title: The effect of risedronate on bone mineralization as measured by micro-computed tomography with synchrotron radiation: correlation to histomorphometric indices of turnover.
abstract: The primary goal of our study was to determine changes in bone mineralization in postmenopausal osteoporotic women treated for 3 years with risedronate or placebo. A secondary goal was to determine the relationship between mineralization and indices of bone turnover measured on the same biopsies. The degree of mineralization was measured by micro-computed tomography using Synchrotron radiation (Synchrotron microCT) in the trabecular bone of paired transiliac biopsies taken at baseline and after 3 years of treatment from patients receiving risedronate 5 mg daily (n=11) or placebo (n=8). In the risedronate-treated patients, the average mineralization (Avg-MIN) and peak mineralization (Peak-MIN) at 3 years were significantly increased from baseline by 4.7% (P<0.0001) and 5.4% (P=0.0003), respectively and showed significant negative correlation to turnover indices. In the placebo-treated patients, the increases in Avg-MIN (2.0%) and Peak-MIN (1.6%) were not significantly different from baseline and correlation to turnover indices was weaker. Risedronate significantly reduced the ratio of low- to high-mineralized bone fractions estimated by volume (BMR-V) and surface area (BMR-S) by 70.1% and 54.1%, respectively from baseline. These changes were consistent with the significant reduction of turnover from baseline assessed by reductions in mineralizing surface, MS/BS (-72.8%); activation frequency, Ac.F (-60.4%); and bone formation rate, BFR-BV (-63.6%) in the same biopsies in the risedronate-treated patients. Comparing the pair-wise changes from baseline, risedronate significantly reduced the low-mineralized bone fraction in comparison to placebo, as indicated by a larger reduction of BMR-V (P=0.015) and BMR-S (P=0.035). In the risedronate group, BMR-V and BMR-S showed significant positive correlation to MS/BS (R2: 0.83 and 0.92, respectively). The correlations to Ac.F and BFR-BV were also significant, with BMR-S showing a strong relation (R2: 0.77 and 0.79, respectively). The data suggest that BMR-V and BMR-S are markers of turnover of trabecular bone and may be used to assess treatment effect on turnover in bone biopsies. The results demonstrate that the reduction of turnover by risedronate increased the degree of mineralization and reduced the ratio of low- to high-mineralized bone fractions which may increase bone's resistance to fracture.
authors.affiliation: Procter & Gamble Pharmaceuticals, Inc., Health Care Research Center, 8700 Mason Montgomery Road, Mason, OH 45040, USA. borah.b@pg.com
authors.forename: Babul
authors.initials: B
authors.lastname: Borah
authors.forename: Erik L
authors.initials: EL
authors.lastname: Ritman
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Dufresne
authors.forename: Steven M
authors.initials: SM
authors.lastname: Jorgensen
authors.forename: Sheng
authors.initials: S
authors.lastname: Liu
authors.forename: Jarek
authors.initials: J
authors.lastname: Sacha
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Phipps
authors.forename: Russell T
authors.initials: RT
authors.lastname: Turner
mesh_terms: D000368:Aged; D001706:Biopsy; D015519:Bone Density; D050071:Bone Density Conservation Agents / Q000494:pharmacology / Q000627:therapeutic use; D002113:Calcification, Physiologic / Q000187:drug effects*; D003627:Data Interpretation, Statistical; D012968:Etidronic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007085:Ilium / Q000187:drug effects / Q000473:pathology; D008159:Lumbar Vertebrae / Q000737:chemistry; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy* / Q000473:pathology; D000068296:Risedronic Acid; D017356:Synchrotrons; D013997:Time Factors; D014057:Tomography, X-Ray Computed / Q000295:instrumentation / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D050071:Bone Density Conservation Agents; D000068296:Risedronic Acid; D012968:Etidronic Acid