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HOME > Endocrinol Metab > Volume 41(2); 2026 > Article
Letter
Mineral, bone & muscle Complete Blood Count Parameters and Bone Health: Clinical and Experimental Evidence (Endocrinol Metab 2025;40:811-20, Jeonghoon Ha et al.)
Federica Tramontana1orcid, Richard Quinton2,3orcid
Endocrinology and Metabolism 2026;41(2):333-334.
DOI: https://doi.org/10.3803/EnM.2026.2955
Published online: April 29, 2026

1Department of Clinical & Experimental Medicine, University of Pisa, Pisa, Italy

2Northern Region Gender Dysphoria Service, Cumbria Northumberland Tyne & Wear NHS Foundation Trust, Newcastle-upon-Tyne, UK

3Department of Metabolism Digestion & Reproduction, Imperial College London, London, UK

Corresponding author: Federica Tramontana. Department of Clinical & Experimental Medicine, University of Pisa, Via Savi 10, Pisa 56126, Italy Tel: +39-50-2211823, E-mail: f.tramontana2@studenti.unipi.it
• Received: January 31, 2026   • Accepted: February 6, 2026

Copyright © 2026 Korean Endocrine Society

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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We read with interest this recent overview of the relationships between hematologic indices and bone health, but were surprised to find no discussion of the key role played by testosterone (T) in both bone health and hematopoiesis [1].
Together with estrogens, T plays an essential role in maintaining bone formation and bone microarchitecture in males. While the regulation of bone resorption predominantly rests on its aromatization to estradiol, T also has a direct anabolic effect on bone through androgen receptor-mediated pathways in osteoblasts and osteocytes in trabecular and cortical bone, independent of aromatization. Androgens are key determinants of the male skeletal phenotype, characterized by larger bones with a thicker cortex and greater strength. In contrast to women, the risk of fragility fractures develops much later in life, in parallel to the age-related decline in both T levels and erythropoietic activity [2,3].
T also plays a key role in promoting erythropoiesis through multiple mechanisms, including enhanced renal erythropoietin secretion, direct stimulation of bone marrow erythroid precursors, and increased iron availability through inhibition of hepatic hepcidin secretion. In hypogonadal men, T replacement therapy induces a dose- and serum level-dependent increase in hemoglobin and hematocrit (Hct), accompanied by parallel positive changes in lean body mass and bone mineral density (BMD). Several studies have shown that T replacement increases BMD and strengthens trabecular bone architecture, whereas low T levels in hypogonadism are associated with accelerated bone loss and reduced BMD [4,5].
The European Male Aging study found 4.1% of men aged ≥40 years to have hypogonadism (distributed equally between functional and pathological causes), increasing to 7.5% of men aged ≥70 (3:1 pathological vs. functional) [6]. This age- and comorbidity-related decline in T levels leads to reduced erythropoietic activity and an increasing prevalence of anemia, which is even more sharply observed with androgen deprivation therapy. In The Testosterone Replacement Therapy for Assessment of Long-term Vascular Events and Efficacy Response in Hypogonadal Men (TRAVERSE) study of T treatment in older men with mild functional (non-pathological) hypogonadism, 16% of subjects had anemia, and this was corrected by T in 45% of cases (vs. 30% on placebo), with significant increases in red blood cells and Hct observed across the board. Crucially, those men whose anemia corrected with T treatment were the only subgroup who experienced improved vitality and physical performance [7].
Pathological hypogonadism is a recognized risk factor for osteoporosis and fractures in men, mediated by reduced bone formation, increased bone resorption, and associated anemia [5]. T treatment improves all measurable aspects of bone structure and health [4]. Although another arm of the TRAVERSE study found an increased incidence of non-fragility fractures [8], this was likely related to behavioral factors in view of the timeline of onset and the fracture sites.
We are, however, pleased that the authors noted how anemia in men not only represents a blood parameter alteration, but may be useful as a marker of undiagnosed hypogonadism, which in turn independently contributes to reduced BMD and impaired erythropoiesis [1]. About 15% of community-dwelling older men with hypogonadism are affected by anemia [7]. However, in a real world study, 56% of older men admitted acutely or to an internal medicine service were anemic, of whom 47% had unexplained anemia. Of those with unexplained anemia, 44% had pathological hypogonadism due to primary testicular insufficiency [9].
Obesity is associated with inflammation and endocrine disorders leading to hematologic changes that may also signal functional hypogonadism in middle-aged and obese men. Excess adiposity promotes hypothalamic–pituitary dysfunction through insulin resistance and pro-inflammatory cytokines. Several studies have shown that excess adiposity has an unfavourable impact on bone microarchitecture despite the increased BMD [5,10].
These data suggest that alterations in blood parameters may represent an early clinical signal of endocrine alterations with relevant skeletal consequences in men. Evaluating T status in men with anemia or unexplained bone loss, thus has important diagnostic and therapeutic implications.
We hope these observations will encourage further discussion on this important topic, considering all of the relevant endocrine factors.

CONFLICTS OF INTEREST

No potential conflict of interest relevant to this article was reported.

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  • 8. Snyder PJ, Bauer DC, Ellenberg SS, Cauley JA, Buhr KA, Bhasin S, et al. Testosterone treatment and fractures in men with hypogonadism. N Engl J Med 2024;390:203–11.ArticlePubMed
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  • 10. Shen J, Nielson CM, Marshall LM, Lee DC, Keaveny TM, Orwoll ES, et al. The association between BMI and QCT-derived proximal hip structure and strength in older men: a cross-sectional study. J Bone Miner Res 2015;30:1301–8.ArticlePubMedPMCPDF

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        Complete Blood Count Parameters and Bone Health: Clinical and Experimental Evidence (Endocrinol Metab 2025;40:811-20, Jeonghoon Ha et al.)
        Endocrinol Metab. 2026;41(2):333-334.   Published online April 29, 2026
        DOI: https://doi.org/10.3803/EnM.2026.2955
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