Bone turnover markers (P1NP, CTX) and sphingosine-1- phosphate (S1P) in determining bone health among chinese adult residents of Puchong and Kajang in Selangor, Malaysia

Prevention of osteoporotic fracture requires identification of individuals at high risk with WHO fracture risk assessment tool (FRAX®) commonly used to estimate fracture probability despite some inadequate predictive discrimination ability. Procollagen-type-1 amino-terminal propeptide (P1NP) and carboxy-terminal-collagen crosslinks (CTX), the current bone turnover markers (BTM) and sphingosine-1-phosphate (S1P), a novel marker of bone metabolism may complement the current model. This study aimed to determine the association of P1NP, CTX, and S1P with sociodemographic factors, clinical characteristics, bone mineral density (BMD) and blood tests for bone profile among Chinese adults in Puchong and Kajang, Malaysia. This was a cross-sectional study involving Chinese subjects aged between 50 to 90 years old in Puchong and Kajang who attended a health screening program in Puchong Specialist Centre from December 2015 to December 2017. Each subject had a BMD determined by a dual-energy x-ray absorptiometry (DXA) at lumbar spine, femoral neck, total hip and total body. 10 ml of fasting blood sample were taken and analysed for 25-hydroxyvitamin D (25(OH)D), parathyroid hormone (iPTH), calcium, phosphate, P1NP, CTX and S1P. Pearson’s and Spearman’s correlation tests were used to determine the associations between P1NP, CTX and S1P with sociodemographics, clinical characteristics, BMD and bone profile. All analyses were stratified by gender and BMD categories (normal BMD, osteopenia and osteoporosis). A total of 131 subjects [45 (34.4%) males and 86 (65.6%) post-menopausal women] with a median age of 65 (IQR=17) years old were recruited. Osteopenia and osteoporosis were diagnosed in 46.6% and 29.0% of subjects, respectively. P1NP and CTX were significantly higher in post-menopausal women (P1NP=61.71ng/ml, CTX=0.489 ng/ml) compared to men (P1NP=46.94 ng/ml, CTX=0.381 ng/ml). Both BTM differed significantly according to BMD categories (p<0.001) with values highest in osteoporosis and lowest in normal BMD. However, there is no difference in S1P levels in men (2.12 ± 0.75 μmol/L) and post-menopausal women (1.96 ± 0.68 μmol/L) did not differ significantly (p=0.235) and did not differ according to BMD categories (p=0.457). S1P did not correlate with any individual BMD measurements nor with P1NP or CTX in both males and females. In post-menopausal women, CTX and P1NP significantly negatively correlated with BMD measurements at all sites except femoral neck. In men, CTX significantly negatively correlated with femoral neck (r=-0.360, p=0.015) and total hip (r=-0.456, p=0.002) whilst P1NP only with total body (r=-0.344, p=0.021). Osteoporosis was diagnosed in 29% of subjects. P1NP and CTX were significantly higher in post-menopausal women compared to men as well as significantly differed between osteoporosis, oeteopenia and normal BMD. In post-menopausal women, P1NP and CTX negatively correlated with all BMD sites measurements except for femoral neck. In men, P1NP only negatively correlated with total body whilst CTX only with femoral neck and total hip. In contrast, S1P did not differ according to BMD characteristics nor gender and not associated with any BMD sites measurement. Thus, in this group of Malaysian Chinese subjects, the current BTM reflects bone loss better than S1P, especially in females.

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