In vivo microfocal computed tomography and micro-magnetic resonance imaging evaluation of antiresorptive and antiinflammatory drugs as preventive treatments of osteoarthritis in the rat.
OBJECTIVE
To determine whether treatment with an antiresorptive drug in combination with an antiinflammatory drug reduces periarticular bone and soft tissue adaptations associated with the progression of posttraumatic secondary osteoarthritis (OA).


METHODS
We used in vivo microfocal computed tomography (micro-CT) to map bony adaptations and in vivo micro-magnetic resonance imaging (micro-MRI) to examine joint inflammation in a rat model of surgically induced OA secondary to knee triad injury. We examined the arthroprotective effects of the bisphosphonates alendronate and risedronate and the nonsteroidal antiinflammatory drug (NSAID) meloxicam.


RESULTS
Micro-CT revealed reduced levels of periarticular trabecular bone loss in animals with knee triad injury treated with the bisphosphonate drugs alendronate or risedronate, or the NSAID meloxicam, compared with untreated animals. Alendronate treatment reduced bony osteophyte development. While risedronate as a monotherapy did not positively impact osteophytogenesis, combination therapy with risedronate and meloxicam reduced osteophyte severity somewhat. Micro-MRI revealed an increased, diffuse water signal in the epiphyses of untreated rats with knee triad injury 8 weeks after surgery, suggestive of a bone marrow lesion-like stimulus. In contrast, meloxicam-treated rats showed a significant reduction in fluid signal compared with both bisphosphonate-treated groups 8 weeks after surgery. Histologic analysis qualitatively confirmed the chondroprotective effect of both bisphosphonate treatments, showing fewer degradative changes compared with untreated rats with knee triad injury.


CONCLUSIONS
Our findings indicate that select combinations of bisphosphonate and NSAID drug therapy in the early stages of secondary OA preserve trabecular bone mass and reduce the impact of osteophytic bony adaptations and bone marrow lesion-like stimulus. Bisphosphonate and NSAID therapy may be an effective disease-modifying drug regimen if administered early after the initial injury.
Pharmacy and Pharmaceutical Sciences, University of Alberta, Dentistry/Pharmacy Centre, Edmonton, Alberta, Canada. mdoschak@ualberta.ca
Michael D
MD
Jones
Charles W
CW
Tran
Guang
G
Li
Walter P
WP
Maksymowych
Ronald F
RF
Zernicke
Michael R
MR
Doschak
D019386:Alendronate / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D004838:Epiphyses / Q000737:chemistry / Q000187:drug effects; D012968:Etidronic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D005269:Femur / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods; D000077239:Meloxicam; D020370:Osteoarthritis, Knee / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D054850:Osteophyte / Q000188:drug therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068296:Risedronic Acid; D013264:Stifle / Q000187:drug effects / Q000473:pathology / Q000601:surgery; D013843:Thiazines / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*; D013977:Tibia / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D014057:Tomography, X-Ray Computed / Q000379:methods; D014867:Water / Q000737:chemistry
D000894:Anti-Inflammatory Agents, Non-Steroidal; D050071:Bone Density Conservation Agents; D013843:Thiazines; D013844:Thiazoles; D014867:Water; D000068296:Risedronic Acid; D012968:Etidronic Acid; D000077239:Meloxicam; D019386:Alendronate