scholarly journals Local treatment of a bone graft by soaking in zoledronic acid inhibits bone resorption and bone formation. A bone chamber study in rats

Bone ◽  
2012 ◽  
Vol 50 ◽  
pp. S119
Author(s):  
O. Belfrage⁎
2021 ◽  
Vol 32 (2) ◽  
pp. 526-530
Author(s):  
Takuya Uemura ◽  
Koichi Yano ◽  
Kiyohito Takamatsu ◽  
Yusuke Miyashima ◽  
Hiroyuki Yasuda ◽  
...  

Romosozumab is a humanized, anti-sclerostin monoclonal antibody used to treat osteoporosis, which increases bone formation and decreases bone resorption. It enhances fracture healing and systemic romosozumab administration may have therapeutic potentials for accelerating bone healing of even nonunion. Herein, a 61-year-old heavy smoker male with distal radius nonunion who achieved successful bone union by combination therapy of romosozumab and spanning distraction plate fixation with bone graft substitutes was presented. Through the dorsal approach, atrophic comminuted nonunion of the distal radius was sufficiently debrided. Reduction of the distal radius was performed using indirect ligamentotaxis, and a 14-hole locking plate was fixed from the third metacarpal to the radial shaft. A beta (β) tricalcium phosphate block was mainly packed into the substantial metaphyseal bone defect with additional bone graft from the resected ulnar head. Postoperatively, systemic administration of monthly romosozumab was continued for six months. Complete bone union was achieved 20 weeks postoperatively and the plate was, then, removed. Wrist extension and flexion improved to 75o and 55o, respectively, without pain, and grip strength increased 52 weeks postoperatively from 5.5 kg to 22.4 kg. During romosozumab treatment, bone formation marker levels increased rapidly and finally returned to baseline, and bone resorption marker levels remained low. In conclusion, combination of systemic romosozumab administration and grafting β-tricalcium phosphate with bridge plating provides an effective treatment option for difficult cases of comminuted distal radius nonunion with risk factors such as smoking, diabetes, and fragility.


2017 ◽  
Vol 33 (05) ◽  
pp. 367-376 ◽  
Author(s):  
Konosuke Yamaguchi ◽  
Osamu Nakamura ◽  
Sachiko Tobiume ◽  
Tetsuji Yamamoto ◽  
Yoshio Kaji

Background Basic fibroblast growth factor (bFGF) is known to stimulate bone formation and angiogenesis. Hydroxyapatite/collagen composite (HAp/Col) is also known to have very strong bone conductive activity. In this study, prefabrication of vascularized allogenic bone (allo-bone) graft was attempted in recipients by implanting vascular bundles from recipients into the transplanted allo-bone graft. Furthermore, the effect of bFGF-containing HAp/Col on the prefabricated vascularized allo-bone graft was investigated. Methods In this study, 32 Sprague-Dawley rats were used as donors, and bone grafts were collected from their femora. Thirty-two Wistar rats (recipients) were divided into four groups, and the allo-bone grafts were transplanted into the thigh region. In the experimental groups, one or both of the flow-through saphenous vascular bundles and 100-μg bFGF-containing HAp/Col were implanted into the medullary cavity of the allo-bone grafts. In the control group, neither was implanted. These rats were sacrificed at 4 weeks after transplantation, and bone formation, angiogenesis, and bone resorption in the transplanted allo-bone grafts were evaluated histologically and genetically. Results Bone formation and angiogenesis in the transplanted allo-bone graft were effectively stimulated by implanting vascular bundles or bFGF-containing HAp/Col on both histological and genetic evaluations compared with the control group. The most significant stimulation was observed in the group in which both were implanted. Bone resorption was not stimulated in any group. Conclusion By implanting a flow-through vascular bundle and bFGF-containing HAp/Col, an ideal vascularized allo-bone graft that had high bone formative and angiogenetic activities and did not stimulate bone resorptive activity was prefabricated.


Author(s):  
A. V. Sukhova ◽  
E. N. Kryuchkova

The influence of general and local vibration on bone remodeling processes is investigated. The interrelations between the long - term exposure of industrial vibration and indicators of bone mineral density (T-and Z-criteria), biochemical markers of bone formation (osteocalcin, alkaline phosphatase) and bone resorption (ionized calcium, calcium/creatinine) were established.


2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Scott A. Scarneo ◽  
Liesl S. Eibschutz ◽  
Phillip J. Bendele ◽  
Kelly W. Yang ◽  
Juliane Totzke ◽  
...  

Abstract Objectives To examine the ability of takinib, a selective transforming growth factor beta-activated kinase 1 (TAK1) inhibitor, to reduce the severity of murine type II collagen-induced arthritis (CIA), and to affect function of synovial cells. Methods Following the induction of CIA, mice were treated daily with takinib (50 mg/kg) and clinical scores assessed. Thirty-six days post-CIA induction, histology was performed on various joints of treated and vehicle-treated animals. Inflammation, pannus, cartilage damage, bone resorption, and periosteal bone formation were quantified. Furthermore, pharmacokinetics of takinib were evaluated by LC-MS in various tissues. Rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) cells were cultured with 10 μM takinib and cytokine secretion analyzed by cytokine/chemokine proteome array. Cytotoxicity of takinib for RA-FLS was measured with 24 to 48 h cultures in the presence or absence of tumor necrosis factor (TNF). Results Here, we show takinib’s ability to reduce the clinical score in the CIA mouse model of rheumatoid arthritis (RA) (p < 0.001). TAK1 inhibition reduced inflammation (p < 0.01), cartilage damage (p < 0.01), pannus, bone resorption, and periosteal bone formation and periosteal bone width in all joints of treated mice compared to vehicle treated. Significant reduction of inflammation (p < 0.004) and cartilage damage (p < 0.004) were observed in the knees of diseased treated animals, with moderate reduction seen in the forepaws and hind paws. Furthermore, the pharmacokinetics of takinib show rapid plasma clearance (t½ = 21 min). In stimulated RA-FLS cells, takinib reduced GROα, G-CSF, and ICAM-1 pro-inflammatory cytokine signaling. Conclusion Our findings support the hypothesis that TAK1 targeted therapy represents a novel therapeutic axis to treat RA and other inflammatory diseases.


Lupus ◽  
2021 ◽  
Vol 30 (6) ◽  
pp. 965-971
Author(s):  
Wang Tianle ◽  
Zhang Yingying ◽  
Hong Baojian ◽  
Gu Juanfang ◽  
Wang Hongzhi ◽  
...  

Objectives SLE is a chronic autoimmune disease, which can affect the level of bone metabolism and increase the risk of osteoporosis and fracture. The purpose of this research is to study the effect of SLE on bone turnover markers without the influence of glucocorticoids. Methods A total of 865 female subjects were recruited from Zhejiang Provincial People’s Hospital and the First Hospital of Jiaxing, including 391 SLE patients without the influence of glucocorticoids and 474 non-SLE people. We detected Bone turnover markers including amino-terminal propeptide of type 1 procollagen (P1NP), C-terminal turnover of β - I collagen (β-CTX), N-terminal midfragment of osteocalcin (NMID) and 25(OH)D, and analyzed the difference in Bone turnover markers between the SLE group and the control group, as well as the influence of age and season on bone metabolism in female SLE patients. Results In the SLE group, the average age was 43.93±13.95 years old. In the control group, the average age was 44.84±11.42 years old. There was no difference between the two groups (t = 1.03, P = 0.30). P1NP, NMID and 25(OH)D in the SLE group were significantly lower than those in the control group (Z = 8.44, p < 0.001; Z = 14.41, p < 0.001; Z = 2.19, p = 0.029), and β-CTX in the SLE group was significantly higher than that in the control group (Z = 2.61, p = 0.009). In addition, the levers of β-CTX, NMID, P1NP and 25(OH)D in older SLE female patients were statistically significantly higher than those in younger (ρ = 0.104, p = 0.041; ρ = 0.223, p < 0.001; ρ = 0.105, p = 0.038; ρ = 0.289, p < 0.001). Moreover, β-CTX reached a high value in summer and PINP reached a low value in winter. Conclusion The bone formation markers of female SLE patients without glucocorticoid were lower than those of normal people and the bone resorption marker was higher than that of normal people. The 25 (OH) D of female SLE patients without glucocorticoid was lower than that of normal people. The risk of osteoporosis and fracture may be higher in elderly women with SLE. The bone resorption level of female SLE patients is high in summer and the bone formation level is low in winter.


2021 ◽  
Vol 22 (15) ◽  
pp. 8182
Author(s):  
Yongguang Gao ◽  
Suryaji Patil ◽  
Jingxian Jia

Osteoporosis is one of the major bone disorders that affects both women and men, and causes bone deterioration and bone strength. Bone remodeling maintains bone mass and mineral homeostasis through the balanced action of osteoblasts and osteoclasts, which are responsible for bone formation and bone resorption, respectively. The imbalance in bone remodeling is known to be the main cause of osteoporosis. The imbalance can be the result of the action of various molecules produced by one bone cell that acts on other bone cells and influence cell activity. The understanding of the effect of these molecules on bone can help identify new targets and therapeutics to prevent and treat bone disorders. In this article, we have focused on molecules that are produced by osteoblasts, osteocytes, and osteoclasts and their mechanism of action on these cells. We have also summarized the different pharmacological osteoporosis treatments that target different molecular aspects of these bone cells to minimize osteoporosis.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Akito Morimoto ◽  
Junichi Kikuta ◽  
Keizo Nishikawa ◽  
Takao Sudo ◽  
Maki Uenaka ◽  
...  

AbstractOsteoclastic bone resorption and osteoblastic bone formation/replenishment are closely coupled in bone metabolism. Anabolic parathyroid hormone (PTH), which is commonly used for treating osteoporosis, shifts the balance from osteoclastic to osteoblastic, although it is unclear how these cells are coordinately regulated by PTH. Here, we identify a serine protease inhibitor, secretory leukocyte protease inhibitor (SLPI), as a critical mediator that is involved in the PTH-mediated shift to the osteoblastic phase. Slpi is highly upregulated in osteoblasts by PTH, while genetic ablation of Slpi severely impairs PTH-induced bone formation. Slpi induction in osteoblasts enhances its differentiation, and increases osteoblast–osteoclast contact, thereby suppressing osteoclastic function. Intravital bone imaging reveals that the PTH-mediated association between osteoblasts and osteoclasts is disrupted in the absence of SLPI. Collectively, these results demonstrate that SLPI regulates the communication between osteoblasts and osteoclasts to promote PTH-induced bone anabolism.


2021 ◽  
Vol 22 (9) ◽  
pp. 4717
Author(s):  
Jin-Young Lee ◽  
Da-Ae Kim ◽  
Eun-Young Kim ◽  
Eun-Ju Chang ◽  
So-Jeong Park ◽  
...  

Lumican, a ubiquitously expressed small leucine-rich proteoglycan, has been utilized in diverse biological functions. Recent experiments demonstrated that lumican stimulates preosteoblast viability and differentiation, leading to bone formation. To further understand the role of lumican in bone metabolism, we investigated its effects on osteoclast biology. Lumican inhibited both osteoclast differentiation and in vitro bone resorption in a dose-dependent manner. Consistent with this, lumican markedly decreased the expression of osteoclastogenesis markers. Moreover, the migration and fusion of preosteoclasts and the resorptive activity per osteoclast were significantly reduced in the presence of lumican, indicating that this protein affects most stages of osteoclastogenesis. Among RANKL-dependent pathways, lumican inhibited Akt but not MAP kinases such as JNK, p38, and ERK. Importantly, co-treatment with an Akt activator almost completely reversed the effect of lumican on osteoclast differentiation. Taken together, our findings revealed that lumican inhibits osteoclastogenesis by suppressing Akt activity. Thus, lumican plays an osteoprotective role by simultaneously increasing bone formation and decreasing bone resorption, suggesting that it represents a dual-action therapeutic target for osteoporosis.


Sign in / Sign up

Export Citation Format

Share Document