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pamidronate appear more effective than orally admin-
istered bisphosphonate (alendronate, residronate) in
decreasing fracture incidence.
36,37
While many children
do respond, there is a sizable population of children
who do not decrease their fracture risk during bisphos-
phonate treatment. Children treated with pamidronate
may also experience limb fractures even when the limb
is rodded.
The generally favorable outcomes in children have
proven more difficult to demonstrate in adults for sev-
eral reasons. First, the measurement of BMD by dual
X-ray absorptiometry (DXA) is more difficult in many
OI adults because of the progression of their bone
deformity over time. OI adults frequently have surgi-
cal hardware in their limbs or spine which affects the
ability of these sites to be measured by DXA. Second,
unlike the relatively high fracture rate in children, the
incidence of fractures decreases dramatically after
puberty. Thus, assessing fracture incidence in response
to treatment during mid-life is more difficult. Finally,
treatment results are harder to assemble in adults
because compliance with both testing schedules and
treatment is less stringent for adults as compared with
children whose parents oversee the details involved in
day-to-day care.
38
Considering the widespread use of bisphospho-
nates in osteoporosis treatment, it was recognized that
they would be administered to adults with OI. This has
involved both oral and intravenous medications; the
results of these trials are summarized below. To date,
these clinical studies are compromised by the relatively
small numbers of each reported OI type. In interpreting
the results of treatment studies, it is important to note
that OI is not equivalent to postmenopausal osteoporo-
sis so that treatment results are not comparable to those
in the osteoporotic population.
Chevrel et al. studied the effects of oral alendro-
nate on BMD in 64 adult patients in a 3-year random-
ized placebo-controlled trial.
39
Patient distribution
was Sillence OI type: type I/type IV; 33/0 and 29/2
for placebo and treatment groups, respectively. Each
patient received 1000 mg elemental calcium and 800 IU
of vitamin D
3
daily. Mean increases in the lumbar spine
BMD were 10.1 ± 9.8%, total hip BMD increased by
3.3 ± 0.5%. Although the sample size was not sufficient
to determine an effect of alendronate on fracture rate
the incidence of vertebral and peripheral fractures was
not significantly different between the alendronate and
placebo groups. Two vertebral and 17 peripheral frac-
tures occurred in eleven patients in the placebo group
versus no vertebral and 17 peripheral fractures in ten
patients in the alendronate group.
Adami et al. treated 46 OI adults for 2 years at 3
month intervals with intravenous neridronate com-
pared with a no-treatment group of 23 individuals.
40
The patients were randomized according to OI type
(type I or type III and IV) to either i.v. neridronate or
no treatment. Spine and hip BMD rose by 3.0 ± 4.6%
(SD) and by 4.3 ± 3.9%, respectively, within the first
12 months of treatment, and an additional 3.91 and
1.49% during the second year. One vertebral fracture
and one limb fracture occurred in the control group
during the first year of observation. One limb fracture
was recorded in the treatment patients, but no frac-
tures occurred in the control group while on treatment
during the second year of follow-up. Overall, 18 clini-
cal fractures during 4 years prior to recruitment had
been reported by 16 patients. The difference in fracture
incidence during treatment and during pooled pre-
recruitment and control times was “at the limit of sig-
nificance” (
p
= 0.03; Fisher's exact t-test). The authors
concluded that a trend for a reduction in fracture rate
was observed, which was significant by pooling retro-
spective and prospective events. Although the study
was not powered for such an endpoint the results may
be considered inconclusive.
Pavon de Paz et al. carried out a prospective non-
randomized study in ten OI patients with “osteoporosis
or severe osteopenia (T score<−2)” who could not use
oral bisphosphonates.
41
Zoledronic acid was admin-
istered i.v. every 6 months. Treatment increased BMD
measured in the lumbar spine after 24 and 36 months.
Significant increases in BMD were also observed after
24 months in the femoral neck. Serum Ca, P, bone alka-
line phosphatase and CTX concentrations remained
unchanged, which is not expected as bone biomarkers
will decrease with zoledronic acid infusions. However,
effect on fracture rate could not be evaluated as none of
the patients had new fractures.
Shapiro et al. analyzed the results of treatment with
oral and intravenously administered bisphosphonates
in 90 adults with OI with the following distribution
of OI types: 63 type I, 15 type III and 12 type IV. The
age range was 17-68 years, mean (SD) age was 39 (11)
years. Males and females were grouped for this analy-
sis. Adults were treated with intravenous pamidronate
(
n
= 28), oral alendronate (
n
= 10), residronate (
n
= 17)
or not treated (
n
= 35). BMD results were observed for
up to 161 months, following an average of 52 months of
treatment (
Figure 55.2A and B
).
This study demonstrated that intravenous pamidro-
nate and the oral bisphosphonates, alendronate and
residronate, both have a positive effect on BMD when
measured as the annualized linear rate of change in
BMD after a minimum of 13 months of treatment. In
type I patients, BMD was increased by both pamidro-
nate and the oral bisphosphonates at L1-L4 and by the
oral bisphosphonates at the total hip. In type III/IV
patients pamidronate increased BMD at the L1-L4
site and at the total hip. The oral agents did not increase
