ABSTRACT
Objective:To perform a prospective cohort study to identify individual susceptibility of glucocorticoid (GC) -associated osteonecrosis of the femoral head (GA-ONFH) and their clinical and genetic risk factors. Methods:The present prospective cohort study enrolled patients who received their first GC therapy between July 2015 and January 2018 at Zhongshan Hospital. All patients did not receive any GC treatment before enrollment. Further, they planned to start GC treatment with the dose (equivalent prednisone) of ≥30 mg/d, lasted ≥3 weeks, or pulse dose ≥200 mg/d, lasted ≥3 d. Blood samples were collected before GC treatment to evaluate bone metabolism and its released factors. Hip MRI was performed at the 1st, 3rd, 6th, 12th and 24th month to diagnose GA-ONFH. All patients were followed-up for ≥2 years. The endpoint was regarded as diagnosis of GA-ONFH or completion of 2 years follow-up. Lasso regression was performed to determine which clinical features were associated with GA-ONFH. A nested case-control sub-cohort (A, n=12) was established prospectively based on the main cohort by 1∶1 matching. Whole exome sequencing was performed to screen differential and functional candidate single nucleotide polymorphisms and insertion-deletions (SNP/InDels). Another sub-cohort (B, n=50) was constructed retrospectively in patients with GA-ONFH and non-ONFH patients received standard high dose GC treatment for more than two years. The candidate SNP/InDels were verified by Sanger sequencing based on the patients from sub-cohort B. Results:A total of 96 patients were enrolled of which 88 of them (32 males and 56 females, mean age 42.30 years) completed follow-up. Eight cases (9.1%) were diagnosed with GA-ONFH. The median time from the start of GC therapy to the diagnosis of ONFH was 53.00(34.00,13.50) days. The baseline characteristics, such as age, sex and body mass index, indicated no significant difference between the ONFH group and the non-ONFH group. The cumulative GC dose of the ONFH patients in the first month was higher than that of non-ONFH [32.74(29.55, 47.05) mg/kg vs. 24.00(21.10, 29.45) mg/kg, Z=-2.410, P=0.016]. However, there was no significant difference of patients who underwent pulse therapy (37.5% vs. 10.0%, adjusted χ 2=2.829, P=0.093). The ratio of serum apolipoprotein B/apolipoprotein A1 (ApoB/ApoA1) in patients with ONFH was higher than that in non-ONFH group before GC use [0.95(0.80, 1.50) vs. 0.70(0.60, 0.80), Z=-2.875, P=0.000]. Due to the multicollinearity, Lasso regression model was performed to reduce overfitting. All variables were included in the model. The results suggested that higher ApoB/ApoA1 ratio, lower serum β-c-terminal telopeptide (β-CTX) and higher cumulative GC dose in the first month were the top three risk factors of GA-ONFH. This model had an accuracy of 0.982 in internal validation. Seven differential candidate SNP/InDels were found by whole exome sequencing of sub-cohort A. We further verified these SNP/InDels in sub-cohort B. The patients with COLEC12 mutation (rs2305027, G1816A) were at risk of GA-ONFH ( OR=6.00, 95% CI: 1.17, 30.73). Conclusion:Higher first-month GC dose, lower serum β-CTX level before treatment, higher ApoB/ApoA1 ratio and COLEC12 mutation (rs2305027, G1816A) could increase the risk of GA-ONFH.
ABSTRACT
Objective To evaluate the clinical efficacy and safety of short-segment pedicle screw fixation combined with vertebroplasty for the treatment of thoracolumbar osteoporotic compression fractures.Methods A retrospective case control study was conducted on 63 patients with fresh thoracic or lumbar osteoporotie compression fractures who were surgically treated from January 2010 to December 2013.There were 26 males and 37 females,with age of 63-87 years [(76.3 ± 5.7) years].According to the surgical method,the patients were assigned to simple vertebroplasty group (Group A),short-segment pedicle screw fixation group (Group B),and short-segment pedicle screw fixation group combined with vertebroplasty group (Group C),with 21 cases in each group.Length of hospital stay,operation time,and blood loss were recorded.The visual analog scale (VAS),anterior vertebral body height,angle of the kyphotic deformity,and complications before operation,immediately after operation,3 months after operation,and at the last follow up were compared among three groups.Complications of each group were recorded.Results The hospital stay,operation time,and blood loss in Group C were significantly higher than those in Group A (P ＜ 0.05),but there were no significant differences between Group B and Group C (P ＞ 0.05),except for a longer operation time in Group C.The pre-operative VAS showed no significant difference among three groups (P ＞ 0.05).However,the mean VAS in Groups A,B and C at the last follow up were 1.0(0.0,2.0)points,1.0(0.0,2.0)points,0.0(0.0,1.0)points,respectively.The VAS in Group C was significantly lower than that in Group B or A (P ＜ 0.05).The mean anterior vertebral body height and angle of the kyphotic deformity in Group C had no significant difference from that in Group A or B before operation and immediately after operation (P ＞ 0.05).At the last follow up,the mean anterior vertebral body height and angle of the kyphotic deformity in Groups A,B and C were (68 ±14.7)％,(72.3 ±9.0)％,(81.5 ±5.6)％ and (10.6 ±3.9)°,(10.7 ±5.0)°,(7.4 ± 5.0) °,respectively.The loss of anterior vertebral body height and angle of the kyphotic deformity correction in Group C were significantly less than that in Group A or B (P ＜ 0.05).Superficial infection was found in Groups B (n =2) and C (n =1),and the infection was cured after antibiotic therapy and dress change.Bone cement leakage was found in Groups A (n =8) and C (n =5),with no nerve compression.Internal fixation failure was seen in Group B (n =3),and the implant was removed directly.Conclusion Short-segment pedicle screw fixation combined with vertebroplasty can effectively reduce the loss of anterior vertebral body height and angle of the kyphotic deformity and hence enhance the clinical efficacy.