Effects of a @entity9045 antagonist on bone markers in XXXX .

@entity1 @entity2338 @entity442 @entity2012 @entity79 @entity31095 @entity1473 @entity9045
OBJECTIVE: Excess GH secretion, as occurs in @entity2012 , is associated with @entity79 markers and @entity79 ( @entity79 ). GH administration in @entity2338 @entity1 causes an @entity79 . @entity442 mediates many of the metabolic actions of GH, although GH may have direct effects upon bone. In @entity1 with @entity2012 who are treated with a @entity9045 antagonist, selective blockade of the @entity9045 results in a decrease in circulating @entity442 levels in the majority of cases. We hypothesized that, in @entity2012 , antagonism of GH receptors would result in a decrease in serum markers of bone turnover, including serum procollagen I @entity1473 -terminal propeptide (PICP), osteocalcin and @entity31095 (NTx). DESIGN AND SUBJECTS: Twenty-seven @entity1 with @entity2012 were enrolled as part of a multicentre 12-week trial of a @entity9045 antagonist and were randomized to placebo (n = 7) or 10, 15 or 20 mg of pegvisomant (n = 20). MEASUREMENTS: Serum markers of bone turnover were determined at baseline and 12 weeks. RESULTS: Baseline bone turnover markers were above the upper limit of normal in 23%, 19% and 32% of subjects for osteocalcin, PICP and NTx, respectively. During the 12-week placebo-controlled period, there were significant decreases in serum markers of bone formation, osteocalcin (-2.2 +/- 0.44 vs. placebo +0.01 +/- 0.39 nmol/l, P = 0.009) and PICP (-23.6 +/- 9.6 vs. placebo +18.1 +/- 12.8 micro g/l, P = 0.022) and a serum marker of bone resorption, NTx (-4.4 +/- 1.4, placebo +1.0 +/- 0.3 nm, P = 0.024). CONCLUSIONS: Using a specific @entity9045 antagonist, we found that normalization of @entity442 is associated with rapid reductions in markers of both bone formation and resorption, and that these processes remain coupled. These data confirm the highly significant effects of GH and @entity442 in modulating bone turnover. The independent contributions of GH and @entity442 to these effects and the long-term effects on @entity79 in this population remain to be determined.
