what-when-how
In Depth Tutorials and Information
BISPH
OSPHONATES AND OI PAT
IENTS
Bisphosphonates have been beneficial for over
a decade in children with moderate to severe OI.
25
IV bisphosphonates have been used to improve the bone
mass and lower bone fragility of OI children, including an
improvement in the cortical mass of long bones.
26,27
Delayed tooth eruption is one of the side effects of
the bisphosphonate therapy in rats, but has also been
reported in humans.
28-30
The delayed tooth eruption and
high number of tooth impactions found in OI patients
is probably caused by a decrease in odontoclasts, osteo-
clast-like cells that result in a decreased resorption rate of
the primary teeth, and migration of permanent teeth into
a non-erupted position.
31,32
The permanent teeth form
but cannot erupt into the arch due to the remaining pri-
mary teeth that act as ankylosed teeth (
Figures 33.5-33.7
).
These retained primary teeth adversely affect the normal
development of the dentoalveolar process, which may
contribute to the lateral open-bites found in OI types III
and IV. Bisphosphonates diminish osteoclastic activity,
and it seems logical that they may further impede nor-
mal dental eruption.
29,30
However, they cannot be solely
responsible for the posterior open-bites for two reasons:
(1) because the lack of eruption takes place only in the
posterior areas while the anterior teeth are not affected
and (2) because the posterior open-bites in OI patients
have been documented years before bisphosphonate
therapies were instituted.
Numerous cases of osteonecrosis of the jaws (usually
of the mandible) in patients who have been treated with
bisphosphonates have been reported in adults. This is
most likely to occur in adult patients who are receiv-
ing IV bisphosphonates, particularly zoledronic acid,
as a part of their cancer treatment to minimize malig-
nant metastases to the skeleton. They are almost always
taking or have taken other medications that may con-
tribute to the development of the localized osteone-
crosis, typically in a site where some form of trauma
has occurred. Some cases of osteonecrosis have also
been reported in adults taking oral bisphosphonates,
although the incidence is very low.
Still, with children and adolescents who have OI
receiving bisphosphonates (usually by IV) since 1998
to increase their bone density and reduce the incidence
of bone fractures, there has been considerable concern
when these patients required dental extractions. One
of the centers, if not the center, with the most experi-
ence in this area is the Montreal Children's Hospital. In
2008 they reported on the dental experiences of 15 chil-
dren and adolescents with OI, 14 of whom had or were
receiving bisphosphonate treatment at the time. There
was a total of 60 dental extractions, mostly involving
primary teeth, in the group. None of the patients devel-
oped osteonecrosis.
33
This conclusion was supported by
FIGURE 33.5
There is an evident lack of eruption of the posterior
teeth. The second primary molars are retained with full roots and the
permanent bicuspids below show their twisted roots.
dental follicle offers this opportunity. It chemo-attracts
the osteoclasts and provides an erupting pathway. If it
is removed, the pathway does not develop. If the den-
tal follicle is maintained, but the developing tooth is
removed and replaced by a dummy, the dummy will
erupt.
20
The collagen in the periodontal ligament forms
a complex network in which the tractional force of the
fibroblasts is mediated. Since the erupting tooth is con-
stantly changing position, this mesh net can afford to
break down in spots without endangering its vitality,
and new fibers are immediately synthetized in order to
support the new dental site.
As mentioned earlier, 27 to 33% of OI children dis-
played posterior lateral open-bites, and DI teeth were
not always involved (meaning that their dental crowns
had normal or quasi-normal bulges and therefore could
not impede with dental eruption). Wise et al. stated
that, while most of the defects in eruptive process were
linked to a genetic basis, one particular genetic trait,
primary failure of eruption (PFE), could be independent
of other systemic involvement. PFE has been associated
with mutations in the parathyroid hormone receptor 1
(
PTHR1
) in at least some families.
21-23
The teeth (usu-
ally posterior, but sometimes also in the anterior) are
not ankylosed,
24
but do not respond to orthodontic trac-
tion. This has been our experience when attempting clo-
sure of the open-bites in OI patients as well. How the
effect of the quantitative and qualitative type I collagen
abnormalities on vertical growth of the maxilla and
alveolar bone interacts with the position and function of
the tongue, and how other mechanisms may also play a
role, remain to be determined.
