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tion and linear bone growth. In faet, these rates were
much lower than those calculated for the rachitic/
pair-fed control animals, and the bone formation indices (OAI) suggested that the osteoblasts on these
surfaces were functionally lethargic. Phosphate was
statistically somewhat more effective than vitamin D
on these parameters and it did cure rickets histologically and histochemically, but there was no overall
improvement which could be attributed to either agent
per se. In contrast, the pace of endosteal lamellar bone
formation was quite independent of treatment, and
osteoblast activity was normal] at all times. It may be
concluded, then, that thinning of the rachitic cortices
is due to deficient periosteal bone formation. It is difficult to estimate the contribution of the partially or
While the present studies do not necessarily contribute to our understanding of the basic biochemical
lesions in cartilage and bone which produce histologic
rickets, evidence has also been presented that the most
mature cells in rachitic cartilage are not producing
significant amounts of collagen (and presumably
chondroitin sulfate) and that this basic cell defect ac-
counts, at least in part, for deficient calcification of
the tissue. The results from this study also suggest
that the rate of bone matrix formation in rachitic bone
is generally normal.
SUMMARY
3H-proline was administered intraperitoneally to
fully reconstituted diets to the observed stunting of
young male rats with nutritional rickets produced by
trition are much more severe if it occurs in young
graphs of the upper tibial epiphyseal cartilages from
untreated control littermates showed tracer incorpora-
bones. But it is known that the effects of undernu-
animals, and that if the nutritional insult is prolonged
they may never attain the body weight or cell growth
of animals reared on a normal diet."
The osteoblast activity indices reported in this
study, based in part upon the thickness of the dense
lines of matrical silver grains, are at the light microscope level of resolution unlikely to be influenced by
changes in the ultrastructure of bone. Poorly oriented
collagen fibers in rachitic osteoid have been described
in dogs5) and in rats?) by electron microscopy. It
should be noted that the fine structure of the rachitic
a low phosphate, vitamin De-free diet. Autoradio-
tion by the cells and extracellular matrix 4 hr and 3
days post-injection, respectively, and this occurred
throughout the proliferative and hypertrophic cell
zones. The pattern of tracer uptake was abnormal in
the thickened cartilages from rachitic rats; the oldest
juxtametaphyseal chondrocytes were unable to syn-
thesize significant amounts of matrical protein and
this effect could not be corrected thereafter by feeding
rachitic rats nutritionally adequate supplements of
phosphate and/or vitamin D.
The rate of bone formation was calculated from the
osteoblast is not entirely normal; broad cysternae
have been observed which contain a moderately dense
displacement (burial) of the labeled lamellae of bone
suggest is collagen which is not yet polymerized to
tion, as well as by the thickness of the linear bands of
following phosphorus and/or vitamin D supplementa-
teum and on the articular surface of the transverse
epiphyseal bone was essentially normal in rats ren-
amorphous material that Robinson and Sheldon'®
matrix from anatomical surfaces 3 days post-injec-
fibrillar form. There is little evidence from the present
study to suggest that the ultrastructural changes contribute to the sharply decreased activity of osteoblasts
silver grains recorded in the photographic emulsion.
Lamellar bone formation at the periosteum, endos-
tion. OAI values approximating 2 were also detected
dered rachitic by the deficient diet. Unexpectedly, the
in the stunted bones from rats on the fully supple-
mented rachitogenic diet (Group 3). Nor is it likely
that the instances where the rate of lamellar bone for-
mation was depressed signal a parathyroid endocrinopathy, for serum calcium concentrations in these
animals were normal or slightly high (vitamin D-
treated)
mal.{87)
explain
Rohr‘!5)
and the ultrastructure of the glands was norInvolvement of parathyroid activity might
the very rapid osteogenesis reported by
in the metaphyses of rachitic rats raised on a
diet which was vitamin D-free and severely deficient
in both calcium (hypocalcemic?) and phosphate.
Parathyroid extract administered to rats and mice,
for instance, elicits a biphasic response in bone—an
initial inhibition and a secondary stimulation of bone
cell amino acid transport and collagen synthesis. (2? 38)
pace of appositional bone growth on the periosteum
and transverse epiphyseal bone was depressed when
rachitic rats were treated with phosphate and/or vitamin D, owing presumably to the functional lethargy
of osteoblasts at these sites. Endosteal lamellar bone
formation rates on the shaft and peripheral to the
metaphysis were independentof treatment.
REFERENCES
1. Sheldon, H. and Robinson, R. A. Studies on rickets. IT. The
fine structure of the cellular components of bone in experimental rickets. Z. Zellforsch. 68, 685-701 (1961).
2. Sheldon, H. and Robinson, R. A. Studies in rickets. I. The
fine structure of uncalcified bone matrix in experimental
rickets. 7. Zellforsch. 53, 671-684 (1961).
3. Kunin, A. 8. and Krane, 5S. M. The effect of dietary phosphorus on the intermediary metabolism of epiphyseal