Osteoprotegerin is strongly associated with calcium and magnesium in seminal fluid but not affected by denosumab
In brief
OPG levels rise with calcium and magnesium in semen and are unchanged by denosumab
In 191 men, seminal osteoprotegerin showed strong positive links to calcium (r up to 0.81) and magnesium (r up to 0.75) but not to phosphate, and these relationships were identical in fertile and infertile participants. A single 60 mg dose of denosumab did not alter seminal calcium, magnesium, phosphate, or OPG after 160 days. The findings suggest prostate-derived OPG mirrors mineral content but is not modifiable by short-term RANKL inhibition.
- Journal
- Journal of endocrinological investigation (Q1)
- Published
- 24 July 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Sam Kafai Yahyavi, Mads Joon Jorsal, Emil Brink Wriedt, Niels Jørgensen, Anders Juul, Rune Holt, et al.
- PMID
- 42496818
- DOI
- 10.1007/s40618-026-02996-z
Why clinicians should know about it
- Picked for Reproductive Medicine (top studies of the week, 26 July 2026).
- Picked for Urology (paper of the day, 25 July 2026): OPG correlates with seminal calcium/magnesium; denosumab has no effect
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.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.