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

作者：Per Magnusson, Laşse Larsson, Gunnar Englund, Brita Larsson, Peter M. Strang, Lena Selin-Sjögren · 发表于：Clinical Chemistry · 年份：1998 · DOI：10.1093/clinchem/44.8.1621 · 被引用次数：48 · 研究领域：Bone health and treatments、Alkaline Phosphatase Research Studies、Bone and Joint Diseases

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.