scholarly journals Kinetic reconstruction reveals time-dependent effects of romosozumab on bone formation and osteoblast function in vertebral cancellous and cortical bone in cynomolgus monkeys

Bone ◽  
2017 ◽  
Vol 101 ◽  
pp. 77-87 ◽  
Author(s):  
Rogely Waite Boyce ◽  
Qing-Tian Niu ◽  
Michael S. Ominsky
Keyword(s):  
Bone Formation ◽  
Cortical Bone ◽  
Time Dependent ◽  
Cynomolgus Monkeys ◽  
Osteoblast Function

scholarly journals Clinically relevant doses of vitamin A decrease cortical bone mass in mice

2018 ◽  
Vol 239 (3) ◽  
pp. 389-402 ◽  
Author(s):  
Vikte Lionikaite ◽  
Karin L Gustafsson ◽  
Anna Westerlund ◽  
Sara H Windahl ◽  
Antti Koskela ◽  
...  
Keyword(s):  
Vitamin A ◽  
Bone Formation ◽  
Cortical Bone ◽  
Negative Impact ◽  
Control Diet ◽  
Time Dependent ◽  
Retinyl Acetate ◽  
Dynamic Histomorphometry ◽  
Supplemental Dose ◽  
Cortical Bone Mass

Excess vitamin A has been associated with decreased cortical bone thickness and increased fracture risk. While most studies in rodents have employed high dosages of vitamin A for short periods of time, we investigated the bone phenotype in mice after longer exposure to more clinically relevant doses. For 1, 4 and 10 weeks, mice were fed a control diet (4.5 µg retinyl acetate/g chow), a diet modeled from the human upper tolerable limit (UTL; 20 µg retinyl acetate/g chow) and a diet three times UTL (supplemented; 60 µg retinyl acetate/g chow). Time-dependent decreases in periosteal circumference and bone mineral content were noted with the supplemented dose. These reductions in cortical bone resulted in a significant time-dependent decrease of predicted strength and a non-significant trend toward reduced bone strength as analyzed by three-point bending. Trabecular bone in tibiae and vertebrae remained unaffected when vitamin A was increased in the diet. Dynamic histomorphometry demonstrated that bone formation was substantially decreased after 1 week of treatment at the periosteal site with the supplemental dose. Increasing amount of vitamin A decreased endocortical circumference, resulting in decreased marrow area, a response associated with enhanced endocortical bone formation. In the presence of bisphosphonate, vitamin A had no effect on cortical bone, suggesting that osteoclasts are important, even if effects on bone resorption were not detected by osteoclast counting, genes in cortical bone or analysis of serum TRAP5b and CTX. In conclusion, our results indicate that even clinically relevant doses of vitamin A have a negative impact on the amount of cortical bone.

scholarly journals Osteopontin Deficiency Induces Parathyroid Hormone Enhancement of Cortical Bone Formation

Endocrinology ◽  
2003 ◽  
Vol 144 (5) ◽  
pp. 2132-2140 ◽  
Author(s):  
Keiichiro Kitahara ◽  
Muneaki Ishijima ◽  
Susan R. Rittling ◽  
Kunikazu Tsuji ◽  
Hisashi Kurosawa ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Bone Formation ◽  
Bone Mass ◽  
Cortical Bone ◽  
Cancellous Bone ◽  
Wild Type ◽  
Mineral Density ◽  
Cortical Bone Mass ◽  
Intermittent Pth

Intermittent PTH treatment increases cancellous bone mass in osteoporosis patients; however, it reveals diverse effects on cortical bone mass. Underlying molecular mechanisms for anabolic PTH actions are largely unknown. Because PTH regulates expression of osteopontin (OPN) in osteoblasts, OPN could be one of the targets of PTH in bone. Therefore, we examined the role of OPN in the PTH actions in bone. Intermittent PTH treatment neither altered whole long-bone bone mineral density nor changed cortical bone mass in wild-type 129 mice, although it enhanced cancellous bone volume as reported previously. In contrast, OPN deficiency induced PTH enhancement of whole-bone bone mineral density as well as cortical bone mass. Strikingly, although PTH suppressed periosteal bone formation rate (BFR) and mineral apposition rate (MAR) in cortical bone in wild type, OPN deficiency induced PTH activation of periosteal BFR and MAR. In cancellous bone, OPN deficiency further enhanced PTH increase in BFR and MAR. Analysis on the cellular bases for these phenomena indicated that OPN deficiency augmented PTH enhancement in the increase in mineralized nodule formation in vitro. OPN deficiency did not alter the levels of PTH enhancement of the excretion of deoxypyridinoline in urine, the osteoclast number in vivo, and tartrate-resistant acid phosphatase-positive cell development in vitro. These observations indicated that OPN deficiency specifically induces PTH activation of periosteal bone formation in the cortical bone envelope.

Labeling studies on cortical bone formation in the antlers of red deer (Cervus elaphus)

Bone ◽  
2013 ◽  
Vol 52 (1) ◽  
pp. 506-515 ◽  
Author(s):  
S. Gomez ◽  
A.J. Garcia ◽  
S. Luna ◽  
U. Kierdorf ◽  
H. Kierdorf ◽  
...  
Keyword(s):  
Bone Formation ◽  
Cortical Bone ◽  
Cervus Elaphus ◽  
Red Deer

scholarly journals A New Synthetic Steroid, Osaterone Acetate (TZP-4238), Increases Cortical Bone Mass and Strength by Enhancing Bone Formation in Ovariectomized Rats

1997 ◽  
Vol 12 (4) ◽  
pp. 590-597 ◽  
Author(s):  
Hiroaki Fuse ◽  
Seiji Fukumoto ◽  
Hideyuki Sone ◽  
Yoshiko Miyata ◽  
Tomoyuki Saito ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Mass ◽  
Cortical Bone ◽  
Ovariectomized Rats ◽  
Cortical Bone Mass

scholarly journals Modeling-based bone formation transforms trabeculae to cortical bone in the sclerotic areas in Buschke-Ollendorff syndrome. A case study of two females with LEMD3 variants

Bone ◽  
2020 ◽  
Vol 135 ◽  
pp. 115313
Author(s):  
M. Frost ◽  
E.T. Rahbek ◽  
C. Ejersted ◽  
P.F. Høilund-Carlsen ◽  
A. Bygum ◽  
...  
Keyword(s):  
Bone Formation ◽  
Cortical Bone

scholarly journals Cortical bone dynamics, strength, and densitometry after induction of emphysema in hamsters

2003 ◽  
Vol 95 (2) ◽  
pp. 631-634 ◽  
Author(s):  
Jill E. Shea ◽  
Scott C. Miller ◽  
David C. Poole ◽  
John P. Mattson
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Bone Formation ◽  
Cortical Bone ◽  
Pulmonary Disease ◽  
Bone Mineral ◽  
Bone Structure ◽  
Chronic Obstructive ◽  
Pathophysiological Mechanism ◽  
Mineral Density ◽  
Obstructive Pulmonary Disease

Recent evidence suggests that patients suffering from chronic obstructive pulmonary disease are also at an increased risk of developing osteoporosis. The pathophysiological mechanism(s) linking these progressive diseases is unknown. The goal of this investigation was to determine whether there were alterations in bone mineral density and content, cortical bone structure and strength, and indexes of bone formation and resorption in the elastase-induced emphysematous hamster. At 3 wk after induction of emphysema, the femoral bone mineral content was 8% less ( P = 0.026) and the femoral fracture strength was 6% less ( P = 0.032) in the emphysematous hamster than in controls. The cortical area was 8.4% less ( P = 0.013) and the periosteal mineral appositional rate was 27% less ( P = 0.05) than in controls. Additionally, the endocortical eroded surface in the emphysematous group was about twice that in the control group ( P = 0.003). Differences in some indexes of bone formation and resorption, paralleled by differences in bone structure and strength, were observed 3 wk after induction of emphysema. These differences in skeletal metabolism and strength may help explain some of the skeletal changes associated with chronic obstructive pulmonary disease in humans.

scholarly journals Cortical bone adaptation to a moderate level of mechanical loading in male Sost deficient mice

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Haisheng Yang ◽  
Alexander Büttner ◽  
Laia Albiol ◽  
Catherine Julien ◽  
Tobias Thiele ◽  
...  
Keyword(s):  
Physical Activity ◽  
Bone Formation ◽  
Bone Mass ◽  
Cortical Bone ◽  
Bone Adaptation ◽  
Moderate Level ◽  
Skeletal Maturation ◽  
Male Mice ◽  
Males And Females

AbstractLoss-of-function mutations in the Sost gene lead to high bone mass phenotypes. Pharmacological inhibition of Sost/sclerostin provides a new drug strategy for treating osteoporosis. Questions remain as to how physical activity may affect bone mass under sclerostin inhibition and if that effect differs between males and females. We previously observed in female Sost knockout (KO) mice an enhanced cortical bone formation response to a moderate level of applied loading (900 με at the tibial midshaft). The purpose of the present study was to examine cortical bone adaptation to the same strain level applied to male Sost KO mice. Strain-matched in vivo compressive loading was applied to the tibiae of 10-, 26- and 52-week-old male Sost KO and littermate control (LC) mice. The effect of tibial loading on bone (re)modeling was measured by microCT, 3D time-lapse in vivo morphometry, 2D histomorphometry and gene expression analyses. As expected, Sost deficiency led to high cortical bone mass in 10- and 26-week-old male mice as a result of increased bone formation. However, the enhanced bone formation associated with Sost deficiency did not appear to diminish with skeletal maturation. An increase in bone resorption was observed with skeletal maturation in male LC and Sost KO mice. Two weeks of in vivo loading (900 με at the tibial midshaft) induced only a mild anabolic response in 10- and 26-week-old male mice, independent of Sost deficiency. A decrease in the Wnt inhibitor Dkk1 expression was observed 3 h after loading in 52-week-old Sost KO and LC mice, and an increase in Lef1 expression was observed 8 h after loading in 10-week-old Sost KO mice. The current results suggest that long-term inhibition of sclerostin in male mice does not influence the adaptive response of cortical bone to moderate levels of loading. In contrast with our previous strain-matched study in females showing enhanced bone responses with Sost ablation, these results in males indicate that the influence of Sost deficiency on the cortical bone formation response to a moderate level of loading differs between males and females. Clinical studies examining antibodies to inhibit sclerostin may need to consider that the efficacy of additional physical activity regimens may be sex dependent.

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