RETRACTED ARTICLE: Relationship between bone density and bone metabolism in adolescent idiopathic scoliosis

Proportional differences were analyzed using the Chi-square test for independence. Correlations among parametric data were assessed by the Pearson’s correlation coefficient test. Student’s T-test was used to determine significant differences between means for two groups of data. When samples had possible unequal variances, Welch’s test was utilized. For ordinal data, the Mann–Whitney U-test was employed. Correlations among nonparametric data were assessed by Spearman’s correlation coefficient rank test. Statistical significance was accepted at p <0.05.

The average BMI was 18.8 ± 2.4 kg/m². Mean BMD and Z scores of each bone area are listed in Table 1. There were 17 subjects (35 %) in normal (Z scores >−1), 25 subjects (51 %) in osteopenia (−2 <Z score ≦ − 1), and 7 subjects (14 %) in osteoporosis (Z score ≦ − 2) by using the lowest femoral Z scores. There were significant correlations between lumbar and right femoral neck BMDs (r = 0.68, p <0.01), lumbar and right proximal femur BMDs (r = 0.79, p <0.01), lumbar and left femoral neck BMDs (r = 0.62, p <0.01), and lumbar and right proximal femur BMDs (r = 0.72, p <0.01).

BAP and TRAP5b serum measurements by age are shown in Fig. 1. Values of BAP were within normal limits for 100 % of the subjects, while 29 subjects (59 %) showed high values of TRAP5b (above +1.88 SDs) (Table 2).

BMDs, Z scores, age of menarche, BMI, and Cobb angle were compared between the subjects with high serum values of TRAP5b and those with normal values. In the high TRAP5b group (n = 29), the age was significantly lower (p = 0.01) and BMI significantly lower (p <0.01) than those of the normal TRAP5b group (n = 20) (Table 3). The lowest femoral Z scores of the high TRAP5b group were significantly lower (p = 0.02) than those of the normal group (Table 3).

Correlations between the lowest femoral Z scores and age of menarche, BMI, bone metabolism markers (BAP, TRAP5b), and Cobb angle are shown in Table 4. The lowest femoral Z scores were positively correlated with BMI and not correlated with age of menarche, serum values of TRAP5b and BAP, and Cobb angle. The Cobb angle was positively correlated with serum values of TRAP5b, but not significantly correlated with age of menarche, BMI, values of BAP, and the lowest femoral Z score (Table 5).

The BMDs are generally evaluated by the DEXA measured in lumbar spine, femoral neck, and total proximal femur and the lowest BMDs of each area were used for analysis [9]. Because the BMDs of rotated lumbar spines changed by degrees like AIS subjects [12] and the BMDs changes by age and sexual growth in adolescent period, the lowest femoral Z score (the age-and sex-matched mean) was used for analysis.

The incidence of osteopenia in AIS has been reported to be about 30 % [2‐6]. In our study, 65 % of AIS patients were osteopenic or osteoporotic by using the lowest femoral Z score. The higher frequency in the present study may be due to the sampling error inherent in our relatively small sample size and the several definitions of osteopenia and osteoporosis.

Previous researchers reported that low BMD in AIS was associated with delayed menarche [6] and low BMI [13]. In our study, the correlation between the lowest femoral Z scores and age of menarche was not significantly correlated. In agreement with a previous report [15], a significant positive correlation between the lowest femoral Z scores and BMI was found in our study.

Bone metabolism in AIS has not been well described. Cheung et al. measured serum concentrations of BAP and urinary concentrations of deoxypyridinoline in 621 AIS patients [7]. They reported serum concentrations of BAP in AIS patients from age13 to 15 years-old were on average 39 % higher than those of age-matched controls and that urinary concentrations of deoxypyridinoline in AIS patients older than 15 years-old were 30 % lower than those of age-matched controls. They concluded that AIS patients had higher bone turnover because they had 39 % higher BAP concentrations. However, their finding that AIS patients had 30 % lower deoxypyridinoline concentrations than age-matched controls is not consistent with their conclusion. A limitation of their study was that they used urinary deoxypyridinoline as a bone resorption marker. Urinary deoxypyridinoline is one of two pyridinum cross-links providing structural stiffness to collagen type 1 in bones and has been reported to be more affected by renal function, fasting, and hourly variations than TRAP5b [16].

Serum TRAP5b is a biomarker for osteoclastic bone resorption activity and has been reported to demonstrate little daily variation; a low variability of 14 % was observed from 09:00–17:00 while urine resorption markers vary as much as 137 % throughout the day. TRAP5b also demonstrated minimal response to fasting, a decrease of only 2 %, whereas other serum and urine resorption markers decrease 18 % during fasting [8]. Although 29 of our AIS subjects (59 %) had high values for TRAP5b, no subject had a high value for BAP. These data suggest there may be high osteoclast activity but normal osteoblast activity and an imbalance in bone metabolism. Examining this imbalance in bone metabolism, Chiru reported that mean RANKL and RANKL to OPG ratios in 15 patients with AIS were increased compared to those in control subjects, suggesting high osteoclast activity and an imbalance in the RANKL/OPG system [17].

In our study, the lowest femoral Z scores were significantly low with high TRAP5b group. This result means the cause of low BMD is increased osteoclast activity as indicated by the high TRAP5b levels. This is the first report describing high values of a bone resorption marker associated with low bone density in AIS patients.

Age and BMI in the high TRAP5b group were significantly lower than those in the normal TRAP5b group. As shown in Fig. 1, the normal average values of TRAP5b were decreasing slowly with age, although the average values of TRAP5b in AIS were decreasing rapidly from abnormal high values. This means abnormal bone metabolism in AIS would start before notice of scoliosis. According to low BMI in the high TRAP5b group, the BMI and BMD had been reported to be positive correlation and high TRAP5b resulted in low BMD.

Reasons for high values of TRAP5b in AIS may include low levels of sex hormones [18], lack of calcium intake from elevated levels of parathyroid hormone [7], deficiency of melatonin affecting the melatonin receptor of osteoblasts, stimulation of stem cell proliferation and cell differentiation [19, 20], and deficiency of leptin, which acts on marrow stromal cells to enhance differentiation to osteoblasts [21] while inhibiting osteoclast generation [19, 22]. Our study did not assess melatonin, leptin, sex hormones, calcium intake, and other causes of high values of TRAP5b. These factors may be intricately intertwined.

A significant relationship between severity of scoliosis and BMD has been reported [5], while another study found no relationship [1]. In a histomorphometric study, pinealectomy in broiler chicken model was reported to induce high turnover osteoporosis, which might contribute to the development of scoliosis in the chicken [23].

Lu et al. reported that anti-osteoporosis treatment could improve bone strength, prevent osteoporosis and rebalance the OPG-RANK-RANKL system, which might help to prevent curve progression in AIS [24]. In our study, the Cobb angle was positively correlated with TRAP5b, but the correlation coefficient was not as strong as the value of 0.3 and the causes of scoliosis progression would be multi factors.

Our study has limitations, including small sample size, varying age of subjects. In addition, data from normal controls reported from previous studies were used because our study did not have normal controls.

This study assessed bone mineral density and bone metabolism in AIS patients using the bone metabolism markers, BAP and TRAP5b. Sixty-five percent of AIS patients had osteopenia or osteoporosis and 59 % of AIS patients had high values for TRAP5b. The AIS patients with high values of TRAP5b had lower Z scores than those with normal values of TRAP5b. Higher rates of bone resorption are associated with low bone density in AIS patients.