ArticleBone2015
Duration-dependent effects of clinically relevant oral alendronate doses on cortical bone toughness in beagle dogs.
Article in Bone, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
16 citing papers in PubMed, 39 citations in OpenAlex.
- Magnetic Resonance Imaging-Based Cohesive Extended Finite Element Modeling of Atypical Femoral Fracture.Journal of biomechanical engineering · 2026Article
- Impending Atypical Femoral Fracture on the Contralateral Side Progressed to a Complete Fracture Early after Surgery for an Atypical Femoral Fracture: A Case Report.Journal of orthopaedic case reports · 2024Article
- The feasibility of discriminating BRONJ lesion bone with Raman spectroscopy.Frontiers in endocrinology · 2023Article
- Resveratrol Attenuates High Glucose-Induced Osteoblast DysfunctionFrontiers in pharmacology · 2022Article
- Diabetoporosis: Role of nitric oxide.EXCLI journal · 2021Review
- The Role of Lower-Limb Geometry in the Pathophysiology of Atypical Femoral Fracture.Current osteoporosis reports · 2019Review
- The effect of long-term bisphosphonate therapy on trabecular bone strength and microcrack density.Bone & joint research · 2017Article
- Improving Combination Osteoporosis Therapy in a Preclinical Model of Heightened Osteoanabolism.Endocrinology · 2017Article
- Undisturbed local bone formation capacity in patients with atypical femoral fractures: a case series.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2017Article
- Raloxifene Improves Bone Mechanical Properties in Mice Previously Treated with Zoledronate.Calcified tissue international · 2017Article
- Effects of combination treatment with alendronate and raloxifene on skeletal properties in a beagle dog model.PloS one · 2017Article
- Role of cortical bone in hip fracture.BoneKEy reports · 2017Review
- Simultaneous, bilateral, complete atypical femoral fractures after long-term alendronate use.Journal of orthopaedics · 2016Article
- Zoledronate treatment has different effects in mouse strains with contrasting baseline bone mechanical phenotypes.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2016Article
- The use of finite element analysis to estimate the changing strength of bone following treatment for osteoporosis.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2016Article
- Osteogenesis imperfecta.Lancet (London, England) · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Bisphosphonates (BPs) have been shown to significantly reduce bone toughness in vertebrae within one year when given at clinical doses to dogs. Although BPs also reduce toughness in the cortical bone when given at high doses, their effect on cortical bone material properties when given at clinical doses is less clear. In part, this may be due to the use of small sample sizes that were powered to demonstrate differences in bone mineral density rather than the bone's material properties. Our lab has conducted several studies in which dogs were treated with alendronate at a clinically relevant dose. The goal of this study was to examine these published and unpublished data collectively to determine whether there is a significant time-dependent effect of alendronate on toughness of the cortical bone. This analysis seemed particularly relevant given the recent occurrence of atypical femoral fractures in humans. Differences in the toughness of ribs taken from dogs derived from five separate experiments were measured. The dogs were orally administered saline (CON, 1ml/kg/day) or alendronate (ALN) at a clinical dose (0.2mg/kg/day). Treatment duration ranged from 3months to 3years. Groups were compared using ANOVA, and time trends analyzed with linear regression analysis. Linear regressions of the percent difference in toughness between CON and ALN at each time point revealed a significant reduction in toughness with longer exposure to ALN. The downward trend was primarily driven by a downward trend in post-yield toughness, whereas toughness in the pre-yield region was not changed relative to CON. These data suggest that a longer duration of treatment with clinical doses of ALN results in deterioration of cortical bone toughness in a time-dependent manner. As the duration of treatment is lengthened, the cortical bone exhibits increasingly brittle behavior. This may be important in assessing the role that long-term BP treatments play in the risk of atypical fractures of the femoral cortical bone in humans.
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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.