Sex-dependent association of serum alkaline phosphatase with grip strength in adults aged 20-59: NHANES 2013-2014

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Previous studies have demonstrated that serum alkaline phosphatase (ALP) is closely associated with muscle mass. Nevertheless, the association between serum alkaline phosphatase (ALP) and grip strength remains unclear. This study is designed to investigate whether there exists a connection between serum ALP levels and grip strength among individuals aged 20 to 59 years. Methods Utilizing data from the National Health and Nutrition Examination Survey (NHANES) conducted in 2013–2014, a cross-sectional survey design was employed to examine 2,182 adults (54.54% male and 45.46% female) aged between 20 and 59 years. Weight-corrected grip strength served as the dependent variable, while serum alkaline phosphatase (ALP) was identified as the primary variable of interest. The relationships were analyzed using generalized linear models, smooth curve fitting, generalized additive models, and stratified analyses. Results We discovered that alkaline phosphatase (ALP) was negatively linked with weight-corrected grip strength. When stratified by gender, age group and race, for all groups except for other races, serum alkaline phosphatase (ALP) were negatively correlated with weight-corrected grip strength. When divided into four groups according to gender and age, serum alkaline phosphatase (ALP) and weight-corrected grip strength showed an N-shaped relationship among male participants aged 20–39 years, and an L-shaped relationship among male participants aged 40–59 years, and among female shows a significant negative correlation regardless of age group. Conclusions Our research identified notable gender differences in the association between alkaline phosphatase (ALP) levels and weight-corrected grip strength among participants aged 20 to 59 years. This finding offers new insights and avenues for understanding how serum alkaline phosphatase affects skeletal muscle health. Serum alkaline phosphatase Grip strength Muscle healthy NHANES Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Background Sarcopenia represents a progressive and generalized skeletal muscle disorder entailing the accelerated depletion of muscle mass and function, which is associated with augmented adverse outcomes such as falls, functional deterioration, frailty, and mortality [ 1 ]. Sarcopenia is correlated with a multitude of factors, including age-related inflammation, inactivity, poor nutrition, and chronic diseases [ 2 ]. Grip strength constitutes an essential factor in the diagnosis of sarcopenia [ 3 ], as muscle strength is not solely dependent on mass [ 4 ]. Lower handgrip strength in healthy adults predicts an elevated risk of functional limitations and disabilities in later life, as well as all-cause mortality [ 5 ]. Considering the high prevalence and severe implications of sarcopenia, there is an immediate and compelling urgency to investigate the mechanisms influencing grip strength. Alkaline phosphatase (ALP) is an enzyme present in diverse tissues throughout the body. The majority of ALP in serum (over 80%) originates from the liver and bones, with a minor portion coming from the intestines [ 6 ]. ALP plays a significant role in inflammation and metabolic syndrome [ 4 ], and elevated ALP is invariably associated with adverse outcomes [ 7 ]. A large cohort study demonstrated that higher serum total ALP levels were significantly associated with the incidence of hip fractures [ 8 ]. Basic research suggests that tissue nonspecific alkaline phosphatase (TNAP) functions within bone and muscle progenitor cells to impact ATP production and mitochondrial respiration [ 9 ], but the exact physiological function of ALP remains largely unknown. In relation to the musculoskeletal system, some researchers have discerned a positive association between serum alkaline phosphatase (ALP) and a low muscle mass index [ 10 ]. Nevertheless, the effect of serum ALP on grip strength remains uncharted. Hence, we initiated this research endeavor to investigate the interrelationship between serum ALP and grip strength within the US population. Methods Study population The National Health and Nutrition Examination Survey (NHANES) is a biennial nationwide study that recruits a representative sample of the general population in the United States. In the 2013–2014 NHANES, We incorporated 3,928 adults aged 20 to 59 years from among 10,175 participants. Those lacking data of alkaline phosphatase (n = 295) and hand grip strength (n = 233) were excluded. Additionally, subjects fulfilling any of the following criteria were also excluded: pregnancy (n = 60); a history of hand surgery (n = 63); neoplastic disease (n = 131); liver disease (n = 92); thyroid disease (n = 203); arthritis (n = 343); osteoporosis (n = 11); and missing covariates (n = 315). "The final study sample comprised 2,182 participants, and a flowchart illustrating the exclusion criteria is provided in Fig. 1 . Measurement of serum alkaline phosphatase In this investigation, serum ALP was designated as the exposure variable. From 2013 to 2014, the DxC800 system adopted a kinetic rate methodology employing a 2-Amino-2-Methyl-1-Propanol (AMP) buffer for the measurement of ALP activity in serum or plasma. In the reaction, ALP catalyzes the hydrolysis of the colorless organic phosphate ester substrate, p-Nitrophenylphosphate, to the yellow-colored product, p-Nitrophenol, and phosphate. This reaction transpires at an alkaline pH of 10.3. The system monitors the rate of alteration in absorbance at 410 nm within a fixed-time interval. This rate of change in absorbance is directly proportional to the ALP activity in the serum. Detailed information about serum alkaline phosphatase can be found in the National Health and Nutrition Examination Survey: Laboratory Procedure Manual at http://www.cdc.gov/nchs/nhanes/ . Measurement of grip strength The grip strength data was collected using the Takei Digital Grip Strength Dynamometer (Model T.K.K.5401). A proficient examiner elaborated and demonstrated the protocol to the participant. Subsequently, the examiner adjusted the grip size of the dynamometer to match the participant's hand size and requested the participant to squeeze the dynamometer for a practice attempt. After the practice session, the participant was instructed to employ one of their hands to squeeze the dynamometer with maximal force. Subsequently, the test was repeated for the opposite hand, with each hand undergoing three trials. Detailed guidelines for implementation are outlined in the NHANES Muscle Strength Procedures Manual. The total grip strength was calculated as the sum of the maximum readings from each hand and expressed in kilograms. Under the same circumstances (including height), individuals with higher body weight typically possess greater strength. Therefore, we employed weight-corrected grip strength as the dependent variable [ 11 ]. Covariates As stated on the NHANES website, qualified personnel at all study sites adhered to standardized protocols for data collection. During household interviews, information regarding sociodemographic factors such as age, gender, and race/ethnicity was gathered. Based on prior literature, the following variables were selected as covariates. The demographic variables encompassed gender (male or female), age groups (20–39 years, 40–59 years, ≥ 60 years), race (Mexican American, Other Hispanic, Non-Hispanic White, Non-Hispanic Black, Non-Hispanic Asian, Other Race), education level (less than high school, high school or equivalent, college or above), marital status (married/living with partner, widowed/divorced/separated/never married), and the monthly poverty level index ( 1.85). We also incorporated smoking status, alcohol consumption status, and physical activity as lifestyle variables. Individuals who had smoked more than 100 cigarettes over their lifetime were categorized as smokers, and those who had not were designated as non-smokers [ 12 ]. Drinking status was categorized as “drinker” if the participant reported having more than 12 alcoholic beverages in the past year and “nondrinker” otherwise [ 13 ]. Physical activity was divided into work activities and recreational activities in accordance with the survey collection, with three levels: none, moderate, and vigorous [ 14 ]. We further included hypertension, diabetes, and high cholesterol status as risk variables. The determination of high blood pressure and high cholesterol status was based on the NHANES questionnaire data. Diabetes was defined as having a history of diabetes, a fasting blood glucose level ≥ 7.0 mmol/L, or a glycosylated hemoglobin (HbA1c) > 6.5%. Statistical analysis Continuous variables encompassed in this study were delineated as means along with standard errors, whilst categorical variables were depicted by the actual number in conjunction with weighted percentages. To appraise the linear correlations between serum alkaline phosphatase (ALP) and grip strength, a Generalized Linear Model was utilized. To adjust for covariates, three different models were utilized. Model A remained unadjusted. In Model B, adjustments were executed for gender, age group, race, education level, marital status, and monthly poverty level index category. Model C, in addition to the adjustments made in Model B, also accounted for smoking status, drinking status, work activity status, recreational activity status, and hypertension, high cholesterol status, diabetes. The nonlinear association between serum ALP and grip strength was scrutinized through smooth curve fitting models and generalized additive models; a recursive approach was adopted to compute the inflection point in this nonlinear connection. Subsequently, two or three-piecewise linear regression models were conducted on either side of these inflection points. Data analysis was carried out employing R software (version 4.2.2) and EmpowerStats ( http://www.empowerstats.com ). A P-value of less than 0.05 was regarded as statistically significant. Results Characteristics of the study population Detailed baseline characteristics of the participants are summarized in Table 1 . A total of 2,182 participants were involved, encompassing 1,190 males (54.54%) and 992 females (45.46%), with a larger proportion being within the 20–39 years age group (58.53%). The majority of participants had a college education or higher (61.32%), with a predominant representation of non-Hispanic White individuals (39.00%).The average level of weight-corrected grip strength was 0.99 ± 0.26. The mean concentration of serum ALP was 63.00 ± 19.60 IU/L. Table 1 Characteristics of participants enrolled in study (n = 2182) Variables Mean (SD) or N (%) Gender, n(%) Male 1190 (54.54) Female 992 (45.46) Age group, n(%) 20–39 y 1287 (58.53) 40–59 y 905 (41.47) Race ethnicity, n(%) Mexican American 321 (14.71) Other Hispanic 196 (8.98) Non-Hispanic White 851 (39.00) Non-Hispanic Black 438 (20.07) Other Race 376 (17.23) Education level, n(%) Less than high school 369 (16.91) High school or equivalent 475 (21.77) College or above 1338 (61.32) Marriage status, n(%) Married/living with partner 1295 (59.35) Widowed/divorced/separated/ never married 887 (40.65) Monthly poverty level index category, n(%) 1.85 1108 (50.78) Smoking status, n(%) Smoker 818 (37.49) Non-smoker 1364 (62.51) Drinking status, n(%) Drinker 1648 (75.53) Non-drinker 534 (24.47) Work activity status, n(%) None 508 (23.28) Moderate 470 (21.54) Vigorous 1204 (55.18) Recreational activity status, n(%) None 705 (32.31) Moderate 553 (25.34) Vigorous 924 (42.35) Hypertension, n(%) Yes 430 (19.71) No 1752 (80.29) High cholesterol status, n(%) Yes 473 (21.68) No 1709 (78.32) Diabetes, n(%) Yes 158 (7.24) No 2024 (92.76) Serum alkaline phosphatase, (IU/L, mean ± SD) 63.00 ± 19.60 Comprehensive grip strength/Weight, (mean ± SD) 0.99 ± 0.26 Relationship between serum ALP and grip strength In Table 2 , we reveal the negative correlation between serum ALP levels and grip strength in Model A (− 0.00121[− 0.00177, − 0.00065] < 0.000022). This inverse relationship remained evident in the adjusted models [Model B: −0.00152 (− 0.00201, − 0.00103) < 0.000001; Model C:−0.00126(− 0.00174,−0.00079) < 0.000001].When stratified by gender, age group and race ,for all groups except for Other races[Model A: −0.00022 (− 0.00130, 0.00085)0.685816; Model C:−0.00086(− 0.00186,0.00013) 0.089622], serum ALP were negatively correlated with grip strength, as shown in Table 3 . It is worth noting that negative correlation between serum ALP and grip strength in female at any age group[Female(20-39y): −0.00260 (− 0.00245, − 0.00175) < 0.000001; Female(40-59y): −0.00096 (− 0.00187, − 0.00005)0.039893], but no significant correlation in male[Male(20-39y): −0.00093 (− 0.00197, 0.00011)0.079788; Male(40-59y):−0.00032(− 0.00126,0.00061) 0.501354],as shown in Table 4 . Table 2 Relationship Between concentrations of serum alkaline phosphatase and grip strength/weight in All Participants Model A β (95% CI) P value Model B β (95% CI) P value Model C β (95% CI) P value alkaline phosphatase (IU/L) -0.00121(-0.00177, -0.00065) 0.000022 -0.00152(-0.00201, -0.00103) < 0.000001 -0.00126(-0.00174, -0.00079) < 0.000001 Model A was not adjusted Model B was adjusted for gender, age group, race, education level, marital status, and monthly poverty level index category Model C was adjusted for gender, age group, race, education level, marital status, and monthly poverty level index category, smoking status, drinking status, work activity status, recreational activity status, and hypertension, high cholesterol status, diabetes Table 3 Stratified analysis of the correlation between serum alkaline phosphatase and grip strength/weight Model A β (95% CI) P value Model B β (95% CI) P value Model C β (95% CI) P value Subgroup analysis stratified by gender Male -0.00117(-0.00189, -0.00046) 0.001373 -0.00097(-0.00170, -0.00024) 0.009170 -0.00082(-0.00154, -0.00011) 0.024574 Female -0.00276(-0.00337, -0.00215) < 0.000001 -0.00222(-0.00284, -0.00161) < 0.000001 -0.00191(-0.00253, -0.00130) < 0.000001 Subgroup analysis stratified by age group 20–39 y -0.00116(-0.00195, 0.00038) 0.003676 -0.00187(-0.00256, -0.00118) < 0.000001 -0.00162(-0.00230, -0.00093) 0.000004 40–59 y -0.00102(-0.00179, -0.00025) 0.009944 -0.00097(-0.00164, -0.00029) 0.005035 -0.00066(-0.00131, -0.00001) 0.048463 Subgroup analysis stratified by race Mexican American -0.00058(-0.00200, 0.00083) 0.418293 -0.00120(-0.00237, -0.00004) 0.044331 -0.00119(-0.00235, -0.00003) 0.045249 Other Hispanic -0.00142(-0.00317, 0.00032) 0.110984 -0.00192(-0.00345, -0.00038) 0.015124 -0.00157(-0.00307, 0.00008) 0.040601 Non-Hispanic White -0.00117(-0.00218, -0.00015) 0.024431 -0.00173(-0.00262, -0.00083) 0.000162 -0.00135(-0.00221, -0.00049) 0.002116 Non-Hispanic Black -0.00135(-0.00268, -0.00001) 0.048203 -0.00141(-0.00253, -0.00028) 0.014623 -0.00138(-0.00248, -0.00027) 0.015144 Other Race -0.00022(-0.00130, 0.00085) 0.685816 -0.00105(-0.00202, -0.00008) 0.034112 -0.00086(-0.00186, 0.00013) 0.089622 Model A was not adjusted Model B was adjusted for gender, age group, race, education level, marital status, and monthly poverty level index category Model C was adjusted for gender, age group, race, education level, marital status, and monthly poverty level index category, smoking status, drinking status, work activity status, recreational activity status, and hypertension, high cholesterol, diabetes In the subgroup analysis stratified by gender, age group, race, the model was not adjusted for gender, age group or race Table 4 Stratified examination of the relationship between serum alkaline phosphatase and grip strength/weight based on gender (age group) Subgroup β (95% CI) P value Male(20-39y) -0.00093(-0.00197, 0.00011) 0.079788 Male(40-59y) -0.00032(-0.00126, 0.00061) 0.501354 Female(20-39y) -0.00260(-0.00245, -0.00175) < 0.000001 Female(40-59y) -0.00096(-0.00187, -0.00005) 0.039893 Race, education level, marital status, and monthly poverty level index category, smoking status, drinking status, work activity status, recreational activity status, and hypertension, high cholesterol, diabetes were adjusted Nonlinear relationship between serum ALP and grip strength We further evaluated the nonlinear relationship between the serum levels of ALP and grip strength using a smoothing curve fitting method, as shown in Fig. 2 . Figure 3 – 6 display fitted smoothing curves describing the nonlinear relationships between serum ALP and grip strength. Figure 3 shows that serum ALP levels and grip strength showed an M-shaped relationship among all male participants. When divided into four groups according to gender and age, Fig. 5 shows that serum ALP levels and grip strength showed an N-shaped relationship among male participants aged 20–39 years, and an L-shaped relationship among male participants aged 40–59 years. In male participants aged 20 to 39 years, the analysis using a three-segment linear regression model indicated that serum alkaline phosphatase levels at the two turning points (k1 and k2) were 39 IU/L and 77 IU/L, respectively, with an effect size of -0.0027 for serum ALP between these values, as shown in Table 5 . In male individuals aged 40 to 59 years, a two-segment linear regression analysis revealed a saturation effect at 60 IU/L, showing an effect size of -0.0046 for serum alkaline phosphatase levels that are below this threshold and 0.0008 for those exceeding 60 IU/L, as shown in Table 6 . Table 5 Threshold effect analysis of serum alkaline phosphatase on Combined grip strength/weight in male(20-39y) using the three-piecewise linear regression model Male(20-39y) Combined grip strength/weight Adjusted β (95% CI) P value Linear model effect -0.0009(-0.0020,0.0001)0.0798 Three-segment linear regression model Turing points(K1,K2) 39,77 K2 effect 3 -0.0003(-0.0026, 0.0020)0.7685 likelihood-ratio test 0.048 Race, education level, marital status, and monthly poverty level index category, smoking status, drinking status, work activity status, recreational activity status, and hypertension, high cholesterol status, diabetes were adjusted Table 6 Threshold effect analysis of serum alkaline phosphatase on Combined grip strength/weight in male(40-59y) using the two-piecewise linear regression model Male(40-59y) Combined grip strength/weight Adjusted β (95% CI) P value Linear model effect -0.0003(-0.0013,0.0006)0.5014 Two-segment linear regression model Turing points(K) 60 K effect 0.0008(-0.0004,0.0020)0.1777 likelihood-ratio test 0.003 Race, education level, marital status, and monthly poverty level index category, smoking status, drinking status, work activity status, recreational activity status, and hypertension, high cholesterol status, diabetes were adjusted Discussion The association between serum ALP levels and grip strength has thus far been inadequately explored. Our research revealed a notable inverse relationship between serum ALP levels and grip strength across the whole study group. Comparable to our findings, A cross-sectional study in South Korea showed that both male and female serum ALP levels were positively correlated with low skeletal muscle mass index (LSMI), interestingly, the predictive power of serum ALP level for LSMI was significantly higher in women [ 10 ]. In our study, subgroup analysis disclosed that in the 20–59 age group among females, a significantly negative correlation existed between serum ALP and hand grip strength; however, it is worth noting that an N-shaped relationship was observed between serum ALP and grip strength in males aged 20–39 years, and an L-shaped relationship was noted in males aged 40–59 years. To the best of our knowledge, this study represents the first exploration of the complex connections between serum ALP levels and grip strength among adults in the United States. Muscle health holds a crucial position in physical function and metabolism [ 15 ]. Muscle function constitutes an important indicator for predicting the outcome of sarcopenia [ 16 ]. Besides primary aging, other secondary causes like malnutrition, endocrine disorders, inflammation, etc., may contribute to the acceleration of muscle loss, ultimately resulting in a decrease in muscle strength [ 17 ]. Sarcopenia is common among the elderly but can also be witnessed in younger individuals [ 18 ]. Paying attention to skeletal muscle health in young and middle-aged people is of critical importance for preventing sarcopenia in the elderly. Serum ALP is a ubiquitous membrane-bound glycoprotein present in nearly all tissues of the body [ 19 ], notably elevated levels are found in the liver, kidneys, bile ducts, bones [ 7 ]. It has been demonstrated that increased plasma levels of serum ALP have been associated with a worse prognosis in several types of diseases [ 20 ], such as renal osteodystrophy [ 7 ] and stroke [ 21 ]. In humans, four distinct isoenzymes of alkaline phosphatase are expressed: tissue-nonspecific ALP, intestinal ALP, placental ALP, and germ cell ALP [ 7 ]. ALP plays a significant role in muscle metabolism. Tissue-nonspecific alkaline phosphatase (TNALP) is the predominant isoenzyme of alkaline phosphatase in the human body. Basic research has discovered that TNAP deficiency can alter mitochondrial activity, reduce muscle strength, and hamper bone mineralization and trabecular formation of bone marrow stromal cells [ 9 ]. Simultaneously, increased basal mitochondrial respiration might induce chronic oxidative stress, leading to superoxide production and inducing muscle pathology [ 22 ]. However, Clinical research indicates that in patients undergoing hemodialysis, there is an inverse relationship between the levels of ALP and their muscle mass, strength, and overall physical function [ 23 ]. A substantial cohort study identified a significant association between elevated serum total ALP levels and the incidence of hip fractures [ 8 ]. A single-center cohort study demonstrated that elevated serum bone-specific ALP levels were correlated with fracture risk, and hemodialyzed patients with increased b-AP had an elevated fracture risk [ 24 ]. The study by Xiao Song Cheng et al. revealed that serum ALP levels in young and middle-aged individuals were negatively correlated with pelvic bone density [ 25 ]. In states of diminished bone density, osteoblasts are activated and produce a substantial quantity of bone alkaline phosphatase, thereby resulting in a significant increase in serum ALP levels [ 26 ]. Lower bone density might indirectly impact muscle function, leading to a reduction in muscle strength. The effect of ALP on bone and mineral homeostasis is a double-edged sword. ALP can enhance bone mineralization, but it may also induce vascular calcification [ 27 ], which may have a negative influence on skeletal muscle health [ 28 ]. The specific mechanisms underlying this relationship call for further meticulous and profound exploration. ALP levels are intimately related to nutritional status and chronic inflammation. The phase angle (PhA), a well-acknowledged nutritional indicator associated with healthy cell membranes, exhibits excellent accuracy in reflecting muscle mass and can also be employed as a facile indicator for gauging muscle mass [ 29 ]. Seok Hui Kang et al. discovered a negative correlation between ALP levels and PhA [ 23 ]. Kim et al. found that ALP is closely associated with metabolic or nutritional disorders, and serum ALP levels showed a positive correlation with body fat mass among the general population in Korea. [ 30 ]. Fermín Sánchez de Medina et al. suggested that ALP seems to be related to the inflammatory process and its regulation [ 31 ]. The activity of ALP is influenced by oxidative stress in both in vitro and in vivo conditions. [ 32 ]. ALP can be utilized as a comprehensive marker of nutritional status and inflammation [ 33 ]. Elevated serum total ALP levels correlate with higher serum C-reactive protein (CRP) levels and increased mortality in the general population [ 34 ]. Experimental studies have shown that inflammatory cytokines can activate numerous molecular pathways associated with skeletal muscle atrophy, resulting in muscle atrophy [ 35 ]. Additional studies are essential to explore the adverse effects of this process on muscle function. Strengths and limitations Firstly, due to the cross-sectional design of this study, it limited the ability to assess the causal relationship between serum ALP and grip strength. Furthermore, some disorders that might notably increase serum ALP, such as biliary obstructive diseases and osteosarcoma, could not be completely excluded. Finally, although a number of covariates were controlled for in our multivariate regression analyses, the existence of some other potential confounders might still bias the results. Conclusions This research uncovered the connection between serum ALP levels and grip strength, highlighting variations in this association based on gender and age. Our analysis revealed a negative correlation between serum alkaline phosphatase and grip strength in females aged 20 to 59 years. In male (20–39 years old) and male (40–59 years old) participants, serum ALP concentration showed an N-type and L-type relationship with grip strength, respectively. This discovery provides new clues and orientations for the mechanism of the influence of serum ALP on skeletal muscle health. To gain a deeper understanding of the relationship between serum ALP and grip strength across different genders and age groups, additional prospective studies involving larger populations are necessary. Abbreviations ALP Alkaline Phosphatase PhA Phase Angle TNALP Tissue-nonspecific alkaline phosphatase LSMI Low skeletal muscle mass index NHANES National Health and Nutrition Examination Survey Declarations Ethics approval and consent to participate The ethics review board of the National Center for Health Statistics approved all NHANES protocols, and each participant signed written informed consent. Consent for publication Not applicable Availability of data and materials The datasets generated and/or analysed during the current study are available in the Health and Nutrition Examination Survey (NHANES) during 2013–2014, at http://www.cdc.gov/nchs/nhanes/. Competing interests The authors declare that they have no competing interests Funding This work was supported by Scientific Research Project of Jiangsu Provincial Health Committee in China (To Guo-yang Zhao, M2022119) , 2021 Zhenjiang City Social Development Guiding Science and Technology Plan Project(To Bo Wang,FZ2021058) and 2023 Zhenjiang Science and Technology Innovation Fund (To Bo Wang,SH2023030) . Author information Ziyi Zhang 1 Affiliated Hospital of Jiangsu University Email: [email protected] Jiajie Zhou 1 Affiliated Hospital of Jiangsu University Email: [email protected] Anpei Ma 2 Yancheng First People’s Hospital Email: [email protected] Honggu Chen 2 Zhejiang Taizhou Hospital Email: [email protected] Bo Wang 2 Affiliated Hospital of Jiangsu University Email: [email protected] Guoyang Zhao 1* Affiliated Hospital of Jiangsu University Email: [email protected] Corresponding author: Guoyang Zhao Email: [email protected] These authors contributed equally: Ziyi Zhang and Jiajie Zhou Authors’ contributions ZYZ, JJZ, contributed to the study design and writing of the manuscript. APM, HGC, BW and contributed to data collection, analysis, and writing of the manuscript. G.Y.Z. project administration, supervision. All authors read and approved the final manuscript. 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Kramer PA, Duan J, Qian WJ, Marcinek DJ. The Measurement of Reversible Redox Dependent Post-translational Modifications and Their Regulation of Mitochondrial and Skeletal Muscle Function. Front Physiol. 2015;6:347. Kang SH, Do JY, Kim JC. Association Between Alkaline Phosphatase and Muscle Mass, Strength, or Physical Performance in Patients on Maintenance Hemodialysis. Front Med (Lausanne). 2021;8:657957. Iimori S, Mori Y, Akita W, Kuyama T, Takada S, Asai T, et al. Diagnostic usefulness of bone mineral density and biochemical markers of bone turnover in predicting fracture in CKD stage 5D patients–a single-center cohort study. Nephrol Dial Transpl. 2012;27(1):345–51. Cheng X, Zhao C. The correlation between serum levels of alkaline phosphatase and bone mineral density in adults aged 20 to 59 years. Med (Baltim). 2023;102(32):e34755. Shu J, Tan A, Li Y, Huang H, Yang J. The correlation between serum total alkaline phosphatase and bone mineral density in young adults. BMC Musculoskelet Disord. 2022;23(1):467. Bover J, Urena P, Aguilar A, Mazzaferro S, Benito S, Lopez-Baez V, et al. Alkaline Phosphatases in the Complex Chronic Kidney Disease-Mineral and Bone Disorders. Calcif Tissue Int. 2018;103(2):111–24. Kim SH, Choi G, Song Y, Yoon H, Jeong HM, Gu JE et al. Low Muscle Mass in Patients Receiving Hemodialysis: Correlations with Vascular Calcification and Vascular Access Failure. J Clin Med. 2021;10(16). Akamatsu Y, Kusakabe T, Arai H, Yamamoto Y, Nakao K, Ikeue K, et al. Phase angle from bioelectrical impedance analysis is a useful indicator of muscle quality. J Cachexia Sarcopenia Muscle. 2022;13(1):180–9. Kim MK, Baek KH, Kang MI, Park SE, Rhee EJ, Park CY, et al. Serum alkaline phosphatase, body composition, and risk of metabolic syndrome in middle-aged Korean. Endocr J. 2013;60(3):321–8. Sanchez de Medina F, Martinez-Augustin O, Gonzalez R, Ballester I, Nieto A, Galvez J, et al. Induction of alkaline phosphatase in the inflamed intestine: a novel pharmacological target for inflammatory bowel disease. Biochem Pharmacol. 2004;68(12):2317–26. Mody N, Parhami F, Sarafian TA, Demer LL. Oxidative stress modulates osteoblastic differentiation of vascular and bone cells. Free Radic Biol Med. 2001;31(4):509–19. Beberashvili I, Samogalska O, Azar A, Stav K, Efrati S. Nutritional Status and Mortality Predictability for Time-Varying Serum Alkaline Phosphatase in Hemodialysis Patients: A Longitudinal Study. J Ren Nutr. 2020;30(5):452–61. Filipowicz R, Greene T, Wei G, Cheung AK, Raphael KL, Baird BC, et al. Associations of serum skeletal alkaline phosphatase with elevated C-reactive protein and mortality. Clin J Am Soc Nephrol. 2013;8(1):26–32. Bano G, Trevisan C, Carraro S, Solmi M, Luchini C, Stubbs B, et al. Inflammation and sarcopenia: A systematic review and meta-analysis. Maturitas. 2017;96:10–5. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 25 Feb, 2025 Read the published version in BMC Musculoskeletal Disorders → Version 1 posted Editorial decision: Revision requested 07 Jan, 2025 Reviews received at journal 06 Jan, 2025 Reviewers agreed at journal 06 Jan, 2025 Reviews received at journal 28 Nov, 2024 Reviewers agreed at journal 18 Nov, 2024 Reviewers invited by journal 11 Nov, 2024 Editor invited by journal 06 Nov, 2024 Editor assigned by journal 06 Nov, 2024 Submission checks completed at journal 05 Nov, 2024 First submitted to journal 27 Oct, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5342416","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":378945183,"identity":"a90213d8-5cad-46b1-b690-149ac993bfd1","order_by":0,"name":"Ziyi Zhang","email":"","orcid":"","institution":"Affiliated Hospital of Jiangsu University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Ziyi","middleName":"","lastName":"Zhang","suffix":""},{"id":378945184,"identity":"d94df388-0572-41aa-8640-73cf66862cc8","order_by":1,"name":"Jiajie Zhou","email":"","orcid":"","institution":"Affiliated Hospital of Jiangsu University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jiajie","middleName":"","lastName":"Zhou","suffix":""},{"id":378945185,"identity":"f22f129a-8321-4372-9a2c-6c1bbcbeeb30","order_by":2,"name":"Anpei Ma","email":"","orcid":"","institution":"Yancheng First People's Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Anpei","middleName":"","lastName":"Ma","suffix":""},{"id":378945186,"identity":"216a2a41-d325-4ba0-8703-147ea6407085","order_by":3,"name":"Honggu Chen","email":"","orcid":"","institution":"Zhejiang Taizhou Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Honggu","middleName":"","lastName":"Chen","suffix":""},{"id":378945187,"identity":"59d36ec1-2267-49ac-9519-9e75694a6432","order_by":4,"name":"Bo Wang","email":"","orcid":"","institution":"Affiliated Hospital of Jiangsu University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Bo","middleName":"","lastName":"Wang","suffix":""},{"id":378945189,"identity":"19d92862-c280-4793-8396-bedb991569d5","order_by":5,"name":"Guoyang Zhao","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA1klEQVRIiWNgGAWjYBAC+wYGxgcfKmx42NgbGx9+IEYLYwMDs+GMM2ly/DyHm40liNTCJs3bcshYckZ6mwAPMVqY+deYSfM2HEjccPNhG4MEg52cbgMBLWwSb4wt5+64k7jhdmLbgwKGZGOzAwS08EicMbzx9swzkJZ2AwmGA4nbCGmRkDhjIMHbdhjosINtEjzEaDHg7zGSBGoBep+RWC0SbMXQQE4EBrIBEX6x7z+8ERqVxx8+/FBhJ0dQC4NEhgGypYSUgwD/8QfEKBsFo2AUjIKRDABO4kp7vVgVJgAAAABJRU5ErkJggg==","orcid":"","institution":"Affiliated Hospital of Jiangsu University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Guoyang","middleName":"","lastName":"Zhao","suffix":""}],"badges":[],"createdAt":"2024-10-27 17:53:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5342416/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5342416/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12891-025-08408-2","type":"published","date":"2025-02-25T15:57:43+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":70403355,"identity":"a6852918-eb0a-492f-9a58-6d53d57daf26","added_by":"auto","created_at":"2024-12-02 22:45:15","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":138304,"visible":true,"origin":"","legend":"\u003cp\u003eFlow diagram of the study participants included in NHANES 2013–2014.\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5342416/v1/e47956bf7d108af3f84cc26d.jpg"},{"id":70403767,"identity":"c7d948e5-92e1-4f77-b88d-80cfdad1f631","added_by":"auto","created_at":"2024-12-02 22:53:15","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1238146,"visible":true,"origin":"","legend":"\u003cp\u003eThe association between serum alkaline phosphatase and grip strength. \u003cstrong\u003ea\u003c/strong\u003e Each black dot signifies an individual sample. \u003cstrong\u003eb\u003c/strong\u003eThe solid red line illustrates the smoothed fitting curve among the variables, while the blue band represents the 95% confidence interval associated with the fit. (gender, age group, race, education level, marital status, and monthly poverty level index category, smoking status, drinking status, work activity status, recreational activity status, and hypertension, high cholesterol, diabetes were adjusted)\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-5342416/v1/0feaf0162fb298df29a42ef2.png"},{"id":70403768,"identity":"65a1fb41-dea4-4aaa-ab7c-23f1e0c8521a","added_by":"auto","created_at":"2024-12-02 22:53:15","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":222527,"visible":true,"origin":"","legend":"\u003cp\u003eThe association between serum alkaline phosphatase and grip strength by gender. Age group, race, education level, marital status, and monthly poverty level index category, smoking status, drinking status, work activity status, recreational activity status, and hypertension, high cholesterol status, diabetes were adjusted were adjusted.\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-5342416/v1/85973c0dbf4d0fd1b2f2a262.png"},{"id":70403356,"identity":"acaa905e-5e21-42f5-aa6d-fb3404f86e85","added_by":"auto","created_at":"2024-12-02 22:45:15","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":224539,"visible":true,"origin":"","legend":"\u003cp\u003eThe association between serum alkaline phosphatase and grip strength by age group. Gender, race, education level, marital status, and monthly poverty level index category, smoking status, drinking status, work activity status, recreational activity status, and hypertension, high cholesterol status, diabetes were adjusted were adjusted.\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-5342416/v1/79bccf5a3817088ac1ac3336.png"},{"id":70403360,"identity":"895e2028-1cb9-40cb-a35d-a0725ff35676","added_by":"auto","created_at":"2024-12-02 22:45:15","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":320434,"visible":true,"origin":"","legend":"\u003cp\u003eThe association between serum alkaline phosphatase and grip strength by gender (age group). Race, education level, marital status, and monthly poverty level index category, smoking status, drinking status, work activity status, recreational activity status, and hypertension, high cholesterol status, diabetes were adjusted were adjusted.\u003c/p\u003e","description":"","filename":"Figure5.png","url":"https://assets-eu.researchsquare.com/files/rs-5342416/v1/e34c8d1578c229f9eefce1d6.png"},{"id":70403358,"identity":"212a397e-9dfe-4c67-8708-55eac9a7891c","added_by":"auto","created_at":"2024-12-02 22:45:15","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":369428,"visible":true,"origin":"","legend":"\u003cp\u003eThe association between serum alkaline phosphatase and grip strength by race. Age group, gender, education level, marital status, and monthly poverty level index category, smoking status, drinking status, work activity status, recreational activity status, and hypertension, high cholesterol status, diabetes were adjusted were adjusted.\u003c/p\u003e","description":"","filename":"Figure6.png","url":"https://assets-eu.researchsquare.com/files/rs-5342416/v1/bebb12b88fe3d85000db6a39.png"},{"id":77622501,"identity":"fd5cddab-62fe-4f97-8be6-e520a69c31fb","added_by":"auto","created_at":"2025-03-03 16:07:37","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2963733,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5342416/v1/6f82a551-d779-450a-9507-a9923d78b888.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Sex-dependent association of serum alkaline phosphatase with grip strength in adults aged 20-59: NHANES 2013-2014","fulltext":[{"header":"Background","content":"\u003cp\u003eSarcopenia represents a progressive and generalized skeletal muscle disorder entailing the accelerated depletion of muscle mass and function, which is associated with augmented adverse outcomes such as falls, functional deterioration, frailty, and mortality [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Sarcopenia is correlated with a multitude of factors, including age-related inflammation, inactivity, poor nutrition, and chronic diseases [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Grip strength constitutes an essential factor in the diagnosis of sarcopenia [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], as muscle strength is not solely dependent on mass [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Lower handgrip strength in healthy adults predicts an elevated risk of functional limitations and disabilities in later life, as well as all-cause mortality [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Considering the high prevalence and severe implications of sarcopenia, there is an immediate and compelling urgency to investigate the mechanisms influencing grip strength.\u003c/p\u003e \u003cp\u003eAlkaline phosphatase (ALP) is an enzyme present in diverse tissues throughout the body. The majority of ALP in serum (over 80%) originates from the liver and bones, with a minor portion coming from the intestines [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. ALP plays a significant role in inflammation and metabolic syndrome [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], and elevated ALP is invariably associated with adverse outcomes [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. A large cohort study demonstrated that higher serum total ALP levels were significantly associated with the incidence of hip fractures [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Basic research suggests that tissue nonspecific alkaline phosphatase (TNAP) functions within bone and muscle progenitor cells to impact ATP production and mitochondrial respiration [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], but the exact physiological function of ALP remains largely unknown.\u003c/p\u003e \u003cp\u003eIn relation to the musculoskeletal system, some researchers have discerned a positive association between serum alkaline phosphatase (ALP) and a low muscle mass index [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Nevertheless, the effect of serum ALP on grip strength remains uncharted. Hence, we initiated this research endeavor to investigate the interrelationship between serum ALP and grip strength within the US population.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy population\u003c/h2\u003e \u003cp\u003eThe National Health and Nutrition Examination Survey (NHANES) is a biennial nationwide study that recruits a representative sample of the general population in the United States. In the 2013\u0026ndash;2014 NHANES, We incorporated 3,928 adults aged 20 to 59 years from among 10,175 participants. Those lacking data of alkaline phosphatase (n\u0026thinsp;=\u0026thinsp;295) and hand grip strength (n\u0026thinsp;=\u0026thinsp;233) were excluded. Additionally, subjects fulfilling any of the following criteria were also excluded: pregnancy (n\u0026thinsp;=\u0026thinsp;60); a history of hand surgery (n\u0026thinsp;=\u0026thinsp;63); neoplastic disease (n\u0026thinsp;=\u0026thinsp;131); liver disease (n\u0026thinsp;=\u0026thinsp;92); thyroid disease (n\u0026thinsp;=\u0026thinsp;203); arthritis (n\u0026thinsp;=\u0026thinsp;343); osteoporosis (n\u0026thinsp;=\u0026thinsp;11); and missing covariates (n\u0026thinsp;=\u0026thinsp;315). \"The final study sample comprised 2,182 participants, and a flowchart illustrating the exclusion criteria is provided in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eMeasurement of serum alkaline phosphatase\u003c/h3\u003e\n\u003cp\u003eIn this investigation, serum ALP was designated as the exposure variable. From 2013 to 2014, the DxC800 system adopted a kinetic rate methodology employing a 2-Amino-2-Methyl-1-Propanol (AMP) buffer for the measurement of ALP activity in serum or plasma. In the reaction, ALP catalyzes the hydrolysis of the colorless organic phosphate ester substrate, p-Nitrophenylphosphate, to the yellow-colored product, p-Nitrophenol, and phosphate. This reaction transpires at an alkaline pH of 10.3. The system monitors the rate of alteration in absorbance at 410 nm within a fixed-time interval. This rate of change in absorbance is directly proportional to the ALP activity in the serum. Detailed information about serum alkaline phosphatase can be found in the National Health and Nutrition Examination Survey: Laboratory Procedure Manual at \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://www.cdc.gov/nchs/nhanes/\u003c/span\u003e\u003cspan address=\"http://www.cdc.gov/nchs/nhanes/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/p\u003e\n\u003ch3\u003eMeasurement of grip strength\u003c/h3\u003e\n\u003cp\u003eThe grip strength data was collected using the Takei Digital Grip Strength Dynamometer (Model T.K.K.5401). A proficient examiner elaborated and demonstrated the protocol to the participant. Subsequently, the examiner adjusted the grip size of the dynamometer to match the participant's hand size and requested the participant to squeeze the dynamometer for a practice attempt. After the practice session, the participant was instructed to employ one of their hands to squeeze the dynamometer with maximal force. Subsequently, the test was repeated for the opposite hand, with each hand undergoing three trials. Detailed guidelines for implementation are outlined in the NHANES Muscle Strength Procedures Manual. The total grip strength was calculated as the sum of the maximum readings from each hand and expressed in kilograms. Under the same circumstances (including height), individuals with higher body weight typically possess greater strength. Therefore, we employed weight-corrected grip strength as the dependent variable [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e\n\u003ch3\u003eCovariates\u003c/h3\u003e\n\u003cp\u003eAs stated on the NHANES website, qualified personnel at all study sites adhered to standardized protocols for data collection. During household interviews, information regarding sociodemographic factors such as age, gender, and race/ethnicity was gathered. Based on prior literature, the following variables were selected as covariates. The demographic variables encompassed gender (male or female), age groups (20\u0026ndash;39 years, 40\u0026ndash;59 years, \u0026ge; 60 years), race (Mexican American, Other Hispanic, Non-Hispanic White, Non-Hispanic Black, Non-Hispanic Asian, Other Race), education level (less than high school, high school or equivalent, college or above), marital status (married/living with partner, widowed/divorced/separated/never married), and the monthly poverty level index (\u0026lt;\u0026thinsp;1.3, 1.3\u0026ndash;1.85, \u0026gt;\u0026thinsp;1.85). We also incorporated smoking status, alcohol consumption status, and physical activity as lifestyle variables. Individuals who had smoked more than 100 cigarettes over their lifetime were categorized as smokers, and those who had not were designated as non-smokers [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Drinking status was categorized as \u0026ldquo;drinker\u0026rdquo; if the participant reported having more than 12 alcoholic beverages in the past year and \u0026ldquo;nondrinker\u0026rdquo; otherwise [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Physical activity was divided into work activities and recreational activities in accordance with the survey collection, with three levels: none, moderate, and vigorous [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. We further included hypertension, diabetes, and high cholesterol status as risk variables. The determination of high blood pressure and high cholesterol status was based on the NHANES questionnaire data. Diabetes was defined as having a history of diabetes, a fasting blood glucose level\u0026thinsp;\u0026ge;\u0026thinsp;7.0 mmol/L, or a glycosylated hemoglobin (HbA1c)\u0026thinsp;\u0026gt;\u0026thinsp;6.5%.\u003c/p\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eContinuous variables encompassed in this study were delineated as means along with standard errors, whilst categorical variables were depicted by the actual number in conjunction with weighted percentages. To appraise the linear correlations between serum alkaline phosphatase (ALP) and grip strength, a Generalized Linear Model was utilized. To adjust for covariates, three different models were utilized. Model A remained unadjusted. In Model B, adjustments were executed for gender, age group, race, education level, marital status, and monthly poverty level index category. Model C, in addition to the adjustments made in Model B, also accounted for smoking status, drinking status, work activity status, recreational activity status, and hypertension, high cholesterol status, diabetes. The nonlinear association between serum ALP and grip strength was scrutinized through smooth curve fitting models and generalized additive models; a recursive approach was adopted to compute the inflection point in this nonlinear connection. Subsequently, two or three-piecewise linear regression models were conducted on either side of these inflection points. Data analysis was carried out employing R software (version 4.2.2) and EmpowerStats (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://www.empowerstats.com\u003c/span\u003e\u003cspan address=\"http://www.empowerstats.com\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e). A P-value of less than 0.05 was regarded as statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eCharacteristics of the study population\u003c/h2\u003e \u003cp\u003eDetailed baseline characteristics of the participants are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. A total of 2,182 participants were involved, encompassing 1,190 males (54.54%) and 992 females (45.46%), with a larger proportion being within the 20\u0026ndash;39 years age group (58.53%). The majority of participants had a college education or higher (61.32%), with a predominant representation of non-Hispanic White individuals (39.00%).The average level of weight-corrected grip strength was 0.99\u0026thinsp;\u0026plusmn;\u0026thinsp;0.26. The mean concentration of serum ALP was 63.00\u0026thinsp;\u0026plusmn;\u0026thinsp;19.60 IU/L.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics of participants enrolled in study (n\u0026thinsp;=\u0026thinsp;2182)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMean (SD) or N (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1190 (54.54)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e992 (45.46)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge group, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e20\u0026ndash;39 y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1287 (58.53)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e40\u0026ndash;59 y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e905 (41.47)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRace ethnicity, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMexican American\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e321 (14.71)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther Hispanic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e196 (8.98)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-Hispanic White\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e851 (39.00)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-Hispanic Black\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e438 (20.07)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther Race\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e376 (17.23)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEducation level, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLess than high school\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e369 (16.91)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHigh school or equivalent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e475 (21.77)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCollege or above\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1338 (61.32)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMarriage status, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMarried/living with partner\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1295 (59.35)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWidowed/divorced/separated/ never married\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e887 (40.65)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMonthly poverty level index category, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;1.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e761 (34.88)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1.3\u0026ndash;1.85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e313 (14.34)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt; 1.85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1108 (50.78)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmoking status, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmoker\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e818 (37.49)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-smoker\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1364 (62.51)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDrinking status, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDrinker\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1648 (75.53)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-drinker\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e534 (24.47)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWork activity status, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e508 (23.28)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eModerate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e470 (21.54)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVigorous\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1204 (55.18)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRecreational activity status, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e705 (32.31)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eModerate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e553 (25.34)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVigorous\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e924 (42.35)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e430 (19.71)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1752 (80.29)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHigh cholesterol status, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e473 (21.68)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1709 (78.32)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e158 (7.24)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2024 (92.76)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum alkaline phosphatase, (IU/L, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e63.00\u0026thinsp;\u0026plusmn;\u0026thinsp;19.60\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eComprehensive grip strength/Weight, (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.99\u0026thinsp;\u0026plusmn;\u0026thinsp;0.26\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eRelationship between serum ALP and grip strength\u003c/h3\u003e\n\u003cp\u003eIn Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, we reveal the negative correlation between serum ALP levels and grip strength in Model A (\u0026minus;\u0026thinsp;0.00121[\u0026minus;\u0026thinsp;0.00177, \u0026minus; 0.00065]\u0026thinsp;\u0026lt;\u0026thinsp;0.000022). This inverse relationship remained evident in the adjusted models [Model B: \u0026minus;0.00152 (\u0026minus;\u0026thinsp;0.00201, \u0026minus;\u0026thinsp;0.00103)\u0026thinsp;\u0026lt;\u0026thinsp;0.000001; Model C:\u0026minus;0.00126(\u0026minus;\u0026thinsp;0.00174,\u0026minus;0.00079)\u0026thinsp;\u0026lt;\u0026thinsp;0.000001].When stratified by gender, age group and race ,for all groups except for Other races[Model A: \u0026minus;0.00022 (\u0026minus;\u0026thinsp;0.00130, 0.00085)0.685816; Model C:\u0026minus;0.00086(\u0026minus;\u0026thinsp;0.00186,0.00013) 0.089622], serum ALP were negatively correlated with grip strength, as shown in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. It is worth noting that negative correlation between serum ALP and grip strength in female at any age group[Female(20-39y): \u0026minus;0.00260 (\u0026minus;\u0026thinsp;0.00245, \u0026minus;\u0026thinsp;0.00175)\u0026thinsp;\u0026lt;\u0026thinsp;0.000001; Female(40-59y): \u0026minus;0.00096 (\u0026minus;\u0026thinsp;0.00187, \u0026minus;\u0026thinsp;0.00005)0.039893], but no significant correlation in male[Male(20-39y): \u0026minus;0.00093 (\u0026minus;\u0026thinsp;0.00197, 0.00011)0.079788; Male(40-59y):\u0026minus;0.00032(\u0026minus;\u0026thinsp;0.00126,0.00061) 0.501354],as shown in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eRelationship Between concentrations of serum alkaline phosphatase and grip strength/weight in All Participants\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eModel A\u003c/p\u003e \u003cp\u003eβ (95% CI) P value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eModel B\u003c/p\u003e \u003cp\u003eβ (95% CI) P value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eModel C\u003c/p\u003e \u003cp\u003eβ (95% CI) P value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ealkaline phosphatase (IU/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.00121(-0.00177, -0.00065) 0.000022\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.00152(-0.00201, -0.00103)\u0026thinsp;\u0026lt;\u0026thinsp;0.000001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.00126(-0.00174, -0.00079)\u0026thinsp;\u0026lt;\u0026thinsp;0.000001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eModel A was not adjusted\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eModel B was adjusted for gender, age group, race, education level, marital status, and monthly poverty level index category\u003c/p\u003e \u003cp\u003eModel C was adjusted for gender, age group, race, education level, marital status, and monthly poverty level index category, smoking status, drinking status, work activity status, recreational activity status, and hypertension, high cholesterol status, diabetes\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eStratified analysis of the correlation between serum alkaline phosphatase and grip strength/weight\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eModel A\u003c/p\u003e \u003cp\u003eβ (95% CI) P value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eModel B\u003c/p\u003e \u003cp\u003eβ (95% CI) P value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eModel C\u003c/p\u003e \u003cp\u003eβ (95% CI) P value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eSubgroup analysis stratified by gender\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.00117(-0.00189, -0.00046) 0.001373\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.00097(-0.00170, -0.00024) 0.009170\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.00082(-0.00154, -0.00011) 0.024574\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.00276(-0.00337, -0.00215)\u0026thinsp;\u0026lt;\u0026thinsp;0.000001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.00222(-0.00284, -0.00161)\u0026thinsp;\u0026lt;\u0026thinsp;0.000001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.00191(-0.00253, -0.00130)\u0026thinsp;\u0026lt;\u0026thinsp;0.000001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSubgroup analysis stratified by age group\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e20\u0026ndash;39 y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.00116(-0.00195, 0.00038) 0.003676\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.00187(-0.00256, -0.00118)\u0026thinsp;\u0026lt;\u0026thinsp;0.000001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.00162(-0.00230, -0.00093) 0.000004\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e40\u0026ndash;59 y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.00102(-0.00179, -0.00025) 0.009944\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.00097(-0.00164, -0.00029) 0.005035\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.00066(-0.00131, -0.00001) 0.048463\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSubgroup analysis stratified by race\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMexican American\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.00058(-0.00200, 0.00083) 0.418293\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.00120(-0.00237, -0.00004) 0.044331\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.00119(-0.00235, -0.00003) 0.045249\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther Hispanic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.00142(-0.00317, 0.00032) 0.110984\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.00192(-0.00345, -0.00038) 0.015124\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.00157(-0.00307, 0.00008) 0.040601\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-Hispanic White\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.00117(-0.00218, -0.00015) 0.024431\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.00173(-0.00262, -0.00083) 0.000162\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.00135(-0.00221, -0.00049) 0.002116\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-Hispanic Black\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.00135(-0.00268, -0.00001) 0.048203\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.00141(-0.00253, -0.00028) 0.014623\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.00138(-0.00248, -0.00027) 0.015144\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther Race\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.00022(-0.00130, 0.00085) 0.685816\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.00105(-0.00202, -0.00008) 0.034112\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.00086(-0.00186, 0.00013) 0.089622\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eModel A was not adjusted\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eModel B was adjusted for gender, age group, race, education level, marital status, and monthly poverty level index category\u003c/p\u003e \u003cp\u003eModel C was adjusted for gender, age group, race, education level, marital status, and monthly poverty level index category, smoking status, drinking status, work activity status, recreational activity status, and hypertension, high cholesterol, diabetes\u003c/p\u003e \u003cp\u003eIn the subgroup analysis stratified by gender, age group, race, the model was not adjusted for gender, age group or race\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eStratified examination of the relationship between serum alkaline phosphatase and grip strength/weight based on gender (age group)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026minus;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSubgroup\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eβ (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale(20-39y)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026minus;\" colname=\"c2\"\u003e \u003cp\u003e-0.00093(-0.00197, 0.00011)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.079788\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale(40-59y)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026minus;\" colname=\"c2\"\u003e \u003cp\u003e-0.00032(-0.00126, 0.00061)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.501354\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale(20-39y)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026minus;\" colname=\"c2\"\u003e \u003cp\u003e-0.00260(-0.00245, -0.00175)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.000001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale(40-59y)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026minus;\" colname=\"c2\"\u003e \u003cp\u003e-0.00096(-0.00187, -0.00005)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.039893\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eRace, education level, marital status, and monthly poverty level index category, smoking status, drinking status, work activity status, recreational activity status, and hypertension, high cholesterol, diabetes were adjusted\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eNonlinear relationship between serum ALP and grip strength\u003c/h2\u003e \u003cp\u003eWe further evaluated the nonlinear relationship between the serum levels of ALP and grip strength using a smoothing curve fitting method, as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Figure\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003e display fitted smoothing curves describing the nonlinear relationships between serum ALP and grip strength. Figure\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e shows that serum ALP levels and grip strength showed an M-shaped relationship among all male participants. When divided into four groups according to gender and age, Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e shows that serum ALP levels and grip strength showed an N-shaped relationship among male participants aged 20\u0026ndash;39 years, and an L-shaped relationship among male participants aged 40\u0026ndash;59 years. In male participants aged 20 to 39 years, the analysis using a three-segment linear regression model indicated that serum alkaline phosphatase levels at the two turning points (k1 and k2) were 39 IU/L and 77 IU/L, respectively, with an effect size of -0.0027 for serum ALP between these values, as shown in Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e. In male individuals aged 40 to 59 years, a two-segment linear regression analysis revealed a saturation effect at 60 IU/L, showing an effect size of -0.0046 for serum alkaline phosphatase levels that are below this threshold and 0.0008 for those exceeding 60 IU/L, as shown in Table\u0026nbsp;\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThreshold effect analysis of serum alkaline phosphatase on Combined grip strength/weight in male(20-39y) using the three-piecewise linear regression model\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale(20-39y)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCombined grip strength/weight\u003c/p\u003e \u003cp\u003eAdjusted β (95% CI) P value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLinear model\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eeffect\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.0009(-0.0020,0.0001)0.0798\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThree-segment linear regression model\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTuring points(K1,K2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39,77\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;K1 effect 1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.0076(-0.0071, 0.0224)0.3113\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eK1-K2 effect 2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.0027(-0.0048, -0.0006)0.0119\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;K2 effect 3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.0003(-0.0026, 0.0020)0.7685\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003elikelihood-ratio test\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.048\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eRace, education level, marital status, and monthly poverty level index category, smoking status, drinking status, work activity status, recreational activity status, and hypertension, high cholesterol status, diabetes were adjusted\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab6\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThreshold effect analysis of serum alkaline phosphatase on Combined grip strength/weight in male(40-59y) using the two-piecewise linear regression model\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale(40-59y)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCombined grip strength/weight\u003c/p\u003e \u003cp\u003eAdjusted β (95% CI) P value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLinear model\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eeffect\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.0003(-0.0013,0.0006)0.5014\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTwo-segment linear regression model\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTuring points(K)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e60\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;K effect\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.0046(-0.0077,0.0016)0.0029\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;K effect\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.0008(-0.0004,0.0020)0.1777\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003elikelihood-ratio test\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eRace, education level, marital status, and monthly poverty level index category, smoking status, drinking status, work activity status, recreational activity status, and hypertension, high cholesterol status, diabetes were adjusted\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe association between serum ALP levels and grip strength has thus far been inadequately explored. Our research revealed a notable inverse relationship between serum ALP levels and grip strength across the whole study group. Comparable to our findings, A cross-sectional study in South Korea showed that both male and female serum ALP levels were positively correlated with low skeletal muscle mass index (LSMI), interestingly, the predictive power of serum ALP level for LSMI was significantly higher in women [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. In our study, subgroup analysis disclosed that in the 20\u0026ndash;59 age group among females, a significantly negative correlation existed between serum ALP and hand grip strength; however, it is worth noting that an N-shaped relationship was observed between serum ALP and grip strength in males aged 20\u0026ndash;39 years, and an L-shaped relationship was noted in males aged 40\u0026ndash;59 years. To the best of our knowledge, this study represents the first exploration of the complex connections between serum ALP levels and grip strength among adults in the United States.\u003c/p\u003e \u003cp\u003eMuscle health holds a crucial position in physical function and metabolism [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Muscle function constitutes an important indicator for predicting the outcome of sarcopenia [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Besides primary aging, other secondary causes like malnutrition, endocrine disorders, inflammation, etc., may contribute to the acceleration of muscle loss, ultimately resulting in a decrease in muscle strength [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Sarcopenia is common among the elderly but can also be witnessed in younger individuals [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Paying attention to skeletal muscle health in young and middle-aged people is of critical importance for preventing sarcopenia in the elderly. Serum ALP is a ubiquitous membrane-bound glycoprotein present in nearly all tissues of the body [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e], notably elevated levels are found in the liver, kidneys, bile ducts, bones [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. It has been demonstrated that increased plasma levels of serum ALP have been associated with a worse prognosis in several types of diseases [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e], such as renal osteodystrophy [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] and stroke [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. In humans, four distinct isoenzymes of alkaline phosphatase are expressed: tissue-nonspecific ALP, intestinal ALP, placental ALP, and germ cell ALP [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. ALP plays a significant role in muscle metabolism. Tissue-nonspecific alkaline phosphatase (TNALP) is the predominant isoenzyme of alkaline phosphatase in the human body. Basic research has discovered that TNAP deficiency can alter mitochondrial activity, reduce muscle strength, and hamper bone mineralization and trabecular formation of bone marrow stromal cells [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Simultaneously, increased basal mitochondrial respiration might induce chronic oxidative stress, leading to superoxide production and inducing muscle pathology [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. However, Clinical research indicates that in patients undergoing hemodialysis, there is an inverse relationship between the levels of ALP and their muscle mass, strength, and overall physical function [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eA substantial cohort study identified a significant association between elevated serum total ALP levels and the incidence of hip fractures [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. A single-center cohort study demonstrated that elevated serum bone-specific ALP levels were correlated with fracture risk, and hemodialyzed patients with increased b-AP had an elevated fracture risk [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. The study by Xiao Song Cheng et al. revealed that serum ALP levels in young and middle-aged individuals were negatively correlated with pelvic bone density [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. In states of diminished bone density, osteoblasts are activated and produce a substantial quantity of bone alkaline phosphatase, thereby resulting in a significant increase in serum ALP levels [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Lower bone density might indirectly impact muscle function, leading to a reduction in muscle strength. The effect of ALP on bone and mineral homeostasis is a double-edged sword. ALP can enhance bone mineralization, but it may also induce vascular calcification [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e], which may have a negative influence on skeletal muscle health [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. The specific mechanisms underlying this relationship call for further meticulous and profound exploration.\u003c/p\u003e \u003cp\u003eALP levels are intimately related to nutritional status and chronic inflammation. The phase angle (PhA), a well-acknowledged nutritional indicator associated with healthy cell membranes, exhibits excellent accuracy in reflecting muscle mass and can also be employed as a facile indicator for gauging muscle mass [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Seok Hui Kang et al. discovered a negative correlation between ALP levels and PhA [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Kim et al. found that ALP is closely associated with metabolic or nutritional disorders, and serum ALP levels showed a positive correlation with body fat mass among the general population in Korea. [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Ferm\u0026iacute;n S\u0026aacute;nchez de Medina et al. suggested that ALP seems to be related to the inflammatory process and its regulation [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. The activity of ALP is influenced by oxidative stress in both in vitro and in vivo conditions. [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. ALP can be utilized as a comprehensive marker of nutritional status and inflammation [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. Elevated serum total ALP levels correlate with higher serum C-reactive protein (CRP) levels and increased mortality in the general population [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. Experimental studies have shown that inflammatory cytokines can activate numerous molecular pathways associated with skeletal muscle atrophy, resulting in muscle atrophy [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. Additional studies are essential to explore the adverse effects of this process on muscle function.\u003c/p\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eStrengths and limitations\u003c/h2\u003e \u003cp\u003eFirstly, due to the cross-sectional design of this study, it limited the ability to assess the causal relationship between serum ALP and grip strength. Furthermore, some disorders that might notably increase serum ALP, such as biliary obstructive diseases and osteosarcoma, could not be completely excluded. Finally, although a number of covariates were controlled for in our multivariate regression analyses, the existence of some other potential confounders might still bias the results.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThis research uncovered the connection between serum ALP levels and grip strength, highlighting variations in this association based on gender and age. Our analysis revealed a negative correlation between serum alkaline phosphatase and grip strength in females aged 20 to 59 years. In male (20\u0026ndash;39 years old) and male (40\u0026ndash;59 years old) participants, serum ALP concentration showed an N-type and L-type relationship with grip strength, respectively. This discovery provides new clues and orientations for the mechanism of the influence of serum ALP on skeletal muscle health. To gain a deeper understanding of the relationship between serum ALP and grip strength across different genders and age groups, additional prospective studies involving larger populations are necessary.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eALP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAlkaline Phosphatase\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePhA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePhase Angle\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTNALP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eTissue-nonspecific alkaline phosphatase\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLSMI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eLow skeletal muscle mass index\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNHANES\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eNational Health and Nutrition Examination Survey\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe ethics review board of the National Center for Health Statistics approved all NHANES protocols, and each participant signed written informed consent.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and/or analysed during the current study are available in the Health and Nutrition Examination Survey (NHANES) during 2013\u0026ndash;2014, at http://www.cdc.gov/nchs/nhanes/.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by Scientific Research Project of Jiangsu Provincial Health Committee in China (To Guo-yang Zhao, M2022119) , 2021 Zhenjiang City Social Development Guiding Science and Technology Plan Project(To Bo Wang,FZ2021058) and\u0026nbsp;2023 Zhenjiang Science and Technology Innovation Fund (To Bo Wang,SH2023030) .\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eZiyi Zhang \u003csup\u003e1\u003c/sup\u003e Affiliated Hospital of Jiangsu University Email: [email protected]\u003c/p\u003e\n\u003cp\u003eJiajie Zhou \u003csup\u003e1\u003c/sup\u003e Affiliated Hospital of Jiangsu University Email: [email protected]\u003c/p\u003e\n\u003cp\u003eAnpei Ma\u003csup\u003e2\u0026nbsp;\u003c/sup\u003eYancheng First People\u0026rsquo;s Hospital Email:\u0026nbsp;[email protected]\u003c/p\u003e\n\u003cp\u003eHonggu Chen\u003csup\u003e2\u0026nbsp;\u003c/sup\u003eZhejiang Taizhou Hospital Email: [email protected]\u003c/p\u003e\n\u003cp\u003eBo Wang\u003csup\u003e2\u003c/sup\u003e Affiliated Hospital of Jiangsu University Email: [email protected]\u003c/p\u003e\n\u003cp\u003eGuoyang Zhao\u003csup\u003e1*\u0026nbsp;\u003c/sup\u003eAffiliated Hospital of Jiangsu University Email: [email protected]\u003c/p\u003e\n\u003cp\u003eCorresponding author: Guoyang Zhao Email: [email protected]\u003c/p\u003e\n\u003cp\u003eThese authors contributed equally: Ziyi Zhang and Jiajie Zhou\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eZYZ, JJZ, contributed to the study design and writing of the manuscript.\u003c/p\u003e\n\u003cp\u003eAPM, HGC, BW and contributed to data collection, analysis, and writing of the manuscript.\u003c/p\u003e\n\u003cp\u003eG.Y.Z. project administration, supervision.\u003c/p\u003e\n\u003cp\u003eAll authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors appreciate the time and effort given by participants during the data collection phase of the NHANES project.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eclinical trial number\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eno applicable\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eCruz-Jentoft AJ, Sayer AA, Sarcopenia. 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Endocr J. 2013;60(3):321\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSanchez de Medina F, Martinez-Augustin O, Gonzalez R, Ballester I, Nieto A, Galvez J, et al. Induction of alkaline phosphatase in the inflamed intestine: a novel pharmacological target for inflammatory bowel disease. Biochem Pharmacol. 2004;68(12):2317\u0026ndash;26.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMody N, Parhami F, Sarafian TA, Demer LL. Oxidative stress modulates osteoblastic differentiation of vascular and bone cells. Free Radic Biol Med. 2001;31(4):509\u0026ndash;19.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBeberashvili I, Samogalska O, Azar A, Stav K, Efrati S. Nutritional Status and Mortality Predictability for Time-Varying Serum Alkaline Phosphatase in Hemodialysis Patients: A Longitudinal Study. J Ren Nutr. 2020;30(5):452\u0026ndash;61.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFilipowicz R, Greene T, Wei G, Cheung AK, Raphael KL, Baird BC, et al. Associations of serum skeletal alkaline phosphatase with elevated C-reactive protein and mortality. Clin J Am Soc Nephrol. 2013;8(1):26\u0026ndash;32.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBano G, Trevisan C, Carraro S, Solmi M, Luchini C, Stubbs B, et al. Inflammation and sarcopenia: A systematic review and meta-analysis. Maturitas. 2017;96:10\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-musculoskeletal-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmsd","sideBox":"Learn more about [BMC Musculoskeletal Disorders](http://bmcmusculoskeletdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://author-welcome.nature.com/12891","title":"BMC Musculoskeletal Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Serum alkaline phosphatase, Grip strength, Muscle healthy, NHANES","lastPublishedDoi":"10.21203/rs.3.rs-5342416/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5342416/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eSerum alkaline phosphatase (ALP) plays a crucial role in bone and muscle health. Previous studies have demonstrated that serum alkaline phosphatase (ALP) is closely associated with muscle mass. Nevertheless, the association between serum alkaline phosphatase (ALP) and grip strength remains unclear. This study is designed to investigate whether there exists a connection between serum ALP levels and grip strength among individuals aged 20 to 59 years.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eUtilizing data from the National Health and Nutrition Examination Survey (NHANES) conducted in 2013\u0026ndash;2014, a cross-sectional survey design was employed to examine 2,182 adults (54.54% male and 45.46% female) aged between 20 and 59 years. Weight-corrected grip strength served as the dependent variable, while serum alkaline phosphatase (ALP) was identified as the primary variable of interest. The relationships were analyzed using generalized linear models, smooth curve fitting, generalized additive models, and stratified analyses.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eWe discovered that alkaline phosphatase (ALP) was negatively linked with weight-corrected grip strength. When stratified by gender, age group and race, for all groups except for other races, serum alkaline phosphatase (ALP) were negatively correlated with weight-corrected grip strength. When divided into four groups according to gender and age, serum alkaline phosphatase (ALP) and weight-corrected grip strength showed an N-shaped relationship among male participants aged 20\u0026ndash;39 years, and an L-shaped relationship among male participants aged 40\u0026ndash;59 years, and among female shows a significant negative correlation regardless of age group.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eOur research identified notable gender differences in the association between alkaline phosphatase (ALP) levels and weight-corrected grip strength among participants aged 20 to 59 years. This finding offers new insights and avenues for understanding how serum alkaline phosphatase affects skeletal muscle health.\u003c/p\u003e","manuscriptTitle":"Sex-dependent association of serum alkaline phosphatase with grip strength in adults aged 20-59: NHANES 2013-2014","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-12-02 22:45:10","doi":"10.21203/rs.3.rs-5342416/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-01-07T05:47:19+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-01-06T23:03:52+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"34379969019069670711877606199133576473","date":"2025-01-06T19:26:11+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-11-28T10:26:30+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"182597446658558716476573625076652472515","date":"2024-11-18T23:44:07+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-11-11T18:34:06+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-11-06T10:01:09+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-11-06T09:50:09+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-11-05T09:04:33+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Musculoskeletal Disorders","date":"2024-10-27T17:39:15+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-musculoskeletal-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmsd","sideBox":"Learn more about [BMC Musculoskeletal Disorders](http://bmcmusculoskeletdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://author-welcome.nature.com/12891","title":"BMC Musculoskeletal Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"3ec9ab98-c7c1-4742-9b57-fff178598821","owner":[],"postedDate":"December 2nd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-03-03T16:01:58+00:00","versionOfRecord":{"articleIdentity":"rs-5342416","link":"https://doi.org/10.1186/s12891-025-08408-2","journal":{"identity":"bmc-musculoskeletal-disorders","isVorOnly":false,"title":"BMC Musculoskeletal Disorders"},"publishedOn":"2025-02-25 15:57:43","publishedOnDateReadable":"February 25th, 2025"},"versionCreatedAt":"2024-12-02 22:45:10","video":"","vorDoi":"10.1186/s12891-025-08408-2","vorDoiUrl":"https://doi.org/10.1186/s12891-025-08408-2","workflowStages":[]},"version":"v1","identity":"rs-5342416","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5342416","identity":"rs-5342416","version":["v1"]},"buildId":"-HB7Z8yhvgn0wM9Nzuekk","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}