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not recommended until 4-6 months after osteotomy
and radiographs have shown adequate healing. When
bisphosphonates have been discontinued in growing
children, the new bone that is formed at the growth
plate of the long bones has a lower density.
20,78
This
interface between treated bone and treatment naive
bone causes a stress riser through which fractures can
occur.
20,79
Some form of maintenance therapy may thus
be warranted until growth is completed. Current trials
are exploring this avenue.
Bisphosphonates are buried in the skeleton where
they have a half-life of many years, so long-term side
effects may still surface.
80
This is particularly of con-
cern in cases where bisphosphonates have been given
to young women who then go on to bear children and
lactate.
81,82
This is a time of greater bone turnover and
may mean higher release of medication from the skel-
eton. At present no such adverse effects have been
seen; however, this cannot be discounted altogether.
83,84
Despite the obvious benefits of treatment, caution is still
advised when starting treatment and the risk-benefit
ratio must always be carefully considered.
TABLE 54.1
Commonly used Bisphosphonate
drugs
Trade name
Application
Pamidronate
Aredia®
i.v.
Zoledronate
Reclast®
i.v.
Alendronate
Fosamax®
oral
Risedronate
Actonel®
oral
Ibandronate
Boniva®
oral
FUTURE TREATMENTS
Inhibitors of receptor activator of nuclear factor
κB-ligand, a key molecule in osteoclastogenesis, and
sclerostin inhibitors, an anabolic approach that neu-
tralizes an inhibitor of bone formation and does not
affect bone resorption, are new drugs that are currently
undergoing clinical trials for the treatment of osteopo-
rosis with promising preliminary results that can be
applicable to the treatment of OI children in the near
future.
92
Indeed, one case series in children with OI
type VI found that antibody treatment against receptor
activator of nuclear factor κB-ligand suppressed bone
resorption more effectively than intravenous therapy
with bisphosphonates.
93
OI murine models are currently used to investigate
gene and cell therapies with the aim of either replacing
or silencing the mutant allele, thus transforming bio-
chemically a severe form of OI into a mild form.
94-97
OT
HER MEDICAL TREATMEN
TS
Growth hormone has long been proposed as a pos-
sible treatment for OI.
85
A few studies suggest that
growth hormone treatment may accelerate short-
term height velocity in some patients.
86-88
Calcium
kinetic studies after 1 year of growth hormone therapy
revealed that bone turnover had increased, but that
calcium retention was unchanged compared to the
pretreatment situation.
87
Increased bone turnover dur-
ing growth hormone therapy was also found in histo-
morphometric studies of iliac bone samples.
88
As bone
turnover is already abnormally high in untreated chil-
dren with OI,
89
further stimulation does not appear to
be a desirable goal. Possibly, growth hormone would be
more useful in combination with bisphosphonate ther-
apy, but this remains to be tested.
Parathyroid hormone is a potent bone anabolic agent
and has been shown to reduce the fracture incidence
in postmenopausal osteoporosis.
90
These results made
parathyroid hormone look like an attractive candidate
for treating children with OI. However, a substantial
proportion of young rats receiving parathyroid hor-
mone subsequently developed osteosarcoma.
91
It can-
not be excluded that a similar effect could happen in
humans. Thus, parathyroid hormone should probably
not be used in children until these issues have been
resolved.
CONCLUSIONS
OI patients require a multi-disciplinary treatment
approach. Bisphosphonates can be useful to support
other treatment modalities and are indicated in mod-
erate to severe OI. Intravenous bisphosphonates are
more effective than oral bisphosphonates. Intravenous
bisphosphonates are
de facto
the current standard
of care for treating moderate to severe OI forms.
Other emergent newer drugs seem to be promising
(
Table 54.1
).
References
