ArticleBone2016
Sclerostin antibody treatment improves fracture outcomes in a Type I diabetic mouse model.
Article in Bone, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 76 citations in OpenAlex.
- Bispecific antibody against sclerostin and DKK1 improves bone health and reduces bone marrow adipose tissue accumulation in experimental chronic kidney disease.Bone research · 2026Article
- Prognostic value of serum estradiol and sclerostin for predicting fracture healing in postmenopausal women with osteoporotic vertebral compression fractures.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2026Article
- Sclerostin in Vascular Calcification: Hypoxia-Driven Regulation and Therapeutic Modulation by Natural Products.Current atherosclerosis reports · 2026Review
- Sclerostin deficiency sensitizes white adipocytes to thermogenic signals that induce beiging in mice.Nature communications · 2026Article
- Anabolic effects of Sost deficiency partially offset Opg deficiency-induced catabolism in cortical bone.Journal of bone and mineral metabolism · 2025Article
- [Influencing fracture healing by specific osteoporosis medications].Zeitschrift fur Rheumatologie · 2025Review
- A myostatin inhibitory antibody combined with insulin, partially rescues the musculoskeletal phenotype of female insulin-deficient diabetic mice.Frontiers in endocrinology · 2025Article
- Cai's herbal tea enhances mitochondrial autophagy of type 1 diabetic mellitus β cells through the AMPK/mTOR pathway and alleviates inflammatory response.Acta diabetologica · 2024Article
- O-GlcNAcylation mediates Wnt-stimulated bone formation by rewiring aerobic glycolysis.EMBO reports · 2024Article
- Impact of osteoporosis and osteoporosis medications on fracture healing: a narrative review.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2024Review
- Article
- Sclerostin as a new target of diabetes-induced osteoporosis.Frontiers in endocrinology · 2024Review
- Advantages and Limitations of Diabetic Bone Healing in Mouse Models: A Narrative Review.Biomedicines · 2023Review
- Muscle-bone crosstalk via endocrine signals and potential targets for osteosarcopenia-related fracture.Journal of orthopaedic translation · 2023Review
- A comparative study of the therapeutic effect of bone marrow mesenchymal stem cells versus insulin on mandibular dento-alveolar complex collagen formation and beta-catenin expression in experimentally induced type I diabetes.The Saudi dental journal · 2023Article
- Article
- Chitosan@Puerarin hydrogel for accelerated wound healing in diabetic subjects by miR-29ab1 mediated inflammatory axis suppression.Bioactive materials · 2023Article
- Preexisting Type 1 Diabetes Mellitus Blunts the Development of Posttraumatic Osteoarthritis.JBMR plus · 2022Article
- Drug discovery of sclerostin inhibitors.Acta pharmaceutica Sinica. B · 2022Review
- The pathophysiology of osteoporosis in obesity and type 2 diabetes in aging women and men: The mechanisms and roles of increased bone marrow adiposity.Frontiers in endocrinology · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Type 1 diabetes mellitus (T1DM) patients have osteopenia and impaired fracture healing due to decreased osteoblast activity. Further, no adequate treatments are currently available that can restore impaired healing in T1DM; hence a significant need exists to investigate new therapeutics for treatment of orthopedic complications. Sclerostin (SOST), a WNT antagonist, negatively regulates bone formation, and SostAb is a potent bone anabolic agent. To determine whether SOST antibody (SostAb) treatment improves fracture healing in streptozotocin (STZ) induced T1DM mice, we administered SostAb twice weekly for up to 21days post-fracture, and examined bone quality and callus outcomes at 21days and 42days post-fracture (11 and 14weeks of age, respectively). Here we show that SostAb treatment improves bone parameters; these improvements persist after cessation of antibody treatment. Markers of osteoblast differentiation such as Runx2, collagen I, osteocalcin, and DMP1 were reduced, while an abundant number of SP7/osterix-positive early osteoblasts were observed on the bone surface of STZ calluses. These results suggest that STZ calluses have poor osteogenesis resulting from failure of osteoblasts to fully differentiate and produce mineralized matrix, which produces a less mineralized callus. SostAb treatment enhanced fracture healing in both normal and STZ groups, and in STZ+SostAb mice, also reversed the lower mineralization seen in STZ calluses. Micro-CT analysis of calluses revealed improved bone parameters with SostAb treatment, and the mineralized bone was comparable to Controls. Additionally, we found sclerostin levels to be elevated in STZ mice and β-catenin activity to be reduced. Consistent with its function as a WNT antagonist, SostAb treatment enhanced β-catenin activity, but also increased the levels of SOST in the callus and in circulation. Our results indicate that SostAb treatment rescues the impaired osteogenesis seen in the STZ induced T1DM fracture model by facilitating osteoblast differentiation and mineralization of bone.
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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.