gms | German Medical Science

German Congress of Orthopaedics and Traumatology (DKOU 2019)

22. - 25.10.2019, Berlin

Combination therapy with selective androgen and estrogen receptor modulators prevents osteoporosis development in orchiectomized rats

Meeting Abstract

  • presenting/speaker Marina Komrakova - Universitätsmedizin Göttingen, Unfallchirurgie, Plastische- und Wiederherstellungschirurgie, Göttingen, Germany
  • Georg Büchler - Universitätsmedizin Göttingen, Unfallchirurgie, Plastische- und Wiederherstellungschirurgie, Göttingen, Germany
  • Kai O. Böker - Universitätsmedizin Göttingen, Unfallchirurgie, Plastische- und Wiederherstellungschirurgie, Göttingen, Germany
  • Daniel B. Hoffmann - Universitätsmedizin Göttingen, Unfallchirurgie, Plastische- und Wiederherstellungschirurgie, Göttingen, Germany
  • Wolfgang Lehmann - Universitätsmedizin Göttingen, Unfallchirurgie, Plastische- und Wiederherstellungschirurgie, Göttingen, Germany
  • Arndt F. Schilling - Universitätsmedizin Göttingen, Unfallchirurgie, Plastische- und Wiederherstellungschirurgie, Göttingen, Germany
  • Stephan Sehmisch - Universitätsmedizin Göttingen, Unfallchirurgie, Plastische- und Wiederherstellungschirurgie, Göttingen, Germany

Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2019). Berlin, 22.-25.10.2019. Düsseldorf: German Medical Science GMS Publishing House; 2019. DocAB41-706

doi: 10.3205/19dkou327, urn:nbn:de:0183-19dkou3271

Published: October 22, 2019

© 2019 Komrakova et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.


Outline

Text

Objectives: Despite the increasing importance of osteoporosis in elderly men, many questions still remain open. As the development of osteoporosis is connected to changes in sex hormones, non-steroidal selective androgen or estrogen receptor modulators (SARMs or SERMs) are possible treatment options. Ostarine (OS), a SARM has been shown to increase muscle mass in patients with tumor cachexia and improve bone parameters in a rat model of postmenopausal osteoporosis. Raloxifene (RAL), a SERM is an approved treatment for post-menopausal osteoporosis and has been reported to prevent bone loss also in osteoporotic males.

The present study now evaluates the effect of a combination therapy of OS and RAL on bone properties in orchiectomized rats and compares it to treatment with the respective single compounds.

Methods: 8-month old male Sprague-Dawley rats were either left intact (Non-Orx, n=15) or orchiectomized (Orx, n=75). Orx rats were divided into 4 groups (n=15 each): 1) no treatment (Orx), 2) OS treatment (OS), 3) RAL treatment (RAL), 4) OS+RAL treatment (OS+RAL). OS and RAL were administered to the rats along with a soy-free diet for up to 18 weeks. The average daily doses were 0.4 mg/kg body weight (BW) for OS and 7 mg/kg BW for RAL. The lumbar vertebral bodies and femora were examined by micro-CT, biomechanical and ashing analyses. The weights of whole body, visceral fat, prostate and levator ani muscle were recorded. Serum alkaline phosphatase (Alp) and collagen type 1 cross-linked C-telopeptide (Ctx) were measured. Statistical analysis was performed using one-way ANOVA and Tukey- test (p <0.05).

Results and conclusion: Treatment with RAL alone prevented bone deterioration maintaining biomechanical and trabecular parameters of Orx rats at the level of Non-Orx rats. Treatment with OS alone affected less bone parameters increasing solely the density and inorganic mass in Orx animals. A combined OS+RAL treatment showed a stronger effect than the single treatments, improving most of the bone parameters. In serum, Ctx was lower and Alp was higher in OS+RAL compared to Orx. Prostate weight was the lowest in Orx and RAL rats, whereas OS enhanced it. The androgenic effect of OS on prostate was diminished, if it was applied in combination with RAL. OS and RAL+OS inhibited the atrophy of levator ani muscle that indicates their high anabolic activity in muscle. RAL and RAL+OS both reduced BW. However, the mechanisms were different: RAL decreased food intake; RAL+OS reduced visceral fat weight. The combination therapy with SERM and SARM (RAL+OS) appeared to be promising in the treatment of aged male osteoporosis and showed fewer side effects than the respective single therapies.