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Peer-reviewedCC BY 4.0Journal of Endocrinological Investigation

Osteoprotegerin is strongly associated with calcium and magnesium in seminal fluid but not affected by denosumab

  • Sam Kafai Yahyavi1,2
  • Mads Joon Jorsal1
  • Emil Brink Wriedt1
  • Niels Jørgensen3,4
  • Anders Juul3,4,5
  • Rune Holt1
  • Martin Blomberg Jensen1,5
5 affiliations
  1. 1Division of Translational Endocrinology, Department of Endocrinology and Internal Medicine, Copenhagen University Hospital - Herlev and Gentofte, Herlev, Denmark
  2. 2Department of Obstetrics and Gynecology, Copenhagen University Hospital - Herlev and Gentofte, Herlev, Denmark
  3. 3Department of Growth and Reproduction, Copenhagen University Hospital – Rigshospitalet, Copenhagen, Denmark
  4. 4International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital – Rigshospitalet, Copenhagen, Denmark
  5. 5Department of Clinical Medicine, Copenhagen University Hospital, Copenhagen, Denmark
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Abstract

Objective: While the effect of the RANKL-inhibitor denosumab on serum minerals is well-documented, its impact on seminal fluid minerals is poorly understood. This study examines the correlation between the high levels of soluble-RANKL, osteoprotegerin (OPG), and minerals in seminal fluid and whether this can be influenced by denosumab.

Methods: Two cohorts comprised this study: 100 young men from the general Danish population with no reported fertility issues, and 91 infertile men who were treated with a single dose of denosumab (60 mg), or placebo in a randomized controlled trial assessing the effect on semen quality. Each man underwent a physical examination and semen analysis, including analysis of soluble RANKL, OPG, calcium, magnesium, and phosphate in the seminal fluid.

Results: In both men from the general population and infertile men, seminal OPG concentrations were positively correlated with seminal calcium (rnormal=0.54 and rinfertile=0.81), seminal magnesium (rnormal=0.58 and rinfertile=0.75), and a weak negative correlation was seen with seminal phosphate (rnormal=-0.17 and rinfertile=-0.34) concentrations. Seminal soluble RANKL was not associated with seminal minerals. Following 60 mg denosumab treatment, no changes were observed after 160 days in seminal calcium (p = 0.42), magnesium (p = 0.55), or phosphate concentrations (p = 0.63). Changes in seminal OPG were moderately negatively correlated with changes in serum AMH (r=-0.32), LH (r=-0.30), and FSH (r=-0.31).

Conclusion: A strong correlation between OPG and minerals in seminal fluids from both normal and infertile men suggests that the release of these factors by the prostate or seminal vesicle is regulated by the same factors, but cannot be modified by a short-term systemic RANKL inhibition with denosumab.

Clinical trial registration: ClinicalTrials.gov NCT03030196. Registered January 24, 2017.

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Cite

BibTeXRIS
BibTeX
@article{yahyavi2026osteoprotegerin,
  title = {{Osteoprotegerin is strongly associated with calcium and magnesium in seminal fluid but not affected by denosumab}},
  author = {Sam Kafai Yahyavi and Mads Joon Jorsal and Emil Brink Wriedt and Niels Jørgensen and Anders Juul and Rune Holt and Martin Blomberg Jensen},
  journal = {Journal of Endocrinological Investigation},
  year = {2026},
  month = jul,
  doi = {10.1007/s40618-026-02996-z},
  url = {https://doi.org/10.1007/s40618-026-02996-z},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Osteoprotegerin is strongly associated with calcium and magnesium in seminal fluid but not affected by denosumab
AU  - Sam Kafai Yahyavi
AU  - Mads Joon Jorsal
AU  - Emil Brink Wriedt
AU  - Niels Jørgensen
AU  - Anders Juul
AU  - Rune Holt
AU  - Martin Blomberg Jensen
PY  - 2026
DA  - 2026/07/24
JO  - Journal of Endocrinological Investigation
DO  - 10.1007/s40618-026-02996-z
UR  - https://doi.org/10.1007/s40618-026-02996-z
AB  - Objective: While the effect of the RANKL-inhibitor denosumab on serum minerals is well-documented, its impact on seminal fluid minerals is poorly understood. This study examines the correlation between the high levels of soluble-RANKL, osteoprotegerin (OPG), and minerals in seminal fluid and whether this can be influenced by denosumab.  Methods: Two cohorts comprised this study: 100 young men from the general Danish population with no reported fertility issues, and 91 infertile men who were treated with a single dose of denosumab (60 mg), or placebo in a randomized controlled trial assessing the effect on semen quality. Each man underwent a physical examination and semen analysis, including analysis of soluble RANKL, OPG, calcium, magnesium, and phosphate in the seminal fluid.  Results: In both men from the general population and infertile men, seminal OPG concentrations were positively correlated with seminal calcium (rnormal=0.54 and rinfertile=0.81), seminal magnesium (rnormal=0.58 and rinfertile=0.75), and a weak negative correlation was seen with seminal phosphate (rnormal=-0.17 and rinfertile=-0.34) concentrations. Seminal soluble RANKL was not associated with seminal minerals. Following 60 mg denosumab treatment, no changes were observed after 160 days in seminal calcium (p = 0.42), magnesium (p = 0.55), or phosphate concentrations (p = 0.63). Changes in seminal OPG were moderately negatively correlated with changes in serum AMH (r=-0.32), LH (r=-0.30), and FSH (r=-0.31).  Conclusion: A strong correlation between OPG and minerals in seminal fluids from both normal and infertile men suggests that the release of these factors by the prostate or seminal vesicle is regulated by the same factors, but cannot be modified by a short-term systemic RANKL inhibition with denosumab.  Clinical trial registration: ClinicalTrials.gov NCT03030196. Registered January 24, 2017.
SN  - 0391-4097
SN  - 1720-8386
ER  -