Winer et al. • Treatment of Hypoparathyroidism with PTH-(1–34)
J Clin Endocrinol Metab, September 2003, 88(9):4214–4220 4219 TABLE 2. Mean BMD and BMC values in the two treatment groups a P value calculations were based on measurements at 0, 0.5, 1, 1.5, 2, 2.5, and 3 yr. b BMD, grams per square centimeter; BMC, grams.
hypercalciuria in the calcitriol-treated group did not cause a
due to hypoparathyroidism and/or an anabolic effect of
decrease in renal function. The reduction of urinary calcium
calcitriol and calcium supplementation.
was achieved in the PTH arm despite the greater number of
At the time of study entry, 19 subjects were receiving PTH
patients with gain of function mutations, who tend to pro-
therapy associated with their participation in prior studies.
duce greater elevations of urinary calcium.
This explains the elevated bone markers at the initial time
Both treatments produced similar bone mineral changes
point in this study. For those patients in the calcitriol arm, the
despite increased levels in bone turnover markers in the PTH
decrease in bone markers suggests that the acute PTH effect
arm. The bone mineral response to PTH in patients with
had largely disappeared within the initial 6 months of the
hypoparathyroidism, who have high normal or above nor-
study. For most subjects mean levels of bone markers re-
mal bone density at baseline, contrasts with that of osteo-
mained elevated in the PTH-treated group at the end of the
porotic patients to once daily PTH administration, which is
3-yr study period. However, three patients demonstrated
associated with high bone turnover and a rapid rise in BMD
normalization of these markers at the end of the PTH treat-
(25, 26). However, the increase in femoral neck BMD and the
ment period, and the 3-yr study period may have been in-
decrease in the distal radius density in the PTH arm may
sufficient to observe normalization in the other subjects.
reflect changes in bone similar to the effects of PTH in pa-
The safety of long-term PTH treatment in humans has been
tients with osteoporosis (18, 27). A closer examination of the
questioned recently due to a report of increased dose-
PTH effect on cortical bone, as measured in the distal radius,
dependent osteosarcoma risk in PTH-treated rats (29). How-
in humans with osteoporosis using volumetric analysis by
ever, our 3-yr study of twice daily PTH as replacement
pQCT shows an overall positive effect with significant in-
therapy showed a rise in markers of bone turnover, but no
creases in cortical bone area, mineral content, and periosteal
apparent adverse changes in the bone or in BMD. To achieve
and endocortical circumferences (28). These observations
more physiological replacement and further minimize the
suggest that PTH treatment of hypoparathyroidism, as in
potential adverse effects on the bone, other treatment options
treatment of osteoporosis, may be associated with some in-
may be considered in the future, such as long-acting PTH,
creased cortical porosity accompanied by concurrent in-
PTH pump therapy, or three times daily PTH injection.
creases in new bone at the periosteal and endocortical
Although subjects described an improved quality of life
and greater physical endurance with PTH therapy, prelim-
In this study the calcitriol-treated group experienced a rise
inary studies of physical endurance showed no difference
in BMD over time, which to our knowledge represents the
between the two treatment groups. A double-blind, placebo-
first longitudinal data showing increasing BMD in calcitriol-
controlled trial would be necessary to definitively investigate
treated adult patients with this disorder. This rise in bone
density presumably results from decreased bone resorption
In conclusion, PTH is a safe and effective alternative to
BAUBESCHREIBUNG Grundstücksbeschreibung 67434 Neustadt an der Weinstraße, Ortsteil Hambach Die geplante Anlage befindet sich in Neustadt an der Weinstraße im Ortsteil Hambach. Derzeit befinden sich ein Haus und ein Lagerschuppen auf diesem Grundstück. Beide Gebäude werden vor der Baumaßnahme abgerissen um Platz und Sicht für das neue Dreifamilienhaus zu schaffen. Durch die aus
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