BACKGROUND: Neoplasia may produce a spectrum of dysregulatory effects on bone and mineral metabolism. The range of these effects and the known molecular mechanisms causing them are reviewed. METHODS: The current review is mainly based on previously published scientific reports from North America, Europe, and Japan that were identified from references in the literature. RESULTS: Osteolysis is the most common skeletal manifestation of neoplasia and may be focal or generalized. When tumors release abundant parathyroid hormone-related peptide (PTHrP) into the circulation, this may act as an endocrine substance to produce generalized osteopenia and, ultimately, hypercalcemia. PTHrP also may act in a paracrine manner to enhance focal osteolysis associated with metastasis and to generate hypercalcemia. The increased circulating PTHrP in tumor states also can augment serum calcium by renal mechanisms. PTHrP may contribute to focal osteolysis by tumor metastases, even in the absence of hypercalcemia. Strategies to reduce PTHrP production or PTHrP signaling, therefore, may be useful to treat the tumor-induced bone resorption induced both in hypercalcemic and nonhypercalcemic states. The most commonly used intervention, bisphosphonates, targets the osteoclast directly. Although osteolytic lesions generally occur with some degree of reactive new bone formation, osteoblastic lesions may be particularly abundant in association with certain tumors, such as prostate carcinoma. The mechanisms underlying these lesions remain unknown; however, a variety of osteoblast growth factors may contribute. These include the urokinase system, which may have growth factor activity as well as enzymatic activity. Finally, osteomalacia may be a manifestation of tumors either through accelerated bone formation with insufficient mineralization or through the production of a phosphaturic substance. CONCLUSIONS: Elucidation of the mechanisms underlying the spectrum of skeletal manifestations of neoplasia is yielding important insights into both tumor diagnosis and patient management.
BACKGROUND:Neoplasia may produce a spectrum of dysregulatory effects on bone and mineral metabolism. The range of these effects and the known molecular mechanisms causing them are reviewed. METHODS: The current review is mainly based on previously published scientific reports from North America, Europe, and Japan that were identified from references in the literature. RESULTS:Osteolysis is the most common skeletal manifestation of neoplasia and may be focal or generalized. When tumors release abundant parathyroid hormone-related peptide (PTHrP) into the circulation, this may act as an endocrine substance to produce generalized osteopenia and, ultimately, hypercalcemia. PTHrP also may act in a paracrine manner to enhance focal osteolysis associated with metastasis and to generate hypercalcemia. The increased circulating PTHrP in tumor states also can augment serum calcium by renal mechanisms. PTHrP may contribute to focal osteolysis by tumor metastases, even in the absence of hypercalcemia. Strategies to reduce PTHrP production or PTHrP signaling, therefore, may be useful to treat the tumor-induced bone resorption induced both in hypercalcemic and nonhypercalcemic states. The most commonly used intervention, bisphosphonates, targets the osteoclast directly. Although osteolytic lesions generally occur with some degree of reactive new bone formation, osteoblastic lesions may be particularly abundant in association with certain tumors, such as prostate carcinoma. The mechanisms underlying these lesions remain unknown; however, a variety of osteoblast growth factors may contribute. These include the urokinase system, which may have growth factor activity as well as enzymatic activity. Finally, osteomalacia may be a manifestation of tumors either through accelerated bone formation with insufficient mineralization or through the production of a phosphaturic substance. CONCLUSIONS: Elucidation of the mechanisms underlying the spectrum of skeletal manifestations of neoplasia is yielding important insights into both tumor diagnosis and patient management.
Authors: Vasilios Liapis; Agatha Labrinidis; Irene Zinonos; Shelley Hay; Vladimir Ponomarev; Vasilios Panagopoulos; Mark DeNichilo; Wendy Ingman; Gerald J Atkins; David M Findlay; Andrew C W Zannettino; Andreas Evdokiou Journal: Cancer Lett Date: 2014-11-15 Impact factor: 8.679
Authors: J A Kiefer; R L Vessella; J E Quinn; A M Odman; J Zhang; E T Keller; P J Kostenuik; C R Dunstan; E Corey Journal: Clin Exp Metastasis Date: 2004 Impact factor: 5.150
Authors: Agatha Labrinidis; Shelley Hay; Vasilios Liapis; Vladimir Ponomarev; David M Findlay; Andreas Evdokiou Journal: Clin Cancer Res Date: 2009-04-28 Impact factor: 12.531