Bone Aging Linked To Sunshine Vitamin Deficiency
From ScienceDaily (7/13)Vitamin D Deficiency Linked to Accelerated Aging of Bones
Everyone knows that as we grow older our bones become more fragile. Now a team
of U.S. and German scientists led by researchers with the U.S. Department of
Energy (DOE)'s Lawrence Berkeley National Laboratory (Berkeley Lab) and the
University of California (UC) Berkeley has shown that this bone-aging process
can be significantly accelerated through deficiency of vitamin D - the sunshine
Vitamin D deficiency is a widespread medical condition that has been linked to
the health and fracture risk of human bone on the basis of low calcium intake
and reduced bone density. However, working at Berkeley Lab's Advanced Light
ALS), a DOE national user facility, the international team demonstrated that
vitamin D deficiency also reduces bone quality.
"The assumption has been that the main problem with vitamin D deficiency is
reduced mineralization for the creation of new bone mass, but we've shown that
low levels of vitamin D also induces premature aging of existing bone," says
Robert Ritchie, who led the U.S. portion of this collaboration. Ritchie holds
joint appointments with Berkeley Lab's Materials Sciences Division and the
University of California (UC) Berkeley's Materials Science and Engineering
Department. "Unraveling the complexity of human bone structure may provide some
insight into more effective ways to prevent or treat fractures in patients with
vitamin D deficiency," says Björn Busse, of the Department of Osteology and Biomechanics at the University
Medical Center in Hamburg, Germany, who led the German portion of the team.
Ritchie and Busse have reported their findings in the journal Science
Translational Medicine. The paper is titled "Vitamin D Deficiency Induces Early
Signs of Aging in Human Bone, Increasing the Risk of Fracture." Co-authors also
include Hrishikesh Bale, Elizabeth Zimmermann, Brian Panganiban, Holly Barth,
Alessandra Carriero, Eik Vettorazzi, Josef Zustin, Michael Hahn, Joel Ager,
Klaus Püschel and Michael Amling.
Vitamin-D is essential for the body to absorb calcium. The body normally
synthesizes vitamin D in the skin following exposure to sunlight - hence the
"sunshine" moniker. However, when vitamin D serum concentrations become
deficient, the body will remove calcium from bone to maintain normal calcium
blood levels. This removal of calcium from existing bone hampers the
mineralization process required for the formation of new bone mass. In
children, vitamin D deficiency can lead to rickets. In adults, vitamin D
deficiency causes osteomalacia, a softening of the bones associated with
defective mineralization that results in bone pain, muscle weakness, and
increased risk of bone deformation and fracture. While treatments with vitamin
D and calcium supplements are effective, success has been achieved with only
modest increases in bone mineral density, suggesting other factors also play a
role in reducing fracture risks.
"We hypothesized that restoring the normal level of vitamin D not only corrects
the imbalance of mineralized and non-mineralized bone quantities, but also
initiates simultaneous multiscale alterations in bone structure that affects
both the intrinsic and extrinsic fracture mechanisms," Ritchie says.
To test this hypothesis, Busse and his German team collected samples of iliac
crest bone cores from 30 participants, half of whom were deficient in vitamin D
and showed early signs of osteomalacia. For this study, a normal vitamin D
level was defined as a serum concentration of 20 micrograms per liter or
higher. For the vitamin D deficiency group the mean serum concentration was 10
micrograms per liter.
The bone samples were sent to Ritchie and his team for analysis at the ALS using
Fourier Transform Infrared (FTIR) spectroscopy and X-ray computed
microtomography. The FTIR spectroscopy capabilities of ALS beamlines 1.4.3 and
5.4.1 provide molecular-level chemical information, and ALS Beamline 8.3.2
provides non-destructive 3D imaging at a resolution of approximately one
"We were interested in spatially resolved data that would help us to follow the
formation of cracks under mechanical loading," Ritchie says. "The ALS beamlines
enabled us to measure the structure/composition and mechanical properties of
the bone samples at different size-scales, ranging from nanometers to
micrometers. We measured the resistance to crack growth and by following crack
growth in real-time were able to observe how cracks and structure interact.
This enabled us to relate mechanical properties to specific structural
Ritchie and his team found that while vitamin D-deficient subjects had less
overall mineralization due to a reduction of mineralized bone, underneath the
new non-mineralized surfaces, the existing bone was actually more heavily
mineralized, and displayed the structural characteristics -- mature collagen
molecules and mineral crystals - of older and more brittle bone.
"These islands of mineralized bone were surrounded by a collagenous boundary
that prevented them from being properly remodeled," Busse says. "Cut off from a
supply of osteoclasts, the cells that normally remodel the bone, these isolated
sections of mineralized bone begin to age, even as overall bone mineralization
decreases from a lack of calcium." Says Ritchie,"In situ fracture mechanics
measurements and CT-scanning of the crack path indicated that vitamin D
deficiency increases both the initiation and propagation of cracks by 22- to
From their study, Busse, Ritchie and their co-authors say that vitamin-D levels
should be checked and kept on well-balanced levels to maintain the structural
integrity of bones and avoid mineralization defects and aging issues that can
lead to a risk of fractures.
The Berkeley portion of this work was supported by Berkeley Lab's Laboratory
Directed Research and Development program. The German portion was supported by
the Federal Ministry of Education and Research. Berkeley Lab's Advanced Light
Source is supported by DOE's Office of Science.