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      Combination therapy with BMP-2 and psoralen enhances fracture healing in ovariectomized mice

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          Abstract

          The advantages of combining local delivery of bone morphogenetic protein (BMP)-2 with systemic or local anti-osteoporosis treatments have also been studied for enhancing osteoporotic fracture healing. The aim of the present study was to evaluate the effect of combination therapy with BMP-2 and psoralen on fracture repair in ovariectomized mice. At 6 weeks after bilateral ovariectomy, mice (n=30) underwent unilateral transverse osteotomy on the femur and were divided into 3 groups. In the model group (n=10), animals were implanted with an absorbable collagen sponge (ACS) alone and administered physiological saline intragastrically (i.g.). In the recombinant human (rh)BMP-2 group (n=10), animals were implanted with an ACS loaded with 2.5 µg rhBMP-2 and administered physiological saline i.g. In the psoralen + rhBMP-2 group (n=10) animals were implanted with an ACS loaded with 2.5 µg rhBMP-2 and administered psoralen i.g. The mice were euthanized after 21 days and their fractured femurs were assessed by micro computed tomography, histological analysis and biomechanical testing. Furthermore, the serum of the animals was analyzed. Psoralen + rhBMP-2 exerted more beneficial effects on callus consolidation and biomechanical strength. In addition, increased bone-specific alkaline phosphatase levels and decreased C-terminal telopeptide of type-1 collagen were observed in the Psoralen + rhBMP-2 group. However, no difference in estrogen levels was detected between the groups. In conclusion, the present study demonstrated that in ovariectomized mice, combination of locally delivered BMP-2 and systemically administered psoralen improved bone healing compared with BMP-2 alone.

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          Natural products for treatment of osteoporosis: The effects and mechanisms on promoting osteoblast-mediated bone formation.

          Osteoporosis is a systemic metabolic bone disease characterized by a reduction in bone mass, bone quality, and microarchitectural deterioration. An imbalance in bone remodeling that is caused by more osteoclast-mediated bone resorption than osteoblast-mediated bone formation results in such pathologic bone disorder. Traditional Chinese medicines (TCM) have long been used to prevent and treat osteoporosis and have received extensive attentions and researches at home and abroad, because they have fewer adverse reactions and are more suitable for long-term use compared with chemically synthesized medicines. Here, we put the emphasis on osteoblasts, summarized the detailed research progress on the active compounds derived from TCM with potential anti-osteoporosis effects and their molecular mechanisms on promoting osteoblast-mediated bone formation. It could be concluded that TCM with kidney-tonifying, spleen-tonifying, and stasis-removing effects all have the potential effects on treating osteoporosis. The active ingredients derived from TCM that possess effects on promoting osteoblasts proliferation and differentiation include flavonoids, glycosides, coumarins, terpenoids (sesquiterpenoids, monoterpenoids, diterpenoids), phenolic acids, phenols and others (tetrameric stilbene, anthraquinones, diarylheptanoids). And it was confirmed that the bone formation effect induced by the above natural products was regulated by the expressions of bone specific matrix proteins (ALP, BSP, OCN, OPN, COL I), transcription factor (Runx2, Cbfa1, Osx), signal pathways (MAPK, BMP), local factors (ROS, NO), OPG/RANKL system of osteoblasts and estrogen-like biological activities. All the studies provided theoretical basis for clinical application, as well as new drug research and development on treating osteoporosis.
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            Burden of illness for osteoporotic fractures compared with other serious diseases among postmenopausal women in the United States.

            To provide a national estimate of the incidence of hospitalizations due to osteoporotic fractures (OFs) in women; compare this with the incidence of myocardial infarction (MI), stroke, and breast cancer; and assess temporal trends in the incidence and length of hospitalizations.
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              Safety and effectiveness of recombinant human bone morphogenetic protein-2 for spinal fusion: a meta-analysis of individual-participant data.

              Recombinant human bone morphogenetic protein-2 (rhBMP-2) is widely used to promote fusion in spinal surgery, but its safety has been questioned. To evaluate the effectiveness and safety of rhBMP-2. Individual-participant data obtained from the sponsor or investigators and data extracted from study publications identified by systematic bibliographic searches through June 2012. Randomized, controlled trials of rhBMP-2 versus iliac crest bone graft (ICBG) in spinal fusion surgery for degenerative disc disease and related conditions and observational studies in similar populations for investigation of adverse events. Individual-participant data from 11 eligible of 17 provided trials sponsored by Medtronic (Minneapolis, Minnesota) (n = 1302) and 1 of 2 other eligible trials (n = 106) were included. Additional aggregate adverse event data were extracted from 35 published observational studies. Primary outcomes were pain (assessed with the Oswestry Disability Index [ODI] or Short Form-36), fusion, and adverse events. At 24 months, ODI scores were 3.5% lower (better) with rhBMP-2 than with ICBG (95% CI, 0.5% to 6.5%) and radiographic fusion was 12% higher (CI, 2% to 23%). At or shortly after surgery, pain was more common with rhBMP-2 (odds ratio, 1.78 [CI, 1.06 to 2.95]). Cancer was more common after rhBMP-2 (relative risk, 1.98 [CI, 0.86 to 4.54]), but the small number of events precluded definite conclusions. The observational studies were diverse and at risk of bias. At 24 months, rhBMP-2 increases fusion rates, reduces pain by a clinically insignificant amount, and increases early postsurgical pain compared with ICBG. Evidence of increased cancer incidence is inconclusive. Yale University Open Data Access Project.
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                Author and article information

                Journal
                Exp Ther Med
                Exp Ther Med
                ETM
                Experimental and Therapeutic Medicine
                D.A. Spandidos
                1792-0981
                1792-1015
                September 2018
                26 June 2018
                26 June 2018
                : 16
                : 3
                : 1655-1662
                Affiliations
                [1 ]Department of Orthopaedics, The First Affiliated Hospital of Yangtze University, Jingzhou, Hubei 434000, P.R. China
                [2 ]Department of Acupuncture-Moxibustion and Orthopaedics-Traumatology, Hubei University of Chinese Medicine, Wuhan, Hubei 430065, P.R. China
                Author notes
                Correspondence to: Professor Ji Zou, Department of Acupuncture-Moxibustion and Orthopaedics-Traumatology, Hubei University of Chinese Medicine, 1 West Road, Wuhan, Hubei 430065, P.R. China, E-mail: dr_zj@ 123456126.com
                Mr. Songming Peng, Department of Orthopaedics, The First Affiliated Hospital of Yangtze University, 8 Hangkong Road, Jingzhou, Hubei 434000, P.R. China, E-mail: psmingdr@ 123456163.com
                Article
                ETM-0-0-6353
                10.3892/etm.2018.6353
                6122261
                30186384
                fd2b827a-846e-4948-be6b-b5a739283a5f
                Copyright: © Huang et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 01 January 2018
                : 17 May 2018
                Categories
                Articles

                Medicine
                recombinant human bone morphogenetic protein-2,fracture healing,osteoporosis,phytoestrogens

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