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

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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.

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Abbreviations

AP:

Alkaline phosphatase

BMD:

Bone mineral density

BV/TV:

Bone volume density

BW:

Body weight

CTX-1:

Cross-linked C-telopeptide of type I collagen

Ct. BMD:

Cortical BMD

Ct. DN:

Cortical density

ERα:

Estrogen receptor alpha

Fmax:

Maximal load

OC:

Osteocalcin

OPG:

Osteoprotegerin

OVX:

Ovariectomy

RANKL:

Receptor activator of NF-κB ligand

S-4:

S-3-(4-acetylamino-phenoxy)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethylphenyl)propionamide

SARM:

Selective androgen receptor modulator

SERM:

Selective estrogen receptor modulator

Tb. BMD:

Trabecular BMD

Tb. Dn:

Trabecular density

TRAP:

Tartrate-resistant acid phosphatase

Tb.Nd:

Number of trabecular nodes

Tb.Th:

Trabecular thickness

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Acknowledgements

This study was supported by the German Research Foundation (DFG, KO 4646/3-1, SE 1966/6-1). The authors are grateful to their colleagues, R. Castro-Machguth and A. Witt

for their technical support.

Funding

This study was funded by Deutsche Forschungsgemeinschaft, KO 4646/3-1, Marina Komrakova, SE 1966/6-1, Stephan Sehmisch.

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Author notes

  1. Stephan Sehmisch and Marina Komrakova contributed equally to this work.

Authors and Affiliations

  1. Department of Trauma, Orthopaedic and Plastic Surgery, Georg-August-University of Goettingen, Robert Koch St. No. 40, 37075, Goettingen, Germany

    Daniel B. Hoffmann, Christoph Derout, Max Müller-Reiter, Kai O. Böker, Arndt F. Schilling, Paul J. Roch, Wolfgang Lehmann, Dominik Saul, Thelonius Hawellek, Stephan Sehmisch & Marina Komrakova

  2. Department of Trauma and Reconstructive Surgery, Eberhard Karls University Tuebingen, BG Trauma Center Tuebingen, Tuebingen, Germany

    Dominik Saul

  3. Department of Medical Microbiology, Subdivision of General Hygiene and Environmental Health, University of Goettingen, Humboldallee 34a, 37073, Goettingen, Germany

    Stefan Taudien

  4. Department of Trauma Surgery, Hannover Medical School, University of Hannover, Carl-Neuberg-Str. 1, 30625, Hannover, Germany

    Stephan Sehmisch

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  1. Daniel B. Hoffmann
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Correspondence to Daniel B. Hoffmann.

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Hoffmann, D.B., Derout, C., Müller-Reiter, M. et al. Effects of ligandrol as a selective androgen receptor modulator in a rat model for osteoporosis. J Bone Miner Metab 41, 741–751 (2023). https://doi.org/10.1007/s00774-023-01453-8

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