cholecalciferol and 6-amino-1-hydroxyhexane-1-1-diphosphonate

Today, androgen deprivation therapy is a cornerstone of treatment for advanced prostate cancer, although it presents important complications such as osteoporosis. Neridronate, a relatively new bisphosphonate, is able to prevent bone loss in patients with prostate cancer during androgen ablation.. Androgen-deprivation therapy (ADT) is a cornerstone of treatment for advanced prostate cancer. This therapy has iatrogenic complications, such as osteoporosis. The aim of our study was to evaluate the efficacy of neridronate, a relatively new bisphosphonate, to prevent bone loss during androgen ablation.. Forty-eight osteoporotic patients with prostate cancer, treated with 3-month depot triptorelina, were enrolled and randomly assigned to two different treatment groups: group A (n = 24) was treated with a daily calcium and cholecalciferol supplement (500 mg of elemental calcium and 400 IU cholecalciferol), and group B (n = 24) received in addition to the same daily calcium and cholecalciferol supplement, 25 mg of neridronate given intramuscularly every month. All patients also received bicalutamide for 4 weeks. Lumbar and femoral BMD was evaluated by DXA at baseline and after 1 year of therapy; moreover, deoxypyridinoline (DPD) and bone alkaline phosphatase (BALP) were determined at the beginning, midway through, and at the end of the study.. After 6 and 12 months, whereas patients treated only with calcium and cholecalciferol (group A) showed a marked bone loss, with increased levels of DPD and BALP compared with baseline values, patients treated also with neridronate (group B) had substantially unchanged levels of these markers. After 1 year of treatment, lumbar and total hip BMD decreased significantly in patients treated only with calcium and cholecalciferol (group A), whereas it did not change significantly at any skeletal site in patients treated also with neridronate (group B). No relevant side effects were recorded during our study.. Neridronate is an effective treatment in preventing bone loss in the hip and lumbar spine in men receiving ADT for prostate cancer.

Topics: Absorptiometry, Photon; Aged; Alkaline Phosphatase; Amino Acids; Androgen Antagonists; Androgens; Antineoplastic Agents, Hormonal; Bone and Bones; Bone Density; Calcium; Cholecalciferol; Diphosphonates; Humans; Male; Osteoporosis; Prostatic Neoplasms; Time Factors; Triptorelin Pamoate

In patients with primary hyperparathyroidism (PHPT) not suitable for surgical correction, a skeletal protection with bisphosphonates is considered a reasonable option, but the long-term effects after treatment discontinuation are not well known. Sixty postmenopausal women with PHPT were given 400-600 IU vitamin D(3) daily and 100 mg neridronate IV every 2 months for 2 years with 2 additional years of follow-up without antiresorptive therapies. Bone mineral density (BMD) progressively rose by 6.7 ± 7.6% (SD) and by 2.9 ± 4.5% at the spine and femoral neck, respectively. During follow-up, mean BMD progressively fell, but after 2 years it was still 3.9 ± 5.5% higher than baseline values at the spine. Bone alkaline phosphatase and serum C-telopeptide of type I collagen decreased significantly within 6 months (28 and 49% versus baseline, respectively) and rose to baseline values within 6-12 months during follow-up. Serum PTH significantly rose from baseline during treatment, but it remained significantly higher than baseline during follow-up. The PTH changes were significantly correlated with serum 25-hydroxyvitamin D (25OHD) levels. In conclusion, in this study we observed that in patients with mild PHPT treatment with bisphosphonates is associated with the expected changes in bone-turnover markers and that the significant increases of both hip and spine BMD are partially maintained for at least 2 years after treatment discontinuation at the vertebral site. The marked increases in serum PTH levels, particularly in subjects with low 25OHD levels, persist after treatment discontinuation and this raises the suspicion that this might reflect a worsening of PHPT.

Topics: Aged; Alkaline Phosphatase; Bone Density Conservation Agents; Cholecalciferol; Collagen Type I; Diphosphonates; Female; Femur Neck; Humans; Hyperparathyroidism, Primary; Middle Aged; Osteoporosis, Postmenopausal; Parathyroid Hormone; Peptides; Time

The objective of this study was to evaluate the metabolic in vitro effect of the bisphosphonate neridronate on normal and pathological human osteoblasts. Primary human osteoblast cultures were obtained from cancellous bone of osteoarthritic (OA) and osteoporotic (OP) patients and a corresponding healthy control group. Osteocalcin production was evaluated by cultured cells in neridronate 10(-4) M and 10(-6) M, both under basal conditions and after vitamin D3 stimulation. In the absence of neridronate, vitamin D3 increased osteocalcin production in all cell cultures; under the same conditions, and in the absence of vitamin D3, OA osteoblasts showed a significantly higher osteocalcin production whereas OP osteoblasts showed a significantly lower osteocalcin production compared to the normal osteoblasts, respectively. In all cellular populations neridronate at a higher concentration (10(-4) M) induced a reduction in osteocalcin synthesis, but in normal and osteoarthritic osteoblasts did not reduce the stimulatory effect of vitamin D3, whereas it inhibited the vitamin D3-induced increase of osteocalcin synthesis in the osteoporotic cells. In normal and osteoporotic osteoblasts stimulation with the lower neridronate concentration (10(-6) M) significantly increased osteocalcin production, which was further enhanced by vitamin D3 as an additional effect of the combined treatment. In OA osteoblasts, neridronate 10(-6) M did not induce an increase in osteocalcin synthesis and the additional effect of combined treatment with vitamin D3 was not observed. Neridronate can modify the metabolic activity of human osteoblasts by enhancing or decreasing their biosynthetic activity, both in normal and in pathological conditions, depending on compound concentration and on different cell types. These results confirm the validity of using neridronate at doses usually administered in treating osteoporosis, and they suggest using it to treat other diseases which show an altered osteoblast metabolism, such as osteoarthritis.

Topics: Adult; Aged; Cells, Cultured; Cholecalciferol; Diphosphonates; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Osteoarthritis; Osteoblasts; Osteocalcin; Osteoporosis