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

Abstract

To evaluate the effects of alendronate (ALN) on the subchondral bone quality and cartilage degeneration in the early phase of experimental model of osteoarthritis after anterior cruciate ligament transaction (ACLT). Thirty male adult healthy Japanese white rabbits after right ACLT or sham operation were divided into three groups (n = 10 per group): Sham; ACLT + ALN [after ACLT, the rabbits were treated with ALN daily starting from 4 days after surgery (10 μg/kg/d subcutaneously)]; and ACLT + NS group (after ACLT, the rabbits were injected saline as a placebo). At 60 days postsurgery, specimens from the affected knees were harvested. Histological analysis (HE and Safranin-O staining) as well as Mankin score were carried out to assess the cartilage degradation. BMP-2 and MMP-13 immunohistochemistry were also performed to demonstrate the alterations of cartilage molecular metabolism. Subchondral bone quality was evaluated by bone mineral density (BMD) and microstructure histomorphometry assay. For bone mineral density evaluation, 1/4 distal femurs, medial and lateral regions of femoral condylus were scanned with dual X-ray absorptiometry to assess the subchondral bone mass. Giemsa, von Kossa stain, and fluorescence technique for undecalcified bone section were carried out to examine the morphometry of the subchondral trabecular bone and subchondral plate. Histological and Mankin score analyses displayed that ALN treatment markedly reduced cartilage lesions and delayed the cartilage degeneration in OA joints. Immunohistochemistry assay further indicated that this cartilage-protective role of ALN was associated with elevating BMP-2 while inhibiting MMP-13 expression. BMD assessment demonstrated that ALN treatment significantly suppressed subchondral bone resorption. The results from histomorphometry assay of subchondral bone revealed that ALN treatment markedly increased the percent trabecular area (BV/TV), trabecular thickness (Tb.Th), and trabecular number (Tb.N). Moreover, both thickness and the porosity of the subchondral plate in ACLT + ALN group presented significantly higher than that in ACLT + NS group, while no significant difference was found between ACLT + ALN and Sham group. ALN plays an important role in cartilage protection in OA joints that is associated with the improvement of subchondral bone quality through reduction of subchondral bone resorption. ALN could be potentially used as a disease-modifying strategy to limit the progression of OA.

Comparison of various SYSADOA for the osteoarthritis treatment: an experimental study in rabbits

“…Early in the pathogenesis of OA, prior to the development of sclerosis, there is a period of periarticular osteopenia [60] and a significant reduction in bone mineral density was reported in patients with mild OA when it was compared to healthy ones [61]. These effects on bone were expected in the animals treated with risedronate, a potent aminobisphophonate, which showed its effectiveness in conserving the periarticular bone [62]. In the same way, high molecular weight hyaluronic acid was shown to promote human osteoblast bone matrix protein expression in vitro [63] and bone formation in vivo [64] as well as to reduce bone resorption, but no study on this effect of diacerein on bones, to the best of the authors’ knowledge, has been published yet.…”

Effect of alendronate on post-traumatic osteoarthritis induced by anterior cruciate ligament rupture in mice

“…ALN has shown the ability to retain subchondral and periarticular bone following initiation of OA in multiple animal models [10-16]. Importantly, ALN has also exhibited chondroprotective effects [10,12,13,16], and has exhibited the ability to reduce the formation of osteophytes [10,12,15]. However, there is some inconsistency in the reported benefits of ALN for preventing OA; some studies have found no chondroprotective effect in animals treated with ALN [14], or even a negative effect on articular cartilage [11].…”

“…Another notable shortcoming in the prior studies is the lack of a non-invasive method of joint injury to initiate PTOA. Prior studies typically used invasive surgical means to initiate PTOA, including anterior cruciate ligament (ACL) transection [10,12,13,16] or medial meniscectomy [12,15]. However, these methods may complicate the outcomes of the study due to unintended effects from the invasive surgical procedures.…”

An OA phenotype may obtain major benefit from bone-acting agents

“…These positive alendronate effects were associated to an increase of OPG/RANKL ratio in both subchondral bone and cartilage and blocking of MMP-13 and MMP-9 expression in articular cartilage and the interface between articular cartilage and subchondral bone [21]. Likewise, cartilage protection associated with the improvement of subchondral bone quality through reduction of subchondral bone resorption was described in the early phase of the ACLT-induced OA in rabbits following alendronate administration [22]. In this experimental model, alendronate suppressed the expression of MMP-13, IL-1β, type-X collagen, vascular endothelial growth factor, and receptor activator of nuclear factor-κB ligand in OA cartilage [23].…”