| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
F508 in primary osteoporotic patients
1 First Dept of Paediatrics, 2 Second Dept of Paediatrics, 3 Research Laboratory for Paediatrics and Nephrology, Hungarian Academy of Sciences, and 4 First Dept of Internal Medicine, Semmelweis University, Budapest, Hungary.
To the Editors:
We read with great interest the paper by King et al. 1 in a recent issue of the European Respiratory Journal. The authors found a strong association between reduced bone mineral density (BMD) and carrier state of 
F508 cystic fibrosis (CF) allele (the most common cystic fibrosis transmembrane regulator (CFTR) gene variant) in an adult CF population. Their results suggest that reduced BMD in CF appears to have a genetic component, independent of the disease severity and nutritional deficits. This fascinating observation is in line with the results found by our group 2. It was found that healthy mothers of CF children (who are obligate heterozygous carriers of a CFTR mutation) have lower than normal BMD values. Furthermore, a correlation with the BMD values of their CF children was demonstrated. Although there are no data on the role of the CFTR gene in bone, it has been reported that not only BMD but also the bone structure of patients with CF was altered compared with healthy individuals 3.
These data further support a possible genetic component in the development of a CF-associated bone deficit. If so, one can speculate that the presence of a single diseased CFTR gene may contribute to the development of osteoporosis in the otherwise healthy adult population.
In a pilot study, we tested the prevalence of the F508 CFTR gene mutation in subjects with severe primary osteoporosis. A total of 137 Caucasian post-menopausal females (aged 46–80 yrs) with osteoporosis were enrolled. Osteoporosis was defined by a T-score of 
–2.5 at the lumbar spine and/or hip sites. Individuals with secondary causes of osteoporosis or bone loss were excluded. All study participants gave informed consent. The prevalence of the F508 variant of CFTR gene was screened by capillary electrophoresis 4.
Three patients with a single F508 allele were detected, which corresponds to the prevalence observed previously in the general Hungarian population 5. These patients did not suffer from a more severe form of osteoporosis than those without a CFTR gene mutation.
These results do not support the hypothesis that the F508 mutation is more common among females with primary osteoporosis. However, a serious limitation of this study is that the number of patients was too low to establish any association between the heterozygosity for the F508 allele and the epidemiology of primary osteoporosis. Given the frequency of the F508 allele in Hungary (3.5%) 5, the number of patients in this study would have been enough to reveal a four-fold difference when the expected allele frequency is 14%, with a power of 85%, among patients with osteoporosis in the overall population. In order to reveal a lower, but still significant difference in the cystic fibrosis transmembrane regulator F508 allele prevalence, the number of patients should be increased dramatically. Hopefully, the worldwide existing large collections of DNA specimens from osteoporotic patients will provide an opportunity to enlighten the possible implication of a cystic fibrosis transmembrane regulator mutation in the development of osteoporosis.
FOOTNOTES
SUPPORT STATEMENT: This study was supported by grants OTKA D048351-T0460086 and NKFP 1A/002/2004 from the Hungarian Government (Budapest). 
REFERENCES
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
