what-when-how
In Depth Tutorials and Information
CHAPTER
54
Bisphosphonate Treatment and Related
A
gents in Children
Frank Rauch
Shriners Hospital for Children, Montreal, QC, Canada
Osteogenesis imperfecta (OI) cannot be cured at
present, so the goal is to “manage” the disease rather
than to heal it. The management of OI includes multi-
disciplinary input with experienced medical, orthope-
dic, physiotherapy and rehabilitation specialties.
1
OI
management ideally should take place in a specialized
center.
The hypothesis initially underlying the use of an
anti-osteoclast medication in an osteoblast disorder
such as OI was that a decrease in the activity of the
bone resorbing system might compensate for the weak-
ness of the bone forming cells. The use of these drugs
in OI and other pediatric disorders became widespread
after the 1998 publication of a series of children and
adolescents with OI who had been treated with cyclical
intravenous pamidronate.
5
Although the quality of the new bone that is formed
remains unchanged, the bones benefit from greater
mechanical strength due to overall increased bone
mass. Traditionally intravenous pamidronate has been
used in children. There is less information on intra-
venously administered bisphosphonates other than
pamidronate.
INTRAVENOUS BISPHOSPHONATE
TREATMENT
Bisphosphonate therapy has been used widely for
over 15 years in children with moderate to severe
OI and is now considered the standard of care.
2,3
Bisphosphonates are potent anti-resorptive agents that
inhibit osteoclast function. The chemical structure of all
bisphosphonates is based on a P-C-P backbone resem-
bling pyrophosphate (P-O-P), a naturally occurring
molecule that is involved in the mineralization process.
4
The chemical structure explains the affinity of bisphos-
phonates for mineralized surfaces. The various mem-
bers of the bisphosphonate family differ in the two side
chains that are attached to this backbone molecule.
More than a dozen bisphosphonates have been
used in humans.
4
From a clinician's perspective, this
class of drugs can be separated into “oral bisphos-
phonates” and “intravenous bisphosphonates.” This
distinction does not indicate some fundamental differ-
ences in physico-chemical characteristics between these
compounds, but rather reflects the marketing deci-
sions of the pharmaceutical companies that produce
bisphosphonates.
Effects of Intravenous Pamidronate
Cyclical intravenous pamidronate is currently the
most widely used medical therapy for children with
moderate to severe OI. Pamidronate is often given
in cycles of 3 days.
6
Cycles are repeated every 2 to 4
months depending on the age of the child. In the most
widely used protocol this corresponds to an annual
dose of 9 mg per kg bodyweight.
6
Another widely used
treatment schedule consists of monthly infusions at a
body surface area adjusted dose.
7-9
Apart from hospital-
based treatment, pamidronate is sometimes given
in home health care settings if adequate support is
available.
10
Bone resorption decreases immediately follow-
ing the first infusion of pamidronate, and the level of
