Increased longitudinal growth in rats on a silicon-depleted diet.
Silicon-deficiency studies in growing animals in the early 1970s reported stunted growth and profound defects in bone and other connective tissues. However, more recent attempts to replicate these findings have found mild alterations in bone metabolism without any adverse health effects. Thus the biological role of silicon remains unknown. Using a specifically formulated silicon-depleted diet and modern methods for silicon analysis and assessment of skeletal development, we undertook, through international collaboration between silicon researchers, an extensive study of long-term silicon depletion on skeletal development in an animal. 21-day old female Sprague-Dawley rats (n=20) were fed a silicon-depleted diet (3.2 microg Si/g feed) for 26 weeks and their growth and skeletal development were compared with identical rats (n=10) on the same diet but with silicon added as Si(OH)(4) to their drinking water (53.2 microg Si/g water); total silicon intakes were 24 times different. A third group of rats, receiving a standard rodent stock feed (322 microg Si/g feed) and tap water (5 microg Si/g water), served as a reference group for optimal growth. A series of anthropometric and bone quality measures were undertaken during and following the study. Fasting serum silicon concentrations and especially urinary silicon excretion were significantly lower in the silicon-deprived group compared to the supplemented group (P=0.03 and 0.004, respectively). Tibia and soft-tissue silicon contents did not differ between the two groups, but tibia silicon levels were significantly lower compared to the reference group (P<0.0001). Outward adverse health effects were not observed in the silicon-deprived group. However, body lengths from week 18 onwards (P<0.05) and bone lengths at necropsy (P</=0.002) were longer in this group. Moreover, these measures correlated inversely with serum silicon concentrations (P</=0.02). A reduction in bone growth plate thickness and an apparent increase in chondrocyte density were also observed in the silicon-deprived animals. No other differences were observed between the two groups, except for tibia phosphorus concentrations, which were lower in the silicon-deprived animals (P=0.0003). Thus in this study we were unable to reproduce the profound deficiency state reported in rats and chicks in the early 1970s. Indeed, although silicon intake and circulating fasting serum levels differed between the silicon-deprived and silicon-supplemented animals, tibia and soft-tissue levels did not and may explain the lack of difference in bone quality and bone markers (except serum CTx) between these two groups. Markedly higher tibia silicon levels in the reference group and nutritional differences between the formulated low-Si and reference diets suggest that one or more co-factors may be absent from the low-Si diet that affect silicon incorporation into bone. However, evidence for urinary silicon conservation (to maintain tissue levels), changes in bone/body lengths, bone calcium:phosphorus ratio and differences at the growth plate with silicon deprivation are all novel and deserve further study. These results suggest that rats actively maintain body silicon levels via urinary conservation, but the low circulating serum silicon levels during silicon deficiency result in inhibition of growth plate closure and increased longitudinal growth. Silicon-responsive genes and Si transporters are being investigated in the kidneys of these rats.
MRC Human Nutrition Research, Elsie Widdowson Laboratory, Fulbourn Road, Cambridge CB1 9NL, UK. ravin.jugdaohsingh@mrc-hnr.cam.ac.uk
Ravin
R
Jugdaohsingh
Mario R
MR
Calomme
Karen
K
Robinson
Forrest
F
Nielsen
Simon H C
SH
Anderson
Patrick
P
D'Haese
Piet
P
Geusens
Nigel
N
Loveridge
Richard P H
RP
Thompson
Jonathan J
JJ
Powell
D000821:Animal Feed; D000818:Animals; D001835:Body Weight; D015519:Bone Density / Q000187:drug effects; D001846:Bone Development; D016723:Bone Remodeling; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D019902:Chondrocytes / Q000187:drug effects; D005260:Female; D051381:Rats; D017207:Rats, Sprague-Dawley; D012825:Silicon / Q000172:deficiency / Q000378:metabolism*; D013752:Tetracycline / Q000494:pharmacology; D013977:Tibia / Q000473:pathology; D014057:Tomography, X-Ray Computed / Q000379:methods
D013752:Tetracycline; D012825:Silicon