Molecular enhancement of fracture healing - Is there a role for Bone Morphogenetic Protein-2, parathyroid hormone, statins, or sclerostin-antibodies?

Henssler, Leopold; Kerschbaum, Maximilian; Mukashevich, Moldakulov Z.; Rupp, Markus; Alt, Volker

doi:10.1016/j.injury.2021.04.068

Cited by 6 publications

(5 citation statements)

References 82 publications

(94 reference statements)

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“…However, supraphysiological concentrations are needed for a good outcome, which results in increased side effects like inflammation and tissue swelling. (7)(8)(9) Therefore, there is the urgent need to identify new molecules to improve fracture healing.…”

Section: Introductionmentioning

confidence: 99%

Wnt1 Boosts Fracture Healing by Enhancing Bone Formation in the Fracture Callus

Haffner‐Luntzer¹,

Ragipoglu²,

Ahmad³

et al. 2020

Journal of Bone and Mineral Research

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Despite considerable improvement in fracture care, 5%-10% of all fractures still heal poorly or result in nonunion formation. Therefore, there is an urgent need to identify new molecules that can be used to improve bone fracture healing. One activator of the Wnt-signaling cascade, Wnt1, has recently gained attention for its intense osteoanabolic effect on the intact skeleton. The aim of the present study was to investigate whether Wnt1 might be a promising molecule to accelerate fracture healing both in skeletally healthy and osteoporotic mice that display a diminished healing capacity. Transgenic mice for a temporary induction of Wnt1 specifically in osteoblasts (Wnt1-tg) were subjected to femur osteotomy. Non-ovariectomized and ovariectomized Wnt1-tg mice displayed significantly accelerated fracture healing based on a strong increase in bone formation in the fracture callus. Transcriptome profiling revealed that Hippo/yes1-associated transcriptional regulator (YAP)-signaling and bone morphogenetic protein (BMP) signaling pathways were highly enriched in the fracture callus of Wnt1-tg animals. Immunohistochemical staining confirmed increased activation of YAP1 and expression of BMP2 in osteoblasts in the fracture callus. Therefore, our data indicate that Wnt1 boosts bone formation during fracture healing via YAP/BMP signaling both under healthy and osteoporotic conditions. To further test a potential translational application of Wnt1, we applied recombinant Wnt1 embedded into a collagen gel during critical-size bone-defect repair. Mice treated with Wnt1 displayed increased bone regeneration compared to control mice accompanied by increased YAP1/BMP2 expression in the defect area. These findings are of high clinical relevance because they indicate that Wnt1 could be used as a new therapeutic agent to treat orthopedic complications in the clinic.

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Section: Introductionmentioning

confidence: 99%

Wnt1 Boosts Fracture Healing by Enhancing Bone Formation in the Fracture Callus

Haffner‐Luntzer¹,

Ragipoglu²,

Ahmad³

et al. 2020

Journal of Bone and Mineral Research

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“…Even in long bone non-unions, rhBMP-2 promoted faster bone healing (HR = 2.78; 95% CI 1.4-5.6, p < 0.001) and higher union rates (89% vs. 47%; p < 0.001) compared to no-BMP group [20]. Although previous studies reported no advantages of rhBMP-2 on fracture healing, recent studies have reported better fracture healing than control or even autogenous iliac bone graft [21,22].…”

Section: Discussionmentioning

confidence: 91%

“…This study revealed that the rhBMP-2 could enhance the healing process of the fractured vertebral body. Regarding the mechanism of rhBMP-2 for fracture healing, Liu et al reported that rhBMP-2 accelerated the migration of bone marrow mesenchymal stem cells via the CDC42/PAK1/LIMK1 pathway and enhanced the fracture healing process [21]. Another study demonstrated the BMP-2-dependent fracture healing through tight control of chemokine C-X-C motif-ligand-12 (CXCL12) expression [23].…”

Section: Discussionmentioning

confidence: 99%

Application of Escherichia coli-Derived Recombinant Human Bone Morphogenic Protein-2 to Unstable Spinal Fractures

Kim,

Lee,

et al. 2023

Bioengineering

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(1) Background: Recently, Escherichia coli-derived recombinant human bone morphogenetic protein-2 (E. coli-derived rhBMP-2) has been increasingly applied to different types of spinal surgeries and reported to achieve successful fusion. This pilot study aimed to evaluate the clinical efficacy and safety of rhBMP-2 in patients undergoing posterior instrumented fusions for unstable spinal fractures. (2) Methods: This study included ten consecutive patients undergoing spinal surgery using E. coli-derived rhBMP-2 with more than one year of follow-up. Radiologic outcomes were compared, including the average fracture healing period, local kyphosis correction, and clinical outcomes between preoperative and the last follow-up. (3) Results: The average time of radiographic union was 99.9 ± 45.4 (62–192) days, with an average use of 5.2 ± 3.9 months of anabolic agents. Radiologic parameters such as anterior vertebral height and vertebral wedge angle were significantly corrected postoperatively and at the last follow-up. Clinical outcomes other than leg pain were significantly improved after the surgery. In addition, four patients with preoperative neurologic deficits showed improved neurologic status. (4) Conclusions: Combined with the anabolic agents, applying E. coli-derived rhBMP-2 to the fractured vertebral body could be an effective surgical treatment for unstable spinal fractures. Further trials are needed to validate this result.

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“…There are several signaling molecules and growth factors to enhance cell migration and osteogenic differentiation, which can also be incorporated into coatings [ 4 , 7 ]. Hereby, the Bone Morphogenetic Protein (BMP) -2 is the most well-researched, which has also been used for clinical application [8] .…”

Section: Implant Advancementmentioning

confidence: 99%