Osteoporosis fought by Vitamin D and Testosterone in Caucasian men – March 2023

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Roles of sex hormones in mediating the causal effect of vitamin D on osteoporosis: A two-step Mendelian randomization study

Front Endocrinol (Lausanne). 2023 Mar 30;14:1159241. doi: 10.3389/fendo.2023.1159241
Yongwei Du 1, Baohui Xie 2, Maoyuan Wang 3, Yanbiao Zhong 3, Zhimai Lv 4, Yun Luo 3, Qiwei He 5, Zhen Liu 3

Background: Although 25-hydroxyvitamin D [25(OH)D] is a risk factor for osteoporosis, it is not clear whether sex hormones mediate this casual association. We aimed to explore how sex hormones affect the association between 25(OH)D and osteoporosis to provide meaningful insights on the underlying mechanisms from a genetic perspective.

Methods: Genetic variations in 25(OH)D, total testosterone (TT), androstenedione (A4), estradiol (E2), and testosterone/17β-estradiol (T/E2) were determined through summary statistics. Taking osteoporosis as the outcome (FinnGen biobank, 332,020 samples), we conducted a Mendelian randomization (MR) analysis to establish the association between 25(OH)D and these sex hormones. The two-step MR analysis quantified the mediatory effects of sex hormones on osteoporosis. The results were further verified by pleiotropy and heterogeneity analyses.

Results: MR results showed that 25(OH)D (OR= 1.27, p = 0.04) and TT (OR= 1.25, p = 0.04) had a causal effect on osteoporosis. No significant associations were observed between the other sex hormones (A4, E2, and T/E2) and osteoporosis (p>0.05). Sensitivity analysis (p>0.05) confirmed the robustness of the MR results. The two-step MR analysis provided evidence that the mediatory effect of TT was 0.014 (the percentage of TT mediation was 5.91%). Moreover, the direct effect of 25(OH)D on osteoporosis was 0.221. A4, E2, and T/E2 were not considered as potential mediators of the role of 25(OH)D as a risk factor for OP.

Conclusion: This study, through MR analysis, showed that TT mediates the causal effect of 25(OH)D on osteoporosis. Interventions targeting TT, therefore, have the potential to substantially reduce the burden of osteoporosis attributable to high 25(OH)D.
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VitaminDWiki – Overview Osteoporosis and vitamin D contains

• FACT: Bones need Calcium (this has been known for a very long time)
• FACT: Vitamin D improves Calcium bioavailability (3X ?)
• FACT: Should not take > 750 mg of Calcium if taking lots of vitamin D (Calcium becomes too bio-available)
• FACT: Adding vitamin D via Sun, UV, or supplements increased vitamin D in the blood
• FACT: Vitamin D supplements are very low cost
• FACT: Many trials, studies. reviews, and meta-analysis agree: adding vitamin D reduces osteoporosis
• FACT: Toxic level of vitamin D is about 4X higher than the amount needed to reduce osteoporosis
• FACT: Co-factors help build bones.
• FACT: Vitamin D Receptor can restrict Vitamin D from getting to many tissues, such as bones
• It appears that to TREAT Osteoporosis:
•        Calcium OR vitamin D is ok
•        Calcium + vitamin D is good
•        Calcium + vitamin D + other co-factors is great
•        Low-cost Vitamin D Receptor activators sometimes may be helpful
• CONCLUSION: To PREVENT many diseases, including Osteoporosis, as well as TREAT Osteoporosis
• Category Osteoporosis has 221 items
• Category Bone Health has 314 items

Note: Osteoporosis causes bones to become fragile and prone to fracture
  Osteoarthritis is a disease where damage occurs to the joints at the end of the bones

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VitaminDWiki – Osteoporosis category contains

• 221 items in category - see also Overview Osteoporosis and vitamin D
• Overview Fractures and vitamin D
• Bone - Health 314 items
• VitaminDWiki pages with BONE MINERAL DENSITY or BMD in title 29+ pages
• Search VitaminDWiki for OSTEOPENIA 1740 items as of July 2020
• 13 articles are in both Osteroporosis and Vitamin D Receptor categories
• 10 articles are in both Osteroporosis and Meta-analysis categories
• 20X increase in vitamin D sold and 36 percent decrease in osteoporosis business in Australia – Nov 2013

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Testosterone and Bone Health in Men: A Narrative Review - Feb 2021

J. Clin. Med. 2021, 10(3), 530; https://doi.org/10.3390/jcm10030530by Kazuyoshi Shigehara *,Kouji IzumiORCID,Yoshifumi Kadono andAtsushi MizokamiORCID
Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, 13-1, Kanazawa, Ishikawa 920-8641, Japan

Bone fracture due to osteoporosis is an important issue in decreasing the quality of life for elderly men in the current aging society. Thus, osteoporosis and bone fracture prevention is a clinical concern for many clinicians. Moreover, testosterone has an important role in maintaining bone mineral density (BMD) among men. Some testosterone molecular mechanisms on bone metabolism have been currently established by many experimental data. Concurrent with a decrease in testosterone with age, various clinical symptoms and signs associated with testosterone decline, including decreased BMD, are known to occur in elderly men. However, the relationship between testosterone levels and osteoporosis development has been conflicting in human epidemiological studies. Thus, testosterone replacement therapy (TRT) is a useful tool for managing clinical symptoms caused by hypogonadism. Many recent studies support the benefit of TRT on BMD, especially in hypogonadal men with osteopenia and osteoporosis, although a few studies failed to demonstrate its effects. However, no evidence supporting the hypothesis that TRT can prevent the incidence of bone fracture exists. Currently, TRT should be considered as one of the treatment options to improve hypogonadal symptoms and BMD simultaneously in symptomatic hypogonadal men with osteopenia.
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(No) Association of total testosterone status with BMD in adults aged 40–60 years - 2021

J. of Orthopaedic Surgery and Research V 16, # 612 (2021) https://doi.org/10.1186/s13018-021-02714-w
Nan Wang, Lixiang Wang & Chengcheng Huang

Objective
Evidence linking total testosterone and bone mineral density (BMD) in adults is very limited. According to our review of the literature, only a few reports have focused on the relationship between total testosterone and bone mineral density in adults. Therefore, the purpose of this study was to determine the relationship between total testosterone and total bone mineral density in adults aged 40–60 years.

Methods
We used a cross-sectional study of a non-institutionalized U.S. population sample from the National Health and Nutrition Examination Survey. A weighted multivariate linear regression model was used to evaluate the relationship between total testosterone and total bone mineral density. Subgroup analyses were further performed.

Results
In multiple regression models adjusted for potential confounders, total testosterone levels were inversely associated with total bone mineral density. However, in the sex-stratified subgroup analysis, the association between total testosterone levels and total bone mineral density was not significant in female adolescents. There was no negative association between total testosterone and total BMD among men, adults 40 to 60 years of age, and other racial/ethnic groups. There is a negative association between total testosterone and total bone mineral density when total testosterone concentration is greater than 500 ng/dL among Non-Hispanic black.

Conclusion
Our statistical results show that the association between total testosterone levels and total bone mineral density varies by gender and race. Elevated total testosterone levels below 500 ng/dL have adverse effects on bone health. Total testosterone concentrations below 500 ng/dL may have no effect on bone health.
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Testosterone supplementation and bone parameters: a systematic review and meta-analysis study - Jan 2022

Journal of Endocrinological Investigation volume 45, pages 911–926 (2022)
G. Corona, W. Vena, A. Pizzocaro, V. A. Giagulli, D. Francomano, G. Rastrelli, G. Mazziotti, A. Aversa, A. M. Isidori, R. Pivonello, L. Vignozzi, E. Mannucci, M. Maggi & A. Ferlin

Background
The role of testosterone (T) replacement therapy (TRT) in subjects with late onset hypogonadism is still the object of an intense debate.

Methods
All observational studies and placebo-controlled or -uncontrolled randomized trials (RCTs) comparing the effect of TRT on different bone parameters were considered.

Results
Out of 349 articles, 36 were considered, including 3103 individuals with a mean trial duration of 66.6 weeks. TRT improves areal bone mineral density (aBMD) at the spine and femoral neck levels in observational studies, whereas placebo-controlled RTCs showed a positive effect of TRT only at lumber spine and when trials included only hypogonadal patients at baseline (total testosterone < 12 nM). The effects on aBMD were more evident in subjects with lower T levels at baseline and increased as a function of trial duration and a higher prevalence of diabetic subjects. Either T or estradiol increase at endpoint contributed to aBMD improvement. TRT was associated with a significant reduction of bone resorption markers in observational but not in controlled studies.

Conclusion
TRT is able to inhibit bone resorption and increase bone mass, particularly at the lumbar spine level and when the duration is long enough to allow the anabolic effect of T and estrogens on bone metabolism to take place.
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Charts of Testosterone dropping by half with age

Medichecks

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MDrive - sells T

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RXHome test sells T tests

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Vitamin D levels have been crashing