The emergence of bone metastases disrupts normal bone homeostasis by perturbing interactions between bone-forming osteoblasts and bone-resorbing osteoclasts [ 2].
This occurs via a number of mechanisms including removal of dead tumour cells, the development of bone sclerosis, re-emergence of yellow marrow, loss of tissue water (Fig. 6), secondary myelofibrosis and decreased tissue perfusion.
The emergence of bone as an endocrine regulator has prompted a re-evaluation of the role of bone mineralization factors in the development of metabolic disease.
The emergence of bone as an endocrine regulator has led to the re-evaluation of the role of bone mineralization factors in the development of metabolic disease.
For these reasons there has been an emergence of bone graft substitutes for trauma applications and in particular synthetic materials based on calcium phosphates and/or apatite calcium sulfates.
Clinical application of earlier microtubule inhibitors, however, unfortunately showed several limits, such as neurological and bone marrow toxicity and the emergence of drug-resistant tumor cells.
As tumour microenvironment has a critical role in tumour aggressiveness and androgen sensitivity is a key feature of CaP cells, it is plausible that bone metastases contribute to the emergence of CRPC.
While vancomycin has long been the gold standard for the treatment of bone and joint infections, the emergence of glycopeptide tolerance and resistance to vancomycin, resulting in clinical failures [ 23, 26, 30, 31], demonstrate the need for alternative treatments.
In complete contrast to the pattern of emergence of the bone metastases, however, the difference in the proportion of patients developing non-osseous metastases only appeared after patients had stopped the clodronate/placebo medication.
An interesting point of view is that low levels of complement could result in a loss of central tolerance in the bone marrow, leading to the emergence of autoreactive clones and predisposing to autoimmunity [ 117– 119], especially autoimmune haemolytic anemia and immune thrombocytopenia.
