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Lookup NU author(s): Satya Varanasi, Emeritus Professor Roger Francis, Dr Christine Berger, Dr Surinder Papiha, Dr Harish Datta
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We have screened the mitochondrial genome of 15 men with symptomatic vertebral fractures (median age 62 years, range 27-72 years) and 17 male control subjects (median age 61 years, range 40-73 years) for the presence of mitochondrial DNA (mtDNA) deletions in peripheral monocyte DNA. Polymerase chain reaction analysis provided evidence of a common age-related (4.9 kb) mtDNA deletion situated between nucleotides 8470 and 13 460 of the genomic sequence in 5 of the 17 controls (29%) and 9 of the 15 patients (60%) investigated. Southern blotting and polymerase chain reaction revealed a novel 3.7 kb deletion in 2 patients. One of the affected patients, a 27-year-old man with severe osteoporosis (lumbar spine bone mineral density (BMD) 0.381 g/cm2; Z-score -6.45) was found to harbor deletion in almost 50% of the mitochondria. The patient had a blood lactic acid level (4.6 nM) that was over 3 times the upper reference range (0-1.3 mM), thus confirming the presence of systemic oxidative stress. Further analysis by modified primer shift polymerase chain reaction showed the 5' breakpoint to be between the nucleotides 10.63 kb and 10.80 kb of the mtDNA. The second patient harboring the 3.7 kb deletion was older (62 years) with less severe osteoporosis (lumbar spine BMD 0.727/cm2 Z-score -2.58) and the proportion of affected mitochondria was lower (25%). The significance of these findings is discussed and the possible relation between oxidative stress and accelerated bone loss is examined.
Author(s): Varanasi SS, Francis RM, Berger CEM, Papiha SS, Datta HK
Publication type: Article
Publication status: Published
Journal: Osteoporosis International
Year: 1999
Volume: 10
Issue: 2
Pages: 143-149
Print publication date: 01/01/1999
ISSN (print): 0937-941X
ISSN (electronic): 1433-2965
Publisher: Springer
URL: http://dx.doi.org/10.1007/s001980050209
DOI: 10.1007/s001980050209
PubMed id: 10501795
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