Abstract
IntroductionOsteoporosis (OP) increases cartilage damage in a combined rabbit model of OP and osteoarthritis (OA). Accordingly, we assessed whether microstructure impairment at subchondral bone aggravates cartilage damage in this experimental model.MethodsOP was induced in 20 female rabbits, by ovariectomy and intramuscular injections of methylprednisolone hemisuccinate for four weeks. Ten healthy animals were used as controls. At week 7, OA was surgically induced in left knees of all rabbits. At 22 weeks, after sacrifice, microstructure parameters were assessed by micro-computed tomography, and osteoprotegerin (OPG), receptor activator of nuclear factor-κB ligand (RANKL), alkaline phosphatase (ALP) and metalloproteinase 9 (MMP9) protein expressions were evaluated by Western Blot at subchondral bone. In addition, cartilage damage was estimated using the histopathological Mankin score. Mann-Whitney and Spearman statistical tests were performed as appropriate, using SPSS software v 11.0. Significant difference was established at P < 0.05.ResultsSubchondral bone area/tissue area, trabecular thickness and polar moment of inertia were diminished in OPOA knees compared with control or OA knees (P < 0.05). A decrease of plate thickness, ALP expression and OPG/RANKL ratio as well as an increased fractal dimension and MMP9 expression occurred at subchondral bone of OA, OP and OPOA knees vs. controls (P < 0.05). In addition, the severity of cartilage damage was increased in OPOA knees vs. controls (P < 0.05). Remarkably, good correlations were observed between structural and remodelling parameters at subchondral bone, and furthermore, between subchondral structural parameters and cartilage Mankin score.ConclusionsMicrostructure impairment at subchondral bone associated with an increased remodelling aggravated cartilage damage in OA rabbits with previous OP. Our results suggest that an increased subchondral bone resorption may account for the exacerbation of cartilage damage when early OA and OP coexist simultaneously in same individuals.
Highlights
Osteoporosis (OP) increases cartilage damage in a combined rabbit model of OP and osteoarthritis (OA)
Tb.Th in groups affected by OP or both conditions showed a downward trend with respect to healthy controls, only the combined OPOA group showed a significant decrease (P < 0.05)
Tb.Sp was increased in OP and OPOA knees with respect to healthy group, yet only OPOA significatively increased it (P < 0.05)
Summary
Osteoporosis (OP) increases cartilage damage in a combined rabbit model of OP and osteoarthritis (OA). Osteoporosis (OP) is a skeletal disorder characterized by a compromised bone strength which substantially increases the by design deficiencies, no radiological confirmation for OA diagnosis, bad patient positioning at X-ray assessment and/or the presence of osteophytes [8,9] In this context, animal models experiencing both pathologies without interference from other factors have become valuable tools. Cartilage damage is frequently associated with thickening of the subchondral plate and osteophytosis during knee OA in humans [14,15,16,18] and animals [19] Besides this hypertrophic OA, some authors contemplate another variant, the atrophic form, which is characterized by the lack of osteophytes and loss of subchondral bone volume in OA patients with hip and knee compromise [20,21,22,23]. The impact of these subchondral bone changes in OA is still debated, partially due to heterogeneity of the disease [30]
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