Objective To summarize the recent development on chondroprotective effect of alendronate (ALN) on articular cartilage in osteoarthritis (OA). Methods The related literature was reviewed and the main achievements in vitro/vivo studies in the fields were summarized. Results ALN can improve the metabolic microenvironment of the articular cartilage in OA, inhibit subchondral bone remodeling, so it has potential protective effect on articular cartilage. Conclusion ALN is expected to become a disease-modifying OA drug in future, but OA treatment still lack a uniform basic and clinical evaluation criteria, so it has guiding significance in development and application of ALN to develope a uniform standard and obtain the clinical data.
Objective To investigate the feasibil ity of alendronate (ALN) in treating osteoarthritis (OA) by observing the effects of ALN on interleukin 1β (IL-1β) induced chondrocytes of rat in vitro. Methods The chondrocytes of knee articular surface from 15 SD rats (1-month-old, female or male, weighing 100-150 g) were cultured. The chondrocytes were observed by inverted phase contrast microscope and identified by toluidine blue staining and HE staining. The third passage chondrocytes were divided into 3 groups: the chondrocytes were cultured with DMEM for 5 days in group A, with 10 ng/mL IL-1β for 2 days and with DMEM for 3 days in group B, and with 10 ng/mL IL-1β for 2 days and with 1 × 10-6 mol/L ALN for 3 days in group C. Immunocytochemistry and real-time PCR were performed to determine the expression levels of collagen type II (Col II), matrix metalloproteinase 13 (MMP-13), and β-catenin. Results Toluidine blue staining proved that the cultured cells were chondrocytes. The integrated absorbency (IA) value of Col II in group C (10.290 7 ± 0.499 2) was lower than that in group A (15.377 0 ± 0.571 8) and higher than that in group B (5.463 2 ± 0.450 4), showing significant differences (P lt; 0.05). The IA value of MMP-13 in group C (3.068 6 ± 0.205 6) was significantly lower than that in group B (6.998 1 ± 0.329 7, P lt; 0.05), but there was no significant differenc when compared with group A (2.777 5 ± 0.199 6, P gt; 0.05). The IA value of β-catenin in group C (6.611 7 ± 0.381 8) was lower than that in group B (11.799 9 ± 0.348 7) and higher than that in group A (4.390 3 ± 0.551 9), showing significant differences (P lt; 0.05). The mRNA expression of Col II in group C was significantly higher than those in groups A and B (P lt; 0.05), the mRNA expression of MMP-13 in group C was significantly lower than that in group B (P lt; 0.05) but there was no significant difference when compared with group A (P gt; 0.05). The mRNA expression of β-catenin in group C was significantly lower than that in group B (P lt; 0.05) and higher than that in group A (P lt; 0.05). Conclusion ALN can protect rat chondrocyte from OA induced by IL-1β in vitro possibly by upregulating Col II and inhibiting the expression of MMP-13 and β-catenin in the chondrocytes.
Objective To examine the effects of alendronate (ALN) on IL-1β-stimulated chondrocyte of rabbit in vitro and on cartilage and subchondral bone in rabbit osteoarthritis (OA) induced by anterior cruciate l igament transection (ACLT). Methods The chondrocytes from articular surface of healthy 3-month-old Japanese White rabbits were obtained by the method of enzyme digestion and cultured in vitro. The third generation chondrocytes were assigned into three groups: thechondrocytes were cultured in DMEM medium with 10 ng/mL IL-1β for 2 days, subsequently with (ALN group, group A1) orwithout (IL-1β group, group B1) 1 × 10-6 mol/L ALN for 3 days; the chondrocytes in vacant group (group C1) were cultured in DMEM medium for 5 days. The expression of Col II and MMP-13 were analyzed by immunocytochemical staining observation and real time RT-PCR test. Another twenty-four 3-month-old male Japanese White rabbits were randomized into three groups (n=8 per group). The OA model was made by ACLT in ACLT+ALN group (group A2) and ACLT group (group B2); the joint cave was sutured after exposure of ACL in sham group (group C2). After 4 days, the rabbits of group A2 received the subcutaneous injection of ALN at a dosage of 10 μg/(kg·d) for 8 weeks. Rabbits of group B2 and C2 received equal normal sal ine treatment. After 8 weeks, the rabbits were executed. The macro-pathologic changes of right knee joints were observed, so were the histological changes of femoral condyles. Expression levels of Col II and MMP-13 were detected by immunohistochemical staining. The bone histomorphometry analysis was appl ied to subchondral bone of proximal tibia. Results In vitro, the Col II immunocytochemical staining showed intensely positive staining in group C1, and the intensity of staining was sl ightly decreased in group A1, but the intensity of Col II immunocytochemical staining was extremely lower in the group B1. The integrated absorbance (IA) value for Col II in group A1 was significantly higher than that of group B1 (P lt; 0.05), but there was no significant difference between group A1 and group C1 (P gt; 0.05). Immunocytochemical detection of MMP-13 showed intense staining in group B1, and the intensity of staining was sl ightly decreased in group A1, but no MMP-13 expression was detected in the group C1. The IA value for MMP-13 in group A1 was significantly lower than that of group B1 (P lt; 0.05), but significantly higher than that of group C1 (P lt; 0.05). The real time RT-PCR analysis showed significantly higher mRNA levels of Col II in group A1 than in group B1 (P lt; 0.05), but there was no significant difference between group A1 and group C1 (P gt; 0.05). The MMP-13 mRNA level of the chondrocytes in group A1 was significantly lower than that of group B1 (P lt; 0.05), but significantly higher than that of group C1 (P lt; 0.05). In vivo, the gross appearance of surface of knee joint showed that there was no ulcer in group C2, and there was some ulcers in group A2, but many and all layers ulcers in group B2. Mankin score of group A2 was significantly lowerthan that of group B2 (P lt; 0.05), but significantly higher than that of group C2 (P lt; 0.05). Immunohistochemical staining showed that Col II in articular cartilage was intensely staining in group C2, the intensity of staining was sl ightly decreased in group A2, and the intensity of Col II immunohistochemical staining was extremely low in group B2, but there was no significant difference between group A2 and group C2 (P gt; 0.05..........
Objective To systematically review the efficacy and adverse events of alendronate on bone mineral density and fractures in men with osteoporosis. Methods We electronically searched MEDLINE (1990 to 2005), EMBASE (1990 to 2005), The Cochrane Library (Issue 3, 2005), Controlled Trials Register and The National Research Register, CBM disc, VIP, and CNKI. We also handsearched some related journals. The search was conducted in Nov., 2005. The quality of included randomized controlled trials (RCTs) was evaluated and meta-analysis was conducted by RevMan 4.2.8. Results We identified 7 studies including 817 patients. Sufficient evidence showed that alendronate plus calcium was superior as preventive treatment to calcium in increasing the bone mineral density (SMD 0.59, 95% CI 0.15 to 1.03, P=0.009) of the lumbar spine. The incidence of withdrawal and lost to follow-up due to adverse events of the alendronate plus calcium was lower than that of calcium (RR 0.32, 95% CI 0.11 to 0.87). Two studies showed that alendronate was superior to placebo in increasing the bone mineral density in men with osteoporosis but with no significantly statistical difference in reducing fractures. Two studies showed alendronate was superior to alfacalcidol in increasing the bone mineral density and reducing the vertebral fractures in men with osteoporosis. One study showed alendronate was not superior to calcitonin or alfacalcidol in increasing the bone mineral density in men at high risk of osteoporosis. One study comparing anledronate or parathyroid hormone with combination of these drugs in men with osteoporosis suggested that anledronate wasn’t superior to parathyroid hormone in increasing the bone mineral density, and the combination did not show any difference compared to parathyroid hormone alone. Conclusions Alendronate is more effective in prevention and treatment of men with osteoporosis compared to placebo. Alendronate is more effective than alfacalcidol in increasing bone mineral density and reducingvertebral fractures in men with osteoporosis. Alendronate is not superior to alfacalcidol or calcitonin in increasing the bone mineral density in preventing men osteoporosis. Alendronate compared to combination of parathyroid hormone does not show more effectiveness in increasing the bone mineral density in men with osteoporosis. More RCTs of high quality, especially multiple center trials are needed to generate ber evidence.
ObjectiveTo explore the clinical outcome of alendronate in the treatment of bone marrow edema syndrome of the hip.MethodsA retrospective analysis of 8 cases (10 hips) of bone marrow edema syndrome of the hip treated with alendronate between December 2017 and January 2020 was conducted. Harris score and MRI exam of hip were used to assess the clinical and radiographical outcomes. Clinical cure rate and length of treatment period were used to evaluate whether alendronate was benefitial for the treatment of bone marrow edema syndrome of the hip.ResultsAll the cases were followed up for at least 3 months and got complete clinical data, the mean follow-up period was (5.2±1.2) months. Seven cases (9 hips) in 8 cases (10 hips) had clinical cure, with a clinical cure rate of 90%. The length of treatment period was 1 to 2 months with a mean value of (1.7±0.2) months. The Harris score increased from 57.8±6.3 before treatment to 98.6±1.0 at the last follow-up, and the difference was statistically significant (t=18.299, P<0.001). One case (1 hip) developed osteonecrosis of femoral head at one month after the initiation of alendronate therapy, who received continuous combination therapy of alendronate, calcium and aspirin, and no collapse or expansion of necrosis was found after 12 months follow-up.ConclusionsBone marrow edema syndrome of the hip is not a self-limiting disease completely, some patients maybe develop osteonecrosis of femoral head. Alendronate is benefitial for alleviating clinical symptom, accelerating bone edema disappearance, and shortening the course of disease.