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TABLE 55.1
Bone Biomarkers
et al. reported that serum levels of total AP and osteo-
calcin were slightly higher in OI adults than in controls
but the differences were not significant. Reports have
indicated that serum procollagen I-N-terminal pro-
peptide (PINP) was lower than in controls, suggesting
a lower rate of type I collagen synthesis.
19-21
However,
Lund et al. reported both osteocalcin and PINP were
normal in OI adults.
22
Shapiro reported that osteocal-
cin values were low in 40% of OI adults.
23
Additionally,
low plasma concentration of PICP (type I collagen
C-propeptide) has been reported in OI patients sug-
gesting diminished osteoblast activity in the presence of
type I collagen mutations.
20,22-26
Adults with OI type I
had lower PICP levels than did adults with OI III and
I V.
22
However, no relationship of biomarker levels to
specific type I collagen mutations has been reported.
Markers of Bone Formation
Source
Osteocalcin
Osteoblast
Type I collagen N-propeptide (PINP)
Cleaved following
collagen processing
Bone-specific alkaline phosphatase (AP)
Osteoblast
Type I collagen C-propeptide (PICP)
Cleaved following
collagen processing
Total alkaline phosphatase
Osteoblast
Markers of Bone Resorption
Source
N-terminal telopeptide (NTX)
Cleaved following
collagen processing
C-terminal telopeptide (CTX)
Collagen crosslinks
Pyridinoline (PYD)
Collagen degradation
products
Bone Biomarkers Reflecting Bone Resorption
Biomarkers of bone resorption may be specifically
helpful in following the response to different treatment
modalities including the response to anti-resorptive
treatment. Shapiro reported low excretion of deoxypyr-
idinoline (DPD) in 40% of OI adults and high excretion
in 20%.
23
Braga et al. reported that urinary DPD and
N-terminal crosslink telopeptide (NTX) were higher in
adults with OI than in controls: patients with OI type
III and IV had significantly higher values than patients
with type I OI. However, serum C-terminal telopep-
tide (CTX) levels were normal.
18,22
In OI adults, Lund
reported that CTX levels were higher in OI type III and
IV than in OI type I.
22
Cepollaro et al. reported that uri-
nary excretion of hydroxyproline (HYP) and pyridino-
line (PYD) were slightly, but not significantly, higher in
OI adults.
20
Garero et al. first reported increased levels
of type I collagen helical peptide and a higher ratio of
the native (αCTX) isoform to isomerized C-telopeptide
(βCTX) in OI adults.
19
Wekre et al. reported that the
bone marker levels in OI adults didn't show a major
difference from normal. However, consistent with
other reports, adults with OI type III had higher bone
resorption marker levels than adults with OI type I or
I V.
27
Garnero et al. have suggested that non-enzymatic
post-translational modifications of collagen, urinary
type I collagen helical peptides and the ratio of the
native (αCTX) to isomerized C-telopeptide (βCTX) may
be more reliable indices of overall bone resorption and
bone matrix maturation in patients with OI.
19
Hydroxyproline (HYP)
Collagen degradation
products
Deoxypyridinoline (DPD or D-Pyr)
Collagen degradation
products
Tartrate-resistant acid phosphatase (TRAP5b)
Osteoclast
in determining the response to various treatments. The
commonly used bone biomarkers are listed in
Table 55.1
.
Rauchenzauner et al. provided sex- and age-specific
reference curves for serum bone formation (osteocalcin
and bone alkaline phosphatase) and bone resorption
markers (ICTP, CTX and TRAP 5b) in children aged
2 months to 18 years.
10
In general, and consistent with
higher rates of bone turnover, higher serum concen-
trations of bone markers are observed in infancy and
mid-puberty.
11-16
Astrom et al. have pointed out that in
children, measurement of biomarkers is more complex
because both bone modeling and remodeling occur,
which are influenced by gender, Tanner stage, whole-
body bone mineral content, height velocity and the
rate of whole-body bone mineral content.
17
Of inter-
est was the observation that there were no significant
differences between OI types I, III and IV and a non-
ambulatory, immobilized comparison group according
to age, gender, serum PTH or urinary deoxypyridino-
line (DPD)/creatinine.
Bone Biomarkers Reflecting Bone Formation in
Adults with OI
In adults with OI, high, normal or low concentra-
tions of bone biomarkers have been reported. Serum
total alkaline phosphatase (AP), bone-specific AP and
osteocalcin were reportedly 50 to 200% higher in OI
adults than in controls.
18
Osteocalcin levels were also
reported to be high in OI adults.
19
However, Cepollaro
Bone Biomarkers as Reflecting Treatment
Results and Compliance
Bisphosphonates are currently the most commonly
prescribed bone active agents for individuals with OI.
Bisphosphonates vary widely in potency but share the
