Contemporary hormone therapy with LHRH agonists for prostate cancer: avoiding osteoporosis and fracture.

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Abstract

Prostate cancer is a large clinical burden across Europe. It is, in fact, the most common cancer in males, accounting for more than 92,300 deaths annually throughout the continent. Prostate cancer is androgen-sensitive; thus an androgen deprivation therapy (ADT) is often used for treatment by reducing androgen to castrate levels. Several ADT agents have achieved benefits with effective palliation, but, unfortunately, severe adverse events are frequent. Contemporary ADT (Luteinising Hormone Releasing Hormone agonist - LHRHa injections) can result in side effects that include osteoporosis and fractures, compromising quality of life and survival.

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Most cited references 21

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Changes in trabecular pattern of the upper end of the femur as an index of osteoporosis.

Shiva M. Singh, A R Nagrath, P Maini (1970)

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The ability of three-dimensional structural indices to reflect mechanical aspects of trabecular bone.

D. Ulrich, B. van Rietbergen, A Laib … (1999)

Bone mineral density (BMD) and bone microarchitecture are important determinants for the mechanical properties of cancellous bone. Although BMD alone is a good predictor of average mechanical properties of cancellous bone, there remains unexplained variation in mechanical properties that might be due to missing information regarding bone microarchitecture. Recent developments in three-dimensional (3D) structural analysis have provided possibilities for measuring a variety of structural indices to characterize bone microarchitecture. The objectives of this study were to calculate structural indices and elastic constants of human cancellous bone from different skeletal sites and to investigate the predictive value of different 3D structural indices for the elastic properties of bone. A total of 237 cancellous bone samples taken from the iliac crest, lumbar spine, femoral head, and calcaneus were imaged with a 3D microcomputed tomography (microCT) system. The segmented 3D images were used to calculate BV/TV, BS/TV, Tb.Th, Tb.Sp, Tb.N, and MII ratio and for microstructural finite-element (microFE) analysis to calculate Young's moduli, shear moduli, and Poisson's ratios. A subgroup of "critical" specimens within each site was selected to represent specimens that could not be identified as osteoporotic or normal on the basis of BMD measurement alone. For these "critical" specimens, structural indices and elastic constants were correlated by means of linear multivariate regression analysis. It was found that the elastic constants clearly correlated better when one of the 3D structural indices was included as independent variable than when BV/TV was the only independent variable. Each of the examined structural indices could improve the correlation: the R2 values were maximally increased from 53% (BV/TV alone) to 82% (BV/TV and MIL ratio). The most effective indices, however, were not the same for the different skeletal sites. Even better correlations were found when more than one of the 3D structural indices were included as independent variables: the R2 values were maximally increased from 53% (BV/TV alone) to 92% (BV/TV, Tb.Sp, and MIL ratio). The prediction of elastic constants for cancellous bone samples is clearly improved when BV/TV is supplemented with 3D structural indices. These results suggest that the determination of mechanical properties of bone and the diagnosis of osteoporosis can be improved if, in addition to BMD, the 3D bone microarchitecture is assessed in vivo.

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Development and application of a Japanese model of the WHO fracture risk assessment tool (FRAX™)

S Fujiwara, T. Nakamura, H. Orimo … (2008)

Summary The present study estimated the 10-year probability using the Japanese version of WHO fracture risk assessment tool (FRAX™) in order to determine fracture probabilities that correspond to intervention thresholds currently used in Japan and to resolve some issues for its use in Japan. Introduction The objective of the present study was to evaluate a Japanese version of the WHO fracture risk assessment (FRAX™) tool to compute 10-year probabilities of osteoporotic fracture in Japanese men and women. Since lumbar spine bone mineral density (BMD) is used preferentially as a site for assessment, and densitometers use Japanese reference data, a second aim was to investigate the suitability and impact of this practice in Japan. Methods Fracture probabilities were computed from published data on the fracture and death hazards in Japan. Probabilities took account of age, sex, the presence of clinical risk factors and femoral neck BMD. Fracture probabilities were determined that were equivalent to intervention thresholds currently used in Japan. The difference between T-scores derived from international reference data and that using Japanese-specific normal ranges was estimated from published sources. The gradient of risk of BMD for fracture in Japan was compared to that for BMD at the lumbar spine in the Hiroshima cohort. Results The 10-year probabilities of a major osteoporosis-related fracture that corresponded to current intervention thresholds ranged from approximately 5% at the age of 50 years to more than 20% at the age of 80 years. The use of femoral neck BMD predicts fracture as well as or better than BMD tests at the lumbar spine. There were small differences in T-scores between those used for the model and those derived from a Japanese reference population. Conclusions The FRAX™ tool has been used to determine possible thresholds for therapeutic intervention, based on equivalence of risk with current guidelines. The approach will need to be supported by appropriate health economic analyses. Femoral neck BMD is suitable for the prediction of fracture risk among Japanese. However, when applying the FRAX™ model to Japan, T-scores and Z-scores should be converted to those derived from the international reference.

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Author and article information

Journal

Journal ID (iso-abbrev): Cent European J Urol

Title: Central European journal of urology

Publisher: Polish Urological Association

ISSN: 2080-4806

ISSN (Print): 2080-4806

Publication date (Electronic): 2015

Volume: 68

Issue: 2

Affiliations

[1 ] Department of Surgery and Cancer, Imperial College, London.

Article

Publisher Item ID: 00513

DOI: 10.5173/ceju.2015.513

PMC ID: 4526606

PubMed ID: 26251735

SO-VID: 19a85193-f51e-41f8-8524-90fec05c9237

History

Keywords: androgen deprivation therapy,fracture imaging,luteinising hormone releasing hormone agonist,osteoporosis,prostate cancer

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Keywords: androgen deprivation therapy, fracture imaging, luteinising hormone releasing hormone agonist, osteoporosis, prostate cancer

Contemporary hormone therapy with LHRH agonists for prostate cancer: avoiding osteoporosis and fracture.

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Cancer Metabolism

Most cited references 21

Changes in trabecular pattern of the upper end of the femur as an index of osteoporosis.

The ability of three-dimensional structural indices to reflect mechanical aspects of trabecular bone.

Development and application of a Japanese model of the WHO fracture risk assessment tool (FRAX™)

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