Department of Trauma Surgery, Orthopaedics and Plastic Surgery, University Medical Center Goettingen, Goettingen, Germany.
Kogod Center on Aging and Division of Endocrinology, Mayo Clinic, Rochester, MN, United States.
Front Endocrinol (Lausanne). 2021 Jul 20;12:706504. doi: 10.3389/fendo.2021.706504. eCollection 2021.
In previous studies, we reported the beneficial impact of two lipoxygenase-inhibitors, Baicalein and Zileuton, on osteoporotic bone in a postmenopausal rat model. Whereas subcutaneous Baicalein predominantly improved cortical bone, Zileuton enhanced vertebral and femoral trabecular bone. In this study, we aimed to reveal whether the oral administration of Baicalein caused similar effects on bone and whether a combined administration of Baicalein and Zileuton could act synergistically to ameliorate the formerly reported effects in the musculoskeletal system.
We treated ovariectomized (OVX) female Sprague-Dawley rats either with Baicalein (10mg/kg BW), Zileuton (10mg/kg BW) or a combination of both (each 10mg/kg BW) for 13 weeks and compared with untreated OVX and NON-OVX groups (n=12-16 rats per group). Lumbar vertebral bodies and femora were analyzed. Tibiae were osteotomized, plate-stabilized (at week 8 after OVX) and likewise analyzed by biomechanical, histological, micro-computed tomographical and ashing tests. The skeletal muscle structure was analyzed.
Oral administration of Baicalein did not confirm the reported favorable cortical effects in neither vertebra nor femur. Zileuton showed a beneficial effect on trabecular vertebra, while the femur was negatively affected. Callus formation was enhanced by all treatments; however, its density and biomechanical properties were unaltered. Lipoxygenase inhibition did not show a beneficial effect on skeletal muscle. The combination therapy did not ameliorate OVX-induced osteoporosis but induced even more bone loss.
The preventive anti-osteoporotic treatments with two lipoxygenase inhibitors applied either alone or in combination showed no benefit for the musculoskeletal system in estrogen deficient rats.
在之前的研究中，我们报道了两种脂氧合酶抑制剂，白杨素和齐留通，对绝经后大鼠模型骨质疏松骨的有益影响。虽然皮下注射白杨素主要改善皮质骨，但齐留通增强了椎骨和股骨小梁骨。在这项研究中，我们旨在揭示口服白杨素是否对骨骼产生类似的影响，以及联合使用白杨素和齐留通是否可以协同作用，以改善以前在肌肉骨骼系统中报告的效果。
我们用白杨素（10mg/kgBW）、齐留通（10mg/kgBW）或两者的组合（各 10mg/kgBW）治疗去卵巢（OVX）雌性 Sprague-Dawley 大鼠 13 周，并与未治疗的 OVX 和 NON-OVX 组（每组 12-16 只大鼠）进行比较。分析腰椎椎体和股骨。胫骨进行截骨、钢板稳定（OVX 后 8 周），并通过生物力学、组织学、微计算机断层扫描和灰化试验进行同样分析。分析骨骼肌结构。
口服白杨素在椎体和股骨中均未证实先前报道的有利皮质作用。齐留通对小梁椎骨有有益作用，而股骨则受到负面影响。所有治疗均增强了骨痂形成；然而，其密度和生物力学特性没有改变。脂氧合酶抑制对骨骼肌没有有益作用。联合治疗并没有改善去卵巢引起的骨质疏松症，反而导致更多的骨丢失。
单独或联合使用两种脂氧合酶抑制剂的预防性抗骨质疏松治疗对去势雌性大鼠的肌肉骨骼系统没有益处。
