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Department of Biochemistry (E.-G.S., A.W.N.) and the Division of Biomedical Sciences (A.W.N.), University of California, Riverside, California 92521; and the Department of Orthopedics, Mount Sinai School of Medicine (T.A.E.), New York, New York 10029
Address all correspondence and requests for reprints to: Prof. Anthony W. Norman, Department of Biochemistry, University of California, Riverside, California 92521. E-mail: norman{at}ucrac1.ucr.edu
We tested the hypothesis that 24R,25-dihydroxyvitamin D3
[24R,25-(OH)2D3] is an essential vitamin D
metabolite for the development of normal bone integrity and the healing
of fractures. The natural 24R,25-(OH)2D3 and
its synthetic epimer 24S,25-dihydroxyvitamin D3
[24S,25-(OH)2D3] were tested alone or in
combination with 1
,25-dihydroxyvitamin D3
[1,25-(OH)2D3], on normal bone development
and other related variables of the Ca2+ homeostasis system
[serum Ca2+, 25-hydroxyvitamin D3
(25OHD3), 24,25-(OH)2D3, and
1,25-(OH)2D3 levels] in chicks. Mechanical
testing of torsional strength was carried out on the femur.
24R,25-(OH)2D3 (80 nmol/kg diet) alone was
sufficient for normal bone growth and integrity similar to that
achieved by the vitamin D3-replete controls. Next, chicks
were fed a 25OHD3-replete diet (75 nmol/kg diet) for 8 days
after hatching, and then 25OHD3 was withdrawn to minimize
any residual circulating metabolites before the imposition of
standardized tibial fractures 14 days later. Vitamin D metabolites were
administered for 2 weeks to determine their effects on the mechanical
properties of healed tibia. 24S,25-(OH)2D3
combined with 1,25-(OH)2D3 or
1,25-(OH)2D3 alone resulted in poor healing
[strength values of 0.158 ± 0.011 and 0.123 ± 0.009 Nm
(Newton · meter), respectively] compared with that in the
25OHD3-treated control group (0.374 ± 0.029 Nm). In
contrast, the fractured tibia of the birds fed
24R,25-(OH)2D3 in combination with
1,25-(OH)2D3 showed healing equivalent to
that in the control group, with strength values of 0.296 ± 0.043
Nm. These results suggest that when
24R,25-(OH)2D3 is present at normal
physiological concentrations, it is an essential vitamin D3
metabolite for both normal bone integrity and healing of fracture in
chicks.
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