ArticleMolecular genetics and metabolism2015
Losartan increases bone mass and accelerates chondrocyte hypertrophy in developing skeleton.
Article in Molecular genetics and metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Angiotensin Receptor Blocker is Associated with a Lower Fracture Risk: An Updated Systematic Review and Meta-Analysis.International journal of clinical practice · 2022Pooled it
- Vascular and musculoskeletal interactions: structure, function, and therapeutic strategies for sarcopenia and osteoporosis.MedScience · 2026Review
- Angiotensin II Promotes Osteocyte RANKL Expression via AT1R Activation.Biomedicines · 2025Article
- Combination Therapy of Losartan and Fisetin Reduces Senescence and Enhances Osteogenesis in Human Bone Marrow-Derived Mesenchymal Stem Cells.Journal of tissue engineering and regenerative medicine · 2025Article
- Association of RAAS inhibitors on osteoporosis and fracture risk in the hypertensive population-A prospective population-based cohort study in Lanzhou, China.BMC musculoskeletal disorders · 2024Article
- Losartan alters osteoblast differentiation and increases bone mass through inhibition of TGFBone reports · 2024Article
- Osteoprotegerin Is Essential for the Development of Endothelial Dysfunction Induced by Angiotensin II in Mice.International journal of molecular sciences · 2024Article
- Antihypertensive drug-associated adverse events in osteoarthritis: a study of a large real-world sample based on the FAERS database.Frontiers in pharmacology · 2024Article
- Classification of osteogenesis imperfecta: Importance for prophylaxis and genetic counseling.World journal of clinical cases · 2023Review
- Advances in Diagnosis and Management of Childhood OsteoporosisJournal of clinical research in pediatric endocrinology · 2022Review
- Osteoprotegerin and RANKL-RANK-OPG-TRAIL signalling axis in heart failure and other cardiovascular diseases.Heart failure reviews · 2022Review
- Effects of oral losartan administration on homeostasis of articular cartilage and bone in a rabbit model.Bone reports · 2022Article
- Repurposing existing products to accelerate injury recovery (REPAIR) of military relevant musculoskeletal conditions.Frontiers in bioengineering and biotechnology · 2022Article
- Pleiotropic Effects of Simvastatin and Losartan in Preclinical Models of Post-Traumatic Elbow Contracture.Frontiers in bioengineering and biotechnology · 2022Article
- Review
- The Role of Osteoprotegerin and Its Ligands in Vascular Function.International journal of molecular sciences · 2019Review
- Losartan improves alveolar bone dynamics in normotensive rats but not in hypertensive rats.Journal of applied oral science : revista FOB · 2019Article
- Angiotensin receptor blockade mediated amelioration of mucopolysaccharidosis type I cardiac and craniofacial pathology.Journal of inherited metabolic disease · 2017Article
- Bilateral atypical femur fractures without bisphosphonate exposure.Skeletal radiology · 2017Article
- c-Raf promotes angiogenesis during normal growth plate maturation.Development (Cambridge, England) · 2016Article
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 1 country.
Funding
Abstract
Angiotensin receptor blockers (ARBs) are a group of anti-hypertensive drugs that are widely used to treat pediatric hypertension. Recent application of ARBs to treat diseases such as Marfan syndrome or Alport syndrome has shown positive outcomes in animal and human studies, suggesting a broader therapeutic potential for this class of drugs. Multiple studies have reported a benefit of ARBs on adult bone homeostasis; however, its effect on the growing skeleton in children is unknown. We investigated the effect of Losartan, an ARB, in regulating bone mass and cartilage during development in mice. Wild type mice were treated with Losartan from birth until 6 weeks of age, after which bones were collected for microCT and histomorphometric analyses. Losartan increased trabecular bone volume vs. tissue volume (a 98% increase) and cortical thickness (a 9% increase) in 6-weeks old wild type mice. The bone changes were attributed to decreased osteoclastogenesis as demonstrated by reduced osteoclast number per bone surface in vivo and suppressed osteoclast differentiation in vitro. At the molecular level, Angiotensin II-induced ERK1/2 phosphorylation in RAW cells was attenuated by Losartan. Similarly, RANKL-induced ERK1/2 phosphorylation was suppressed by Losartan, suggesting a convergence of RANKL and angiotensin signaling at the level of ERK1/2 regulation. To assess the effect of Losartan on cartilage development, we examined the cartilage phenotype of wild type mice treated with Losartan in utero from conception to 1 day of age. Growth plates of these mice showed an elongated hypertrophic chondrocyte zone and increased Col10a1 expression level, with minimal changes in chondrocyte proliferation. Altogether, inhibition of the angiotensin pathway by Losartan increases bone mass and accelerates chondrocyte hypertrophy in growth plate during skeletal development.
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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.