Deflazacort Increases Osteoclast Formation in Mouse Bone Marrow Culture and the Ratio of<i>RANKL/OPG</i>mRNA Expression in Marrow Stromal Cells

Chung, Habong; Kang, Yu; Hwang, Chang Sun; Moon, In Kul; Yim, Chang Hoon; Choi, Kee‐Hyun; Han, Kyoung-Sik; Jang, Hak Chul; Yoon, Hyun Sik; Han, In K.

doi:10.3346/jkms.2001.16.6.769

Cited by 9 publications

(6 citation statements)

References 24 publications

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“…Either in a cell membrane-bound or in a soluble form, RANKL, receptor activator of NF-kappa β (RANK), stimulates osteoclastogenesis and osteoclastic bone resorption. Factors that stimulate bone resorption increase RANKL expression and, with some exceptions, decrease OPG expression [69]. In the present study, animals of HFD-fed group showed a significant decrease in serum level of OPG (Figure 3(b)) and a significant increase in serum level of RANKL (Figure 3(a)), compared to control group of rats.…”

Section: Discussionsupporting

confidence: 56%

Protective Role of Black Tea Extract against Nonalcoholic Steatohepatitis-Induced Skeletal Dysfunction

Karmakar

Majumdar

Maiti

et al. 2011

Journal of Osteoporosis

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Aim. This paper aimed to examine the chemoprotective actions of aqueous black tea extract (BTE) against nonalcoholic steatohepatitis- (NASH-) induced skeletal changes in rats. Material. Wistar rats (body wt. 155–175 g) of both sexes, aged 4–5 months, were randomly assigned to 3 groups; Group A (control), Group B (60% high-fat diet; HFD), and Group C (HFD + 2.5% BTE). Methods. Several urinary (calcium, phosphate, creatinine, and calcium-to-creatinine ratio) serum (alkaline phosphatase and serum tartrate-resistant acid phosphatase), and molecular markers of bone turnover (receptor activator of NF-κB ligand (RANKL), osteoprotegerin (OPG), and estrogen) were tested. Also, several bone parameters (bone density, bone tensile strength, bone mineral content, and bone histology) and calcium homeostasis were checked. Results. Results indicated that HFD-induced alterations in urinary, serum, and bone parameters as well as calcium homeostasis, all could be significantly ameliorated by BTE supplementation. Conclusion. Results suggest a potential role of BTE as a protective agent against NASH-induced changes in bone metabolism in rats.

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Section: Discussionsupporting

confidence: 56%

Protective Role of Black Tea Extract against Nonalcoholic Steatohepatitis-Induced Skeletal Dysfunction

Karmakar

Majumdar

Maiti

et al. 2011

Journal of Osteoporosis

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“…18,23 Experimental studies suggest that deflazacort may have bone-sparing effects via its effects on bone formation in comparison with dexamethasone or cortisol. [24][25][26] Deflazacort and dexamethasone have similar effects on stimulating osteoclast formation. 26 Evidence of the relative bone sparing in children is based on reports in nephrotic syndrome and rheumatologic conditions where nonsignificant differences in densitometry results were reported.…”

Section: Daily Deflazacort Daily Prednisolone Intermittent Deflazacor...mentioning

confidence: 99%

“…[24][25][26] Deflazacort and dexamethasone have similar effects on stimulating osteoclast formation. 26 Evidence of the relative bone sparing in children is based on reports in nephrotic syndrome and rheumatologic conditions where nonsignificant differences in densitometry results were reported. [27][28][29] Owing to its improved tolerability, deflazacort is often maintained at higher doses.…”

Section: Daily Deflazacort Daily Prednisolone Intermittent Deflazacor...mentioning

confidence: 99%

Fractures and Linear Growth in a Nationwide Cohort of Boys With Duchenne Muscular Dystrophy With and Without Glucocorticoid Treatment

et al. 2019

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Based on studies with relatively small sample size, fragility fractures are commonly reported in glucocorticoid (GC)-treated boys with Duchenne muscular dystrophy (DMD). OBJECTIVE To determine the fracture burden and growth impairment in a large contemporary cohort of boys with DMD in the United Kingdom and in relation to GC regimen. DESIGN, SETTING, AND PARTICIPANTS A retrospective review of fracture morbidity and growth from 832 boys with DMD in the UK NorthStar database (2006-2015), which systematically captures information from 23 participating centers. A total of 564 boys had more than 1 visit. No numbers of boys who refused were collected, but informal data from 2 centers in London and from Scotland show that refusal is very low. Data were analyzed between October 2006 and October 2015. MAIN OUTCOMES AND MEASURES Fracture incidence rate per 10 000 person-years was determined. Cox regression analysis was used to identify factors associated with first fracture. RESULTS Median age at baseline was 6.9 years (interquartile range, 4.9-7.2 years). At baseline, new fractures were reported in 7 of 564 participants (1.2%). During a median follow-up of 4 years (interquartile range, 2.0-6.0 years), incident fractures were reported in 156 of 564 participants (27.7%), corresponding to an overall fracture incidence rate of 682 per 10 000 person-years (95% CI, 579-798). The highest fracture incidence rate was observed in those treated with daily deflazacort at 1367 per 10 000 person-years (95% CI, 796-2188). After adjusting for age at last visit, mean hydrocortisone equivalent dose, mobility status, and bisphosphonate use prior to first fracture, boys treated with daily deflazacort had a 16.0-fold increased risk for first fracture (95% CI, 1.4-180.8; P = .03). Using adjusted regression models, change in height standard deviation scores was −1.6 SD lower (95% CI, −3.0 to −0.1; P = .03) in those treated with daily deflazacort compared with GC-naive boys, whereas there were no statistical differences in the other GC regimen. CONCLUSIONS AND RELEVANCE In this large group of boys with DMD with longitudinal data, we document a high fracture burden. Boys treated with daily deflazacort had the highest fracture incidence rate and the greatest degree of linear growth failure. Clinical trials of primary bone protective therapies and strategies to improve growth in boys with DMD are urgently needed, but stratification based on GC regimen may be necessary.

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“…RANKL and osteoprotegerin (OPG) are cytokines related to osteoclast formation, and the RANKL:OPG ratio is frequently used as a measure to indicate whether a system has the potential to generate osteoclasts [ 19 ]. When this ratio is favorable to osteoclastogenesis, the RANK–RANKL interaction will lead to differentiation of the osteoclast precursor into osteoclasts [ 20 ]. In RANKL-deficient mice, the effect of transgenically induced RANKL expression by T and B cells normalizes osteoclast formation in long bones but not in the jaw.…”

mentioning

confidence: 99%

Jaw and Long Bone Marrows Have a Different Osteoclastogenic Potential

et al. 2010

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Osteoclasts, the multinucleated bone-resorbing cells, arise through fusion of precursors from the myeloid lineage. However, not all osteoclasts are alike; osteoclasts at different bone sites appear to differ in numerous respects. We investigated whether bone marrow cells obtained from jaw and long bone differed in their osteoclastogenic potential. Bone marrow cells from murine mandible and tibiae were isolated and cultured for 4 and 6 days on plastic or 6 and 10 days on dentin. Osteoclastogenesis was assessed by counting the number of TRAP+ multinucleated cells. Bone marrow cell composition was analyzed by FACS. The expression of osteoclast- and osteoclastogenesis-related genes was studied by qPCR. TRAP activity and resorptive activity of osteoclasts were measured by absorbance and morphometric analyses, respectively. At day 4 more osteoclasts were formed in long bone cultures than in jaw cultures. At day 6 the difference in number was no longer observed. The jaw cultures, however, contained more large osteoclasts on plastic and on dentin. Long bone marrow contained more osteoclast precursors, in particular the myeloid blasts, and qPCR revealed that the RANKL:OPG ratio was higher in long bone cultures. TRAP expression was higher for the long bone cultures on dentin. Although jaw osteoclasts were larger than long bone osteoclasts, no differences were found between their resorptive activities. In conclusion, bone marrow cells from different skeletal locations (jaw and long bone) have different dynamics of osteoclastogenesis. We propose that this is primarily due to differences in the cellular composition of the bone site-specific marrow.

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Deflazacort Increases Osteoclast Formation in Mouse Bone Marrow Culture and the Ratio ofRANKL/OPGmRNA Expression in Marrow Stromal Cells

Cited by 9 publications

References 24 publications

Protective Role of Black Tea Extract against Nonalcoholic Steatohepatitis-Induced Skeletal Dysfunction

Protective Role of Black Tea Extract against Nonalcoholic Steatohepatitis-Induced Skeletal Dysfunction

Fractures and Linear Growth in a Nationwide Cohort of Boys With Duchenne Muscular Dystrophy With and Without Glucocorticoid Treatment

Jaw and Long Bone Marrows Have a Different Osteoclastogenic Potential

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