Geochemical Assay Proving Useful as Real-Time Marker of Bone Change
Changes in calcium isotope ratios may signal bone loss and can be used as a near-real time, rapid test for monitoring both common bone conditions, like osteoporosis, and rarer conditions, like multiple myeloma (MM), according to an abstract presented at Goldschmidt 2015, a geochemistry conference, (Czech Republic; Aug. 16-21). The proof-of-principle has been validated in a series of small studies on bedridden individuals, NASA astronauts in space, rats, and patients with MM. Variant Identified With Large Effect on Bone Density, Fracture Risk Researchers identified a novel, low-frequency, non-coding genetic variant that is associated with large effects on bone mineral density (BMD) and fracture risk in individuals of European ancestry, according to a letter published online Sept. 14 in Nature. What’s more, the study, the largest population genome sequencing effort to date, demonstrates the value of whole-genome sequencing (WGS) in large populations to identify variants tied to complex traits and disease in the general population. In the current population-based study the researchers conducted WGS in 2,882 participants from UK10K, whole-exome sequencing (3,549 participants in five cohorts), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (26,534), and de novo replication genotyping (20,271). A low-frequency non-coding variant near a […]
Changes in calcium isotope ratios may signal bone loss and can be used as a near-real time, rapid test for monitoring both common bone conditions, like osteoporosis, and rarer conditions, like multiple myeloma (MM), according to an abstract presented at Goldschmidt 2015, a geochemistry conference, (Czech Republic; Aug. 16-21). The proof-of-principle has been validated in a series of small studies on bedridden individuals, NASA astronauts in space, rats, and patients with MM.
| Variant Identified With Large Effect on Bone Density, Fracture Risk |
Researchers identified a novel, low-frequency, non-coding genetic variant that is associated with large effects on bone mineral density (BMD) and fracture risk in individuals of European ancestry, according to a letter published online Sept. 14 in Nature. What’s more, the study, the largest population genome sequencing effort to date, demonstrates the value of whole-genome sequencing (WGS) in large populations to identify variants tied to complex traits and disease in the general population. In the current population-based study the researchers conducted WGS in 2,882 participants from UK10K, whole-exome sequencing (3,549 participants in five cohorts), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (26,534), and de novo replication genotyping (20,271). A low-frequency non-coding variant near a novel locus, EN1, had an effect size four-fold larger than the mean of previously reported common variants BMD (which only account for a small fraction of BMD-related genetic variance) and a three-fold larger effect than those previously identified for fracture. EN1 was also associated with a significantly decreased risk of fracture (cases = 98,742 and controls = 409,511). “These findings provide evidence that low-frequency, non-coding variants have large effects on BMD and fracture, thereby providing rationale for whole-genome sequencing and improved imputation reference panels to study the genetic architecture of complex traits and disease in the general population,” write the authors led by Hou-Feng Zheng, from McGill University in Canada. |
This effort is a collaboration between biomedical researchers and geochemists, who have developed “extremely accurate” ways of measuring calcium isotope ratios. The relative ratios of the light calcium isotopes (δ44/42Ca) in bone can be determined using mass spectrometry. The rate of change of bone mass can be calculated by measuring the ratios of the two isotopes in blood or urine, as the light calcium isotopes are absorbed from the blood during bone formation and released into the blood during bone destruction.
“The big advantage of these measurements is that they show what is happening in the bone, whereas traditional bone health measurements, such as DXA scans, show what has happened,” explains lead author Ariel Anbar, Ph.D., from Arizona State University (ASU), in a statement. Markers of short-term changes in bone metabolism may enable earlier disease detection and evaluation of treatment efficacy.
The researchers piloted the marker in bed-bound individuals prone to bone loss due to unloading and then evaluated urine samples from 30 astronauts (who experience rapid bone loss in space because of zero gravity conditions) before, during, and after space travel. Overall, the researchers found a systematic shift toward excretion of lighter Ca isotopes during unloading or space travel. The isotope ratio was further assessed (in collaboration with the Mayo Clinic) in 71 adult patients diagnosed with MM or asymptomatic precursor diseases. Patients with active disease had statistically significant lower mean δ44/42Ca than those with non-active disease.
“Physicians treating osteoporosis and other calcium disorders of bone, including multiple myeloma, have very few tools at their disposal to quickly determine whether the treatments they’re providing are actually making a difference,” says Scott Parazynski, M.D., former NASA astronaut, and current professor at ASU. “It’s tremendous to see a sophisticated geochemical assay being translated into what could become a really significant medical diagnostic tool.”
Takeaway: “Physicians treating osteoporosis and other calcium disorders of bone, including multiple myeloma, have very few tools at their disposal to quickly determine whether the treatments they’re providing are actually making a difference,” says Scott Parazynski, M.D., former NASA astronaut, and current professor at ASU. “It’s tremendous to see a sophisticated geochemical assay being translated into what could become a really significant medical diagnostic tool.”
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