A Single-dose Zoledronic Acid Infusion Prevents Antiretroviral Therapy–induced Bone Loss in Treatment-naive HIV-infected Patients: A Phase IIb Trial
Open accessAbstract
BACKGROUND: Human immunodeficiency virus (HIV) infection and antiretroviral therapy (ART) are associated with bone loss leading to increased fracture rate among HIV-infected individuals. ART-induced bone loss is most intense within the first 48 weeks of therapy, providing a window for prophylaxis with long-acting antiresorptives. METHODS: In a phase 2, double-blind, placebo-controlled trial, we randomized 63 nonosteoporotic, ART-naive adults with HIV initiating ART with atazanavir/ritonavir + tenofovir/emtricitabine to a single zoledronic acid (ZOL) infusion (5 mg) vs placebo to determine the efficacy of ZOL in mitigating ART-induced bone loss. Plasma bone turnover markers and bone mineral density (BMD) were performed at weeks 0, 12, 24, and 48 weeks. Primary outcome was change in C-terminal telopeptide of collagen at 24 weeks. Repeated-measures analyses using mixed linear models were used to estimate and compare study endpoints. RESULTS: The ZOL arm had a 65% reduction in bone resorption relative to the placebo arm at 24 weeks (0.117 ng/mL vs 0.338 ng/mL; P < .001). This effect of ZOL occurred as early as 12 weeks (73% reduction; P < .001) and persisted through week 48 (57% reduction; P < .001). The ZOL arm had an 8% higher lumbar spine BMD at 12 weeks relative to the placebo arm (P = .003), and remained 11% higher at 24 and 48 weeks. Similar trends were observed in the hip and femoral neck. CONCLUSIONS: A single dose of ZOL administered at ART initiation prevented ART-induced bone loss through the first 48 weeks of ART, the period when ART-induced bone loss is most pronounced. Validation of these results in larger multicenter randomized clinical trials is warranted. CLINICAL TRIALS REGISTRATION: NCT01228318.
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Phase 2 trials reported that zoledronic acid prevents bone loss in HAART-treated HIV patients.
“Phase 2 trials have reported that zoledronic acid prevents bone loss in HAART‐treated HIV patients (Ofotokun et al, 2016).”
From The struggle of a good friend getting old: cellular senescence in viral responses and therapy (2021) · cites this paper as Ofotokun et al, 2016
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The struggle of a good friend getting old: cellular senescence in viral responses and therapy
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- Authors
- Ofotokun, I., Titanji, K., Lahiri, C. D., Vunnava, A., Foster, A., Sanford, S. E., Sheth, A. N., Lennox, J. L., Knezevic, A., Ward, L., Easley, K. A., Powers, P., & Weitzmann, M. N.
- Affiliations
- Grady Memorial Hospital (US)
- Emory University (US)
- Corresponding author
- Ofotokun, Ighovwerha
- ORCID
- Venue
- Clinical Infectious Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 2016-05-18
- Volume
- 63
- Issue
- 5
- Pages
- 663-671
- ISSN
- 1058-4838 (ISSN-L)
- 1537-6591
- PMC
- PMC4981757
- OpenAlex
- W2408046757
- Cited by
- 50
- References
- 24
- Citations by year
- 2025: 3 · 2024: 4 · 2023: 1 · 2022: 5 · 2021: 7 · 2020: 6 · 2019: 4 · 2018: 8 · 2017: 6 · 2016: 6
- FWCI
- 10.58
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Clinical Infectious Diseases (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- National Institutes of Health
- NIH (UL1TR000454, KL2TR000455)
- National Institute on Aging (R01AG040013)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) (R01AR059364, R01AR068157)
- Veterans Affairs Office of Research and Development (5I01BX000105)
- NIAMS (R01AR056090, R01AR053898)
- National Center for Advancing Translational Sciences (UL1TR000454)
- National Institute for Allergy and Infectious Diseases (NIAID) (1K23AI114407)
- NIAID (P30AI050409)
- Topics
- Health Sciences › Medicine › Emergency Medicine › HIV-related health complications and treatments
- Health Sciences › Medicine › Infectious Diseases › HIV/AIDS drug development and treatment
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Keywords
- zoledronic acid, HIV infection, bone resorption, bone mineral density, atazanavir/ritonavir, tenofovir/emtricitabine, lumbar spine
- MeSH terms
- Zoledronic Acid, Adult, Diphosphonates, Female, Humans, Imidazoles, Male, Middle Aged, Osteoporosis, RNA, Viral, HIV Infections, Anti-Retroviral Agents, Bone Density Conservation Agents
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