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Original Article
ARTICLE IN PRESS
doi:
10.25259/AUJMSR_44_2025

Correlation of poor bone health with serum testosterone levels in males with acquired immunodeficiency syndrome wasting syndrome

Department of Medicine, Guru Gobind Singh Medical College and Hospital, Faridkot, Punjab, India.
Author image

*Corresponding author: Kamaldeep Kaur, Department of Medicine, Guru Gobind Singh Medical College and Hospital, Faridkot, Punjab, India. kamaldeepsdh@gmail.com

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This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, transform, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

How to cite this article: Brar HS, Kaur K, Bansal A, Bhandal S, Kaur A. Correlation of poor bone health with serum testosterone levels in males with acquired immunodeficiency syndrome wasting syndrome. Adesh Univ J Med Sci Res. doi: 10.25259/AUJMSR_44_2025

Abstract

Objectives:

Acquired immunodeficiency syndrome (AIDS) Wasting Syndrome, marked by unintentional weight loss and muscle wasting, is a common complication in individuals with human immunodeficiency virus (HIV). Hypogonadism – characterized by low serum testosterone – is frequently observed in this population and may contribute to poor bone health. This study aimed to examine the relationship between serum testosterone levels and bone mineral density (BMD) in males with AIDS Wasting Syndrome.

Material and Methods:

A cross-sectional observational study was conducted over 6 months at Guru Gobind Singh Medical College and Hospital, Faridkot, involving 60 HIV-positive male patients aged 18–50 years who met Centers for Disease Control and Prevention criteria for AIDS Wasting Syndrome. Patients with other causes of weight loss or hormonal abnormalities were excluded. Early morning serum total testosterone was measured using a chemiluminescence assay, and BMD at the calcaneus was assessed through quantitative ultrasonography. Based on T-scores, participants were categorized into normal BMD, osteopenia, or osteoporosis groups.

Results:

Out of 60 patients, 55 (91.7%) had low serum testosterone levels, and among them, 92.7% exhibited abnormal BMD. Of the five patients with normal testosterone, 60% also had reduced BMD. A statistically significant correlation was found between low testosterone levels and decreased BMD (P = 0.0195). The lowest mean testosterone and CD4 counts were observed in patients with osteoporosis, suggesting more advanced disease and greater bone loss.

Conclusion:

This study found a strong correlation between low serum testosterone and poor bone health in males with AIDS Wasting Syndrome. Testosterone deficiency may serve as an early predictor of low BMD, highlighting the importance of hormonal screening and timely intervention in this high-risk group.

Keywords

Acquired immunodeficiency syndrome wasting syndrome
Bone mineral density
Human immunodeficiency virus infections
Hypogonadism
Serum testosterone

INTRODUCTION

The human immunodeficiency virus (HIV) is the cause of the dangerous and frequently fatal disease known as acquired immunodeficiency syndrome (AIDS). By attacking CD4+ T cells, the virus impairs immunity, increasing susceptibility to infections and several types of cancer. When a person contracts certain opportunistic infections or their CD4 count falls below 200 cells per microliter of blood, they are diagnosed with AIDS.[1]

Over the past 10 years, India has witnessed hopeful developments, despite the fact that the disease burden is still high. Both prevalence and incidence have decreased as a result of improved diagnostics, increased awareness, and easier access to treatment. HIV prevalence decreased from 0.32% to 0.21% in India and from 0.35% to 0.28% in Punjab between 2010 and 2021. Incidence rates and deaths from AIDS also decreased, with Punjab’s AIDS mortality rate falling from 14.72 to 1.91/100,000 people.[2]

Wasting syndrome is one of the most difficult of the numerous consequences associated with AIDS. It is characterized by symptoms including fever, weakness, or diarrhea that last longer than a month, as well as involuntary weight loss of more than 10% of body weight, or going below 90% of one’s optimum weight. Although fat loss may account for a portion of the weight reduction, the loss of muscle mass, or “wasting,” is a bigger worry.[3]

Although the precise origin of wasting syndrome is unknown, a variety of factors that differ from person to person are thought to be involved. Hormonal imbalances, inflammatory processes, poor diet, and issues with nutritional absorption all contribute. A significant hormonal component is a lack of testosterone. Nearly half of males living with AIDS suffer from hypogonadism or low testosterone levels. Loss of lean body mass is intimately linked to this low testosterone, which might worsen as the illness worsens.[4,5]

Men who have low testosterone frequently suffer from erectile dysfunction, low mood, lethargy, and decreased sex drive. Less obvious signs including muscle loss, thinning body hair, difficulties sleeping, concentration issues, and an increased risk of bone loss may also be present in certain people. Adult men with hypogonadism may not always exhibit visible symptoms such as breast enlargement or decreasing testicles, in contrast to boys with childhood-onset hypogonadism.[6]

Numerous studies have demonstrated that low bone mineral density (BMD) is more common among HIV-positive individuals, regardless of age. According to a significant review, people with HIV have an almost three-fold higher rate of osteoporosis than people without the virus. Indeed, fractures associated with inadequate bone density are also becoming increasingly common. Although there are numerous potential causes, low testosterone is believed to be a key one. By directly affecting bone tissue, testosterone helps maintain bone strength, and low levels can hasten the disintegration of bone. Consequently, osteopenia and osteoporosis are more common in men with HIV.[7,8]

MATERIAL AND METHODS

Following approval from the Institutional Research Committee and Ethics Committee for Biomedical and Health Research, Guru Gobind Singh Medical College and Hospital (GGSMCH), Faridkot, this cross-sectional observational study was conducted in the Department of Medicine over a period of 6 months.

A total of 60 male patients were included in the study. The sample size was determined based on the feasibility of recruitment during the study period, considering the prevalence of AIDS Wasting Syndrome in the patient population attending the ART center at GGSMCH. A purposive sampling technique was used, wherein eligible patients presenting during the study duration were enrolled consecutively after applying inclusion and exclusion criteria.

Inclusion criteria

  1. HIV-positive males aged between 18 and 50 years

  2. Individuals fulfilling the Centers for Disease Control and Prevention (CDC) criteria for AIDS Wasting Syndrome.

Exclusion criteria

  1. Patients with known causes of weight loss or muscle wasting unrelated to HIV (e.g., malignancies)

  2. Patients on medications known to affect testosterone levels or contribute to wasting (e.g., steroids, antipsychotics)

  3. Patients with severe psychiatric illness that may affect nutritional intake or self-care

  4. History suggestive of testicular pathology (e.g., orchitis, orchidectomy, trauma) or prior use of hormonal therapy (e.g., testosterone, analogs) in the past 6 months.

After obtaining written informed consent, each patient underwent a comprehensive clinical evaluation, including detailed medical history with particular attention to HIV disease duration and associated complications. A complete general physical and systemic examination was conducted to exclude other HIV-related or unrelated illnesses contributing to weight loss or wasting. All the included patients were treated with tld (tenofovir alafenamide + lamivudine+ dolutegravir) regimen.

Patients were classified as having AIDS Wasting Syndrome based on the CDC definition: involuntary weight loss of more than 10% of baseline body weight or body weight <90% of ideal, accompanied by persistent diarrhea, weakness, or fever lasting more than 30 days.

To account for physiological diurnal variation in testosterone levels, fasting blood samples were collected between 8:00 and 10:00 a.m. for measurement of serum total testosterone. A fully automated chemiluminescence immunoassay (CLIA) was used for hormone estimation.

BMD was assessed using quantitative ultrasound (QUS) at the calcaneus (heel) bone while the patient was in a seated position. Measurements were performed using the Achilles Insight QUS device, a non-invasive, validated screening tool for skeletal BMD.

Investigations performed in each participant

  • Complete hemogram (hemoglobin, total and differential leukocyte counts, platelet count)

  • HIV 1/2 qualitative antibody detection through rapid testing kits

  • Serum total testosterone estimation (through fully automated CLIA)

  • Calcaneal BMD assessment (through quantitative ultrasound).

RESULTS

Patients were categorized into three groups based on their BMD T-scores as follows:

  • Group A (Normal BMD): T-score between −1 and +1

  • Group B (Osteopenia): T-score between −2.5 and −1

  • Group C (Osteoporosis): T-score <−2.5.

The comparison of clinical and laboratory parameters across the three groups is presented in Table 1.

Table 1: Comparison of clinical and laboratory parameters across BMD groups.
Parameter Group A (Normal BMD) Group B (Osteopenia) Group C (Osteoporosis)
Mean age±SD (Years) 35.66±7.67 34.30±7.44 37.50±7.63
Mean
weight±SD (kg)
74.50±3.09 65.96±3.76 57.75±1.30
Mean hemoglobin±SD (g/dL) 11.78±0.68 11.22±1.07 11.53±0.62
Mean CD4 Count±SD
(cells/µL)
725.00±92.00 539.34±52.89 409.25±7.39
Mean T-score±SD 0.32±0.88 −1.54±0.75 −2.67±0.08
Mean serum testosterone±SD (ng/mL) 2.15±0.85 0.96±0.44 0.34±0.03

BMD: Bone mineral density, SD: Standard deviation

Mean age and weight

Compared to patients in the other two groups, those with osteoporosis (Group C) were marginally older on average (37.50 ± 7.63 years). From Group A (74.50 ± 3.09 kg) to Group C (57.75 ± 1.30 kg), the mean body weight gradually dropped, indicating a pattern of weight loss as bone health deteriorated.

Hemoglobin and CD4 count

There was no discernible anemia, and mean hemoglobin levels were pretty similar between groups. There may be a connection between immunosuppression and poor bone health, as seen by the declining trend in CD4 counts with worsening BMD. Group A had the greatest mean CD4 count (725 ± 92), whereas Group C had the lowest (409.25 ± 7.39).

Serum testosterone and T-score

The mean T-scores decreased from normal BMD to osteoporosis, as predicted. Crucially, there was a similar pattern in blood testosterone levels, with patients in Group A having the highest levels (2.15 ± 0.85 ng/mL) and those in Group C having far lower levels (0.34 ± 0.03 ng/mL). This implies a link between declining BMD and decreased testosterone levels.

Correlation between testosterone levels and BMD

Additional analysis was done on the connection between BMD and blood testosterone levels. Only four (7.3%) of the 55 individuals with reduced testosterone had normal BMD, while 51 (92.7%) had abnormal BMD (osteopenia or osteoporosis). Two (40%) and three (60%) of the five patients with normal testosterone levels had normal BMD and abnormal BMD, respectively. With a P-value of 0.0195, the relationship between blood testosterone levels and BMD was shown to be statistically significant, suggesting that lower testosterone levels were substantially linked to decreased bone density [Table 2 and Figure 1].

Table 2: Correlation between testosterone levels and BMD.
Testosterone level Normal BMD Abnormal BMD
(Osteopenia+ Osteoporosis)
P-value
<0.05
Normal 2 3 0.0195
Decreased 4 51

BMD: Bone mineral density

Correlation between testosterone levels and bone mineral density. BMD: Bone mineral density
Figure 1:
Correlation between testosterone levels and bone mineral density. BMD: Bone mineral density

DISCUSSION

Low testosterone levels and inadequate BMD in HIV-positive men with AIDS Wasting Syndrome were found to be significantly correlated in this study. Compared to 60% of patients with normal testosterone, the majority of patients with decreased testosterone (92.7%) had abnormal BMD. Hypogonadism and poorer bone health in this population are strongly correlated, according to the statistical significance (P = 0.0195).

These results are consistent with previous Indian research by Aggarwal et al.,[9] which demonstrated that testosterone levels are positively correlated with CD4 counts and tend to be lower in HIV-infected men. Our findings also showed a correlation between immune suppression and hormonal imbalance, with patients with lower CD4 counts exhibiting both lower testosterone levels and a higher incidence of bone loss.

Low BMD is a well-known issue among those living with HIV worldwide. More than half of HIV-positive people had lower BMD, according to a Chinese study by Meng et al.,[10] with low body weight, prolonged disease duration, and low testosterone levels being contributory factors. Our patients showed similar risk patterns, with lower weight, lower testosterone, and more severe disease, especially those with osteoporosis.

To keep bones strong, testosterone is essential. It aids in calcium retention, controls bone remodeling, and promotes osteoblast function. Bone thinning and weakness result from increased bone turnover brought on by a decline in testosterone levels. Thomas and Doherty’s[11] earlier findings that HIV infection is a risk factor for osteoporosis, perhaps because of both direct viral impacts and related endocrine dysfunction, are in line with this.

According to a large study by Monroe et al.,[12] men with HIV had a considerably greater overall frequency of hypogonadism (24.0%) than men without HIV (7.8%). It is interesting to note that many HIV-positive males had low free testosterone but normal total testosterone, which was not the case for the HIV-negative group. This implies that calculating total testosterone alone may understate hypogonadism in those with HIV.

All things considered, our results lend credence to the notion that testosterone deprivation is a major contributing factor to the bone loss observed in HIV-positive males, particularly those who exhibit wasting. This highlights how crucial it is to test for hypogonadism in these patients, both as a means of identifying individuals at risk for osteoporosis and as part of a general endocrine review. Given the possible hazards and comorbidities involved, rigorous evaluation and individualized decision-making are crucial, even if testosterone replacement therapy may be beneficial for certain people.

CONCLUSION

This study demonstrates a direct correlation between decreased BMD and low serum testosterone levels in male HIV-positive individuals with AIDS Wasting Syndrome. In this population, low testosterone levels seem to be a major cause of poor bone health. Osteoporosis may be prevented or lessened with early detection and treatment of hypogonadism, highlighting the significance of regular hormone testing as a component of comprehensive HIV care.

Ethical approval:

The research/study was approved by the Institutional Review Board at Guru Gobind Singh Medical College, Faridkot, number GGS/IEC/06, dated 30th April 2024.

Declaration of patient consent:

The authors certify that they have obtained all appropriate patient consent.

Conflicts of interest:

There are no conflicts of interest.

Use of artificial intelligence (AI)-assisted technology for manuscript preparation:

The authors confirm that there was no use of artificial intelligence (AI)-assisted technology for assisting in the writing or editing of the manuscript and no images were manipulated using AI.

Financial support and sponsorship: Nil.

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