Modulatory effect of farnesyl pyrophosphate synthase (FDPS) rs2297480 polymorphism on the response to long-term amino-bisphosphonate treatment in postmenopausal osteoporosis.
BACKGROUND
Polymorphisms of genes encoding enzymes of the mevalonate pathway could modulate the response to amino-bisphosphonate treatment in postmenopausal osteoporosis.


METHODS
A characterisation of 234 Danish osteoporotic postmenopausal women (as part of the Prospective Epidemiological Risk Factors study (PERF)), treated for at least 2 years with amino-bisphosphonates, with respect to the adenosine/cytosine (A/C) rs2297480 farnesyl pyrophosphate synthase (FDPS) gene polymorphism, was carried out by PCR-based enzymatic digestion and quantitative PCR allelic discrimination on genomic DNA extracted from blood leukocytes. The association between these polymorphism genotypes and the response of spine and femur bone mineral density (BMD) and of biochemical bone biomarkers to treatment with amino-bisphosphonates was statistically examined.


RESULTS
FDPS polymorphism did not show any relationship to baseline spinal and femoral BMD in Danish postmenopausal women. BMD response to treatment with amino-bisphosphonates was similar in the AA and the AC genotypes, while the CC genotype showed a lower BMD response to 2-year-treatment with amino-bisphosphonates at all examined skeletal sites (p=0.60 at the spine and p=0.59 at the femur). Interestingly, after 2 years of treatment the response of urinary Cross-laps to amino-bisphosphonates treatment was significantly (p<0.05) lower in the CC genotype when compared to both the AC and AA genotypes. Even the response of serum osteocalcin was lower in the CC genotype, but without reaching a statistical significance (p=0.65).


CONCLUSIONS
Danish postmenopausal women with osteoporosis bearing the homozygous CC genotype for rs2297480 FDPS polymorphism showed a decreased response of bone turnover markers to amino-bisphosphonate therapy, when compared to the heterozygous AC and to the homozygous AA genotypes. Further investigation on larger and different populations, together with polymorphism functional studies are required to confirm these data.
Marini
Francesca
F
Department of Internal Medicine, University of Florence, Florence, Italy.
Falchetti
Alberto
A
Silvestri
Sandra
S
Bagger
Yu
Y
Luzi
Ettore
E
Tanini
Annalisa
A
Christiansen
Claus
C
Brandi
Maria Luisa
ML
D000368:Aged; D015519:Bone Density; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D016723:Bone Remodeling; D004164:Diphosphonates / Q000627:therapeutic use*; D005260:Female; D005838:Genotype; D051228:Geranyltranstransferase / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D011110:Polymorphism, Genetic; D017698:Postmenopause
D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D051228:Geranyltranstransferase