Growth plate dysfunction, reduced osteogenesis, increased osteocyte apoptosis and osteoclastogenesis in methotrexate chemotherapy-induced bone growth defects

Bone ◽  
2011 ◽  
Vol 48 ◽  
pp. S247
Author(s):  
C. Fan ◽  
Y.S. Ng ◽  
T. Shandala ◽  
K.R. Georgiou ◽  
T.J. King ◽  
...  
Keyword(s):  
Growth Plate ◽  
Bone Growth ◽  
Osteocyte Apoptosis ◽  
Growth Defects ◽  
Methotrexate Chemotherapy

Mechanisms for methotrexate chemotherapy-induced bone growth defects and protective effects of folinic acid supplementary treatment

Bone ◽  
2007 ◽  
Vol 40 (6) ◽  
pp. S87-S88
Author(s):  
C.J. Xian ◽  
J. Cool ◽  
M. Scherer ◽  
C. Macsai ◽  
C. Fan ◽  
...  
Keyword(s):  
Folinic Acid ◽  
Bone Growth ◽  
Protective Effects ◽  
Growth Defects ◽  
Supplementary Treatment ◽  
Methotrexate Chemotherapy

Cellular mechanisms for methotrexate chemotherapy-induced bone growth defects

Bone ◽  
2007 ◽  
Vol 41 (5) ◽  
pp. 842-850 ◽  
Author(s):  
Cory J. Xian ◽  
Johanna C. Cool ◽  
Michaela A. Scherer ◽  
Carmen E. Macsai ◽  
Chiaming Fan ◽  
...  
Keyword(s):  
Bone Growth ◽  
Cellular Mechanisms ◽  
Growth Defects ◽  
Methotrexate Chemotherapy

scholarly journals Methotrexate Toxicity in Growing Long Bones of Young Rats: A Model for Studying Cancer Chemotherapy-Induced Bone Growth Defects in Children

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Chiaming Fan ◽  
Kristen R. Georgiou ◽  
Tristan J. King ◽  
Cory J. Xian
Keyword(s):  
Growth Plate ◽  
Animal Studies ◽  
Bone Growth ◽  
High Dose ◽  
Childhood Cancers ◽  
Paediatric Cancer ◽  
Growth Defects ◽  
Clinical Observations ◽  
Skeletal Defects ◽  
Underlying Mechanisms

The advancement and intensive use of chemotherapy in treating childhood cancers has led to a growing population of young cancer survivors who face increased bone health risks. However, the underlying mechanisms for chemotherapy-induced skeletal defects remain largely unclear. Methotrexate (MTX), the most commonly used antimetabolite in paediatric cancer treatment, is known to cause bone growth defects in children undergoing chemotherapy. Animal studies not only have confirmed the clinical observations but also have increased our understanding of the mechanisms underlying chemotherapy-induced skeletal damage. These models revealed that high-dose MTX can cause growth plate dysfunction, damage osteoprogenitor cells, suppress bone formation, and increase bone resorption and marrow adipogenesis, resulting in overall bone loss. While recent rat studies have shown that antidote folinic acid can reduce MTX damage in the growth plate and bone, future studies should investigate potential adjuvant treatments to reduce chemotherapy-induced skeletal toxicities.

scholarly journals Release of CXCL12 from Apoptotic Skeletal Cells Contributes to Bone Growth Defects Following Dexamethasone Therapy in Rats

2020 ◽  
Vol 35 (8) ◽  
pp. 1612-1613
Author(s):  
Qian Tang ◽  
Yu‐Wen Su ◽  
Chia‐Ming Fan ◽  
Rosa Chung ◽  
Mohammadhossein Hassanshahi ◽  
...  
Keyword(s):  
Bone Growth ◽  
Growth Defects ◽  
Dexamethasone Therapy

scholarly journals Bone, Growth Plate and Mineral Metabolism

2010 ◽  
pp. 65-81 ◽  
Author(s):  
Terhi Heino ◽  
Dov Tiosano ◽  
Aneta Gawlik ◽  
Lars Sävendahl
Keyword(s):  
Growth Plate ◽  
Bone Growth ◽  
Mineral Metabolism

scholarly journals Effect of Pulsed Electromagnetic Field Stimulation on the Growth Plate of the Tibia Bone of Rats: An In Vivo Study

2021 ◽  
Vol 11 (16) ◽  
pp. 7571
Author(s):  
Yoon-Young Sung ◽  
Jae-Woo Shin ◽  
Won-Kyung Yang ◽  
Min-Jin Kim ◽  
Ja-Ik Koo ◽  
...  
Keyword(s):  
Electromagnetic Field ◽  
Growth Plate ◽  
Bone Growth ◽  
Articular Chondrocytes ◽  
Growth Promotion ◽  
Control Group ◽  
Pulsed Electromagnetic Field ◽  
Tibia Bone ◽  
Pulsed Electromagnetic

Currently, many children undergo precocious puberty, resulting in short stature due to premature closure of the growth plate. Pulsed electromagnetic field (PEMF) stimulation induces cell proliferation of articular chondrocytes. We developed a method for growth promotion using equipment with PEMF. In this study, we aimed to evaluate the effects of PEMF on the growth rate of growth plates using an animal model. An experimental study was conducted on 16 3-week-old rats to validate the effects of the growth care device on growth and development by PEMF stimulation at 28 Hz and 20 Gauss. The tibia bones of the groups with and without PEMF administration were dissected after 10 days, and then, the length of the growth plate of the knee and levels of insulin-like growth factor (IGF)-1 hormone in serum were measured. The length of the growth plate on the tibia bone and the levels of circulating IGF-1 were significantly increased by 25.6% and 13.6%, respectively, in the experimental group to which PEMF was applied compared to those of the control group, without any side effects. These results suggest that PEMF can safely stimulate growth of the growth plate in a non-invasive manner to promote bone growth.

scholarly journals Long Term Cyclic Pamidronate Reduces Bone Growth by Inhibiting Osteoclast Mediated Cartilage-to-Bone Turnover in the Mouse

2008 ◽  
Vol 2 (1) ◽  
pp. 121-125 ◽  
Author(s):  
K.D Evans ◽  
L.E Sheppard ◽  
D.I Grossman ◽  
S.H Rao ◽  
R.B Martin ◽  
...  
Keyword(s):  
Bone Turnover ◽  
Growth Plate ◽  
Bone Growth ◽  
Cathepsin K ◽  
Chondrocyte Apoptosis ◽  
Cell Numbers ◽  
Hypertrophic Chondrocyte ◽  
Osteoclast Function ◽  
And Function

Bisphosphonates, used to treat diseases exhibiting increased osteoclast activity, reduce longitudinal bone growth through an as yet undefined mechanism. Pamidronate, an aminobisphosphonate, was given weekly to mice at 0, 1.25, or 2.50 mg/kg/wk beginning at 4 weeks of age. At 12 weeks of age, humeral length, growth plate area, regional chondrocyte cell numbers, chondrocyte apoptosis, TRAP stained osteoclast number, and osteoclast function assessed by cathepsin K immunohistochemistry were quantified. Humeral length was decreased in pamidronate treated mice compared to vehicle control mice, and correlated with greater growth plate areas reflecting greater proliferative and hypertrophic chondrocyte cell numbers with fewer hypertrophic cells undergoing apoptosis. Pamidronate treatment increased TRAP stained osteoclast numbers yet decreased cathepsin K indicating that pamidronate repressed osteoclast maturation and function. The data suggest that long term cyclic pamidronate treatment impairs bone growth by inhibition of osteoclast maturation thereby reducing cartilage-to-bone turnover within the growth plate.

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