Metabolic effects of single-dose pamidronate administration in prostate cancer patients with bone metastases.
BACKGROUND
Increased osteolysis usually accompanies sclerotic bone metastases from prostate cancer. This provides a rationale for the use of bisphosphonates to treat bone pain and prevent skeletal complications.


METHODS
The fasting urinary levels of calcium, hydroxyproline (OHPRO), pyridinolines (PYD), deoxypyridinolines (DPYD), collagen cross-linked N-telopeptide (NTX) and the serum values of calcium, total alkaline phosphatase and relevant bone isoenzyme, bone gla protein (BGP), carboxy-telopeptide of type I collagen (ICTP) and parathyroid hormone (PTH) were determined at baseline and on the 15th, 30th, 60th and 90th days after single-dose (90 mg) pamidronate administration in 35 consecutive prostate cancer patients with bone metastases. These biochemical indices and serum interleukin 6 (IL-6) were also measured after four days in the last consecutive 17 cases.


RESULTS
PYD, DPYD and NTX showed a significant decrease lasting four weeks (p<0.01, <0.01 and <0.001, respectively). OHPRO and ICTP did not change significantly. The NTX decline was greater than that of PYD and DPYD (maximum percent decrease: -71.3, -23.1 and -28.2, respectively). Bone formation markers and serum calcium did not change significantly. Serum PTH showed a rapid initial increase followed by a slow decrease (p<0.001). DPYD and NTX patterns did not correlate with changes in bone pain. As observed in the last 17 cases, the maximum osteolysis inhibition after pamidronate occurred on the fourth day after drug infusion. Serum IL-6 levels showed a short-lived decrease preceded by a transient rise on the fourth day.


CONCLUSIONS
Pamidronate is able to induce a decrease in bone resorption without significantly influencing bone formation. The maximum decrease in bone resorption occurs very early. NTX is the most sensitive bone resorption marker in bisphosphonate therapy monitoring. Changes in IL-6 but not bone resorption markers may be useful in the prediction of symptomatic response.
Berruti
A
A
Department of Medical Oncology, University of Torino, San Luigi Hospital, Orbassano, TO, Italy.
Dogliotti
L
L
Tucci
M
M
Tarabuzzi
R
R
Guercio
S
S
Torta
M
M
Tampellini
M
M
Dovio
A
A
Poggio
M
M
Scarpa
R M
RM
Angeli
A
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000556:secondary*; D001862:Bone Resorption / Q000378:metabolism; D002118:Calcium / Q000097:blood; D024042:Collagen Type I; D004164:Diphosphonates / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D000077268:Pamidronate; D010281:Parathyroid Hormone / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D010455:Peptides; D011347:Procollagen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
D000970:Antineoplastic Agents; D024042:Collagen Type I; D004164:Diphosphonates; D015850:Interleukin-6; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; C052929:collagen type I trimeric cross-linked peptide; D000077268:Pamidronate; D002118:Calcium