Metabolic effects of single-dose pamidronate administration in prostate cancer patients with bone metastases

• Published in: The International journal of biological markers Vol. 17; no. 4; pp. 244 - 252
• Main Authors: BERRUTI, A, DOGLIOTTI, L, ANGELI, A, TUCCI, M, TARABUZZI, R, GUERCIO, S, TORTA, M, TAMPELLINI, M, DOVIO, A, POGGIO, M, SCARPA, R. M
• Format: Journal Article
• Language: English
• Published: Milano Wichtig 01-10-2002
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Bone Neoplasms - secondary; Bone Resorption - metabolism; Bones, joints and connective tissue. Antiinflammatory agents; Calcium - blood; Collagen Type I; Diphosphonates - pharmacology; Diphosphonates - therapeutic use; Humans; Interleukin-6 - biosynthesis; Male; Medical sciences; Middle Aged; Nephrology. Urinary tract diseases; Parathyroid Hormone - blood; Peptide Fragments - blood; Peptides; Pharmacology. Drug treatments; Procollagen - blood; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Tumors of the urinary system; Urinary tract. Prostate gland; Adenocarcinoma; Human; Urinary system disease; Biochemical analysis; Prognosis; Prostate disease; Treatment efficiency; Diseases of the osteoarticular system; Single dose; Biological marker; Resorption; Male; Bone disease; Malignant tumor; Metastasis; Bisphosphonates; Pamidronic acid; Response; Chemotherapy; Treatment; Bone; Male genital diseases; Prostate
• ISSN: 0393-6155; 1724-6008
• DOI: 10.1177/172460080201700405

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.
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.
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.
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.