title: Evidence that treatment with risedronate in women with postmenopausal osteoporosis affects bone mineralization and bone volume.
abstract: Risedronate is used in osteoporosis treatment. Postmenopausal women enrolled in the Vertebral Efficacy with Risedronate Therapy trial received either risedronate (5 mg/day) or placebo for 3 years. Subjects received calcium and vitamin D supplementation if deficient at baseline. Lumbar spine bone mineral density (BMD) was measured at baseline and at 3 years. Quantitative back-scattered electron imaging (qBEI) was performed on paired iliac crest biopsies (risedronate, n = 18; placebo, n = 13) before and after treatment, and the mineral volume fraction in the trabecular bone was calculated. Combining dual-energy X-ray absorptiometric values with the mineral volume fraction for the same patients allowed us to calculate the relative change in trabecular bone volume with treatment. This showed that the effect on BMD was likely to be due partly to changes in matrix mineralization and partly due to changes in bone volume. After treatment, trabecular bone volume in the lumbar spine tended to increase in the risedronate group (+2.4%, nonsignificant) but there was a significant decrease (-3.7%, P < 0.05) in the placebo group. Calcium supplementation with adequate levels of vitamin D led to an approximately 3.3% increase in mineral content in the bone material independently of risedronate treatment. This increase was larger in patients with lower matrix mineralization at baseline and likely resulted from correction of calcium/vitamin D deficiency as well as from reduced bone remodeling. Combining BMD and bone mineralization density distribution data show that in postmenopausal osteoporosis 3-year treatment with risedronate preserves or may increase trabecular bone volume, unlike placebo. This analysis also allows, for the first time, separation of the contributions of bone volume and matrix mineralization to the increase in BMD.
authors.affiliation: Department of Biomaterials, Max Planck Institute of Colloids and Interfaces, Research Campus Golm, D-14424, Potsdam, Germany. fratzl@mpikg.mpg.de
authors.forename: Peter
authors.initials: P
authors.lastname: Fratzl
authors.forename: Paul
authors.initials: P
authors.lastname: Roschger
authors.forename: Nadja
authors.initials: N
authors.lastname: Fratzl-Zelman
authors.forename: Eleftherios P
authors.initials: EP
authors.lastname: Paschalis
authors.forename: Roger
authors.initials: R
authors.lastname: Phipps
authors.forename: Klaus
authors.initials: K
authors.lastname: Klaushofer
mesh_terms: D015502:Absorptiometry, Photon; D000368:Aged; D001706:Biopsy; D050071:Bone Density Conservation Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016723:Bone Remodeling / Q000187:drug effects / Q000502:physiology; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D002113:Calcification, Physiologic / Q000187:drug effects* / Q000502:physiology; D002118:Calcium / Q000172:deficiency / Q000378:metabolism / Q000494:pharmacology; D012968:Etidronic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007085:Ilium / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D008159:Lumbar Vertebrae / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D000068296:Risedronic Acid; D016896:Treatment Outcome; D014807:Vitamin D / Q000378:metabolism / Q000494:pharmacology; D014808:Vitamin D Deficiency / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology
chemical_list: D050071:Bone Density Conservation Agents; D014807:Vitamin D; D000068296:Risedronic Acid; D012968:Etidronic Acid; D002118:Calcium