title: Anti-resorptive agents reduce the size of resorption cavities: a three-dimensional dynamic bone histomorphometry study.
abstract: Alterations in resorption cavities and bone remodeling events during anti-resorptive treatment are believed to contribute to reductions in fracture risk. Here, we examine changes in the size of individual remodeling events associated with treatment with a selective estrogen receptor modulator (raloxifene) or a bisphosphonate (risedronate). Adult female rats (6months of age) were submitted to ovariectomy (n=17) or sham surgery (SHAM, n=5). One month after surgery, the ovariectomized animals were separated into three groups: untreated (OVX, n=5), raloxifene treated (OVX+Ral, n=6) and risedronate treated (OVX+Ris, n=6). At 10months of age, the lumbar vertebrae were submitted to three-dimensional dynamic bone histomorphometry to examine the size (depth, breadth and volume) of individual resorption cavities and formation events. Maximum resorption cavity depth did not differ between the SHAM (23.66±1.87μm, mean±SD) and OVX (22.88±3.69μm) groups but was smaller in the OVX+Ral (14.96±2.30μm) and OVX+Ris (14.94±2.70μm) groups (p<0.01). Anti-resorptive treatment was associated with reductions in the surface area of resorption cavities and the volume occupied by each resorption cavity (p<0.01 each). The surface area and volume of individual formation events (double-labeled events) in the OVX+Ris group were reduced as compared to other groups (p<0.02). Raloxifene treated animals showed similar amounts of bone remodeling (ES/BS and dLS/BS) compared to sham-operated controls but smaller cavity size (depth, breadth and volume). The current study shows that anti-resorptive agents influence the size of resorption cavities and individual remodeling events and that the effect of anti-resorptives on individual remodeling events may not always be directly related to the degree of suppression of bone remodeling.
authors.affiliation: Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, NY, USA; Department of Biomedical Engineering, Cornell University, Ithaca, NY, USA.
authors.forename: J B
authors.initials: JB
authors.lastname: Matheny
authors.forename: C R
authors.initials: CR
authors.lastname: Slyfield
authors.forename: E V
authors.initials: EV
authors.lastname: Tkachenko
authors.forename: I
authors.initials: I
authors.lastname: Lin
authors.forename: K M
authors.initials: KM
authors.lastname: Ehlert
authors.forename: R E
authors.initials: RE
authors.lastname: Tomlinson
authors.forename: D L
authors.initials: DL
authors.lastname: Wilson
authors.forename: C J
authors.initials: CJ
authors.lastname: Hernandez
mesh_terms: D000818:Animals; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D016723:Bone Remodeling / Q000187:drug effects*; D001862:Bone Resorption / Q000188:drug therapy*; D012968:Etidronic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D010052:Ovariectomy; D020849:Raloxifene Hydrochloride / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068296:Risedronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D020849:Raloxifene Hydrochloride; D000068296:Risedronic Acid; D012968:Etidronic Acid
keywords: Bisphosphonates; Bone histomorphometry; Bone remodeling; Osteoporosis; Ovariectomy; SERMS