Serum bone metabolic marker affects the lumbar osteoarthritis in a japanese population study

Purpose: To clarify the relationship between bone metabolic measurements (bone mineral density: BMD, serum biomarker) and the severity of lumbar osteoarthritis (LOA) Methods: 689 volunteers participated in the present study (Male: 272, Female: 417, Age: 54.4±14.9, BMI: 23.0±3.3kg/m2). Lateral lumbar radiographs were evaluated in each intervertebral section (L1/2 to L5/S1) by Kellgren-Lawrence grade (KLG). If at least one intervertebral section was determined as KLG 2 or more severe, the subjects were defined as LOA. The summation of each section was determined as the severity score of LOA. BMD was evaluated by osteo-sono assessment index at the calcaneus bone. Blood samples were taken in early morning before breakfast. Serum bone alkaline phosphatase (BAP; μg/ml), N-telopeptide of typeI collagen (NTx; nMBCE/l), and pentosidine (Pen; nmol/l) were examined as the index of bone metabolism. Multiple linear regression analysis was conducted with the severity score of LOA as an independent variable, and age, sex, BMI, BMD, and the value of serum samples (BAP, NTx, Pen) as dependent variables. Results: The total number of LOA subjects was 474 (68.5%). The frequency of LOA in males (n=199, 73.2%) was higher than that of females (n=273, 65.5%; P=0.036, χ2 test). The mean severity score of LOA was 7.1±4.4 in total subjects, 7.8±4.4 in male, and 6.8±4.4 in female (P=0.006, Mann-Whitney U test). The mean value of BMD was 2.7±0.4×106 in total subjects, 2.9±0.4×106 in male, and 2.5±0.3×106 in female (P<0.001, Mann-Whitney U test). The mean value of BAP was 15.4±11.8 in total subjects, 15.8±15.8 in male, and 15.2±8.2 in female. The mean value of NTx was 18.7±8.7 in total subjects, 19.0±10.7 in male, and 18.5±7.1 in female. The mean value of Pen was 120.7±54.8 in total subjects, 132.7±50.2 in male, and 112.9±56.2 in female (P<0.001, Mann-Whitney U test, Table 1). In addition, the mean value of age, BMI, BMD, BAP, NTx, and Pen was significantly different with and without LOA in each gender (Table 2). In multiple regression model, age (β=0.600, P<0.001), sex (male=1, female=2; β=−0.136, P<0.001), BMI (β=0.148, P<0.001), BAP (β=0.101, P=0.025), and Pen (β=0.120, P<0.001) significantly affected the severity score of LOA in a total population. Only age (β=0.642, P<0.001) and BMI (β=0.155, P=0.002) affected the severity score of LOA in the male population, on the other hand, age (β=0.568, P<0.001), BMI (β=0.138, P=0.001), BAP (β=0.174, P<0.001), and Pen (β=0.145, P<0.001) significantly affected the severity score of LOA in the female population. Conclusions: The present study epidemiologically clarified that serum BAP and pentosidine levels positively correlated with the severity of LOA in cross-sectional data. Pentosidine is one of the advanced glycation end products (AGEs). In in-vitro study, pentosidine was reported to directly deteriorate the elastic property of collagen fibers making the cross-links, or indirectly degrade cartilage tissue affecting the specific receptor for AGEs (RAGE) which induces several catabolic factors (ILs, MMPs) via intracellular signal. Although serum pentosidine has been established as the biomarker of bone quality, the utility for the biomarker of LOA needs to be paid attention longitudinally in the future.Table 1Comparison of demographic data, bone mineral density, the severity of lumbar osteoarthritis, and serum bone metabolic markers between males and femalesTotalMaleFemaleP-valueAge54.4 ± 14.953.3 ± 15.355.2 ± 14.70.121BMI23.0 ± 3.323.7 ± 3.122.6 ± 3.3<0.001∗P<0.05, Mann-Whitney U test.BMD2.6 ± 0.42.9 ± 0.42.5 ± 0.3<0.001∗P<0.05, Mann-Whitney U test.LOA7.1 ± 4.47.7 ± 4.46.8 ± 4.40.006∗P<0.05, Mann-Whitney U test.BAP15.4 ± 11.815.8 ± 15.815.2 ± 8.20.770NTx18.7 ± 8.719.0 ± 10.718.5 ± 7.10.663Pen120.7 ± 54.8132.7 ± 50.2112.9 ± 56.2<0.001∗P<0.05, Mann-Whitney U test.BMD: bone mineral density (osteo-sono assessment index), LOA: the summation of Kellgren-Lawerence grade in each intervertebral section (L1/5 to L5/S1) with lateral X-ray image, BAP: bone alkaline phosphatase (μg/ml), NTx: N-telopeptide of type I collagen (nMBCE/l), Pen: pentosidine (nmol/l)∗ P<0.05, Mann-Whitney U test. Open table in a new tab Table 2Comparison of demographic data, bone mineral density, serum bone metabolic markers with and without lumbar osteoarthritis in each genderMaleFemaleOA−OA +POA−OA +PAge40.5 ± 13.058.0 ± 13.2<0.001*44.8 ± 12.760.7 ± 12.5<0.001*BMI23.4 ± 3.823.8 ± 2.80.06521.6 ± 2.723.1 ± 3.5<0.001*BMD3.0 ± 0.52.8 ± 0.40.1512.6 ± 0.32.4 ± 0.3<0.001*BAP18.7 ± 29.214.7 ± 5.10.49613.3 ± 6.216.2 ± 8.9<0.001*NTx21.7 ± 19.018.0 ± 4.50.08517.8 ± 7.018.9 ± 7.10.044*Pen120.71 ± 34.5137.1 ± 54.30.016*106.31 ± 30.5116.41 ± 65.60.164If at least one intervertebral section is determined as Kellgren-Lawrence grade 2 or more severe, the subjects are defined as OA+. BMD: bone mineral density (osteo-sono assessment index), BAP: bone alkaline phosphatase (μg/ml), NTx: N-telopeptide of type I collagen (nMBCE/l), Pen: pentosidine (nmol/l)*P<0.05, Mann-Whitney U test Open table in a new tab BMD: bone mineral density (osteo-sono assessment index), LOA: the summation of Kellgren-Lawerence grade in each intervertebral section (L1/5 to L5/S1) with lateral X-ray image, BAP: bone alkaline phosphatase (μg/ml), NTx: N-telopeptide of type I collagen (nMBCE/l), Pen: pentosidine (nmol/l) If at least one intervertebral section is determined as Kellgren-Lawrence grade 2 or more severe, the subjects are defined as OA+. BMD: bone mineral density (osteo-sono assessment index), BAP: bone alkaline phosphatase (μg/ml), NTx: N-telopeptide of type I collagen (nMBCE/l), Pen: pentosidine (nmol/l) *P<0.05, Mann-Whitney U test