骨肌串扰防治骨肌共减症的作用及机制

The Role and Mechanism of Bone Muscle Crosstalk in The Prevention and Treatment of Osteoscarcopenia

骨肌共减症(osteosarcopenia,OS)是一种常见的老年退行性综合症,表现为个体在衰老过程中骨量和肌肉含量同时减少,引起骨质疏松症和肌少症,导致机体平衡能力下降,容易跌倒、骨折,严重威胁老年人的生活质量和生存寿命。由于骨骼和肌肉都属于运动系统,骨质疏松症与肌少症在遗传、内分泌、旁分泌和脂肪浸润方面有共同的致病因素,彼此相互影响、相互调节。因此,本文综述了诱导骨肌共减症的力学串扰、细胞因子串扰、信号通路间相互串扰的分子机制和临床诊断方法,通过运动、营养和药物的干预,对提高老年人的寿命和生存质量,实践“健康老龄化”具有重要的意义。

Osteoscarcopenia(OS)is a common degenerative syndrome in the elderly,which is caused by a decrease in both bone and muscle mass during the aging process,leading to osteoporosis and sarcopenia,a decrease in body balance,and a risk of falls and fractures,posing a serious threat to the quality of life and lifespan of the elderly.Osteoskeletal dystrophy increases with age,and its occurrence is higher in females than that in males.At present,there is no unified diagnostic standard,making it impossible to achieve early detection and intervention.The commonly used diagnostic methods include quantitative computed tomography(CT),magnetic resonance imaging(MRI),dual energy X-ray absorptiometry(DXA),muscle mass bioelectrical impedance analysis(BIA),as well as daily gait speed(UGS),short physical performance battery(SPPB),timed start test(TUG),and biochemical evaluation indicators to improve early diagnosis and screening.Due to the fact that both bones and muscles belong to the motor system,osteoporosis and sarcopenia share common pathogenic factors in genetics,endocrine,paracrine,and fat infiltration,which interact and regulate each other,inducing the occurrence of osteoscarcopenia.Osteoporosis and sarcopenia,two age-related diseases,share the same pathogenesis and regulatory pathways,as well as common drug targets.For example:somatostatinα‑actin-3,peroxisome proliferator activated receptorγcoactivation factor-1α(PGC-1α),myocyte enhancer factor-2(MEF2C),sterol regulatory element binding transcription factor 1(SREBF1),protoadhesion 7(PCDH7)and methyltransferase like 21C(METTL21C),osteocalcin and bone derived bone factor gap junction connexin 43(Cx43),growth hormone(GH),sex hormones,and diseases(such as tumors,diabetes,polycystic ovary syndrome,cardiovascular disease,anemia,disability,inflammatory disease),aging,nutrition,and poor living habits are closely related to osteosarcopenia.Osteoporosis is characterized by low bone mass and microstructural degeneration of bone tissue,while sarcopenia is characterized by loss of muscle mass,strength,and function,both of which often coexist in the elderly population.Exercise regulates muscle and skeletal cytokines such as myostatin(MSTN)and irisinβ‑aminoisobutyric acid(BAIBA),brain derived neutrophil factor(BDNF),interleukin,prostaglandin E2,Wnt,osteocalcin(OCN),and transforming growth factor‑β(TGF‑β)and receptor activator of NF-κB ligand(RANKL)interfere with each other to prevent and treat osteoscarcopenia.Wnt/β‑catenin signaling pathway can simultaneously regulate the growth and metabolism of bones and muscles,and promote osteoblast proliferation,maturation,and mineralization by increasing OPG/RANKL,which is beneficial for bone mass increase and induces proliferation of muscle satellite cells,stimulating and promoting increased muscle synthesis.NF‑κB pathway is the main regulatory factor for inflammation mediated muscle atrophy.Meanwhile,NF‑κB DNA can participate in RANKL inducing osteoclast differentiation in bone tissue,thereby reducing bone mass.Although exercise and nutrition can improve the symptoms of osteoporosis,they cannot be completely cured,and there are no specific drugs in clinical practice that can cure sarcopenia.Because osteoscarcopenia has a common crosstalk mechanism in the aging process,it is of great significance to prevent osteoscarcopenia by improving bone mass and muscle content through exercise,nutrition,and medication.