goserelin and Bone-Diseases--Metabolic

Although androgen deprivation therapy (ADT) has been associated with bone loss in patients with prostate cancer, its mechanism remains unclear. The growth hormone (GH)/insulin-like growth factor-1 (IGF-1)/parathyroid hormone (PTH) axis plays a critical role in bone synthesis, but its activity during ADT is also unknown.. Seventy-one patients with localized prostate cancer, who received ADT, were prospectively studied based on their bone mineral density (BMD) and blood and urine samples at the baseline and after ADT for 6 months.. The IGF-1 level was correlated with BMD before ADT (rs = 0.325, P = 0.007), but such a relationship disappeared after ADT (P = 0.565). Following ADT, the serum IGF-1 level increased compared with that at the baseline (22 +/- 6 nmol/L vs. 19 +/- 5 nmol/L, respectively, P < 0.001). The serum PTH level was reduced after ADT (41 +/- 33 ng/L) compared with the baseline (55 +/- 44 ng/L) (P < 0.001), but no change was observed in the serum GH level (P = 0.691). Bone resorption markers such as blood N-telopeptide (NTx), urinary NTx, calcium, and inorganic phosphorus levels increased after ADT (P < 0.001 in all). The ratio of the IGF-1 level after ADT/before ADT was associated with the ratio of the value after ADT/before ADT of alkaline phosphatase (rs = 0.266, P = 0.025) and calcium (rs = 0.242, P = 0.042).. Despite the unaffected GH and upregulated bone resorption, the serum IGF-1 level was elevated by ADT. The IGF-1 level was correlated with BMD before ADT, but the relationship was disrupted after ADT. IGF-1 or its receptor in the bone may be functionally inactivated during ADT.

Topics: Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Bone Density; Bone Diseases, Metabolic; Flutamide; Goserelin; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Male; Middle Aged; Orchiectomy; Parathyroid Hormone; Prospective Studies; Prostatic Neoplasms

The Austrian Breast and Colorectal Cancer Study Group trial-12 (ABCSG-12) bone substudy assesses zoledronic acid for preventing bone loss associated with adjuvant endocrine therapy and reports on long-term findings of bone-mineral density (BMD) during 3 years of treatment and 2 years after completing adjuvant treatment with or without zoledronic acid. The aim of this substudy is to gain insight into bone health in this setting.. ABCSG-12 is a randomised, open-label, phase III, 4-arm trial comparing tamoxifen (20 mg/day orally) and goserelin (3.6 mg subcutaneously every 28 days) versus anastrozole (1 mg/day orally) and goserelin (3.6 mg subcutaneously every 28 days), both with or without zoledronic acid (4 mg intravenously every 6 months) for 3 years in premenopausal women with endocrine-responsive breast cancer. This prospective bone subprotocol measured BMD at 0, 6, 12, 36, and 60 months. The primary endpoint of the bone substudy (secondary endpoint in the main trial) was change in BMD at 12 months, assessed by dual-energy X-ray absorptiometry in assessable patients. Analyses were intention to treat. Statistical significance was assessed by t tests. The ABCSG-12 trial is registered on the ClinicalTrials.gov website, number NCT00295646.. 404 patients were prospectively included in the bone substudy and randomly assigned to endocrine therapy alone (goserelin and anastrozole or goserelin and tamoxifen; n=199) or endocrine therapy concurrent with zoledronic acid (goserelin, anastrozole, and zoledronic acid or goserelin, tamoxifen, and zoledronic acid; n=205). After 3 years of treatment, endocrine therapy alone caused significant loss of BMD at the lumbar spine (-11.3%, mean difference -0.119 g/cm(2) [95% CI -0.146 to -0.091], p<0.0001) and trochanter (-7.3%, mean difference -0.053 g/cm(2) [-0.076 to -0.030], p<0.0001). In patients who did not receive zoledronic acid, anastrozole caused greater BMD loss than tamoxifen at 36 months at the lumbar spine (-13.6%, mean difference -0.141 g/cm(2) [-0.179 to -0.102] vs -9.0%, mean difference -0.095 g/cm(2) [-0.134 to -0.057], p<0.0001 for both). 2 years after the completion of treatment (median follow-up 60 months [range 15.5-96.6]), patients not receiving zoledronic acid still had decreased BMD at both sites compared with baseline (lumbar spine -6.3%, mean difference -0.067 g/cm(2) [-0.106 to -0.027], p=0.001; trochanter -4.1%, mean difference -0.03 g/cm(2) [-0.062 to 0.001], p=0.058). Patients who received zoledronic acid had stable BMD at 36 months (lumbar spine +0.4%, mean difference 0.004 g/cm(2) [-0.024 to 0.032]; trochanter +0.8%, mean difference 0.006 g/cm(2) [-0.018 to 0.028]) and increased BMD at 60 months at both sites (lumbar spine +4.0%, mean difference 0.039 g/cm(2) [0.005-0.075], p=0.02; trochanter +3.9%, mean difference 0.028 g/cm(2) [0.003-0.058], p=0.07) compared with baseline.. Goserelin plus tamoxifen or anastrozole for 3 years without concomitant zoledronic acid caused significant bone loss. Although there was partial recovery 2 years after completing treatment, patients receiving endocrine therapy alone did not recover their baseline BMD levels. Concomitant zoledronic acid prevented bone loss during therapy and improved BMD at 5 years.

Topics: Adult; Anastrozole; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Bone Density; Bone Density Conservation Agents; Bone Diseases, Metabolic; Breast Neoplasms; Chemotherapy, Adjuvant; Diphosphonates; Female; Goserelin; Humans; Imidazoles; Linear Models; Nitriles; Osteoporosis; Premenopause; Prospective Studies; Tamoxifen; Triazoles; Zoledronic Acid

This study examined individual and combined effects of the cancer treatments goserelin acetate (GA) and doxorubicin (DOX) on bone and determined if treadmill running (TM) provides osteoprotection.. Ten-week-old female Sprague-Dawley rats were randomly assigned to sedentary (SED) or TM groups. SED received GA, DOX, combined GA and DOX (GA+DOX), or placebo and maintained normal cage activity. TM received GA, DOX, GA+DOX, or placebo and participated in a progressive motorized treadmill protocol. After 8 weeks, tibiae were evaluated using micro computed tomography.. Negative drug effects were observed in cancellous bone (bone volume/tissue volume, trabecular number, trabecular thickness, trabecular spacing; P<0.05). An additive bone volume/tissue volume and trabecular spacing effect was observed in SED GA+DOX (vs. SED+GA and SED+DOX, P<0.05) but not in TM GA+DOX (vs. TM+GA and TM+DOX, P>0.05). Negative drug effects were observed in cortical bone (cross-sectional volume, cortical volume, marrow volume; P<0.05), but combined GA+DOX did not exacerbate these effects. Additionally, there were no protective cortical bone effects observed in TM.. Combined GA+DOX exacerbates cancellous osteopenia in the tibia, and treadmill running provided only minor protection.

Topics: Animals; Antineoplastic Agents, Hormonal; Bone Diseases, Metabolic; Doxorubicin; Female; Goserelin; Physical Conditioning, Animal; Rats; Rats, Sprague-Dawley