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Teriparatide in the treatment of glucocorticoid-induced
College of Physicians and Surgeons, Columbia University, New York,
The rationale for considering that parathyroid hormone or its
foreshortened N-terminal fragment, teriparatide [PTH(1–34)], might
be an attractive candidate for the treatment of glucocorticoid-
induced osteoporosis (GIO) is based on the data that argue against
PTH being pathophysiologically related to the disease itself. PTH
levels are not increased in GIO; the histomorphometric picture of
GIO is completely different from that of PTH excess; and fractures
that occur in GIO (mainly of cancellous bone) are those that should
be protected by excess PTH. In addition, PTH is an attractive
candidate for the therapy of GIO because it protects against
osteoblast apoptosis and increases osteoblast cell number and
activity. PTH administration induces an initial increase in bone
formation followed by a more gradual increase of bone resorption.
According to the concept of the ‘anabolic window’, PTH rapidly
stimulates processes associated with bone formation and then is
associated with the stimulation of processes associated with bone
resorption. The sequence of these events has given rise to the
concept of the “anabolic window” the period of time when the
anabolic properties of PTH are optimized.
PTH has been shown to be effective in postmenopausal women and
in men with osteoporosis. The hypothesis that PTH might be useful in
GIO has been tested in postmenopausal women with rheumatoid
arthritis receiving prednisone and estrogens Data from Lane et al. have
shown that when PTH is administered to postmenopausal women
with GIO, vertebral and hip bone mineral density increase.
Saag et al. conducted a multicenter, randomized, controlled study
to compare the effects of teriparatide (20 μg daily) with those of
alendronate (10 mg daily) on lumbar spine BMD in patients under-
going long-term glucocorticoid therapy. The primary outcome index
was to compare differences in BMD between the two treatment
regimens. The 328 subjects had an average T-score in the lumbar spine
of −2.5 and at the femoral neck, −2.1. After 18 months, bone density
increased with both treatment regimens but with teriparatide, the
increase was significantly greater than with alendronate (8.2% vs.
3.9%; p <0,001). There were also significantly greater increases at the
total hip and femoral neck with teriparatide as compared to the
alendronate. As expected, bone markers increased with teriparatide
and decreased with alendronate. Incident vertebral fractures deter-
mined radiologically were much lower in the teriparatide group (0.6%)
than the alendronate group (6.1%; p<0.01). After 36 months, the
vertebral fracture data continued to show marked differences in the
incidence of factures in the teriparatide arm (1.7%) versus the
alendronate arm (7.7%; p<0.01). There were no differences in the
incidence of clinical vertebral or non-vertebral fractures when the two
treatment groups were compared to each other.
Based upon mechanism and results, it is clear that teriparatide
represents an attractive therapeutic option for the treatment of GIO.
Strontium ranelate in the therapeutic strategies for osteoporosis,
Department of Public Health Sciences, University of Liège, Liège, Belgium
Strontium ranelate is a new agent, widely used for the manage-
ment of postmenopausal osteoporosis. Its unique mode of action
includes a decrease in bone resorption and a concomitant stimulation
of bone formation. In postmenopausal osteoporosis, strontium
ranelate efficacy and safety were tested in a large development
programme. Reduction in clinical vertebral and non vertebral frac-
tures was evidenced after 1, 3 and 4 years of follow up. In elderly
women, with a mean age of 79 years, at baseline, strontium ranelate,
significantly reduced the rate of vertebral, non vertebral and major
non vertebral fractures after 3 and 5 years. Moreover, strontium
ranelate has also been shown to decrease the rate of hip fractures, by
43%, in women over the age of 74 years, with low bone density at the
femoral neck. As of today, it is the only compound for which a
reduction in hip fracture has been demonstrated in such a long-term
trial. The very-long term efficacy of strontium ranelate has been
confirmed by a 3-year open-label extension of the previous trials,
showing that the compound does not lose its antifracture efficacy,
after 8 years of treatment. On safety grounds, strontium ranelate has
a profile that compares favourably with the other therapeutic classes
used in osteoporosis. Due to this outstanding risk/benefit profile and
its mode of action, targeting two of the main determinants of
glucocorticoid-induced osteoporosis (decrease in osteoblast activity
and increase in bone resorption), strontium ranelate could be
considered as a potential treatment of choice for GIO.
Abstracts / Bone 45 (2009) S120–S134 S131