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Clinical Chemistry 44: 1621-1628, 1998;
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(Clinical Chemistry. 1998;44:1621-1628.)
© 1998 American Association for Clinical Chemistry, Inc.

Enzymes and Protein Markers

Differences of bone alkaline phosphatase isoforms in metastatic bone disease and discrepant effects of clodronate on different skeletal sites indicated by the location of pain

Per Magnusson1,a, Lasse Larsson1, Gunnar Englund2, Brita Larsson1, Peter Strang3, and Lena Selin-Sjögren4

1 Bone and Mineral Metabolic Unit, Division of Clinical Chemistry, Department of Biomedicine and Surgery, Linköping University Hospital, S-581 85 Linköping, Sweden.

2 Department of Mathematical Statistics, Royal Institute of Technology, S-100 44 Stockholm, Sweden.

3 Division of Oncology, Department of Biomedicine and Surgery, Linköping University Hospital, S-581 85 Linköping, Sweden.

4 Clinical Research, Medical Department, Astra Läkemedel AB, S-151 85 Södertälje, Sweden.
a Author for correspondence. Fax 46-13-223240; e-mail Per.Magnusson{at}klk.liu.se.

We compared clodronate with placebo administration in 42 primarily or secondarily hormone-refractory prostate cancer patients with skeletal metastases and persisting pain. Serum total alkaline phosphatase (ALP), bone ALP isoforms, osteocalcin, cross-linked carboxy-terminal telopeptide of type I collagen, and prostate-specific antigen were analyzed before and after 1 month of treatment. Six ALP isoforms were quantified by HPLC: one bone/intestinal, two bone (B1, B2), and three liver ALP isoforms. The most apparent difference compared with healthy males was observed for the bone ALP isoform B2. Patients and healthy males had a B2 activity corresponding to 75% and 35% of the total ALP activity, respectively (P <0.0001). We propose that the different bone ALP isoforms reflect different stages of osteoblast differentiation during the extracellular matrix maturation phase of osteogenesis. All bone markers except osteocalcin increased after 1 month of clodronate administration. These increases were associated with pain only in the upper part of the body. We suggest that the uptake of clodronate by the skeleton was not uniform during our treatment period.




The following articles in journals at HighWire Press have cited this article:


Home page
 J. Clin. Endocrinol. Metab.Home page
B. Fohr, C. R. Dunstan, and M. J. Seibel
Markers of Bone Remodeling in Metastatic Bone Disease
J. Clin. Endocrinol. Metab., November 1, 2003; 88(11): 5059 - 5075.
[Abstract] [Full Text] [PDF]


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