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  3. Effects of ligandrol as a selective androgen receptor modulator in a rat model for osteoporosis

Effects of ligandrol as a selective androgen receptor modulator in a rat model for osteoporosis

  • J Bone Miner Metab. 2023 Nov;41(6):741-751. doi: 10.1007/s00774-023-01453-8.
Daniel B Hoffmann 1,  Christoph Derout 2,  Max Müller-Reiter 2,  Kai O Böker 2,  Arndt F Schilling 2,  Paul J Roch 2,  Wolfgang Lehmann 2,  Dominik Saul 2 3,  Thelonius Hawellek 2,  Stefan Taudien 4,  Stephan Sehmisch # 2 5,  Marina Komrakova # 2
Affiliations

Affiliations

  • 1 Department of Trauma, Orthopaedic and Plastic Surgery, Georg-August-University of Goettingen, Robert Koch St. No. 40, 37075, Goettingen, Germany. daniel.hoffmann@med.uni-goettingen.de.
  • 2 Department of Trauma, Orthopaedic and Plastic Surgery, Georg-August-University of Goettingen, Robert Koch St. No. 40, 37075, Goettingen, Germany.
  • 3 Department of Trauma and Reconstructive Surgery, Eberhard Karls University Tuebingen, BG Trauma Center Tuebingen, Tuebingen, Germany.
  • 4 Department of Medical Microbiology, Subdivision of General Hygiene and Environmental Health, University of Goettingen, Humboldallee 34a, 37073, Goettingen, Germany.
  • 5 Department of Trauma Surgery, Hannover Medical School, University of Hannover, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
  • # Contributed equally.
PMID: 37407738 DOI: 10.1007/s00774-023-01453-8
Abstract

Introduction: The selective Androgen Receptor Modulator ligandrol (LGD-4033 or VK5211) has been shown to improve muscle tissue. In the present study, the effect of ligandrol on bone tissue was investigated in ovariectomized rat model.

Materials and methods: Three-month-old Sprague Dawley rats were either ovariectomized (OVX, n = 60) or left intact (NON-OVX, n = 15). After 9 weeks, OVX rats were divided into four groups: untreated OVX (n = 15) group and three OVX groups (each of 15 rats) treated with ligandrol orally at doses of 0.03, 0.3, or 3 mg/kg body weight. After five weeks, lumbar vertebral bodies (L), tibiae, and femora were examined using micro-computed tomographical, biomechanical, ashing, and gene expression analyses.

Results: In the 3-mg ligandrol group, bone structural properties were improved (trabecular number: 38 ± 8 vs. 35 ± 7 (femur), 26 ± 7 vs. 22 ± 6 (L), 12 ± 5 vs. 6 ± 3 (tibia) and serum phosphorus levels (1.81 ± 0.17 vs.1.41 ± 0.17 mmol/l), uterus (0.43 ± 0.04 vs. 0.11 ± 0.02 g), and heart (1.13 ± 0.11 vs. 1.01 ± 0.08 g) weights were increased compared to the OVX group. Biomechanical parameters were not changed. Low and medium doses did not affect bone tissue and had fewer side effects. Body weight and food intake were not affected by ligandrol; OVX led to an increase in these parameters and worsened all bone parameters.

Conclusion: Ligandrol at high dose showed a subtle anabolic effect on structural properties without any improvement in biomechanical properties of osteoporotic bones. Considering side effects of ligandrol at this dose, its further investigation for the therapy of postmenopausal osteoporosis should be reevaluated.

Keywords

Ligandrol; Osteoporosis; Rat model; Selective androgen receptor modulator.

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