, France. Delmas led the IMPACT
study, designed to assess the effect of how physician
patients’ willingness to continue drug therapy.
Positive or neutral reinforcement by physicians helps
patients to keep up with risedronate medication, Delmas
and colleagues reported. This was discovered by
monitoring bone turnover markers, small molecules that
can be detected in the blood or
urine and which indicate response to treatment.
Based on measurements of these markers, patients who
were told their condition was improving were more likely
to continue with their medication than those whose
condition continued to deteriorate. “We found that
persistence in patients is improved by 30% over the
course of a year, if patients know they are getting
better,” said Delmas.
Those who persisted with medication were also found to
have better improvement in bone mineral density (BMD), a
commonly used measure of bone strength. Patients who
stayed on their medication showed greater improvement in
BMD than people who stopped taking the drug.
Results from two clinical trials
suggest that strontium ranelate can reduce the risk of
hip fractures in women with osteoporosis, and reduce the
risk of both hip and vertebral fractures in women with
Osteopenia, which is defined as low bone mineral
density, is a condition that precedes osteoporosis and
is generally considered an important risk factor for
fractures. Major studies to determine whether strontium
ranelate is effective include the TROPOS (for TReatment
Of Peripheral OSteoporosis) and SOTI (for Spinal
Osteoporosis Therapeutic Intervention) studies. Both
were andomised, doubleblind, placebo controlled trials
enrolling a total of over 5,000 volunteers. Subsets of
the data were analyzed by two collaborative efforts led
by Dr Jean.
Yves Reginster, WHO Collaborating Center in Liège,
Belgium and Dr Ego Seeman at Austin Hospital, University
Australia. Both Reginster and Seeman are IOF Board
members. “The data showed that strontium ranelate
significantly reduces the risk of experiencing a hip
fracture by 36% in at-risk patients,” said Reginster,
executive secretary of IOF and coauthor of both studies.
“And for the first time, in patients with osteopenia, or
low bone mass (measured at their spine) but who were not
yet osteoporotic, we
have a treatment that is capable of reducing the
vertebral fracture risk by 59%,” he continued.
Hormones and hormone modulators
Estrogen plays a major role in bone formation in both
women and men. For this reason postmenopausal women are
at increased risk for osteoporosis and hormone
replacement therapy has become widely used both as a
prophylactic and a treatment. However,
because estrogen therapy carries an increased risk for
some cancers and cardiovascular disease, researchers
have turned to alternate approaches such as the use of
selective estrogen receptor modulators (SERM), drugs
that mimic some of the actions of estrogens.
One promising drug under study is a next generation SERM
called lasofoxifene. Dr Michael Bolognese, from the
Research Center, Bethesda, USA, and colleagues reported
the results of a second phase II clinical trial to
determine the safety and
efficacy of low doses of this SERM.
Healthy postmenopausal women, aged between 50 and 74,
were given lasofoxifene for one year. Doses as low as 17
microgrammes per day resulted in an increase in BMD over
the time of the trial. At the highest dosestested, 500
microgrammes, BMD increased by an average of 2.2%, while
those on placebo saw a drop in BMD of 0.25% over the
same time frame.
The drug was well tolerated and has an acceptable safety
profile, the authors report.
Other potential benefits are also under investigation.
For example, some doses tested resulted in a
statistically significant lowering of
low-density lipoprotein cholesterol, the so-called “bad
cholesterol”. This level fell from an average of 129 mg/dL
in the placebo group,
to 106 mg/dL in the group receiving the highest dose of
lasofoxifene. “Lasofoxifene, a next generation SERM, may
play an important role in the health of postmenopausal
women,” said Bolognese.
Not everything works
One treatment patients can stop,
without missing out on any benefit, is topical natural
From analysis of a two-year, double blind,
placebocontrolled trial, Dr Gill Pearson and colleagues
at Southampton General Hospital, and elsewhere in the
UK, conclude that these creams do not prevent boneloss
in postmenopausal women.
Pearson began the research because she questioned
widely-promoted claims in women’s magazines and the
Internet that these creams can prevent bone loss and
even increase BMD by as much as 5-7% per year. Results
of the twoyear trial showed that
though the progesterone (40 - 80 mg applied per day) was
absorbed through the skin, BMD actually fell over the
two-year period of the study. In contrast, women taking
hormone replacement (50 microgrammes estradiol and 170
micrograms of norethisterone)z=increased BMD by an
average of 10% over the two years.
“Despite strong marketing claims to the contrary,
doctors should advise women not to use these
progesterone creams as protection against osteoporosis,”
said Pearson. Perhaps a different dose or delivery
system could be more effective on bone, she added,
noting that progesterone has been shown to stimulate
bone formation in animalstudies.