Association of serum bone- and muscle-derived factors with age, sex, body composition, and physical function in community-dwelling middle-aged and elderly adults: a cross-sectional study

Abstract

Background Understanding interactions between bone and muscle based on endocrine factors may help elucidate the relationship between osteoporosis and sarcopenia. However, whether the abundance or activity of these endocrine factors is affected by age and sex or whether these factors play a causal role in bone and muscle formation and function is unclear. We aimed to evaluate the association of serum bone- and muscle-derived factors with age, sex, body composition, and physical function in community-dwelling middle-aged and elderly adults. Methods In all, 254 residents (97 men, 157 women) participated in this cross-sectional study conducted in Japan. The calcaneal speed of sound (SOS) was evaluated by quantitative ultrasound examination. Skeletal muscle mass index (SMI) was calculated by bioelectrical impedance analysis. Grip strength was measured using a dynamometer. Gait speed was measured by optical-sensitive gait analysis. Serum sclerostin, osteocalcin (OC), insulin-like growth factor-1 (IGF-1), myostatin, and tartrate-resistant acid phosphatase-5b (TRACP-5b) concentrations were measured simultaneously. The difference by sex was determined using t test. Correlations between serum bone- and muscle-derived factors and age, BMI, SOS, SMI, grip strength, gait speed, and TRACP-5b in men and women were determined based on Pearson’s correlation coefficients. Multiple regression analysis was performed using the stepwise method. Results There was no significant difference with regard to age between men (75.0 ± 8.9 years) and women (73.6 ± 8.1 years). Sclerostin was significantly higher in men than in women and tended to increase with age in men; it was significantly associated with SOS and TRACP-5b levels. OC was significantly higher in women than in men and was significantly associated with TRACP-5b levels and age. IGF-1 tended to decrease with age in both sexes and was significantly associated with SOS and body mass index. Myostatin did not correlate with any assessed variables. Conclusions Sclerostin was significantly associated with sex, age, and bone metabolism, although there was no discernable relationship between serum sclerostin levels and muscle function. There was no obvious relationship between OC and muscle parameters. This study suggests that IGF-1 is an important modulator of muscle mass and function and bone metabolism in community-dwelling middle-aged and elderly adults.

Crucial role of androgen receptor in resistance and endurance trainings-induced muscle hypertrophy through IGF-1/IGF-1R- PI3K/Akt- mTOR pathway

“…The important positive effect of IGF-1 on muscle mass was demonstrated in humans including communitydwelling middle-aged and elderly adults [30], and IGF-1 is considered as a promising therapeutic agent for sarcopenia resulted from aging or hypogonadism and muscle weakness from staving [31]. As mentioned in the Introduction, AR's role in increasing muscle mass at unstrained state was mediated by IGF-1/IGF-1R in vivo and in vitro [15], and our Fig.…”

“…For genomic mechanism, AR mediates protein synthesis and degradation of skeletal muscle via modulating target genes such as myogenic regulatory factor (MRF) and ubiquitin ligases, which mostly cost more than 24 h to exert effects for completing transcription and translation of target genes. While the non-genomic mechanism of AR, characteristic of quick response to AR, recently have been proven an increasing importance in muscle protein balance (prompting protein synthesis and inhibiting degradation), is fulfilled through interactions of AR with other molecules such as IGF-1 and myostatin, especially IGF-1 [30].…”

Osteosarcopenia: A case of geroscience

“…Of those, osteocalcin, a key player in bone energetics, upregulates pancreatic β‐cells and insulin secretion in muscle, correlating with leg strength in older women . However, a recent cross‐sectional study of middle‐aged and older adults found that serum IGF‐1, but not sclerostin or osteocalcin, was associated with muscle mass and function as well as bone metabolism in this cohort. Stromal cells in bone marrow also stimulate myoblast proliferation via the paracrine release of vascular endothelial growth factor, providing further evidence of endocrine cross talk between these organs.…”

“…More growth factors secreted by myotubes, notably IGF‐1 and fibroblast growth factor‐2 (FGF‐2), are anabolic to not only muscle, but also bone . In vivo and in vitro models indicate IGF‐1 and FGF‐2, localized in the periosteum, stimulate osteoblastogenesis and bone remodelling .…”

Crucial role of androgen receptor in resistance and endurance trainings-induced muscle hypertrophy through IGF-1/IGF-1R- PI3K/Akt- mTOR pathway

“…The important positive effect of IGF-1 on muscle mass was demonstrated in humans including community-dwelling middle-aged and elderly adults [30] , and IGF-1 is considered as a promising therapeutic agent for sarcopenia resulted from aging or hypogonadism and muscle weakness from staving [31] . As mentioned in the Introduction, AR's role in increasing muscle mass at unstrained state was mediated by IGF-1/IGF-1R in vivo and in vitro [15] , and our previous work in two kinds of myoblasts (C2C12 cells with high AR expression level, while L6 cells without detectable AR) using flutamide, AR over-expression, exogenous IGF-1 and IGF-1R neutralizing antibody (inhibiting IGF-1R signaling) demonstrated that the essential role of AR in myoblasts proliferation resulted from mechanical stretch (mimic muscle movement) was mediated by IGF-1/IGF-1R in vitro [23,24] .…”