Pathophysiological aspects and therapeutic approaches of tumoral osteolysis and hypercalcemia.
Malignant tumors can affect the integrity of the skeletal tissue and the homeostasis of the two main components of bone mineral, calcium (Ca) and inorganic phosphate (Pi). Various tumoral cell products can increase bone resorption by influencing the number of osteoclasts and/or their activity. These tumoral products could act either directly on bone cells of the osteoblastic or osteoclastic lineages, or indirectly by influencing cells secreting osteotropic factors, such as interleukin-1, tumor necrosis factors, transforming growth factors, and colony-stimulating factor. Among the classical calciotropic hormones, 1,25-dihydroxyvitamin D3 could be implicated in lymphoma. In hypercalcemia of malignancy, an increase in bone resorption is observed in most patients. However, in many cases an increased tubular reabsorption of Ca has been documented as well. This phenomenon when present after adequate rehydration is probably due to the secretion by the tumoral cells of a parathyroid hormone-related peptide (PTHrP). This factor has been recently identified as a protein containing 141 amino acids. This protein or some very close analogs have been shown to be secreted by lung, kidney and also breast carcinoma. Besides increasing bone resorption and stimulating tubular reabsorption of Ca, PTHrP also selectively decreases the tubular reabsorption of Pi, an action that may explain the hypophosphatemia observed in some types of neoplasm. Therapeutically, administration of antiresorbing agents such as clodronate or other bisphosphonates can normalize the increased osteolysis and, if present, the associated elevation in the plasma level of Ca in most cancer patients. However in some cases, wherein the prevailing hypercalcemic mechanism is due to an enhancement in the tubular reabsorption of Ca, other therapeutic means should be associated with the antiosteolytic bisphosphonate therapy.
Bonjour
J P
JP
Department of Medicine, University Hospital, Geneva, Switzerland.
Rizzoli
R
R
D001842:Bone and Bones / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism; D006801:Humans; D006934:Hypercalcemia / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D007668:Kidney / Q000503:physiopathology; D009369:Neoplasms / Q000150:complications*; D010014:Osteolysis / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*
D002118:Calcium