Two doses of sclerostin antibody in cynomolgus monkeys increases bone formation, bone mineral density, and bone strength

2010 ◽  
Vol 25 (5) ◽  
pp. 948-959 ◽  
Author(s):  
Michael S Ominsky ◽  
Fay Vlasseros ◽  
Jacquelin Jolette ◽  
Susan Y Smith ◽  
Brian Stouch ◽  
...  

Bone ◽  
2008 ◽  
Vol 43 (5) ◽  
pp. 840-848 ◽  
Author(s):  
Hiroshi Mori ◽  
Makoto Tanaka ◽  
Ryoji Kayasuga ◽  
Taisei Masuda ◽  
Yasuo Ochi ◽  
...  


Bone ◽  
2016 ◽  
Vol 88 ◽  
pp. 157-164 ◽  
Author(s):  
Makoto Tanaka ◽  
Hiroshi Mori ◽  
Kazuhito Kawabata ◽  
Tasuku Mashiba


Endocrinology ◽  
2010 ◽  
Vol 151 (6) ◽  
pp. 2641-2649 ◽  
Author(s):  
Robert S. Weinstein ◽  
Robert L. Jilka ◽  
Maria Almeida ◽  
Paula K. Roberson ◽  
Stavros C. Manolagas

Glucocorticoids act directly on bone cells to decrease production of osteoblasts and osteoclasts, increase osteoblast and osteocyte apoptosis, and prolong osteoclast life span. Conversely, daily injections of PTH decrease osteoblast and osteocyte apoptosis and increase bone formation and strength. Using a mouse model, we investigated whether the recently demonstrated efficacy of PTH in glucocorticoid-induced bone disease results from the ability of this therapeutic modality to counteract at least some of the direct effects of glucocorticoids on bone cells. Glucocorticoid administration to 5- to 6-month-old Swiss-Webster mice for 28 d increased the prevalence of osteoblast and osteocyte apoptosis and decreased osteoblast number, activation frequency, and bone formation rate, resulting in reduced osteoid, wall and trabecular width, bone mineral density, and bone strength. In contrast, daily injections of PTH caused a decrease in osteoblast and osteocyte apoptosis and an increase in osteoblast number, activation frequency, bone formation rate, bone mineral density, and bone strength. The decreased osteocyte apoptosis was associated with increased bone strength. When the two agents were combined, all the adverse effects of glucocorticoid excess on bone were prevented. Likewise, in cultured osteoblastic cells, PTH attenuated the adverse effects of glucocorticoids on osteoblast survival and Wnt signaling via an Akt phosphorylation-dependent mechanism. We conclude that intermittent PTH administration directly counteracts the key pathogenetic mechanisms of glucocorticoid excess on bone, thus providing a mechanistic explanation of its efficacy against glucocorticoid-induced osteoporosis.



2014 ◽  
Vol 99 (4) ◽  
pp. 1322-1329 ◽  
Author(s):  
Pouneh K. Fazeli ◽  
Irene S. Wang ◽  
Karen K. Miller ◽  
David B. Herzog ◽  
Madhusmita Misra ◽  
...  


Bone ◽  
2006 ◽  
Vol 38 (3) ◽  
pp. 27-28 ◽  
Author(s):  
Z.G. Luo ◽  
A.T. Wang ◽  
W.S. Yu ◽  
Y. Zhao ◽  
P. Hu ◽  
...  


2013 ◽  
Vol 144 (5) ◽  
pp. S-86
Author(s):  
Nicholas K. Weber ◽  
Jeff L. Fidler ◽  
Bart L. Clarke ◽  
Sundeep Khosla ◽  
Joel G. Fletcher ◽  
...  


2018 ◽  
Vol 18 (2) ◽  
pp. 206-210 ◽  
Author(s):  
Mehmet Dagli ◽  
Ali Kutlucan ◽  
Sedat Abusoglu ◽  
Abdulkadir Basturk ◽  
Mehmet Sozen ◽  
...  

A decrease in bone mass is observed in hemophilic patients. The aim of this study was to evaluate bone mineral density (BMD), parathyroid hormone (PTH), 25-hydroxy vitamin D (vitamin D), and a bone formation and resorption marker, procollagen type I N-terminal propeptide (PINP) and urinary N-terminal telopeptide (uNTX) respectively, in hemophilic patients and healthy controls. Laboratory parameters related to the pathogenesis of bone loss such as neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) were also evaluated. Thirty-five men over 18 years of age, with severe hemophilia (A and B) and receiving secondary prophylaxis, were included in the study. The same number of age-, sex-, and ethnicity-matched healthy controls were evaluated. Anthropometric, biochemical, and hormonal parameters were determined in both groups. No significant difference in anthropometric parameters was found between the two groups. The BMD was low in 34% of hemophilic patients. Vitamin D, calcium, and free testosterone levels were significantly lower (p < 0.001, p = 0.011, p < 0.001, respectively), while PTH, PINP, and activated partial thromboplastin time (aPTT) levels were significantly higher (p < 0.014, p = 0.043, p < 0.001, respectively), in hemophilic patients compared to controls. There was no significant difference between the two groups in NLR, PLR, phosphorus, thyroid-stimulating hormone, and uNTX level. The reduction of bone mass in hemophilic patients may be evaluated using the markers of bone formation and resorption, enabling early detection and timely treatment.



2021 ◽  
Vol 7 ◽  
Author(s):  
Fabio Massimo Ulivieri ◽  
Luca Rinaudo

For a proper assessment of osteoporotic fragility fracture prediction, all aspects regarding bone mineral density, bone texture, geometry and information about strength are necessary, particularly in endocrinological and rheumatological diseases, where bone quality impairment is relevant. Data regarding bone quantity (density) and, partially, bone quality (structure and geometry) are obtained by the gold standard method of dual X-ray absorptiometry (DXA). Data about bone strength are not yet readily available. To evaluate bone resistance to strain, a new DXA-derived index based on the Finite Element Analysis (FEA) of a greyscale of density distribution measured on spine and femoral scan, namely Bone Strain Index (BSI), has recently been developed. Bone Strain Index includes local information on density distribution, bone geometry and loadings and it differs from bone mineral density (BMD) and other variables of bone quality like trabecular bone score (TBS), which are all based on the quantification of bone mass and distribution averaged over the scanned region. This state of the art review illustrates the methodology of BSI calculation, the findings of its in reproducibility and the preliminary data about its capability to predict fragility fracture and to monitor the follow up of the pharmacological treatment for osteoporosis.



2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Melissa Sum ◽  
Laurel Mayer ◽  
Michelle P. Warren

Osteopenia and osteoporosis are major complications of anorexia nervosa (AN). Since bone is a tissue requiring large amounts of energy, we examined the disproportionate increase in resting energy expenditure (REE) that occurs with refeeding of AN patients to determine if it was related to bone accretion. Thirty-seven AN patients aged23.4±4.8years underwent a behavioral weight-gain protocol lasting a median of 66 days; 27 remained amenorrheic, and 10 regained menses. Sixteen controls aged25.1±4.7years were age- and % IBW matched with patients. REE was measured using a respiratory chamber-indirect calorimeter. Significant correlations were found between REE and changes in spine (r=0.48,P<0.02) and leg (r=0.43,P<0.05) BMDs in AN patients. Further subgroup analysis of the amenorrheics revealed significant correlation between REE and change in spine BMD (r=0.59,P<0.02) and higher IGF-1 after weight gain compared to controls. Amenorrheics also had lower BMDs. These findings were absent in the regained menses group. The increase in REE seen in women with AN during nutritional rehabilitation may be related to active bone formation, which is not as prominent when menses have returned.



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