Low bone turnover and low BMD in Down syndrome: effect of intermittent PTH treatment.
Trisomy 21 affects virtually every organ system and results in the complex clinical presentation of Down syndrome (DS). Patterns of differences are now being recognized as patients' age and these patterns bring about new opportunities for disease prevention and treatment. Low bone mineral density (BMD) has been reported in many studies of males and females with DS yet the specific effects of trisomy 21 on the skeleton remain poorly defined. Therefore we determined the bone phenotype and measured bone turnover markers in the murine DS model Ts65Dn. Male Ts65Dn DS mice are infertile and display a profound low bone mass phenotype that deteriorates with age. The low bone mass was correlated with significantly decreased osteoblast and osteoclast development, decreased bone biochemical markers, a diminished bone formation rate and reduced mechanical strength. The low bone mass observed in 3 month old Ts65Dn mice was significantly increased after 4 weeks of intermittent PTH treatment. These studies provide novel insight into the cause of the profound bone fragility in DS and identify PTH as a potential anabolic agent in the adult low bone mass DS population.
Department of Physiology & Biophysics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
Tristan W
TW
Fowler
Kent D
KD
McKelvey
Nisreen S
NS
Akel
Jaclyn
J
Vander Schilden
Anthony W
AW
Bacon
John W
JW
Bracey
Timothy
T
Sowder
Robert A
RA
Skinner
Frances L
FL
Swain
William R
WR
Hogue
Donna B
DB
Leblanc
Dana
D
Gaddy
Galen R
GR
Wenger
Larry J
LJ
Suva
D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D016723:Bone Remodeling; D002454:Cell Differentiation; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D008297:Male; D051379:Mice; D010006:Osteoblasts / Q000166:cytology; D010010:Osteoclasts / Q000166:cytology; D010281:Parathyroid Hormone / Q000494:pharmacology / Q000627:therapeutic use*
D010281:Parathyroid Hormone