|Research Finds Vitamin D Deficiency Affects Bone Quality|
Vitamin D deficiency is a widespread medical condition that plays a major role in human bone health. Scientists know that a lack of vitamin D can cause bone diseases such as rickets and osteomalacia. Now a team of researchers working at the ALS has also found that vitamin D deficiency plays a significant role in the bone-aging process. Low levels of vitamin D, the “sunshine vitamin,” have been previously linked to the health and fracture risk of human bone on the basis of low calcium intake and reduced bone density. The recent ALS research demonstrates that vitamin D deficiency also reduces bone quality.
Fracture susceptibility in the context of low vitamin D levels has been primarily associated with defective mineralization of the collagenous matrix in bones (osteoid). However, bone’s fracture resistance is due to toughening mechanisms at various hierarchical levels ranging from the nano- to the microstructure. The team of U.S. and German scientists working at the ALS found that the characteristic increase in osteoid-covered surfaces in vitamin D–deficient bone hampers remodeling of the remaining mineralized bone tissue.
Using spatially resolved synchrotron bone mineral density distribution analyses and spectroscopic techniques, the researchers observed that the bone tissue within the osteoid frame has a higher mineral content with mature collagen and mineral constituents, which are characteristic of aged tissue. In situ fracture mechanics measurements and synchrotron radiation microcomputed tomography of the crack path indicated that vitamin D deficiency increases both the initiation and propagation of cracks by 22 to 31 percent. Thus, vitamin D deficiency is not simply associated with diminished bone mass. The assumption has always been that the main problem with vitamin D deficiency is reduced mineralization for the creation of new bone mass, but this research shows that low levels of vitamin D also induce premature aging of existing bone.
The researchers hypothesized that restoring the normal level of vitamin D would not only correct the imbalance of mineralized and nonmineralized bone quantities, but also initiate simultaneous multiscale alterations in bone structure that affect both the intrinsic and extrinsic fracture mechanisms. To test this hypothesis, the international 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, a disease in which bone is too soft because of excessive collagenous matrix and its inadequate mineralization. For this study, a normal vitamin D level was defined as a serum concentration of above 20 micrograms per liter or higher. For the vitamin D deficiency group the mean serum concentration was below 20 micrograms per liter.
The bone samples were analyzed at the ALS using Fourier transform infrared (FTIR) spectroscopy and x-ray computed microtomography. The FTIR spectroscopy capabilities of ALS Beamline 1.4.3 and Beamline 5.4.1 provided molecular-level chemical information, and ALS Beamline 8.3.2 provides nondestructive 3D imaging at a resolution of approximately one micron. The beamlines allowed researchers to measure the structure/composition and mechanical properties of the bone samples at different size scales, ranging from nanometers to micrometers. They 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 them to relate mechanical properties to specific structural changes.
The team found that while vitamin D–deficient subjects had less overall mineralization due to a reduction of mineralized bone, underneath the new nonmineralized 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. This research expands the current clinical understanding of the pathophysiology of vitamin D deficiency and helps explain why well-balanced vitamin D levels are essential to maintain bone’s structural integrity.
Research conducted by: B. Busse, E. Vettorazzi, J. Zustin, M. Hahn, K. Püschel, and Michael Amling (Univ. Medical Center Hamburg and Berkeley Lab); H.A. Bale, B. Panganiban, A. Carriero, J.W. Ager III, and R.O. Ritchie (Berkeley Lab); E.A. Zimmermann (Univ. Medical Center Hamburg, Berkeley Lab, and UC Berkeley); and H.D. Barth (Berkeley Lab and UC Berkeley).
Research funding: Berkeley Lab Laboratory Directed Research and Development program and the German Federal Ministry of Education and Research. Operation of the ALS is supported by the U.S. Department of Energy, Office of Basic Energy Sciences.
Publication about this research: B. Busse, H. Bale, E. Zimmermann, B. Panganiban, H. Barth, A. Carriero, E. Vettorazzi, J. Zustin, M. Hahn, J. Ager, K. Püschel, and M. Amling, “Vitamin D Deficiency Induces Early Signs of Aging in Human Bone, Increasing the Risk of Fracture,” Science Translational Medicine 5, 193ra88 (2013).
ALS Science Highlight #287