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In Depth Tutorials and Information
FIGURE 54.1
Lateral lumbar spine radiographs of a boy with OI type III at age 1.0 year (A), 9.8 years (B) and 13.0 years (C). Pamidronate
treatment was started at the age of 10.1 years. Vertebral bodies flattened before treatment were started (A and B). This was partially corrected
after 3 years of pamidronate treatment (C).
(From ref.
33
)
bone formation markers falls as well.
8,11-13
The litera-
ture reports an increase in well-being and decrease in
chronic bone pain within 1 or 2 weeks following the
start of therapy.
5,14-18
Bone mass and density usually
increase markedly in the months following the start
of pamidronate therapy.
9,12,14,18-23
Cortical thickness
increases as measured at the second metacarpal
5
and in
trans-iliac bone biopsy specimens.
24
Radiographically,
the cycles of pamidronate leave dense sclerotic bands at
the metaphysis of long bones.
25-32
These may contribute
to the increased strength of the bones.
Fracture rates in treated children can be difficult to
assess as with increased mobility there may be a tran-
sient increase in fractures. However, a decrease in over-
all fracture rate has been demonstrated after therapy
when compared to historical controls.
5
Compressed
vertebral bodies have been shown to recover when
therapy is given during growth (
Figure 54.1
).
33-36
Patients with OI types I, III and IV showed a significant
improvement in height Z-scores after 4 years of pami-
dronate therapy.
37
Similar observations were made on a
group of prepubertal children with OI types I and IV.
38
Muscle force measured by maximal isometric grip force
of the non-dominant hand showed significant increases
with pamidronate therapy that was maintained over 2
years.
39
When pamidronate is commenced early in life it
can lead to significant improvement in ambulation. The
two largest studies report improved mobility in more than
half the patients.
7,40
There were also beneficial effects on
everyday activities.
14
Overall, bisphosphonate treatment
is associated with a reduction of the number of outpatient
department consultations and operative interventions.
41
The effects of bisphosphonates seem to be ampli-
ied by the growth process, but do not appear to vary
much with OI type. Even though OI types I, III and
IV constitute the large majority of patients studied
until now, responses to pamidronate treatment were
observed also in OI types V to VII, even though fracture
incidence remained relatively high in OI type VI.
42-44
Among patients with mutations affecting collagen
type I, no correlation between mutation type and treat-
ment response has been reported.
45
The greatest treatment effect is realized in the first
2 years with benefits in terms of density and possibly
fracture reduction being maintained but not showing
the same degree of improvement thereafter.
46
Intravenous Bisphosphonates Other than
Pamidronate
A controlled trial on prepubertal OI patients who
received intravenous neridronate, a bisphosphonate
similar to pamidronate, yielded results that were com-
parable to those observed with pamidronate.
34,47,48
Observational studies on the effects of intravenous iban-
dronate have also been encouraging.
49,50
Zoledronate is
a newer intravenously applied bisphosphonate that has
been used in a few studies.
51-53
Zoledronic acid is a bisphosphonate which has recently
been the subject of an international multi-center drug
trial comparing its efficacy and safety to that of pamidro-
nate. The results of this trial have not yet been published.
However, because zoledronic acid is an infusion given
over 45 minutes for 1 day, its advantage in terms of dura-
tion of treatment may result in zoledronic acid becoming
the bisphosphonate of choice. Some observational studies
have found that intravenous zoledronic acid is an effec-
tive mode of treatment in children with OI.
52-54
ORAL BISPHOSPHONATES
Oral medication has obvious practical advantages
over intravenous infusions, at least in patients who are
