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

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 3-month-old female Sprague-Dawley 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 (µCT), 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.

Parathyroid hormone(1-34) exhibits more comprehensive effects than celecoxib in cartilage metabolism and maintaining subchondral bone micro-architecture in meniscectomized guinea pigs.

OBJECTIVE: To evaluate the effects of PTH(1-34) on cartilage, subchondral bone mass and structure in medial meniscectomized guinea pigs and compare them to those of celecoxib (CLX). METHOD: Forty-eight 3-month-old male Hartley albino guinea pigs received either sham or medial meniscectomy (MNX) operations. One week after the procedure, meniscectomized animals began 12 weeks of treatment by oral administration of CLX (20 mg/kg, daily), subcutaneous injection of PTH (1-34) (24 µg/kg, 5 days/week), or normal saline for MNX group. All animals were euthanized 12 weeks later, cartilage degeneration and subchondral bone micro-architecture was analyzed. RESULTS: OARSI scores indicated cartilage degeneration was partially inhibited by either CLX or PTH(1-34). Cartilage was significantly thicker in PTH(1-34)-treated animals than in CLX-treated animals. Both CLX and PTH(1-34) treatment were associated with lower ADAMTS-4 and periostin expression than MNX. MMP-13 expression in PTH(1-34) group was significantly lower than that in CLX group. However, AGG expression and the ratio of Col-II/MMP-13 expression in PTH(1-34) group were significantly higher than in the CLX group. Micro-CT analysis showed BMD, BV/TV, and Tb.Th levels to be significantly lower in the MNX group and CLX groups than in the sham group, but these parameters were significantly higher in the PTH(1-34) group than in either the MNX group or CLX group. CONCLUSIONS: Both CLX and PTH(1-34) exhibits protective effects on cartilage degeneration in meniscectomized guinea pigs. However, PTH(1-34) exhibited superior performance to CLX not only in metabolism of cartilage tissue but also in maintenance of subchondral bone micro-architecture.