ArticleThe Journal of clinical investigation2004
The HIV protease inhibitor ritonavir blocks osteoclastogenesis and function by impairing RANKL-induced signaling.
Article in The Journal of clinical investigation, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
56 citing papers in PubMed, 1 synthesis or guideline pooled it, 117 citations in OpenAlex.
- Incident fractures in HIV-infected individuals: a systematic review and meta-analysis.AIDS (London, England) · 2013Pooled it
- Efavirenz is associated with higher bone mass in South African children with HIV.AIDS (London, England) · 2016Trial
- Less Bone Loss With Maraviroc- Versus Tenofovir-Containing Antiretroviral Therapy in the AIDS Clinical Trials Group A5303 Study.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2015Trial
- Effect of supplementation with cholecalciferol and calcium on 2-y bone mass accrual in HIV-infected children and adolescents: a randomized clinical trial.The American journal of clinical nutrition · 2012Trial
- Longitudinal changes in bone mineral density among children living with HIV over 96 weeks following switch to second-line antiretroviral therapy in Uganda.PLOS global public health · 2026Article
- Cartilage-protective effects of lopinavir/ritonavir: in vitro and in silico exploration of the HIF-1α/SOX9/IL-1β pathway.Journal of orthopaedic surgery and research · 2025Article
- Bone Tissue Changes in Individuals Living with HIV/AIDS: The Importance of a Hierarchical Approach in Investigating Bone Fragility.Journal of personalized medicine · 2024Review
- Ritonavir Has Reproductive Toxicity Depending on Disrupting PI3K/PDK1/AKT Signaling Pathway.Toxics · 2024Article
- Reproductive toxicity of ritonavir in male: Insight into mouse sperm capacitation.Reproductive toxicology (Elmsford, N.Y.) · 2022Article
- Bone Quality in Relation to HIV and Antiretroviral Drugs.Current HIV/AIDS reports · 2022Review
- Gain-of-Function Lrp5 Mutation Improves Bone Mass and Strength and Delays Hyperglycemia in a Mouse Model of Insulin-Deficient Diabetes.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2021Article
- Bone outcomes in virally suppressed youth with HIV switching to tenofovir disoproxil fumarate.Southern African journal of HIV medicine · 2021Article
- Low bone mass in people living with HIV on long-term anti-retroviral therapy: A single center study in Uganda.PloS one · 2021Article
- Influence of HIV Infection and Antiretroviral Therapy on Bone Homeostasis.Frontiers in endocrinology · 2020Review
- Designing, synthesis and characterization of 2-aminothiazole-4-carboxylate Schiff bases; antimicrobial evaluation against multidrug resistant strains and molecular docking.BMC chemistry · 2019Article
- Inhibition of osteoblast differentiation by ritonavir.Biomedical reports · 2018Article
- Recent Advances in Electrochemical Biosensors Based on Enzyme Inhibition for Clinical and Pharmaceutical Applications.Sensors (Basel, Switzerland) · 2018Review
- Vitamin D Status and the Relationship with Bone Fragility Fractures in HIV-Infected Patients: A Case Control Study.International journal of molecular sciences · 2018Article
- The HIV co-receptor CCR5 regulates osteoclast function.Nature communications · 2017Article
- Bone and the Immune System.Toxicologic pathology · 2017Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Highly active antiretroviral therapy (HAART), which includes HIV protease inhibitors (PIs), has been associated with bone demineralization. To determine if this complication reflects accelerated resorptive activity, we studied the impact of two common HIV PIs, ritonavir and indinavir, on osteoclast formation and function. Surprisingly, we find that ritonavir, but not indinavir, inhibits osteoclast differentiation in a reversible manner and also abrogates bone resorption by disrupting the osteoclast cytoskeleton, without affecting cell number. Ritonavir given in vivo completely blunts parathyroid hormone-induced osteoclastogenesis in mice, which confirms that the drug is bone sparing. In keeping with its antiresorptive properties, ritonavir impairs receptor activator of nuclear factor kappaB ligand-induced (RANKL-induced) activation of NF-kappaB and Akt signaling pathways, both critical to osteoclast formation and function. In particular, ritonavir is found to inhibit RANKL-induced Akt signaling by disrupting the recruitment of TNF receptor-associated factor 6/c-Src complex to lipid rafts. Thus, ritonavir may represent a bone-sparing PI capable of preventing development of osteopenia in patients currently on HAART.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.