Preventing bone loss during androgen deprivation therapy for prostate cancer: early experience with neridronate.
OBJECTIVE
Androgen-deprivation therapy (ADT) is the usual treatment for locally advanced or metastatic prostate cancer. Osteoporosis is a common complication of ADT. The aim of our study was to evaluate the efficacy of neridronate, a relatively new bisphosphonate to prevent bone loss during androgen ablation.


METHODS
Sixty patients with prostate cancer and osteoporosis were enrolled and randomly assigned to 2 different treatment regimes: group A (30 patients) treated with maximum androgenic blockage (MAB), and group B (30 patients) treated with bicalutamide 150 mg. Each group was divided in 2 subgroups A1-A2 and B1-B2. All patients received calcium and cholecalciferol supplements (500 mg of elemental calcium and 400 IU cholecalciferol) daily. The A2 and B2 subgroups were also treated with neridronate (25 mg intramuscular monthly). Lumbar and femoral bone mineral density (BMD) was evaluated by dualenergy X-ray absorptiometry (DXA), both at baseline and after one year of treatment. Deoxypyridinoline (DPD) and bone-alkaline phosphatase (B-ALP) were determined at the beginning, midstudy and at the end.


RESULTS
Patients treated only with calcium and cholecalciferol (A1, B1 subgroups) showed a marked bone loss after 6, and 12 months, with increased levels of DPD and BALP, compared to baseline values. Patients treated with neridronate (A2 et B2 subgroups) showed unchanged levels of these markers. After one year of treatment, lumbar and total hip BMD decreased significantly in patients treated only with calcium and cholecalciferol (A1 subgroup: -4.9% and -1.9% respectively). BMD did not change significantly at any site in patients treated also with neridronate (A2 subgroup: +1% and +0.8% respectively). Lumbar and total hip BMD did not change significantly (-1.5% and -1% respectively) in B1 subgroup. In B2 subgroup an important increase in lumbar spine and the total hip BMD was shown (+2.5% and 1.6% respectively). No relevant side effects were recorded during our study.


CONCLUSIONS
In conclusion, neridronate is an effective and safe treatment in preventing bone loss in men receiving ADT for prostate cancer.
Magno
Carlo
C
Department of Urology, University of Messina, Via Garibaldi 118, 98122, Messina, Italy. carlo.magno@tin.it
Anastasi
Giuseppina
G
Morabito
Nunziata
N
Gaudio
Agostino
A
Maisano
Domenica
D
Franchina
Fabio
F
Galì
Alessandro
A
Frisina
Nicola
N
Melloni
Darwin
D
D015502:Absorptiometry, Photon; D000368:Aged; D000369:Aged, 80 and over; D000596:Amino Acids / Q000097:blood; D000726:Androgen Antagonists / Q000009:adverse effects* / Q000627:therapeutic use; D000813:Anilides / Q000009:adverse effects* / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000187:drug effects; D002118:Calcium / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D004164:Diphosphonates / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D004958:Estradiol / Q000097:blood; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D009570:Nitriles; D010024:Osteoporosis / Q000097:blood / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000517:prevention & control*; D010281:Parathyroid Hormone / Q000097:blood; D010758:Phosphorus / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy*; D013739:Testosterone / Q000097:blood; D014105:Tosyl Compounds; D016896:Treatment Outcome; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood
D000596:Amino Acids; D000726:Androgen Antagonists; D000813:Anilides; D015415:Biomarkers; D004164:Diphosphonates; D009570:Nitriles; D010281:Parathyroid Hormone; D014105:Tosyl Compounds; D014807:Vitamin D; D010758:Phosphorus; D013739:Testosterone; D004958:Estradiol; C053389:6-amino-1-hydroxyhexane-1,1-diphosphonate; C036020:deoxypyridinoline; C053541:bicalutamide; C104450:25-hydroxyvitamin D; D002118:Calcium