Raloxifene retards cartilage degradation and improves subchondral bone micro-architecture in ovariectomized rats with patella baja-induced - patellofemoral joint osteoarthritis

Abstract

Objective: Abnormal remodeling of subchondral bone (SB) induced by estrogen deficiency has been shown to be involved in osteoarthritis (OA). Raloxifene (RAL) is commonly used to treat postmenopausal osteoporosis (OP). However, little is known about its effects on OA combined with estrogen deficiency. This study was performed to evaluate the efficacy of RAL on patella baja-induced patellofemoral joint OA (PFJOA) in an ovariectomized rat model. Design: Patellar ligament shortening (PLS) and ovariectomy (OVX) were performed simultaneously in 3month-old female SpragueeDawley rats, which were treated with RAL (10 mg/kg/day) or vehicle at 72 h postoperatively for 10 weeks. PFJOA was assessed by immunohistochemistry (IHC), real-time polymerase chain reaction (PCR), tartrate-resistant acid phosphatase (TRAP) staining, enzyme-linked immunosorbent assay (ELISA), micro-computed tomography (mCT), histomorphology and behavioral analyses. Results: X-ray examinations showed that patella baja was successfully established by PLS. Histomorphological analysis revealed that PFJOA was significantly exacerbated by OVX and markedly alleviated by RAL. Moreover, RAL improved cartilage metabolism by decreasing MMP-13, ADAMTS-4, and caspase-3 and increasing Col-II and aggrecan at both the protein and mRNA levels. Furthermore, RAL markedly improved bone mass and SB microarchitecture and reduced osteoclast numbers and the serum osteocalcin and CTX-I levels. Although RAL showed a trend toward reducing pain sensitivity based on mechanical allodynia testing, this result was not statistically significant. Conclusion: These findings demonstrate that RAL treatment retards PFJOA progression in an ovariectomized rat model, suggesting that it may be a potential candidate for amelioration of the progression of PFJOA accompanied by postmenopausal OP.

Treating osteoporotic osteoarthritis, or the art of cutting a balding man's hair

“…Bei et al also demonstrate a remarkable effect of Raloxifene, a second-generation selective estrogen receptor modulator approved for the treatment of postmenopausal osteoporosis, on PFJOA progression through improvement of SB microarchitecture 4 . Raloxifene increased BMD, lowered markers of bone formation and resorption, and reduced the number of osteoclasts.…”

“…The authors also explore the interaction between OA and osteopenia in this experimental model and show that ovariectomy aggravates cartilage matrix degradation and the SB damage evoked by patellar ligament shortening 4 . Thus, this study could be considered another proof-of-concept for the interaction between the two processes and recreates the complexity of real-world OA, i.e., a mechanical disease modifiable by several risk factors.…”

“…In this issue of Osteoarthritis and Cartilage, Bei M-J et al introduce a rat model of patellofemoral OA (PFJOA) that accurately mimics clinical characteristics of patella baja 4 . Intriguingly, PFJOA is one of the least studied subtypes of knee OA, particularly with regard to the response to drugs, despite its common occurrence as an isolated entity.…”

“…Intriguingly, PFJOA is one of the least studied subtypes of knee OA, particularly with regard to the response to drugs, despite its common occurrence as an isolated entity. Patella baja is a well-recognized risk factor for the development of PFJOA 4 ; therefore, animal models for this condition are of considerable interest. The experimental procedure developed by Bei et al comprises a surgical shortening of the patellar ligament, which closely reflects human PFJOA and causes severe damage to cartilage and SB.…”

“…The findings from Bei et al indicate that the deterioration of the SB microstructure could be due to its increased turnover 4 . In consonance, a study performed in human tibiae showed a reduction in the elastic module of the trabecular SB in early OA compared with normal joints, despite the relative increase in bone volume 9 .…”