scholarly journals Treatment-Induced Bone Loss and Fractures in Cancer Patients Undergoing Hormone Ablation Therapy: Efficacy and Safety of Denosumab

2012 ◽  
Vol 6 ◽  
pp. CMO.S8511 ◽  
Author(s):  
Allan Lipton ◽  
Matthew R. Smith ◽  
Georgiana K. Ellis ◽  
Carsten Goessl
Keyword(s):  
Prostate Cancer ◽  
Bone Mass ◽  
Human Monoclonal Antibody ◽  
Osteoclast Formation ◽  
Mineral Density ◽  
Ablation Therapy ◽  
Markers Of Bone Turnover ◽  
Hormone Ablation ◽  
And Function ◽  
Hormone Ablation Therapy

Hormone ablation therapy (HALT) for breast or prostate cancer accelerates the development of osteoporosis in both men and women by causing estrogen deficiency, which increases the risk for fracture by promoting bone resorption mediated by osteoclasts. Denosumab, a fully human monoclonal antibody that inhibits osteoclast formation and function, increases bone mass in patients undergoing hormone ablation therapy. In the HALT study of 1,468 men with prostate cancer on androgen-deprivation therapy, denosumab significantly reduced the risk of new vertebral fractures, increased bone mineral density (BMD), and reduced markers of bone turnover. In a study of 252 women with breast cancer undergoing adjuvant aromatase inhibitor (AI) therapy, denosumab increased BMD at 12 and 24 months, overall and in all patient subgroups. The overall rates of adverse events were similar to placebo. Clinicians should consider fracture risk assessment and therapies such as denosumab to increase bone mass in patients on hormone ablation therapy who are at high risk for fracture.

scholarly journals Dietary n-3 Polyunsaturated Fatty Acids Enhance Hormone Ablation Therapy in Androgen-Dependent Prostate Cancer

2008 ◽  
Vol 173 (1) ◽  
pp. 229-241 ◽  
Author(s):  
Michael F. McEntee ◽  
Carol Ziegler ◽  
Danielle Reel ◽  
Kenneth Tomer ◽  
Ahmed Shoieb ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Fatty Acids ◽  
Polyunsaturated Fatty Acids ◽  
Ablation Therapy ◽  
Hormone Ablation ◽  
Hormone Ablation Therapy

scholarly journals Pharmacotherapy Options in Cancer Treatment-induced Bone Loss: Focus on Bisphosphonates

2009 ◽  
Vol 1 ◽  
pp. CMT.S2064
Author(s):  
Kouta Ito
Keyword(s):  
Breast Cancer ◽  
Prostate Cancer ◽  
Bone Loss ◽  
Cancer Survivors ◽  
Cancer Treatment ◽  
Small Sample ◽  
Ablation Therapy ◽  
Prostate Cancer Survivors ◽  
Hormone Ablation ◽  
Hormone Ablation Therapy

Bone loss and its associated risk of fracture is a serious long-term health issue for breast cancer and prostate cancer survivors. Hormone ablation therapy, in particular aromatase inhibitors (AIs) for breast cancer and androgen deprivation therapy (ADT) for prostate cancer, causes marked reduction in circulating estrogen or testosterone levels, resulting in increased bone resorption, decreased bone mineral density (BMD), and an increased risk of fragility fracture. In several clinical trials with small sample sizes and short follow-up periods, oral and intravenous bisphosphonates have been shown to improve BMD, but not actual fracture rates, in cancer patients on hormone ablation therapy. A number of professional organizations and expert panels recommend the use of bisphosphonates for selected patients at risk. Although bisphosphonates are generally well tolerated, physicians should be aware of safety concerns, including the risk of osteonecrosis of the jaw. With the growing number of older breast and prostate cancer survivors, additional research is needed to characterize patients who would benefit from pharmacotherapy and optimize strategies to prevent cancer treatment-induced bone loss.

Effect of denosumab on bone mineral density (BMD) in women with breast cancer (BC) and men with prostate cancer (PC) undergoing hormone ablation therapy

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 9520-9520
Author(s):  
M. R. Smith ◽  
G. Ellis ◽  
F. Saad ◽  
T. Tammela ◽  
H. Bone ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Primary Endpoint ◽  
Human Monoclonal Antibody ◽  
Mineral Density ◽  
Ablation Therapy ◽  
Skeletal Site ◽  
Hormone Ablation ◽  
History Of ◽  
Secondary Endpoints ◽  
Vitamin D Supplements

9520 Background: Hormone ablation therapies, including adjuvant aromatase inhibitor (AI) therapy and androgen deprivation therapy (ADT), improve recurrence-free survival in patients (pts) with BC and PC, respectively. However, these treatments increase bone resorption, leading to bone loss and fractures. RANKL is a key mediator of osteoclast-mediated bone resorption. In this 24 month (mo) comparison, we investigated the effects of denosumab, a fully human monoclonal antibody against RANKL, on preserving BMD across both populations. Methods: Two trials were conducted: a 24-mo BC study and a 36-mo PC study. Postmenopausal women with low BMD receiving AI therapy for nonmetastatic BC and men receiving ADT for nonmetastatic PC (with low BMD or history of osteoporotic fracture if < 70 yrs) were randomized to receive placebo or denosumab 60mg subcutaneously every 6 mos. All pts in both studies were prescribed calcium and vitamin D supplements. The primary endpoint was % change from baseline in lumbar spine (LS) BMD at 12 mos for the BC study and at 24 mos for the PC study. Herein, we present changes in BMD at 24 mos at LS, total hip (TH), and 1/3 radius from both studies. Power calculations were based on enrollment of at least 208 patients in the BC study (for primary endpoint only) and 1226 in the PC study (for primary and key secondary endpoints). The actual numbers randomized were 252 and 1468, respectively. Results: Denosumab increased BMD of the LS, TH, and 1/3 radius compared with placebo at 24 mos in both pt populations ( Table ). In both studies, differences between denosumab and placebo at each skeletal site were consistent, and the effects of denosumab were statistically significantly different from placebo as early as 1 month at the LS in both studies. The overall safety profile was similar to placebo in each study. Conclusions: Denosumab consistently increased BMD at all 3 skeletal sites compared with placebo in both women with BC undergoing AI therapy and in men with PC undergoing ADT. [Table: see text] [Table: see text]

Effect of castration on endothelin receptors

2002 ◽  
Vol 103 (s2002) ◽  
pp. 442S-445S ◽  
Author(s):  
Robert J. PADLEY ◽  
Douglas B. DIXON ◽  
J. Ruth WU-WONG
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Receptor Expression ◽  
Growth Disorders ◽  
Binding Studies ◽  
Ablation Therapy ◽  
Significant Difference ◽  
Hormone Ablation ◽  
Hormone Refractory ◽  
Hormone Ablation Therapy

Endothelin (ET) plays a pivotal role in the pathogenesis of cell growth disorders such as cancer. Atrasentan (ABT-627), a selective antagonist for the ET receptor A (ETA), has shown benefit in controlling disease progression in men with hormone refractory prostate cancer who have undergone aggressive hormone ablation therapy. It is not known how hormone ablation affects ET-binding sites, although ET-1 and ETA expression are found to be elevated in prostate cancer patients. In this study, we examined the effect of castration on ET receptor binding in male beagle dogs. Three dogs were surgically castrated and another three sham-operated. The animals were sacrificed 1 week after operation and membranes were prepared from the prostate, heart, brain, kidney, liver and lung for ET-1, ET-3 and angiotensin II (A-II, as a control) binding studies. No significant difference in A-II binding was observed between castrated and sham-operated animals. However, ET-1 and ET-3 binding to prostate and brain membranes were altered significantly. From saturation binding studies using ET-1 in the prostate, the Kd and Bmax values increased from 0.043nM and 0.094pmol/mg respectively in sham-operated dogs to 0.104nM and 0.311pmol/mg respectively in castrated animals. These results indicate that surgical castration in dogs produces a change in the ET receptor density in the prostate and brain, and may have implications for the effect of hormone ablation therapy on ET receptor expression in prostate cancer patients.

scholarly journals MicroRNA-29a represses osteoclast formation and protects against osteoporosis by regulating PCAF-mediated RANKL and CXCL12

2019 ◽  
Vol 10 (10) ◽  
Author(s):  
Wei-Shiung Lian ◽  
Jih-Yang Ko ◽  
Yu-Shan Chen ◽  
Huei-Jing Ke ◽  
Chin-Kuei Hsieh ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Mass ◽  
Osteoclast Differentiation ◽  
Osteoclast Formation ◽  
Estrogen Deficiency ◽  
Biomechanical Property ◽  
Mineral Density ◽  
Cxcl12 Expression ◽  
Osteogenic Cells

Abstract Osteoporosis deteriorates bone mass and biomechanical strength, becoming a life-threatening cause to the elderly. MicroRNA is known to regulate tissue remodeling; however, its role in the development of osteoporosis remains elusive. In this study, we uncovered that silencing miR-29a expression decreased mineralized matrix production in osteogenic cells, whereas osteoclast differentiation and pit formation were upregulated in bone marrow macrophages as co-incubated with the osteogenic cells in transwell plates. In vivo, decreased miR-29a expression occurred in ovariectomy-mediated osteoporotic skeletons. Mice overexpressing miR-29a in osteoblasts driven by osteocalcin promoter (miR-29aTg/OCN) displayed higher bone mineral density, trabecular volume and mineral acquisition than wild-type mice. The estrogen deficiency-induced loss of bone mass, trabecular morphometry, mechanical properties, mineral accretion and osteogenesis of bone marrow mesenchymal cells were compromised in miR-29aTg/OCN mice. miR-29a overexpression also attenuated the estrogen loss-mediated excessive osteoclast surface histopathology, osteoclast formation of bone marrow macrophages, receptor activator nuclear factor-κ ligand (RANKL) and C–X–C motif chemokine ligand 12 (CXCL12) expression. Treatment with miR-29a precursor improved the ovariectomy-mediated skeletal deterioration and biomechanical property loss. Mechanistically, miR-29a inhibited RANKL secretion in osteoblasts through binding to 3′-UTR of RANKL. It also suppressed the histone acetyltransferase PCAF-mediated acetylation of lysine 27 in histone 3 (H3K27ac) and decreased the H3K27ac enrichment in CXCL12 promoters. Taken together, miR-29a signaling in osteogenic cells protects bone tissue from osteoporosis through repressing osteoclast regulators RANKL and CXCL12 to reduce osteoclastogenic differentiation. Arrays of analyses shed new light on the miR-29a regulation of crosstalk between osteogenic and osteoclastogenic cells. We also highlight that increasing miR-29a function in osteoblasts is beneficial for bone anabolism to fend off estrogen deficiency-induced excessive osteoclastic resorption and osteoporosis.

scholarly journals Regression of prostate tumors upon combination of hormone ablation therapy and celecoxib in vivo

The Prostate ◽  
2010 ◽  
Vol 71 (8) ◽  
pp. 813-823 ◽  
Author(s):  
Parisa Abedinpour ◽  
Véronique T. Baron ◽  
John Welsh ◽  
Per Borgström
Keyword(s):  
Prostate Tumors ◽  
Ablation Therapy ◽  
Hormone Ablation ◽  
Hormone Ablation Therapy
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