Bone Tissue Changes in Individuals Living with HIV/AIDS: The Importance of a Hierarchical Approach in Investigating Bone Fragility
Abstract
:1. Introduction
2. Literature Search Strategy
3. Osteodensitometry Findings in PLWHIV
4. Antiretroviral Therapy Effects on Osteodensitometry Findings in PLWHIV
5. The Importance of Multi-Scale Bone Assessment in PLWHIV
Study (Reference) | Study Design | Number of Patients with HIV | Imaging Method | Assessed Skeletal Site | Main Results on Bone Micro-Architecture |
---|---|---|---|---|---|
Serrano S. et al. [58] | Case–control study | n = 22 male, n = 13 female, n = 9 | Optic microscopy | Iliac bone | No significant difference in BVTV, Tb.Th, or Tb.N; significantly reduced osteoid volume and mildly altered osteoblast activity in PLWHIV. |
Yin M. et al. [59] | Case–control study | n = 46 female, n = 46 on ART, n = 37 | HRpQCT | DR, DT | No significant difference in trabecular or cortical micro-architecture in DR; reduced tibial Ct.Th was noted in postmenopausal WLWHIV; cART did not display a significant effect on bone micro-architecture. |
Calmy A. et al. [60] | Case–control study | n = 22 female, n = 22 on ART, n = 22 | HRpQCT | DR, DT | No significant difference in radial micro-architecture; low tibial Tb.N and high tibial Tb.Sp were noted in premenopausal WLWHIV; cART did not display a significant effect on bone micro-architecture. |
Biver E. et al. [61] | Case–control study | n = 28 male, n = 28 on ART, n = 28 | HRpQCT | DR, DT | Significantly low radial Tb.N and Ct.Th, coupled with high radial Tb.Sp, were noted in PLWHIV; reduced tibial Tb.Th was noted in men older than 60 years with long-term HIV infection. |
Lo Re V. et al. [62] | Case–control study | n = 100 female, n = 100 HCV/HIV, n = 50 | HRpQCT | DT | Low tibial Ct.Th was noted in WLWHIV, while tibial trabecular density and Ct.Th were lower in individuals with HCV/HIV confection. |
Sellier P et al. [63] | Case–control study | n = 100 male, n = 53 on TDF, n = 53 | HRpQCT | DR, DT | Trabecular micro-architecture deteriorated, while no significant changes were noted in the cortical compartment of PLWHIV treated with TDF. |
Tan D. et al. [55] | Case–control study | n = 46 male, n = 36 with fracture, n = 23 | HRpQCT | DR, DT | PLWHIV with prior bone fracture had a lower tibial trabecular bone mass and Ct.Th, coupled with a mild trend toward higher radial cortical porosity. |
Kazakia G. et al. [64] | Case–control study | n = 8 male, n = 8 on ART, n = 8 | MRI HRpQCT | PF, DR, DT | Lower Tb.Th and Tb.N of the femoral head, coupled with lower tibial Tb.N and higher tibial Tb.Sp in PLWHIV, compared to uninfected controls. |
Foreman S. et al. [65] | Cross-sectional study | n = 43 male, n = 37 on ART, n = 43 | HRpQCT | UDR, UDT | Malnutrition, physical activity, longer duration of HIV infection, and use of the TDF/PI combination were associated with an altered bone micro-architecture in PLWHIV. |
MacDonald H. et al. [66] | Case–control study | n = 50 female, n = 50 on ART, n = 50 | HRpQCT | DR, DT | Lower radial Tb.N and Tb.Th, coupled with lower tibial Tb.Th, were noted in WLWHIV. Tenofovir treatment may contribute to these bone deficits. |
Shiau S. et al. [69] | Case–control study | n = 172 boys, n = 86 on ART, n = 172 | pQCT | DR, DT | Reduced trabecular area, Ct.Th, and periosteal cortical circumference were noted in children living with HIV compared to uninfected controls. |
6. The Molecular Mechanisms Involved in Etiopathogenesis of Skeletal Alterations in PLWHIV
7. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Study (Reference) | Study Design | Number of Patients | Assessed Skeletal Site | Main Results on ART-Induced BMD Alterations |
---|---|---|---|---|
Moore A. et al. [25] | Case–control study | male, n = 221 NRTI, n = 42 PI, n = 147 | Total body, LV | Low total body BMD was associated with low body weight prior to commencing cART, while low lumbar BMD was associated with increased lactate concentrations. |
Carr A. et al. [26] | Cross-sectional study | n = 105 male, n = 75 NNRTI, n = 47 | LV, PF, FN | Low BMD was associated with using a PI-based cART regimen. Age, sex, race, and smoking were not associated with skeletal outcomes. |
Knobel H. et al. [27] | Cross-sectional study | n = 80 male, n = 58 PI, n = 37 | LV, PF | Low BMD was noted in PLWHIV, but without a significant association with any of the specific cART regimens. |
Bruera D. et al. [16] | Case–control study | n = 142 male, n = 113 PI, n = 42 non-PI, n = 36 | Total body, LV, PF | Low BMD at all assessed skeletal sites was noted in PLWHIV, irrespective of the cART regimen used. |
Fernandez-Rivera J. et al. [28] | Prospective study | n = 89 PI, n = 32 NNRTI, n = 15 | LV, FN | Low BMD was associated with PI-based cART, low plasma albumin level, and male sex. Bone loss did not substantially progress after 1 year of continued therapy. |
Amiel C. et al. [29] | Cross-sectional study | n = 148 PI, n = 49 non-PI, n = 51 | LV, FN | Low BMD was noted in PLWHIV, predominantly related to the low body weight, irrespective of the cART regimen used. |
Garcia Aparicio A. et al. [30] | Cross-sectional study | n = 30 PI, n = 17 | LV, PF, FN | The use of PI-based cART regimens was not associated with BMD alterations, while vitamin D deficiency and hypogonadism contributed to bone loss in the included individuals. |
Brown T. et al. [23] | Meta-analysis | n = 884 ART, n = 824 PI, n = 791 | LV, PF | Use of cART and especially the use of PI-based cART regimens were associated with low BMD. |
Arnsten J. et al. [31] | Cross-sectional study | n = 328 ART, n = 285 PI, n = 242 | LV, FN | Low BMD at both analyzed skeletal sites was associated with HIV infection after adjusting for age, weight, race, testosterone level, and prednisone and illicit drug use, irrespective of the cART regimen. |
Madeddu G. et al. [32] | Longitudinal study | n = 67 ART, n = 62 PI, n = 27 | LV, PF | Low BMD was associated with cART use in PLWHIV. Bone alterations may persist over time and further worsen with accelerated turnover, particularly in patients receiving PI-based cART regimens. |
Stellbrink H. et al. [33] | Multicenter longitudinal study | n = 328 TDF, n = 193 | LV, PF | More prominent bone alterations were noted in patients treated with tenofovir–emtricitabine than in patients treated with abacavir–lamivudine. |
McComsey G. et al. [34] | Randomized control trial | n = 328 male, n = 228 | LV, PF | Patients treated with TDF-FTC had significantly lower BMD compared to patients treated with ABC-3TC. Patients treated with ATV/r had lower lumbar BMD but not femoral BMD in comparison to EFV-treated individuals. |
Baranek B. et al. [35] | Meta-analysis | Total number of individuals not reported | LV, PF | TDF caused more substantial BMD loss compared to other ART regimens. The effect was less prominent if used for pre-exposure prophylaxis than as a treatment for PLWHIV. |
Mills A. et al. [36] | Randomized control trial | n = 1448 TDF, n = 477 TAF, n = 959 | LV, PF | Switching to a TAF-containing regimen from the TDF-based regimen was non-inferior for the maintenance of viral suppression and led to improved BMD and renal function. |
Pozniak A. et al. [37] | Randomized control trial | n = 242 | LV, PF | After switching to a TAF-based cART regimen, proteinuria, proximal renal tubular function, and BMD significantly improved over 48 weeks compared to individuals initially on TDF-based cART. |
Hill A. et al. [38] | Meta-analysis | n = 811,134, male, n = 6732 | LV, PF | TDF boosted with ritonavir or cobicistat was associated with higher risks of skeletal alterations and lower HIV RNA suppression rates when compared with TAF. In contrast, when ritonavir and cobicistat were not used, there were no efficacy differences between TAF and TDF, and marginal differences were noted in drug safety. |
Walmsley S. et al. [39] | Randomized control trial | n = 34, female, n = 34 | LV | The trend was noted toward increased lumbar BMD after a switch from a TDF-based cART regimen to a TAF-based cART regimen in perimenopausal and early postmenopausal WLWHIV. |
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Jadzic, J.; Dragovic, G.; Lukic, R.; Obradovic, B.; Djuric, M. Bone Tissue Changes in Individuals Living with HIV/AIDS: The Importance of a Hierarchical Approach in Investigating Bone Fragility. J. Pers. Med. 2024, 14, 791. https://doi.org/10.3390/jpm14080791
Jadzic J, Dragovic G, Lukic R, Obradovic B, Djuric M. Bone Tissue Changes in Individuals Living with HIV/AIDS: The Importance of a Hierarchical Approach in Investigating Bone Fragility. Journal of Personalized Medicine. 2024; 14(8):791. https://doi.org/10.3390/jpm14080791
Chicago/Turabian StyleJadzic, Jelena, Gordana Dragovic, Relja Lukic, Bozana Obradovic, and Marija Djuric. 2024. "Bone Tissue Changes in Individuals Living with HIV/AIDS: The Importance of a Hierarchical Approach in Investigating Bone Fragility" Journal of Personalized Medicine 14, no. 8: 791. https://doi.org/10.3390/jpm14080791