Endocrine Abstracts

Introduction: Amino-Bisphosphonates (N-BPs) are potent inhibitors of the bone resorption, they inhibit enzymes of the intracellular mevalonate pathway required for prenylation of different important signaling proteins. In order to study the genetic basis of the variability in therapy response we have analysed the polymorphism of farnesyl pyrophosphate-synthase (FDPS) gene in 234 postmenopausal Danish women treated with N-BPs for 1 and 2 years.

Methods: The polymorphism of the FDPS was analysed in peripheral blood samples from 234 women, who previously completed treatment with N-BPs for 1 or 2 years in different randomised clinical trials. The PCR product was digested with endonuclease and the digestion products were separated on agarose gel depending on their length, revealing the presence or absence of restriction site. All women had baseline measurements of BMD of spine, femur and distal arm. BMD was followed annually. Bone markers were measured at 6, 12, and 24 months.

Results: The genotype distribution followed the Hardy-Weinberger equilibrium. There was no difference in baseline BMD of spine, femur nor arm with the A/C polymorphism. The BMD response to treatment with N-BPs was similar for A/A and A/c genotypes while there was a tendency (borderline significant) for the c/c genotype to have a lower response in BMD in all sites as well as in bone markers after 1 year of treatment. The c/c genotype had a significant (P<0.05) lower response in bone markers after 2 years treatment with N-BPs.

Conclusions: The polymorphism of the FDPS gene didn’t show relation to baseline BMD in Danish postmenopausal women. There was a tendency that c/c genotype had a lower response to treatment wit N-BPs in all skeletal sites examined, confirmed from a significant lower response in bone markers after 2 years of treatment. Even if further studies including larger populations are needed, the prospect of genotyping aiding in the selection of specific treatments for each patient is tempting.