Calcified Tissue International

, Volume 79, Issue 4, pp 255–261 | Cite as

Antiremodeling Agents Influence Osteoblast Activity Differently in Modeling and Remodeling Sites of Canine Rib

  • M. R. Allen
  • H. Follet
  • M. Khurana
  • M. Sato
  • D. B. Burr


Antiremodeling agents reduce bone loss in part through direct actions on osteoclasts. Their effects on osteoblasts and bone formation activity are less clear and may differ at sites undergoing modeling vs. remodeling. Skeletally mature intact beagles, 1–2 years old at the start of the study, were treated daily with clinically relevant doses of alendronate (0.10 or 0.20 mg/kg), risedronate (0.05 or 0.10 mg/kg), raloxifene (0.50 mg/kg), or vehicle (1 mL/kg). Dynamic bone formation parameters were histologically assessed on periosteal, endocortical/trabecular, and intracortical bone envelopes of the rib. Raloxifene significantly increased periosteal surface mineral apposition rate (MAR), a measure of osteoblast activity, compared to all other treatments (+108 to +175%, P < 0.02), while having no significant effect on MAR at either the endocortical/trabecular or intracortical envelope. Alendronate (both 0.10 and 0.20 doses) and risedronate (only the 0.10 dose) significantly (P ≤ 0.05) suppressed MAR on the endocortical/trabecular envelope, while none of the bisphosphonate doses significantly altered MAR at either the periosteal or intracortical envelopes compared to vehicle. Based on these results, we conclude that (1) at clinically relevant doses the two classes of antiremodeling agents, bisphosphonates and selective estrogen receptor modulators, exert differential effects on osteoblast activity in the canine rib and (2) this effect depends on whether modeling or remodeling is the predominant mechanism of bone formation.


Bisphosphonate Raloxifene Alendronate Risedronate Periosteal 



The authors thank Dr. Keith Condon, Diana Jacob, and Lauren Waugh for histological preparation. This work was supported by National Institutes of Health grants R01-AR047838 and T32-AR007581 and research grants from The Alliance for Better Bone Health (Procter & Gamble Pharmaceuticals and Sanofi-Aventis) and Lilly Research Laboratories. Merck kindly provided the alendronate. This investigation utilized an animal facility constructed with support from Research Facilities Improvement Program grant C06 RR10601-01 from the National Center for Research Resources, National Institutes of Health.


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Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • M. R. Allen
    • 1
  • H. Follet
    • 1
  • M. Khurana
    • 1
  • M. Sato
    • 1
    • 3
  • D. B. Burr
    • 1
    • 2
    • 4
  1. 1.Department of Anatomy and Cell BiologyIndiana University School of MedicineIndianapolisUSA
  2. 2.Department of Orthopedic SurgeryIndiana University School of MedicineIndianapolisUSA
  3. 3.Lilly Research LaboratoriesIndianapolisUSA
  4. 4.Department of Biomedical EngineeringIndiana University-Purdue University at IndianapolisIndianapolisUSA

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