what-when-how
In Depth Tutorials and Information
to bisphosphonate treatment.
33
A total of 210 patients
were studied. A favorable response to bisphosphonate
therapy was seen in 47% (
N
= 99/210). As noted above
by Peris, patients with a mean 25(OH)D ≥33 ng/ml
had ~4.5-fold greater odds of a favorable response
(
P
<0.0001). Confirming the relationship between serum
25(OH)D levels and the response to bisphosphonate, a
1 ng/ml decrease in 25(OH)D was associated with an
~5% decrease in odds of responding.
Although the applicability of these results to the gen-
erally negative bisphosphonate treatment response in
adults with OI is not clear, it would appear that adults
with OI should maintain normal serum 25(OH)D lev-
els in order to maintain adequate calcium and phos-
phorus absorption and adequate bone mineralization.
However, excessive intake with vitamin D (or calcium)
is not warranted in order to avoid increasing urinary
calcium excretion and a potential increase in renal stone
formation.
effect of inhibiting the mevalonate pathway and pro-
tein prenylation in the osteoclast, thus decreasing bone
resorption.
28
Shortly after starting treatment serum CTX
will decrease followed by a decline in osteocalcin and
alkaline phosphatase. The extent of these changes will
vary with the individual bisphosphonate, being more
profound with the newer nitrogen-containing bisphos-
phonates (see Chapter 53).
Although several studies have suggested that bone
biomarkers may help predict the fracture risk in the
osteoporotic elderly,
29-31
no consensus on the relation-
ship of bone biomarkers and fracture rate has been
reached in adult OI patients.
In summary, conflicting data for the effects of treat-
ment on bone biomarkers may be due to (1) the
patient's ambulatory status may alter biomarker levels,
and (2) environmental factors (medications, hormonal
status, physical activities, etc.) could confound interpre-
tation of the bone biomarker levels.
23
VITAMIN D AND THE RESPONSE TO
TRE
ATMENT IN ADULTS WIT
H OI
DIETARY CALCIUM SUPPLEMENTS IN
ADULTS WITH OI
Vitamin D metabolism in OI is discussed in
Chapter 56. As is common to other adult populations,
vitamin D insufficiency occurs in approximately 50%
of OI adults. In postmenopausal osteoporosis, serum
25-hydroxyvitamin D [25(OH)D] levels are associ-
ated with the response to bisphosphonate treatment.
33
However, the relationship of vitamin D sufficiency to
pharmacological treatment in adults with OI has not
been addressed. Peris et al. assessed the role of vitamin
D in determining the response to standard bisphos-
phonate treatment for 120 postmenopausal osteopo-
rotic women (aged 68 ± 8 years) receiving alendronate
or risedronate.
32
This study analyzed the change in
bone mineral density (BMD) serum PTH, 25(OH)D and
urinary NTx levels. Inadequate response to anti-
osteoporotic treatment was based on a BMD loss >2%
and/or the presence of fragility fractures during the
preceding year. Thirty percent of patients showed
inadequate response to blood pressure treatment, with
significantly lower levels of 25(OH)D (22.4 ± 1.3 vs.
26.6 ± 0.3 ng/ml), a higher frequency of 25(OH)D lev-
els <30 ng/ml (91% vs. 69%) and higher urinary NTx
values. The probability of an inadequate response to
bisphosphonate was four-fold higher in patients with
25(OH)D <30 (OR, 4.42; 95% CI, 1.22-15.97,
p
= 0.02).
Patients with 25(OH)D >30 ng/ml had a greater signifi-
cant increase in lumbar BMD than women with values
<30 ng/ml (3.6% vs. 0.8%).
In a similar manner, Carmel et al. found that in post-
menopausal osteoporosis patients, serum 25(OH)D
level was strongly associated with a positive response
Total daily calcium intake by adults with OI is
highly variable. Standards for calcium supplemen-
tation in all adults have been recommended by the
Institute of Medicine Committee convened to Review
Dietary Reference Intakes for Vitamin D and Calcium.
34
Recommended values proposed for healthy individu-
als were as estimated average requirements (EARs)
and recommended dietary allowances (RDAs) or,
alternatively, adequate intakes (AIs). The recommen-
dations for adults 19 through 50 years of age were:
EAR 800 mg/day and RDA 1000 mg/day. For men 51
through 70 years of age: EAR 800 mg/day calcium; for
women 51 through 70 years of age: EAR 1000 mg/day
calcium, RDA 1200 mg/day calcium. And for adults
>70 years of age: EAR 1000 mg/day calcium, RDA
1200 mg/day calcium. Such standards for adults with
OI have not been determined. Important considerations
for this would include total diet intake in addition to
supplements, the influence of body size on calcium
requirements and the potential negative effect which
includes hypercalcuria or renal stone formation.
BISPHOSPHONATE TREATMENT IN
ADULTS WITH OI
The results of bisphosphonate treatment in children
have in general been positive: decreasing musculoskel-
etal pain, permitting vertebral growth and decreasing
fracture risk by approximately 50%.
35
However, several
exceptions exist: intravenous bisphosphonates such as
