Hypophosphatemic Hypovitaminosis D Induces Osteomalacia in the Adult Female Rat
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Hypophosphatemic Hypovitaminosis D Induces Osteomalacia in the Adult Female Rat. / Durup, Darshana; Diaz-delCastillo, Marta; Morgenlykke, Jesper; Jensen, Lars Thorbjorn; Frandsen, Erik; Abelson, Klas S P; Pedersen, Lars; Lykkesfeldt, Jens; Ding, Ming; Jørgensen, Niklas R; Syberg, Susanne; Petersen, Solveig; Heegaard, Anne-Marie.
In: Endocrinology, Vol. 161, No. 8, bqaa100, 2020.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Hypophosphatemic Hypovitaminosis D Induces Osteomalacia in the Adult Female Rat
AU - Durup, Darshana
AU - Diaz-delCastillo, Marta
AU - Morgenlykke, Jesper
AU - Jensen, Lars Thorbjorn
AU - Frandsen, Erik
AU - Abelson, Klas S P
AU - Pedersen, Lars
AU - Lykkesfeldt, Jens
AU - Ding, Ming
AU - Jørgensen, Niklas R
AU - Syberg, Susanne
AU - Petersen, Solveig
AU - Heegaard, Anne-Marie
N1 - © Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
PY - 2020
Y1 - 2020
N2 - Osteomalacia is a bone-demineralizing disease of adulthood, often caused by hypovitaminosis D. Current animal models of the disease mimic osteomalacia as a consequence of gastric bypass or toxic exposure to metals, but a relevant model of diet-induced osteomalacia is lacking. For that purpose, 7-month-old female Sprague Dawley rats were randomly assigned into 2 weight-stratified groups and maintained for 4 months on synthetic diets containing negligible or normal levels of vitamin D. The dietary regimen resulted in vitamin D deficiency as measured by 25-hydroxyvitamin D serum levels; however, hypovitaminosis D per se did not affect biomarkers of calcium metabolism and bone turnover, nor did it result in increased osteoid. Thus, vitamin D depletion through the diet was found to be insufficient to induce an osteomalacia-like phenotype in the adult rat. After 4 months, the phosphate content of the vitamin D-depleted diet had decreased to 0.16% (calcium:phosphorus ratio of 5.85), resulting in an osteomalacic-like condition (trabecular osteoid surface/bone surface constituted 33%; CI, 26-40). The diet change also affected both metabolic and bone turnover biomarkers, including significantly suppressing serum fibroblast growth factor 23. Furthermore, decreased dietary phosphate in a vitamin D-depleted diet led to microarchitectural changes of trabecular and cortical bone, lower bone mass density, lower bone mass content and decreased bone strength, all indicating reduced bone quality. Taken together, our results show that osteomalacia can be induced in the adult female rat by depleting vitamin D and lowering phosphate content in the diet.
AB - Osteomalacia is a bone-demineralizing disease of adulthood, often caused by hypovitaminosis D. Current animal models of the disease mimic osteomalacia as a consequence of gastric bypass or toxic exposure to metals, but a relevant model of diet-induced osteomalacia is lacking. For that purpose, 7-month-old female Sprague Dawley rats were randomly assigned into 2 weight-stratified groups and maintained for 4 months on synthetic diets containing negligible or normal levels of vitamin D. The dietary regimen resulted in vitamin D deficiency as measured by 25-hydroxyvitamin D serum levels; however, hypovitaminosis D per se did not affect biomarkers of calcium metabolism and bone turnover, nor did it result in increased osteoid. Thus, vitamin D depletion through the diet was found to be insufficient to induce an osteomalacia-like phenotype in the adult rat. After 4 months, the phosphate content of the vitamin D-depleted diet had decreased to 0.16% (calcium:phosphorus ratio of 5.85), resulting in an osteomalacic-like condition (trabecular osteoid surface/bone surface constituted 33%; CI, 26-40). The diet change also affected both metabolic and bone turnover biomarkers, including significantly suppressing serum fibroblast growth factor 23. Furthermore, decreased dietary phosphate in a vitamin D-depleted diet led to microarchitectural changes of trabecular and cortical bone, lower bone mass density, lower bone mass content and decreased bone strength, all indicating reduced bone quality. Taken together, our results show that osteomalacia can be induced in the adult female rat by depleting vitamin D and lowering phosphate content in the diet.
U2 - 10.1210/endocr/bqaa100
DO - 10.1210/endocr/bqaa100
M3 - Journal article
C2 - 32591825
VL - 161
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0013-7227
IS - 8
M1 - bqaa100
ER -
ID: 245614953