Research design and methods: A characterisation of 225 European (Russian) osteoporotic postmenopausal women, treated for 2 years with amino-bisphosphonate zoledronic acid (zol), 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 bone turnover markers (BTM): b-crosslaps (CTX) and osteocalcin (OC) to treatment with zol was statistically examined.
Results: 225 postmenopausal Russian women with mean age of 59 years old (between 54 and 66 years old, mean length of menopause of 7 years (213), and mean BMI of 27.2 (23.629.05) kg/m2. were characterized for (AA:AC:CC) allele distribution in FDPS gene. The ratio of alleles was AA 55.1 (n=144): AC 39.5 (n=103), and CC 5.4 (n=14). There was no statistically significant correlation between the FDPS genotype and baseline levels of BTM. The average BMD in the spine/femur indicated presence of osteoporosis. All the patients were treated i.v. with 5 mg of zol once in 12 months for 2 years. Additionally all the patients were taking Ca at 1000 mg/day and vitamin D at 800 ME/day. Difference in BMKP after zol infusion was FDPS genotype dependent.
There was a statistically significant decrease in CTX 92% (9193%) in patients with C/C genotype (P=0.0056) in comparison to 82% in A allele carriers 6-month post first infusion (P=0.07). Nine months after infusion CTX were up to 75% in A allele carriers with osteocalcine being 44.4% of the baseline. In the meatime, C/C genotype carriers still had low CTX (87%) and OC (53.6%) levels (P=0.056). By the 12th month of treatment CTX and OC levels were increasing in A allele carriers but in the C/C allele genotype stayed within the limits of the lower levels of normal for pre-menoupause. Patients carrying C/C genotype showed significant decrease in BMD (5.6%) and bone turnover markers after the second infusion of zol (not sure about abbreviations and my translation)
Conclusions: The difference in reaction to zol treatment in postmenopausal women correlated with FDPS gene polymorphism. Zol therapy in C/C genotype was characterized by hypersuppression of bone turnover and possibly is a reason for the negative dynamics of MPK in the spine after 2-year therapy.