Effectiveness of alendronate treatment in postmenopausal women with osteoporosis: relationship with BsmI vitamin D receptor genotypes.

OBJECTIVE: To assess whether there is a relationship between the effectiveness of alendronate treatment in postmenopausal women with osteoporosis and BsmI vitamin D receptor (VDR) genotypes. DESIGN: Prospective baseline-controlled clinical trial. PATIENTS: Sixty-eight Italian osteoporotic women were enrolled and treated with alendronate at a dose of 10 mg/day for 12 months. MEASUREMENTS: At entry and after treatment, lumbar bone mineral density (BMD) and serum osteocalcin (OC) and urinary deoxypyridinoline/creatinine ratio (DPD-Cr) levels were evaluated. DNA was extracted from blood and analysed for the BsmI polymorphism of the VDR gene. RESULTS: The mean percentage (% +/- SD) change from baseline in lumbar BMD was significantly higher (P < 0.01) in bb than in BB BsmI VDR genotypes (7.92 +/- 4.31 vs. 3.40 +/- 1.81). No significant difference in lumbar BMD was observed in Bb VDR patients (6.01 +/- 3.89) in comparison with other groups. The mean percentage of change in serum OC and urinary DPD-Cr levels was significantly (P < 0.01) lower in individuals with bb than in those with BB BsmI VDR genotypes (-14.34 +/- 2.87 vs.-10.39 +/- 1.43 and -9.61 +/- 5.56 vs.-4.61 +/- 2.31). No significant difference in serum OC and urinary DPD-Cr levels was observed in Bb VDR patients (-12.31 +/- 2.11 and -6.52 +/- 2.65) in comparison with other groups. CONCLUSION: The different BsmI vitamin D receptor genotypes modify the pharmacological response to alendronate treatment in postmenopausal women with osteoporosis.

Raloxifene administration in post-menopausal women with osteoporosis: effect of different BsmI vitamin D receptor genotypes.

BACKGROUND: The vitamin D receptor (VDR) gene polymorphism has been considered a factor influencing the effectiveness of the anti-osteoporotic treatments. The aim of this study was to correlate the effectiveness of raloxifene treatment in post-menopausal women with osteoporosis to BsmI VDR genotypes. METHODS: Between January and August 2000, 75 Italian osteoporotic women were enrolled and treated with raloxifene at a dose of 60 mg/day. At entry and after 1 year of treatment, lumbar bone mineral density (BMD), serum osteocalcin (OC) and urinary creatinine-corrected free deoxypyridinoline (DPD) levels were evaluated. DNA was extracted from blood and analysed with restriction endonuclease BsmI for VDR gene. RESULTS: After treatment, a significant increase in lumbar BMD and a significant reduction in serum OC and urinary DPD levels were observed. The percentage of change (mean +/- SD) in lumbar BMD, and in serum OC and urinary DPD levels was significantly different in homozygous bb (1.58 +/- 0.80, -5.15 +/- 2.36 and -7.71 +/- 2.89 for BMD, OC and DPD respectively) in comparison with BB (4.13 +/- 2.26, -13.59 +/- 4.68 and -15.16 +/- 4.65 for BMD, OC and DPD respectively) BsmI VDR genotypes. Heterozygous Bb VDR patients showed an intermediate percentage (mean +/- SD) of BMD, serum OC and urinary DPD change (2.49 +/- 1.54, -8.69 +/- 2.60 and -10.52 +/- 2.56 for BMD, OC and DPD respectively) not significantly different in comparison with homozygous BB and bb. CONCLUSIONS: In post-menopausal women with osteoporosis the effectiveness of raloxifene treatment on bone metabolism seems to be controlled by different BsmI VDR genotypes.