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biomarkers to 50% above baseline for the first 6 months,
then a return to values within 28% of baseline.
77
The
most commonly reported adverse effects with use of
odanacatib include back pain, arthralgia, extremity pain
and nasopharyngitis, with an increase in urinary tract
infections and cystitis.
77
No significant changes in serum
calcium levels have been observed.
77
A large phase 3
clinical trial in postmenopausal women was recently ter-
minated because of clearly favorable results concerning
both safety and anti-fracture efficacy. The evidence of
reduced bone resorption and increased periosteal bone
formation with odanacatib therapy, and the recent pre-
liminary report of anti-fracture efficacy in osteoporosis,
supports consideration for its use in OI. Further evi-
dence regarding the nature of its effects on bone metab-
olism, and its effects on fracture risk, will determine
whether trials in OI may be worth consideration.
of the pathways underlying bone remodeling has led
to the development of several new anabolic and anti-
resorptive agents with potential use in osteoporosis.
Although not yet evaluated, they may be safe and
effective in OI. These drugs affect the ratio of bone
resorption and bone deposition, with the intention of
improving bone strength and reducing fracture rates.
This approach should be most effective for the man-
agement of type I OI, in which bone microarchitecture
is relatively maintained. As observed with bisphos-
phonates, these newer agents may also reduce fracture
rates and improve growth in OI types III-VIII, but
overall bone quality will be more difficult to address
in OI types III-VIII. Most importantly, while newer
drugs may provide feasible management options, the
underlying collagen mutations in OI remain unad-
dressed. As research continues in OI, future areas of
focus may include methods of targeting and reversing
specific mutations identified in the type I collagen for-
mation pathways.
FUT
URE TARGETS FOR THER
APY
There are several unique aspects of OI that make
the use of drugs developed for osteoporosis more chal-
lenging. For the most part new medications for osteo-
porosis have been evaluated in older adults. Patients
with OI are likely to benefit most from treatment ini-
tiated in childhood and it is unclear at this time what
effects these new therapies may have on the develop-
ing skeleton. An additional issue regarding osteoporo-
sis medications is the limited information concerning
the most appropriate period of use. Antiresorptive
agents (bisphosphonates and denosumab) have not
yet been evaluated for long term administration, and
teriparatide should be administered for only two years.
Pharmacological approaches for OI would be most use-
ful if they possessed sustained effects or the capacity
for use over prolonged periods. Finally, while the new
agents discussed above may provide benefit in patients
with OI, none address the collagen mutations underly-
ing OI. Ideal therapies for OI would involve targeted
treatment of specific genetic mutations. Since there are
many mutations that may give rise to the various clini-
cal phenotypes of the disease, OI is an ideal target for
genetic interventions and the development of personal-
ized medicine.
References
CONCLUSIONS
[10]
To attempt to counteract the fragility resulting from
genetic mutations affecting proper collagen forma-
tion, pharmacologic treatment of osteogenesis imper-
fecta has consisted of available anti-resorptive agents
(bisphosphonates) in combination with vitamin D and
calcium supplementation. A greater understanding
[11]
[12]
