Prostate Cancer, Serum Parathyroid Hormone, and the Progression of Skeletal Metastases

Abstract

Bony metastases from prostate cancer are a significant cause of morbidity and mortality. These metastases are predominantly blastic (bone-forming) and commonly cause increased serum levels of parathyroid hormone (PTH) as calcium ions are transferred from serum into blastic bone. The epidemiologic and clinical significance of secondary hyperparathyroidism in advanced prostate cancer have not been widely appreciated. Prostate cancer bony metastases show increased expression of the PTH receptor (PTH-IR) and PTH promotes the growth and invasiveness of prostate cancer cells in bone. Thus, blastic metastases appear to induce a ''vicious cycle'' in which PTH resorbs normal bone to support the growth of blastic bone. Recognition of the potential role of PTH in the progression of skeletal metastases suggests novel opportunities for prostate cancer secondary prevention. In particular, we propose that suppressing serum PTH in advanced prostate cancer may reduce morbidity by decreasing fractures and pain caused by bone resorption and may reduce mortality by retarding the progression of metastatic disease. (Cancer Epidemiol Biomarkers Prev 2008; 17(3):478 -83)

A Prospective Study of Total and Ionized Serum Calcium and Time to Fatal Prostate Cancer

“…Finally, our results may have been influenced by the inclusion of occult, metastatic cancer. However, because metastatic prostate cancer is characterized by low normocalcemia and/or hypocalcemia, this would bias our results in a conservative direction (33).…”

Prostate cancer in African-American men and polymorphism in the calcium-sensing receptor

“…Serum levels of PTH are known to be positively correlated with serum levels of PSA and to promote the progression of prostate cancer metastases to bone. 12,31 Thus, the association of the G allele of the CaSR with lower levels of PTH could provide a mechanism for the lower prevalence of advanced disease and the significantly older age at diagnosis that we observed for men with the GG (EE) genotype. Further studies of the association of CaSR polymorphisms with prostate cancer risk are warranted.…”

“…12,13 These findings suggest that factors that influence serum levels of calcium and/or PTH may play roles in the pathogenesis of prostate cancer. Polymorphisms in the CaSR gene have been examined in studies of colorectal cancer but have not previously been examined in prostate cancer.…”

Pathogenesis and Bisphosphonate Treatment of Skeletal Events and Bone Pain in Metastatic Cancer: Focus on Ibandronate

“…Of these, the former is the most common and is associated with increased osteoclast activity and subsequent bone destruction [3].Osteoblasticlesionsarelesscommon,areseenat sitesofpreviousosteoclasticboneresorption,andarecharacterisedbyweakandpoorlyorganisedwovenbonethatfractures easily [9]. Breast cancer bone metastases tend to be either osteolytic (approximately 50%) or mixed osteolytic/ osteoblastic(approximately40%) [10],whereasbonelesions from prostate cancer are predominantly osteoblastic (althoughtheydocontainalyticcomponent) [11].…”