Bone Health in People Living with HIV/AIDS: An Update of Where We Are and Potential Future Strategies

Ahmed, Musaab; Mital, Dushyant; Abubaker, Nuha Eljaili; Panourgia, Maria; Owles, Henry; Papadaki, Ioanna; Ahmed, Mohamed H.

doi:10.3390/microorganisms11030789

Cited by 8 publications

(5 citation statements)

References 114 publications

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“…The dysregulation of the bone remodeling system, which involves the interaction between osteoblasts and osteoclasts, can result in osteolytic bone disease, which is a common complication of HIV infection. Several studies have reported that HIV infection contributes to the emergence of osteolytic illness ( 41 – 44 ). For instance, HIV-infected human macrophages secrete RANK-L, which enhances osteoclast recruitment ( 45 ).…”

Section: Discussionmentioning

confidence: 99%

Massively HIV-1-infected macrophages exhibit a severely hampered ability to differentiate into osteoclasts

et al. 2023

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IntroductionOsteoclasts play a crucial role in bone resorption, and impairment of their differentiation can have significant implications for bone density, especially in individuals with HIV who may be at risk of altered bone health. The present study aimed to investigate the effects of HIV infection on osteoclast differentiation using primary human monocyte-derived macrophages as precursors. The study focused on assessing the impact of HIV infection on cellular adhesion, cathepsin K expression, resorptive activity, cytokine production, expression of co-receptors, and transcriptional regulation of key factors involved in osteoclastogenesis.MethodsPrimary human monocyte-derived macrophages were utilized as precursors for osteoclast differentiation. These precursors were infected with HIV, and the effects of different inoculum sizes and kinetics of viral replication were analyzed. Subsequently, osteoclastogenesis was evaluated by measuring cellular adhesion, cathepsin K expression, and resorptive activity. Furthermore, cytokine production was assessed by monitoring the production of IL-1β, RANK-L, and osteoclasts. The expression levels of co-receptors CCR5, CD9, and CD81 were measured before and after infection with HIV. The transcriptional levels of key factors for osteoclastogenesis (RANK, NFATc1, and DC-STAMP) were examined following HIV infection.ResultsRapid, massive, and productive HIV infection severely impaired osteoclast differentiation, leading to compromised cellular adhesion, cathepsin K expression, and resorptive activity. HIV infection resulted in an earlier production of IL-1β concurrent with RANK-L, thereby suppressing osteoclast production. Infection with a high inoculum of HIV increased the expression of the co-receptor CCR5, as well as the tetraspanins CD9 and CD81, which correlated with deficient osteoclastogenesis. Massive HIV infection of osteoclast precursors affected the transcriptional levels of key factors involved in osteoclastogenesis, including RANK, NFATc1, and DC-STAMP.ConclusionsThe effects of HIV infection on osteoclast precursors were found to be dependent on the size of the inoculum and the kinetics of viral replication. These findings underscore the importance of understanding the underlying mechanisms to develop novel strategies for the prevention and treatment of bone disorders in individuals with HIV.

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Section: Discussionmentioning

confidence: 99%

Massively HIV-1-infected macrophages exhibit a severely hampered ability to differentiate into osteoclasts

et al. 2023

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“…The question remains open whether these urethral macrophage virus reservoirs are locally formed early after sexual transmission or later during HIV-1 infection progression. Finally, HIV-1 spreading in bone OCs [ 55 , 56 , 57 , 58 ], myeloid multinucleated cells involved in bone tissue homeostasis, could be responsible for the bone loss and disorders observed in infected patients, even when they are treated with efficient cART (for recent reviews, see [ 59 , 60 ]).…”

Section: Macrophages As Cellular Targets Of Hiv-1 In Vivomentioning

confidence: 99%

Macrophages: Key Cellular Players in HIV Infection and Pathogenesis

Woottum,

Yan,

Sayettat

et al. 2024

Viruses

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Although cells of the myeloid lineages, including tissue macrophages and conventional dendritic cells, were rapidly recognized, in addition to CD4+ T lymphocytes, as target cells of HIV-1, their specific roles in the pathophysiology of infection were initially largely neglected. However, numerous studies performed over the past decade, both in vitro in cell culture systems and in vivo in monkey and humanized mouse animal models, led to growing evidence that macrophages play important direct and indirect roles as HIV-1 target cells and in pathogenesis. It has been recently proposed that macrophages are likely involved in all stages of HIV-1 pathogenesis, including virus transmission and dissemination, but above all, in viral persistence through the establishment, together with latently infected CD4+ T cells, of virus reservoirs in many host tissues, the major obstacle to virus eradication in people living with HIV. Infected macrophages are indeed found, very often as multinucleated giant cells expressing viral antigens, in almost all lymphoid and non-lymphoid tissues of HIV-1-infected patients, where they can probably persist for long period of time. In addition, macrophages also likely participate, directly as HIV-1 targets or indirectly as key regulators of innate immunity and inflammation, in the chronic inflammation and associated clinical disorders observed in people living with HIV, even in patients receiving effective antiretroviral therapy. The main objective of this review is therefore to summarize the recent findings, and also to revisit older data, regarding the critical functions of tissue macrophages in the pathophysiology of HIV-1 infection, both as major HIV-1-infected target cells likely found in almost all tissues, as well as regulators of innate immunity and inflammation during the different stages of HIV-1 pathogenesis.

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“…Conversely, this correlation was absent in individuals with severely decreased CD4+ counts (<200 cells/µL), indicating a complex impact of T-cell dynamics on bone health, dependent on the level of CD4+ depletion [19]. In summary, HIV immune-mediated systemic responses seem to stimulate osteoclastogenesis and disrupt the bone remodeling process, leading to an increased risk of osteopenia, osteoporosis, and ultimately, fractures [20].…”

Section: Hiv and Bone Loss Pathophysiologymentioning

confidence: 99%

Bone Disease in HIV: Need for Early Diagnosis and Prevention

Schinas,

Ntampanlis

et al. 2024

Life

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The transformation of HIV into a manageable chronic condition has unveiled new clinical challenges associated with aging-related pathologies, including bone disease. This review explores the intricate relationship between HIV, antiretroviral therapy (ART), and bone disease, highlighting the necessity of early diagnosis and preventative strategies to mitigate the increased risk of osteopenia, osteoporosis, and fractures in people living with HIV (PLWHIV). It synthesizes the current literature to elucidate the multifactorial etiology of bone pathology in this population, that includes direct viral effects, chronic immune activation, ART-associated risks, and the impact of traditional risk factors for bone loss. Through a critical examination of modern diagnostic methods, lifestyle modifications, evidence-based preventive actions, and pharmacological treatments, the necessity for comprehensive management is highlighted, along with recommendations for integrated healthcare approaches vital for achieving optimal patient outcomes. By advocating for a proactive, patient-centered, and multidisciplinary strategy, this review proposes a plan to integrate bone health into standard HIV care through active risk identification, vigilant screening, effective preventive measures, tailored treatments, and informed decision-making, in an effort to ultimately enhance the quality of life for PLWHIV.

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Bone Health in People Living with HIV/AIDS: An Update of Where We Are and Potential Future Strategies

Cited by 8 publications

References 114 publications

Massively HIV-1-infected macrophages exhibit a severely hampered ability to differentiate into osteoclasts

Massively HIV-1-infected macrophages exhibit a severely hampered ability to differentiate into osteoclasts

Macrophages: Key Cellular Players in HIV Infection and Pathogenesis

Bone Disease in HIV: Need for Early Diagnosis and Prevention

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