Anti-resorptive agents reduce the size of resorption cavities: a three-dimensional dynamic bone histomorphometry study

Bone. 2013 Nov;57(1):277-83. doi: 10.1016/j.bone.2013.08.018. Epub 2013 Aug 26.

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.

Keywords: Bisphosphonates; Bone histomorphometry; Bone remodeling; Osteoporosis; Ovariectomy; SERMS.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bone Density Conservation Agents / therapeutic use*
  • Bone Remodeling / drug effects*
  • Bone Resorption / drug therapy*
  • Etidronic Acid / analogs & derivatives*
  • Etidronic Acid / therapeutic use
  • Female
  • Ovariectomy
  • Raloxifene Hydrochloride / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley
  • Risedronic Acid

Substances

  • Bone Density Conservation Agents
  • Raloxifene Hydrochloride
  • Risedronic Acid
  • Etidronic Acid