In vivo microfocal computed tomography and micro–magnetic resonance imaging evaluation of antiresorptive and antiinflammatory drugs as preventive treatments of osteoarthritis in the rat

Abstract

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, meloxicamtreated 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.Conclusion. 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.

Enhancement of subchondral bone quality by alendronate administration for the reduction of cartilage degeneration in the early phase of experimental osteoarthritis

“…But more and more researches have demonstrated that increasing subchondral bone mass was beneficial to the reduction of cartilage degradation, such as ALN administration in OA, hip osteonecrosis, or other diseases in different models [9,[35][36][37]. The present study was focused on the examination of ALN effects on subchondral bone quality to further evaluate the relationship between subchondral bone and cartilage degeneration in OA progress.…”

Sustained intra-cartilage delivery of low dose dexamethasone using a cationic carrier for treatment of post traumatic osteoarthritis

“…This was used to create 3D models of osteophytic bone for quantitative volumetric assessment. Osteophyte severity from 3D μCT models of the tibia for each knee was graded on a 4 point scale by three investigators (RDLV, TJF and AGB) in a blinded fashion, where 0 = no observed osteophyte, 1 = local and less severe osteophytes, 2 = widespread, but moderately severe osteophytes and 3 = widespread and very severe osteophytes (Jones et al , 2010; Shirai et al , 2011). …”

(−)-Epigallocatechin-3-gallate improves bone microarchitecture in ovariectomized rats

“…The coefficients of variation were 2.0% (BV/TV), 1.1% (TbN), 0.66% (TbTh), and 1.30% (TbSp) for morphometric parameters. 38 Cortical bone volume fraction (BV/TV; %) and cortical thickness were also calculated using the Skyscan software CTan.…”