Serum type I collagen carboxyl-terminal peptide β glypeptide was positively associated with osteoporosis and skeletal muscle loss

doi:10.21203/rs.3.rs-1648392/v1

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Serum type I collagen carboxyl-terminal peptide β glypeptide was positively associated with osteoporosis and skeletal muscle loss

https://doi.org/10.21203/rs.3.rs-1648392/v1

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Background

Previous studies have presented osteoporosis and sarcopenia frequently occur concomitantly in elderly. Type I collagen carboxyl-terminal peptide β (β-CTX) usually increases in osteoporosis. However, the relationship between β-CTX and muscle mass remains unclear. This study aimed to explore the association between serum β-CTX and the risk of sarcopenia in elderly inpatients.

Methods

228 patients > 65 years were recruited in this cross-sectional study. Dual-energy X-ray scanning (DXA) was used to access skeletal muscle and bone mass. Skeletal muscle mass index (SMI) was defined as appendicular skeletal muscle mass (ASM) divided by height². Serum markers of bone remodeling were detected by electrochemical immunofluorescence assay.

Results

Serum concentration of β-CTX as well as the prevalence of osteoporosis were higher in low SMI group than in the normal SMI group. Correlation analysis showed that serum β-CTX levels negatively correlated with SMI and bone mass. Across the quartiles of serum β-CTX, total skeletal muscle mass (TSM), ASM, SMI, total bone mass (TBM) and bone mass at various sites including the limbs, spine and pelvis decreased significantly, wherea the prevalence of low SMI and osteoporosis increased. Logistic regression analysis showed the higher quartiles of serum β-CTX had an increased risk of low SMI and osteoporosis, compared to the lowest quartile (the third and fourth quartiles for low SMI and the fourth quartile for osteoporosis).

Conclusions

With increasing serum β-CTX levels, muscle and bone mass decreased in Chinese elderly inpatients. Serum β-CTX was positively associated with the risk of osteoporosis and muscle loss.

elderly

β-CTX

skeletal muscle mass

bone mass

The present study first reported that both muscle and bone mass decreased with serum β-CTX increasing in elderly Chinese inpatients. Serum β-CTX levels positively associated with the risk of osteoporosis as well as muscle mass loss. The results indicated that increasing activity of osteoclasts might contribute to the process of skeletal muscle reduction, which provides a new direction for the treatment of sarcopenia.

Osteoporosis is a skeletal disease characterized by low bone mineral density (BMD) and microarchitectural deterioration of bone tissue, and a consequent increase in bone fragility and susceptibility to fracture ^[1]. It is important to note that the prevalence of osteoporosis and its related complications are expected to increase as the aging populations increase worldwide ^[2]. Recent estimates indicate more than 70 million people suffered osteoporosis, and a prevalence of about 20.7% in women and 14.4% in men of osteoporosis among people aged ≥ 50 years in the China^{[3, 4]}. In addition to osteoporosis, sarcopenia is also an age-related disease that predominantly effect older individuals, which is characterized by progressive and generalized loss of skeletal muscle mass and strength ^[5]. Both osteoporosis and sarcopenia are associated with a higher risk for falls and fractures, as well as significant morbidity, disability, poor mobility, frailty and hospitalization ^[6–8]. As aging has an overwhelming effect on bone and skeletal muscle, and due to the interactions between bone and skeletal muscle tissues meanwhile, osteoporosis and sarcopenia often coexist in the same older individual and lead to similar consequences. Regarding the current secular trends of population aging, the burden of both diseases may continue to increase.

In addition to the similar population in which they occur, there is also growing evidence of the close relationship between osteoporosis and sarcopenia ^[9]. It has been shown that low muscle mass or function contributed to low BMD in postmenopausal women ^{[10, 11]}. Previous study recognized sarcopenia as an independent risk factor for decreased BMD and osteoporosis condition among older people ^{[12, 13]}. On the contrary, patients existing with low bone mass would suffer higher risk of sarcopenia ^{[14, 15]}.

Since skeletal muscle and bone are closely linked, there are several potential explanations for these interrelationships. Later evidences provide support that a bidirectional bone-muscle crosstalk exists, which is probably mediated by citokines, osteokines, myokines and other growth factors ^{[16, 17]}. It was reported cytokines from bone would affect skeletal muscle by autocrine and paracrine ^[17]. Meanwhile, as skeletal muscle is supposed to be the largest endocrine organ in the body, myogenic cytokines also could regulate bone structure and function ^[16].

The development and maintenance of bone tissue mostly depends on the coordinated actions of bone forming osteoblasts and bone resorbing osteoclasts. Majority studies have presented the relationship between osteoblasts and skeletal muscle ^{[17, 18]}. However, whether the activity of osteoclast is related to sarcopenia was unclear. Therefore, β-CTX, an index reflecting the activity of osteoclasts, was researched to explore the relationship between osteoclasts and sarcopenia as well as osteoporosis in the present study.

Participants

228 patients hospitalized in the Geriatric Department of Zhongshan Hospital, affiliated with Fudan University (Shanghai, China), from October 2017 to December 2019 were recruited. All of the participants had the ability of independent daily performance. None of the subjects underwent acute conditions, including infection, acute stroke, acute cardiovascular events or surgical stress. Participants were excluded as follows:1) 6 patients lack of data of DXA; 2) 42 patients suffered malignant tumors, mobility disorders, serious liver and kidney disease, and cardiac insufficiency; 3) 14 patients lack of serum index of bone metabolism. Finally, 166 participants were included in the analysis (130 male and 36 female).

This study was approved by the Research Ethics Committee of Zhongshan Hospital affiliated with Fudan University. Written informed consent were received from all participants.

Data collection

During hospitalization, the patients’ information about their lifestyle, medical history, and prior medications were collected. Weight and height were measured while the participant was clothed in a light gown. Body mass index (BMI) was calculated as weight divided by squared height (kg/m²).

After at least a 10 h overnight fast, a venous blood sample was collected for the examination of bone remodeling markers. Serum concentration of calcium and phosphorus was tested by colorimetry on a model 7600 automated bio-analyzer (cobas c702, Roche, Germany). Osteocalcin, β-CTX, 25 hydroxyvitamin D, parathyrin (PTH) and procollagen type I N-peptide (PINP) were tested by radioimmunoassay on a model 8000 automatic immune analyzer (cobas e801, Roche, Germany).

Body composition including lean mass, fat mass and bone mass were measured using DXA scanner (Discovery, S/N 88576, Hologic). All measurements were carried out by a single, trained technician at a single clinical center. Manual DXA analysis software was used to analyze all of the DXA scans. Lean mass was considered as skeletal muscle mass. SMI was calculated as ASM/height². According to the criteria of Asian sarcopenia working group (AWGS) ^[10], SMI < 7. 0 kg /m² in male, SMI < 5.4 kg /m² in female was defined as low SMI. Total BMD and BMD at limbs, lumbar 1–4 and femoral neck was detected. According to WHO criteria, when the T-Score of BMD was less than 1 standard deviation below peak bone value of healthy adults in the same gender and race was normal; the degree of reduction equal to or greater than 2.5 standard deviations was osteoporosis ^[11].

Statistical analysis

All statistical analyses were performed using SPSS software version 21.0 (SPSS, Chicago, IL, USA). Continuous variables were presented as the means ± SD except for skewed variables. The subjects were divided into four groups according to quartiles of β-CTX as follows: Q1: ≦0.220 ng/ml; Q2: 0.221 ~ 0.310 ng/ml; Q3: 0.311 ~ 0.480 ng/ml; Q4: ≧0.481 ng/ml. Analysis of variance (ANOVA) was used for inter-group comparisons of continuous data and the χ² test was applied for the categorical variables. Pearson analysis was performed to access the relationship between β-CTX with muscle mass and bone mass. Multivariate logistic regression analyses were used to investigate the association between the quartiles of β-CTX and the risk of osteoporosis as well as low SMI. Odds ratio (OR) and 95% confidence intervals (CIs) for the unadjusted and adjusted risk factors were calculated via the logistic regression models. For all analyses, p < 0.05 was considered statistically significant.

Characteristics of the subjects

The mean age of the population was 82.68 ± 7.91 years old. The prevalence of osteoporosis, low SMI and low SMI with osteoporosis was 81 (48.8%), 40 (24.1%) and 25 (15.1%), respectively. The prevalence of osteoporosis was much higher in low SMI group (62.5% vs 44.4%, P = 0.035). Regarding to bone remodeling markers, the individuals in the low SMI group presented higher β-CTX and osteocalcin, while compared to the normal group. The characteristics of the subjects were presented in Table 1.

Table 1

Characteristics of the subjects
	Total (n = 166)	Low SMI (n = 40)	Normal (n = 126)	P value
Male (n,%)	130, 78.3%	29, 72.5%	101, 80.2%	0.209
Age (years)	82.68 ± 7.91	86.02 ± 6.78	81.49 ± 8.76	0.002
BMI (kg/m²)	24.23 ± 3.20	21.18 ± 1.86	24.98 ± 2.93	< 0.001
TSM (kg)	52.34 ± 9.23	43.58 ± 7.21	53.78 ± 8.58	< 0.001
ASM ( kg)	20.91 ± 4.07	16.76 ± 3.15	21.63 ± 3.74	< 0.001
SMI (kg/m²)	7.46 ± 1.04	6.12 ± 0.64	7.74 ± 0.87	< 0.001
TBM (kg)	2.21 ± 0.44	1.92 ± 0.39	2.26 ± 0.44	< 0.001
TBMD	1.11 ± 0.13	1.05 ± 1.21	1.12 ± 1.28	0.001
ABM (kg)	1.17 ± 0.27	0.97 ± 0.22	1.21 ± 0.27	< 0.001
ABMD	0.98 ± 0.12	0.89 ± 0.11	0.99 ± 0.12	< 0.001
SBM (kg)	0.19 ± 0.05	0.16 ± 0.05	0.20 ± 0.06	0.003
SBMD	1.01 ± 0.20	0.92 ± 0.16	1.03 ± 0.21	0.006
PBM (kg)	0.21 ± 0.06	0.17 ± 0.05	0.22 ± 0.07	< 0.001
PBMD	1.15 ± 0.20	1.03 ± 0.16	1.18 ± 0.20	< 0.001
Osteoporosis (n,%)	81, 48.8%	25, 62.5%	56, 44.4%	0.035
Calcium (mmol/l)	2.23 ± 0.11	2.22 ± 0.10	2.24 ± 0.11	0.588
Phosphorus (mmol/l)	1.07 ± 0.15	1.10 ± 0.15	1.06 ± 0.16	0.159
Osteocalcin (ng/ml)	14.63 ± 7.82	18.47 ± 11.04	13.60 ± 6.92	0.001
β-CTX (ng/ml)	0.39 ± 0.23	0.52 ± 0.35	0.34 ± 0.19	< 0.001
PINP (ng/ml)	47.79 ± 28.00	54.55 ± 27.94	44.94 ± 27.75	0.059
25(OH)Vit D (nmol/l)	48.12 ± 25.81	52.89 ± 35.80	48.43 ± 23.69	0.365
PTH (pg/ml)	44.17 ± 18.33	46.03 ± 20.19	42.93 ± 17.29	0.349
ALP (U/l)	65.61 ± 25.97	64.57 ± 15.63	65.31 ± 28.26	0.876
TSM: total muscle mass; ASM: appendicular muscle mass; FM: fat mass; FM%: percentage of fat mass; TBM: total bone mass; TBMD: total bone mineral density; LBM: appendicular bone mass; ABMD: appendicular bone mineral density; SBM: spinal bone mass; SBMD: spinal bone mineral density; PBM: pelvis bone mass; PBMD: pelvis bone mineral density; β-CTX: Type I collagen carboxyl-terminal peptide β; 25(OH)VitD: 25 hydroxyvitamin D; PTH: parathyrin; PINP: procollagen Type I N-peptide; ALP: alkaline phosphatase.

Association of β-CTX with skeletal muscle mass and bone mass

Pearson analysis presented serum β-CTX levels were positively associated with age, osteocalcin, PINP, PTH (all p < 0.05). Regarding to the body compositions, β-CTX was negatively related with BMI, SMI, total skeletal muscle mass (TSM), appendicular skeletal muscle mass (ASM), total bone mass (TBM), spinal bone mass (SBM), appendicular bone mass (ABM) and pelvic bone mass (PBM) as well as BMD at the corresponding sites (all P < 0.001), which is shown in Table 2. To further explore the relationship between serum β-CTX and skeletal muscle mass as well as bone mass, the participants were stratified by the β-CTX quartiles. Compared to the participants in the lowest β-CTX quartile, the participants in the higher quartiles were older and presented lower BMI. Across the quartiles of β-CTX, SMI, TSM, ASM as well as TBM, SBM, ABM and PBM and BMD at the corresponding sites all decreased. The prevalence of low SMI was 7.5%, 22.8%, 22.4% and 38.5%, respectively (Fig. 1). The index of bone formation including osteocalcin, PTH and PINP all increased across the quartiles. The results were presented in Table 3.

Table 2

Pearson analysis of the association of β-CTX and clinical Characteristics
Age	0.184, 0.017
BMI	-0.244, 0.002
Ca	-0.090, 0.247
Calcium	0.070, 0.370
Phosphorus	0.052, 0.479
osteocalcin	0.850, < 0.001
PINP	0.655, < 0.001
25Vit D	-0.080, 0.306
PTH	0.344, < 0.001
TSM	-0.228, 0.003
ASM	-0.253, 0.001
SMI	-0.340, < 0.001
TBM	-0.227, 0.003
TBMD	-0.203, 0.009
ABM	-0.258, 0.001
ABMD	-0.279, < 0.001
SBM	-0.151, 0.053
SBMD	-0.166, 0.032
PBM	-0.277, < 0.001
PBMD	-0.325, < 0.001

Table 3

Characteristics of the subjects according to the quartiles of serum β-CTX
	Q1 Q = 46	Q2 Q = 37	Q3 Q = 42	Q4 Q = 41	P value
Age (years)	80.65 ± 7.92	82.19 ± 7.49	83.78 ± 7.35	84.15 ± 8.58	0.147
BMI (kg/m²)	24.75 ± 3.48	24.05 ± 3.37	24.39 ± 2.80	23.15 ± 2.94	0.121
Calcium(mmol/l)	2.26 ± 0.12	2.21 ± 0.09	2.21 ± 0.11	2.23 ± 0.11	0.106
Phosphorus(mmol/l)	1.07 ± 0.16	1.06 ± 0.16	1.02 ± 0.17	1.11 ± 0.12	0.054
osteocalcin	8.98 ± 2.93	12.15 ± 3.97	14.25 ± 4.26	23.09 ± 9.08	< 0.001
PINP	28.59 ± 9.08	41.64 ± 15.73	49.21 ± 32.39	70.16 ± 28.16	< 0.001
25Vit D	48.79 ± 24.79	44.21 ± 24.88	58.70 ± 29.73	46.33 ± 27.11	0.075
PTH	34.98 ± 17.17	43.79 ± 16.25	44.25 ± 12.14	53.47 ± 21.13	< 0.001
ALP (U/L)	61.78 ± 40.97	61.57 ± 15.48	65.07 ± 16.68	71.02 ± 16.95	0.306
TSM (kg)	54.07 ± 9.69	52.24 ± 8.82	52.18 ± 8.57	47.94 ± 9.65	0.023
ASM (kg)	21.83 ± 4.33	21.05 ± 3.67	20.63 ± 3.83	19.02 ± 4.21	0.015
SMI (kg/m²)	7.82 ± 1.14	7.52 ± 1.01	7.33 ± 0.93	6.92 ± 0.96	0.001
TBM (kg)	2.27 ± 0.47	2.31 ± 0.44	2.16 ± 0.37	1.97 ± 0.46	0.003
TBMD	1.13 ± 0.14	1.15 ± 0.12	1.09 ± 0.11	1.05 ± 0.13	0.003
ABM (kg)	1.22 ± 0.26	1.21 ± 0.25	1.15 ± 0.25	1.03 ± 0.30	0.003
ABMD	1.01 ± 0.12	1.00 ± 0.12	0.95 ± 0.11	0.91 ± 0.13	0.001
SBM (kg)	0.19 ± 0.06	0.20 ± 0.06	0.19 ± 0.05	0.16 ± 0.05	0.026
SBMD	1.04 ± 0.19	1.05 ± 0.23	0.99 ± 0.21	0.92 ± 0.16	0.023
PBM (kg)	0.23 ± 0.08	0.22 ± 0.07	0.20 ± 0.05	0.17 ± 0.05	0.001
PBMD	1.22 ± 0.24	1.17 ± 0.19	1.13 ± 0.17	1.04 ± 0.15	0.001
The quartiles of serum β-CTX: Q1: ≦0.220 ng/ml; Q2: 0.221–0.310 ng/ml; Q3: 0.311–0.480 ng/ml; Q4: >0.480 ng/ml

Logistic analysis of the relationship between β-CTX and osteoporosis as well as low SMI

To further conform the association between serum β-CTX and low SMI, as well as osteoporosis, logistic analysis was performed. The results indicated that the higher quartiles of serum β-CTX were associated with increasing risk of skeletal muscle loss and osteoporosis, while compared to the lowest quartile. After multiple adjustments, the third and fourth quartiles of serum β-CTX had an increased risk of low SMI (the third quartile: OR = 5.843, 95%CI 1.205–28.341, P = 0.028; the fourth quartile: OR = 6.803, 95%CI 1.377–33.604, P = 0.019); and the fourth quartile of serum β-CTX had an increased risk of osteoporosis (OR = 3.385, 95%CI 1.200–9.550, P = 0.021). (Table 4)

Table 4

Logistic analysis of the relationship between quartile of serum β-CTX and osteoporosis as well as low SMI
	Q1	Q2	Q3	Q4
osteoporosis
unadjusted	1	3.176 (1.198–8.425, 0.020)	1.920 (0.741–4.974, 0.179)	6.750 (2.515–18.115, < 0.001)
Model 1	1	3.112 (1.163–8.328, 0.024)	1.634 (0.614–4.347, 0.325)	5.180 (1.857–14.449, 0.002)
Model 2	1	2.909 (1.060–7.983, 0.038)	1.548 (0.572–4.192, 0.390)	4.356 (1.526–12.433, 0.006)
Model 3	1	2.886 (1.027–8.109, 0.044)	1.615 (0.582–4.485, 0.357)	4.413 (1.507–12.927, 0.007)
Model 4	1	2.625 (0.961–7.172, 0.060)	1.385 (0.514–3.734, 0.520)	3.385 (1.200–9.550, 0.021)
low SMI
unadjusted	1	3.654 (0.886–15.607, 0.073)	3.978 (1.005–15.745, 0.049)	7.708 (2.015–29.492, 0.003)
Model 1	1	3.414 (0.816–14.288, 0.093)	3.454 (0.851–14.028, 0.083)	6.414 (1.593–25.834, 0.009)
Model 2	1	3.092 (0.535–17.865, 0.207)	6.289 (1.057–37.418, 0.043)	6.975 (1.161–41.897, 0.034)
Model 3	1	2.769 (0.489–15.668, 0.249)	5.793 (1.020-32.893, 0.047)	6.437 (1.102–37.612, 0.039)
Model 4	1	2.830 (0.594–13.487, 0.192)	5.843 (1.205–28.341, 0.028)	6.803 (1.377–33.604, 0.019)
Model 1: gender, age
Model 2: gender, age, BMI
Model 3: gender, age, BMI, VitD medication
Model 4: gender, age, BMI, VitD medication, low SMI (for osteoporosis); gender, age, BMI, VitD medication, osteoporosis (for low SMI)

In the present study, the elderly subjects suffered low SMI had higher prevalence of osteoporosis. Skeletal muscle loss was closely associated with osteoporosis, which was similar to previous researches ^[9–11]. The results confirmed not only BMD but also bone mass reduction was associated with muscle loss, which further supports the close association between sarcopenia and osteoporosis. As skeletal muscle and bone are the two major components of the musculoskeletal system, they have a close mechanical relationship as well as biochemical crosstalk ^[19]. Bone provides attachment sites for muscle, and skeletal muscle imparts a force on the bone to facilitate locomotion of the organism. In addition, muscle-derived force is also the main source of mechanical loads that generate the strain in the bone. It has been proposed that several cytokines involving in muscle and bone biochemical crosstalk, such as insulin-like growth factor-1 (IGF-1), fibroblast growth factor-23 (FGF-23), Irisin, FGF-23, IL-6, sclerostin ^[20]. Besides, some well-known genes are associated to muscle loss and osteoporosis concurrently, for example myostatin, proliferator-activated receptor gamma coactivator 1-α (PGC-1α), myocyte enhancer factor-2 C (Mef-2C) and methyltransferase-like 21C (METTL21C) ^[21].

Our study first revealed that serum β-CTX was not only associated with osteoporosis but also skeletal muscle loss. With β-CTX increasing, both bone and skeletal muscle mass decreased. Osteoblasts and osteoclasts are the main factors involved in bone remodeling in the bone micro-environment. Osteoporosis is a chronic, systemic endocrine and metabolic disorder, which is associated with imbalance of bone remodeling. Osteoclasts involved in bone resorption plays an important role in the occurrence and development of osteoporosis. As the degradation products of type I collagen, the serum concentration of β-CTX reflects bone turnover activity, and the relationship between β-CTX and osteoporosis has been well confirmed ^[22]. The patients with osteoporosis often presented elevated β-CTX which prompted increasing activity of bone resorption ^[23]. The present study showed with β-CTX increasing, both bone mass and BMD at corresponding sites decreased, which means the activity of osteoclasts affects not only bone contents but also bone microstructure. With serum β-CTX increasing, bone formation markers such as PINP and osteocalcin increased simultaneously. This indicated that with the activity of osteoclast increasing, the function of osteoblasts might compensatory enhance.

However, whether skeletal muscle was related with serum β-CTX was still unclear so far. Previous study has reported that extracellular vesicles secreted from mouse muscle might be a crucial mediator of muscle-bone interactions, which suppressed osteoclast formation by receptor activator of nuclear factor κB ligand (RANKL) ^[24]. Myostatin, a negative myokine of both muscle and bone through activin receptor type II B-mediated TGF-β-specific Smad2/3 signaling, could have an effect on osteoclastogenesis and subperiosteal resorption ^{[25, 26]}. Other skeletal-muscle secreted myokines such as irisin, could increase bone resorption on several substrates in situ ^[27]. On the other hand, the linkage from osteoblasts to muscle was also investigated. For example, mechano growth factor (MGF) is highly expressed in osteoblasts in response to mechanical stimuli, promoting the proliferation and the migration of osteoblasts. MGF has been shown to stimulate muscle satellite cells to re-enter cell cycle and proliferate, resulting in new muscle cells to replace injured fibers^[28]. RANKL, a key mediator in osteoclast differentiation, binding to its receptor RANK expressed on osteoclasts was reported involved in the muscle weakness of dystrophic mdx mice ^[29]. All these evidences support the close association between muscle atrophy and osteoclast action. However, most previous researches were about animal models, the relationship between serum concentration of β-CTX and muscle loss in humans hasn’t been reported. The present study first discovered serum β-CTX in elderly inpatients was positively associated with the risk of skeletal muscle mass, which supported the viewpoint that increasing osteoclast activity might contribute to skeletal muscle reduction. The results indicate that besides osteoporosis, osteoclast-derived factors might also be potential therapeutic targets against sarcopenia.

The novelty of the results and objective measures of skeletal muscle mass and osteoporosis are strengths of the present study. The study adds further support to the growing evidence that sarcopenia and osteoporosis exits close association. Furthermore, the data first showed increasing serum concentration of β-CTX was positively associated with the risk of muscle loss in Chinese elderly inpatients. This indicated that increasing activity of osteoclasts contributed to the process of skeletal muscle decay, which provides a new direction for the treatment of sarcopenia.

Several limitations should also be recognized. First, the major limitations of this study is the relative small sample size of the subjects, which could have affected the strength and significance of associations between osteoclasts and skeletal muscle. Second, it was a cross-sectional research, and the results needed to be further evaluated in longitudinal studies. Third, considering that current sarcopenia definitions specify the presence of low muscle strength or physical function for the diagnosis of sarcopenia, the information of physical activity, handgrip strength or gait speed are still needed in further studies. In the future, researches about mechanism of the crosstalk between muscle and osteoclasts are needed, which might provide a deep understanding of the association between β-CTX and muscle loss.

In summary, our results first demonstrated a significant correlation of serum β-CTX and skeletal muscle mass. Osteoporosis was closely associated with muscle degeneration, and serum β-CTX was positively associated with the risk of muscle loss in elderly Chinese inpatients. Further prospective studies and animal models on the causal effect of osteoclasts activity on skeletal muscle reduction were required, which might not only expand our understanding of the mechanism of the relationship between osteoclasts and muscle, but also assist in the discovery of new prevention strategies for sarcopenia.

β-CTX: type I collagen carboxyl-terminal peptide β glypeptide

SMI: skeletal muscle mass index

ASM: appendicular skeletal muscle mass

TSM: total skeletal muscle mass

TBM: total bone mass

BMD: bone mineral density

DXA: Dual-energy X-ray scanning

BMI: body mass index

PTH: parathyrin

PINP: procollagen type I N-peptide

AWGS: Asian sarcopenia working group

ANOVA: Analysis of variance

OR: Odds ratio

CI: confidence interval

TSM: total skeletal muscle mass

ASM: appendicular skeletal muscle mass

TBM: total bone mass

SBM: spinal bone mass

ABM: appendicular bone mass

PBM: pelvic bone mass

IGF-1: insulin-like growth factor-1

FGF-23: fibroblast growth factor-23

PGC-1α: proliferator-activated receptor gamma coactivator 1-α

Mef-2: myocyte enhancer factor-2 C

METTL21C: methyltransferase-like 21C

RANKL: receptor activator of nuclear factor κB ligand

MGF: mechano growth factor

Funding

The study was funded by the Shanghai Municipal Health Commission (No. 202040070).

Competing Interest

Lingyan Chen, Jiayu Wu, Chu Liu, Weiying Ren, Xi Li, Man Luo and Yu Hu declare that they have no conflict of financial or non-financial interest.

Availability Of Data And Material

The data analyzed during the current study are available from the corresponding authors on reasonable request.

Code Availability

Not applicable.

Authors' Contributions

Chen LY, Luo M and Hu Y designed the research. Chen LY, Wu JY, Ren WY and Li X recruited the subjects; collected, managed and analyzed the data. The paper was written by Chen LY and Wu JY, and revised by Hu Y and Luo M.

Ethics Approval

This study was approved by the Research Ethics Committee of Zhongshan Hospital affiliated to Fudan University (No. B2017-079R). Written informed consent was obtained from all individual participants included in the study.

Consent For Publication

Both the authors and the participants agreed with the publication.

Acknowledgement

Not Applicable

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05 Dec, 2022
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Serum type I collagen carboxyl-terminal peptide β glypeptide was positively associated with osteoporosis and skeletal muscle loss

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