Light Source Links Vitamin D Deficiency to Accelerated Bone Aging

Sunshine may be bad for your skin, but it is good for your bones, and now researchers in California and Germany have discovered that a deficiency in vitamin D — the sunshine vitamin — can accelerate premature bone aging by increasing the risk of fracture.

Vitamin D, essential for the body to absorb calcium, is synthesized in the skin following exposure to sunlight. However, when vitamin D serum concentrations become deficient, the body removes calcium from bone to maintain the balance, hindering the mineralization process required for the formation of new bone mass. In children, such deficiencies can lead to rickets; in adults, they can cause osteomalacia — a softening of the bones associated with bone pain, muscle weakness and increased risk of bone deformation and fracture.

Treatments with vitamin D and calcium supplements are effective, but success has been achieved with only modest increases in bone mineral density, suggesting other factors can play a role in reducing fracture risks.

Robert Ritchie (left) and Hrishikesh Bale used a combination of FTIR spectroscopy and x-ray CT at the Advanced Light Source to find that vitamin D deficiency speeds the aging process of bone and reduces its quality. Courtesy of Roy Kaltschmidt.

Working at Lawrence Berkeley National Laboratory’s Advanced Light Source (ALS), researchers from Berkeley Lab, the University of California, Berkeley, and University Medical Center in Hamburg, Germany, are now demonstrating 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,” said Robert Ritchie, who led the US portion of the collaboration. Ritchie holds joint appointments with Berkeley Lab’s Materials Sciences Div. and UCBerkeley’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,” said Björn Busse of the Department of Osteology and Biomechanics at the University Medical Center, who led the German portion of the team.

The investigators hypothesized that restoring the normal level of vitamin D would not only correct the imbalance of mineralized and nonmineralized bone quantities, but also would initiate “simultaneous multiscale alterations in bone structure that affect both the intrinsic and extrinsic fracture mechanisms,” Ritchie said.

To test the 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 µg/l or higher. For the vitamin D deficiency group, the mean serum concentration was 10 µg/l.

The 3-D reconstructions of crack paths in the normal bone (left) show pronounced crack deflection by splitting along the interfaces of the osteons accompanied by the formation of crack bridges. In a vitamin D-deficient sample, the crack takes a tortuous breaking path across the osteons with no crack bridging. Courtesy of Ritchie and Bale.

The bone samples were sent to Ritchie and his team for analysis at the ALS using Fourier transform IR (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 nondestructive 3-D imaging at a resolution of approximately 1 µm.

“We were interested in spatially resolved data that would help us to follow the formation of cracks under mechanical loading,” Ritchie said. “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 changes.”

The US investigators discovered that, although vitamin D-deficient subjects had less overall mineralization because of a reduction of mineralized bone, underneath the new nonmineralized surfaces, the existing bone was actually more heavily mineralized and displayed the structural characteristics of older, more brittle bone.

“These islands of mineralized bone were surrounded by a collagenous boundary that prevented them from being properly remodeled,” Busse said. “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.”

“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 31 percent,” Ritchie said.

Based on their findings, the researchers suggest that vitamin D levels should be checked and kept on well-balanced levels to maintain the structural integrity of bones and to avoid mineralization defects and aging issues that can lead to fractures.

The findings were reported in Science Translational Medicine (doi: 10.1126/scitranslmed.3006286).

For more information, visit: www.lbl.gov