No effect of risedronate on articular cartilage damage in the Dunkin Hartley guinea pig model of osteoarthritis

Scand J Rheumatol. 2013;42(5):408-16. doi: 10.3109/03009742.2013.774046. Epub 2013 Mar 26.


Objectives: To investigate whether treatment with a bisphosphonate would influence the subchondral bone plate stiffness and the development of cartilage damage in Dunkin Hartley guinea pigs, which develop osteoarthritis (OA) spontaneously.

Method: Fifty-six 3-month-old male Dunkin Hartley guinea pigs were randomized into a baseline group and six groups receiving either the bisphosphonate risedronate (30 µg/kg) or vehicle five times a week for 6, 12, or 24 weeks. The medial condyle of the right stifle joint was investigated by histology, using the Osteoarthritis Research Society International (OARSI) score, along with static and dynamic histomorphometry. The subchondral bone plate of the left tibia was tested mechanically with indentation testing. Degradation products of C-terminal telopeptides of type II collagen (CTX-II) were measured in serum.

Results: The OARSI score did not differ between risedronate-treated and control animals at any time point. The fraction of bone surfaces covered with osteoclasts (Oc.S/BS) was significantly suppressed in risedronate-treated animals at all time points, as were the fractions of mineralizing surfaces (MS/BS) and osteoid-covered surfaces (OS/BS), and also serum CTX-II. This was accompanied by a significant increase in the epiphyseal content of calcified tissue and in the thickness of the subchondral bone plate. However, this did not result in a stiffer subchondral bone at any time point.

Discussion: The risedronate treatment inhibited osteoclastic resorption of calcified cartilage in the primary spongiosa under the epiphyseal growth plate, explaining the risedronate-mediated decrease in CTX-II. Moreover, the serum CTX-II level was not related to the OA-induced articular cartilage degradation seen in this model.

Conclusions: Risedronate did not influence the OARSI score and subchondral plate stiffness, but decreased serum CTX-II in Dunkin Hartley guinea pigs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Density Conservation Agents / pharmacology*
  • Bone Resorption / drug therapy
  • Bone Resorption / pathology
  • Calcification, Physiologic / drug effects
  • Cartilage, Articular / drug effects*
  • Cartilage, Articular / metabolism
  • Collagen Type II / blood
  • Disease Models, Animal
  • Elasticity / drug effects
  • Epiphyses / drug effects
  • Epiphyses / pathology
  • Etidronic Acid / analogs & derivatives*
  • Etidronic Acid / pharmacology
  • Growth Plate / drug effects
  • Growth Plate / pathology
  • Guinea Pigs
  • Male
  • Osteoarthritis / blood
  • Osteoarthritis / drug therapy*
  • Osteoarthritis / pathology
  • Osteoclasts / drug effects
  • Osteoclasts / pathology
  • Peptide Fragments / blood
  • Risedronic Acid
  • Stifle / drug effects
  • Stifle / metabolism
  • Stifle / pathology
  • Tibia / drug effects
  • Tibia / pathology


  • Bone Density Conservation Agents
  • Collagen Type II
  • Peptide Fragments
  • collagen II C-telopeptide
  • Risedronic Acid
  • Etidronic Acid