Special attention is given to their utility in clinical trials testing the efficacy of drugs for the treatment of osteoporosis and how they supplement bone mass measurements. Recent evidence suggests that biochemical markers may provide information on bone age that may have indirectly relates to bone quality; the latter is receiving increasing attention. A more targeted use of biomarkers could further optimize identification of high-risk patients, the process of drug discovery, and monitoring of the efficacy of osteoporosis treatment in clinical settings.
The aim of this review is to discuss the potential usefulness of a novel class of biochemical markers, designated neoepitopes. Neoepitopes are post-translational modifications (PTMs) of proteins and are derived by processes, such as protease cleavage, citrullination, nitrosylation, glycosylation and isomerization. Each PTM results from a specific local physiological or pathobiological process. Identification of each modification to a tissue-specific protein may reveal a unique disease-specific biochemical marker. During cancer metastasis, the host tissue is extensively degraded and replaced by cancer-associated extracellular matrix (ECM) proteins. Furthermore, severe cellular stress and inflammation, caused by cancer, results in generation of PTMs, which will be distributed throughout the ECM. This gives rise to release of protein-specific fragments to the circulation. Here we highlight the importance of remodeling of the ECM in cancer and the generation of PTMs, which may be cancer specific and reflect disease progression; thus having potential for biochemical marker development.
The World Health Organization defines osteoporosis as a systemic disease characterized by decreased bone tissue mass and microarchitectural deterioration, resulting in increased fracture risk. Since this statement, a significant amount of data has been generated showing that these two factors do not cover all risks for fracture. Other independent clinical factors, such as age, as well as aspects related to qualitative changes in bone tissue, are believed to play an important role. The term "bone quality" encompasses a variety of parameters, including the extent of mineralization, the number and distribution of microfractures, the extent of osteocyte apoptosis, and changes in collagen properties. The major mechanism controlling these qualitative factors is bone remodeling, which is tightly regulated by the osteoclast/osteoblast activity. We focus on the relationship between bone remodeling and changes in collagen properties, especially the extent of one posttranslational modification. In vivo, measurements of the ratio between native and isomerized C-telopeptides of type I collagen provides an index of bone matrix age. Current preclinical and clinical studies suggests that this urinary ratio provides information about bone strength and fracture risk independent of bone mineral density and that it responds differently according to the type of therapy regulating bone turnover.
Background: Osteoarthritis is associated with increased bone resorption and increased cartilage degradation in the subchondral bone and joint. The objective of the present study was to determine whether Tibolone, a synthetic steroid with estrogenic, androgenic, and progestogenic properties, would have similar dual actions on both bone and cartilage turnover, as reported previously with some SERMS and HRT.
BackgroundA number of biomarkers have been proven potentially useful for their ability to indicate bone metastases (BM) in cancer patients. The aim of this study was to investigate the relative utility of a newly developed N-terminal propeptide of collagen type I (PINP) human serum assay for the detection of BM in cancer patients. This assay has a corresponding rat PINP assay which in the future might help in translational science between rodent and human trials.MethodsParticipants were 161 prostate, lung and breast cancer patients stratified by number of BM (Soloway score). PINP was assessed and correlated to number of BM. Additionally, the PINP marker was correlated to bone resorption of young (ALPHA CTX-I)- and aged bone (BETA CTX-I); number of osteoclasts (Tartrate-resistant acid phosphatase 5b, TRACP5B) and osteoclast activity (CTX-I/ TRACP5B).ResultsPINP was significantly elevated in breast- and prostate cancer patients +BM, compared to −BM (P < 0.001), however not in lung cancer patients. A strong linear association was seen between PINP and the number of BMs. Significant elevation of PINP was observed at Soloway scores 1–4 (<0 BM) compared with score 0 (0 BM) (P < 0.001). The correlation between bone resorption of young bone or aged bone and bone formation was highly significant in patients +BM and −BM (P < 0.0001).ConclusionsData suggest that the present PINP potentially could determine skeletal involvement in patients with breast or prostate cancer. Correlations suggested that coupling between bone resorption and bone formation was maintained in breast- and prostate cancer patients.
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