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CHAPTER
56
Pharmacologic Treatment of
Osteogenesis Imperfecta: New Agents
and their Potential Implications for
Ost
eogenesis Imperfe
cta
Eric S. Orwoll and Elizabeth Martin
Oregon Health and Science University, Portland, OR, USA
INTRODUCTION
given the lifelong course of disease and need for differ-
ent outcomes in children as compared to adults with
OI. Experience with pamidronate in children suggests
that the bisphosphonates, which act by uncoupling
bone remodeling and increasing cortical both mass
and density, decrease fracture rate and allow improved
growth.
7
However these agents do not affect the under-
lying mutation resulting in collagen defects, altered bone
deposition, or poor bone quality observed in OI.
4
In chil-
dren and adolescents with OI, improvements in corti-
cal bone mineral density are correlated with decreased
fractures and improved growth, as well as decreased
measures of chronic bone pain.
6,7
Bone mineral density
and reductions in chronic pain are similarly important in
the adult population, but the use of bisphosphonates or
osteoporosis medications has not been as well described
in adults with OI.
8
In this group increases in bone min-
eral density from bisphosphonate therapy have not been
clearly associated with decreased fracture rates, possible
due to mineralization defects associated with OI.
Recent research has led to the development of
several new pharmacologic agents currently in clini-
cal trials, and led to a better understanding of other
agents approved for use in osteoporosis treatment that
may also have potential benefits for OI. While none of
these agents correct the underlying collagen defects
and affected bone quality in OI, they may warrant trials
in the OI population. In this chapter we will describe
supplements currently under question for use in OI in
Our understanding of bone remodeling has
expanded greatly in the past decade, as has our
understanding of the collagen defects underlying
types of osteogenesis imperfecta (OI). The pheno-
types classified as OI types I-IV, originally described
by Sillence et al., involve primary collagen muta-
tions in COL1A1 and COL1A2. These mutations
result in either
1
secretion of a decreased quantity of
collagen in type I OI, or
2
collagen production incor-
porating mutated procollagen chains, thereby result-
ing in a qualitative
9,10
defect in the synthesis of bone
in other OI types.
11-13
Description of new mutations
underlying other OI types, including the CRTAP and
LEPRE1 mutations affecting procollagen hydroxyl-
ation, similarly lead to qualitative defects in collagen
formation.
12,13
To date pharmacologic treatment of OI consists of
agents developed for osteoporosis. Currently bisphos-
phonates are the mainstay of pharmacologic treatment
in OI, with both oral and intravenous forms described
predominantly in the pediatric population.
1-4
They
are frequently used in combination with vitamin D
and calcium supplementation. Bisphosphonates were
originally developed in the 1800s, and while not rec-
ognized to have biologic effects on bone remodeling
until 1968, they now have a well-established role in the
treatment of osteoporosis.
5
Their use in OI is unique
