Subchondral bone microstructural damage by increased remodelling aggravates experimental osteoarthritis preceded by osteoporosis

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.

The Association between Osteoarthritis and Osteoporosis: In Bad Company?

“…However, both of them not often present together in same patients [9]. Particularly, several works have demonstrated the existence of an inverse association between them in the hip and knee joints [8].…”

“…Like osteoporosis, osteoarthritis is a widespread degenerative disease that frequently causes disability in aged population [8]. This disease impacts on all anatomical joint structures [9]. It is characterized by joint pain and stiffness, cartilage degeneration, thickening of subchondral bone, loss of function and reduction in mobility [2,10].…”

“…Despite of this fact that an elevated amount of body mass could decrease the risk of osteoporosis [14], Hart et al [13] have reported a small raise in bone mineral density in middle-aged women with osteophyte osteoarthritis. A number of studies by emphasis on this point that osteoporosis is a skeletal disease accentuated an inverse relationship between these two diseases [9]. Furthermore, most of the studies by consideration of three main risk factors for osteoporosis, including physical inactivity, decrease of body weight and oestrogen deficiency, have mentioned a negative relationship with osteoarthritis.…”

Osteoporosis y artrosis: ¿dos enfermedades mutuamente excluyentes o dos entidades relacionadas?

“…For their part, Bellido et al 52 , using a similar model, arrived at the conclusion that the increase in resorption which is observed in the subchondral bone of the animals with osteoporosis would alter its quality, which would aggravate the damage in the cartilage of the joint.…”

Characterization of skeletal alterations in a model of prematurely aging mice

“…After crushing the tibia with a mortar in liquid nitrogen, total protein was extracted with 50 mM Tris-HCl, pH 7.5, 150 mM NaCl, 2 mM EDTA, 2 mM EGTA, 0.2% Triton X-100, 0.3% NP-40, 1 mM dithiothreitol, and a protease inhibitor cocktail (Sigma-Aldrich, St. Louis, MO, USA) (Bellido et al 2011). Protein concentration was measured by BCA protein assay (Pierce, Rockford, IL, USA).…”