低强度振动与左氮联合治疗被认为能够在年轻和骨骼成熟的小鼠中进行完全雌激素缺乏状态时，保留骨骼质量和肌肉力量，并减少与脂肪沉淀相关的问题。通过手术切除卵巢（OVX）和每日注射芳香化酶抑制剂（AI）来实施完全雌激素缺乏（OVX / AI）的治疗，共进行28周。在开始进行LIV治疗或对照组（无LIV）时，给予8周大的C57BL / 6雌性小鼠4周的治疗。此外，16周大的C57BL / 6雌性小鼠接受±LIV两次每天治疗，并补充±ZA（2.5ng / kg /周）。到第28周，通过双能X线吸收法测量的瘦组织质量在年轻的OVX / AI + LIV（y）小鼠中增加，在股四头肌肌纤维横截面积增加。握力比OVX / AI（y）小鼠更强，在整个实验期间，与OVX / AI（y）小鼠相比，OVX / AI + LIV（y）小鼠的脂肪质量始终较低。 OVX / AI + LIV（y）小鼠比OVX / AI（y）小鼠显示出改善的耐受葡萄糖能力和减少的瘦素和游离脂肪酸。与OVX / AI（y）小鼠相比，在OVX / AI + LIV（y）小鼠的椎骨中，小梁骨容积分数和连通密度增加；但是，在年龄较大的雌激素缺乏小鼠中，特别是在OVX / AI + ZA小鼠中，这种效应被减弱，需要使用联合LIV和ZA来增加小梁骨容积和强度。在OVX / AI + LIV + ZA小鼠中，观察到了皮质骨厚度和股骨中段横截面积的类似改善，从而导致了更强的骨折抗力。我们的研究结果表明，低强度振动和抑骨细胞破解治疗的联合应用，如ZA，可以改善经历完全雌激素缺乏状态的小鼠的椎体小梁骨和股骨皮质骨、增加瘦体质量和减少脂肪沉积。简单概括一下：低强度振动结合左氮可以抑制完全雌激素缺乏小鼠的骨骼和肌肉损失以及脂肪沉积。

Combination treatment of Low-Intensity Vibration (LIV) with zoledronic acid (ZA) was hypothesized to preserve bone mass and muscle strength while reducing adipose tissue accrual associated with complete estrogen (E 2 )-deprivation in young and skeletally mature mice. Complete E 2 -deprivation (surgical-ovariectomy (OVX) and daily injection of aromatase inhibitor (AI) letrozole) were performed on 8-week-old C57BL/6 female mice for 4 weeks following commencement of LIV administration or control (no LIV), for 28 weeks. Additionally, 16-week-old C57BL/6 female E 2 -deprived mice were administered ±LIV twice daily and supplemented with ±ZA (2.5 ng/kg/week). By week 28, lean tissue mass quantified by dual-energy X-ray absorptiometry was increased in younger OVX/AI+LIV(y) mice, with increased myofiber cross-sectional area of quadratus femorii. Grip strength was greater in OVX/AI+LIV(y) mice than OVX/AI(y) mice. Fat mass remained lower in OVX/AI+LIV(y) mice throughout the experiment compared with OVX/AI(y) mice. OVX/AI+LIV(y) mice exhibited increased glucose tolerance and reduced leptin and free fatty acids than OVX/AI(y) mice. Trabecular bone volume fraction and connectivity density increased in the vertebrae of OVX/AI+LIV(y) mice compared to OVX/AI(y) mice; however, this effect was attenuated in the older cohort of E 2 -deprived mice, specifically in OVX/AI+ZA mice, requiring combined LIV with ZA to increase trabecular bone volume and strength. Similar improvements in cortical bone thickness and cross-sectional area of the femoral mid-diaphysis were observed in OVX/AI+LIV+ZA mice, resulting in greater fracture resistance. Our findings demonstrate that the combination of mechanical signals in the form of LIV and anti-resorptive therapy via ZA improve vertebral trabecular bone and femoral cortical bone, increase lean mass, and reduce adiposity in mice undergoing complete E 2 -deprivation. One Sentence Summary: Low-magnitude mechanical signals with zoledronic acid suppressed bone and muscle loss and adiposity in mice undergoing complete estrogen deprivation.Postmenopausal patients with estrogen receptor-positive breast cancer treated with aromatase inhibitors to reduce tumor progression experience deleterious effects to bone and muscle subsequently develop muscle weakness, bone fragility, and adipose tissue accrual. Bisphosphonates (i.e., zoledronic acid) prescribed to inhibit osteoclast-mediated bone resorption are effective in preventing bone loss but may not address the non-skeletal effects of muscle weakness and fat accumulation that contribute to patient morbidity. Mechanical signals, typically delivered to the musculoskeletal system during exercise/physical activity, are integral for maintaining bone and muscle health; however, patients undergoing treatments for breast cancer often experience decreased physical activity which further accelerates musculoskeletal degeneration. Low-magnitude mechanical signals, in the form of low-intensity vibrations, generate dynamic loading forces similar to those derived from skeletal muscle contractility. As an adjuvant to existing treatment strategies, low-intensity vibrations may preserve or rescue diminished bone and muscle degraded by breast cancer treatment.