Kwong Man Lee

Generalized low areal and volumetric bone mineral density in adolescent idiopathic scoliosis.

Adolescent idiopathic scoliosis (AIS) may be associated with generalized low bone mineral status. The bone mineral density (BMD) of 75 girls of 12–14 years of age and diagnosed as having AIS were compared with 94 age‐matched female control subjects. Areal BMD (aBMD) of the lumbar spine (L2‐L4) and the bilateral proximal femur were measured using ‐energy X‐ray absorptiometry (DEXA), and volumetric BMD (vBMD) of the nondominant distal radius and bilateral distal tibias was measured with peripheral quantitative computer tomography (pQCT). Relevant anthropometric parameters and the severity of the spinal deformity (Cobbs angle) also were evaluated and correlated with the BMD measurements. Results revealed the presence of a generalized lower bone mineral status in AIS patients. Detailed analysis showed that the aBMD and vBMD measured at the bilateral lower extremities were significantly lower in AIS patients when compared with the same in the normal controls. The most significant effect was seen in the trabecular BMD (tBMD) of the distal tibias. Of all the AIS girls, 38% of the aBMD and 36% of the vBMD were below −1 SD of the normal. BMD was found to correlate better with “years since menarche” (YSM) than with chronological age. When the BMD was evaluated for the 3 YSM groups, aBMD of the proximal femur and tBMD of distal tibias were found to be significantly lower in the AIS patients. Neither the aBMD nor the vBMD of AIS patients was found to be associated with the severity of spinal deformity. In addition, anthropometric measurements showed significantly longer arm span and lower extremities in the AIS girls. We concluded that the AIS girls had generalized lower aBMDs and vBMDs.

Low intensity pulsed ultrasound stimulates osteogenic activity of human periosteal cells

The effect of low intensity pulsed ultrasound on human periosteal cells was investigated. Normal human periosteum was obtained to culture the periosteal cells. After characterization, cultures of periosteal cells at Days 2 and 4 were treated with ultrasound for 5, 10, and 20 minutes respectively. Assessments were done to assess total number of viable cells, cell proliferation, alkaline phosphatase activity, osteocalcin secretion, vascular endothelial growth factor expression, and calcium nodule formation. With the cells not treated with ultrasound as the control, the results showed that ultrasound did not affect the total number of viable cells. It stimulated cell proliferation at the early phase of cell culture. The activity of alkaline phosphatase was increased significantly in the culture at Day 4. A similar effect was seen with osteocalcin secretion and the responses were dose-dependent. The vascular endothelial growth factor secretion increased in Day 2 and Day 4 cultures with the dose-dependent effect. Formation of calcium nodules was significantly higher with ultrasound treatment. We think that low intensity pulsed ultrasound stimulated periosteal cell proliferation and differentiation toward osteogenic lineage. The dose-dependent effect on osteogenic activities may modify the existing treatment regimen. Ultrasound treatment should be started from the beginning of fracture healing.

Abnormal peri-pubertal anthropometric measurements and growth pattern in adolescent idiopathic scoliosis : a study of 598 patients

Study Design. A cross-sectional study of anthropometric parameters in adolescent idiopathic scoliosis (AIS). Objective. To compare anthropometric parameters and growth pattern of AIS girls versus normal controls during peri-puberty. Summary of Background Data. Abnormal pattern of growth has been reported in AIS patients. The sequential changes of growth and the correlation with curve severity have not been properly studied. Materials and Methods. Five hundred ninety-eight AIS girls and 307 healthy girls entered the study. Weight, height, body mass index (BMI), arm span, sitting height, and leg length were determined using standard techniques. Height and sitting height were adjusted by using the greatest Cobb angle to correct for spinal deformity (Bjure’s formula). Puberty was graded by Tanner’s staging. Results. AIS girls had significantly shorter height (P = 0.001), corrected height (P = 0.005), arm span (P = 0.022), sitting height (P = 0.005) and leg length (P = 0.004) than the controls at pubertal stage I. From pubertal stages II through V, corrected height (P ≤ 0.033) and arm span (P ≤ 0.038) were significantly longer in the AIS than controls. Corrected sitting height was also longer in AIS from stages II through IV (P ≤ 0.043). Furthermore, BMI of AIS was significantly lower than that of controls from stages II through IV (P ≤ 0.038). In addition, significant correlations of the curve severity versus weight, BMI, and arm span were also found (P ≤ 0.048). Conclusions. Various body segmental lengths were initially significantly shorter in AIS before puberty. However, after the onset of puberty, significantly longer corrected height, arm span, and various body segments were found. And there were significant correlations between anthropometric parameters and the scoliotic curve severity. Results of this large-scale study revealed the presence of abnormal growth in AIS patients during peripubertal development.

Top theories for the etiopathogenesis of adolescent idiopathic scoliosis.

BackgroundDespite considerable advances in the past few decades, there is no generally accepted “top theory or theories” of the etiology of adolescent idiopathic scoliosis (AIS). This article aims to provide an overview of the current main hypothetical “concepts” on the etiopathogenesis of AIS. MethodsAn extensive literature review on hypothetical concepts on the etiology and etiopathogenesis of AIS. ResultsConcepts of etiopathogenesis in AIS were summarized and highlighted under 6 subgroups: genetics factors, abnormalities in nervous system, abnormal skeletal growth, hormones and metabolic dysfunction, biomechanical factors, and environmental and life style factors. An integrative model on the etiopathogenesis of AIS is proposed. ConclusionsThe current knowledge is still fragmented and many fundamental questions have remained to be answered. In moving forward in the perusal of further advancement of our understanding of the etiopathogenetic mechanisms and future evidence-based prevention and management of AIS, multidisciplinary and multicenter innovative research collaboration is imminently important and necessary. Clinical RelevanceWith a relatively comprehensive review on the current understanding on the etiology and etiopathogenesis of AIS, the article would help to stimulate further innovative thoughts, research, and especially collaborative research in this area of great interest.

Osteopenia: A New Prognostic Factor of Curve Progression in Adolescent Idiopathic Scoliosis

BACKGROUND Studies have shown that 27% to 38% of girls with adolescent idiopathic scoliosis have systemic osteopenia. The aim of this study was to investigate whether osteopenia could serve as one of the important prognostic factors in predicting curve progression. METHODS A prospective study was performed in 324 adolescent girls with adolescent idiopathic scoliosis who had a mean age of thirteen and a half years. Bone mineral density of the spine and both hips was measured at the time of the clinical diagnosis of scoliosis. All patients were followed longitudinally until skeletal maturity or until the curve had progressed > or =6 degrees . The univariate chi-square test and stepwise logistic regression were used to predict the prevalence of curve progression, and a receiver operating characteristic curve was plotted. RESULTS The overall prevalence of curve progression was 50%. The prevalence of osteopenia at the spine and hips was 27.5% and 23.1%, respectively. A larger initial Cobb angle (odds ratio = 4.6), a lower Risser grade (odds ratio = 4.7), premenarchal status (odds ratio = 2.5), osteopenia in the femoral neck of the hip on the side of the concavity (odds ratio = 2.3), and a younger age at the time of diagnosis (odds ratio = 2.1) were identified as risk factors in predicting curve progression. A predictive model was established, and the area under the receiver operating characteristic curve of the model was 0.80 (p < 0.01). CONCLUSION Osteopenia may be an important risk factor in curve progression. The measurement of bone mineral density at the time of diagnosis may serve as an additional objective measurement in predicting curve progression in adolescent idiopathic scoliosis. The bone mineral density-inclusive predictive model may be used in treatment planning for patients with adolescent idiopathic scoliosis who are at high risk of curve progression.

Triamcinolone suppresses human tenocyte cellular activity and collagen synthesis.

Glucocorticoid injection is widely used in tendon disorders. Despite previous studies on the histologic and biomechanical changes in tendons after glucocorticoid injections, the role of glucocorticoid in tendon rupture still is controversial. It was hypothesized that glucocorticoid has a direct deleterious effect on human tenocytes, suppressing its cellular activity and collagen production. Primary cultures of human tenocytes were obtained from explants of healthy patellar tendon harvested during anterior cruciate ligament reconstructions. The effects on cell viability and cell proliferation were measured by [3-(4,5-demethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay and 5-bromo-deoxyuridine incorporations. The effect on collagen synthesis was measured by 3H-proline incorporation assay. Triamcinolone acetonide at 10−9 to 10−4 mol/L decreased human tenocyte viability to 45% to 88% of control in a dose-dependent manner. Cell proliferation was suppressed to 87% ± 8% at all doses. Treatment with 1 μmol/L triamcinolone acetonide reduced the amount of collagen synthesis as measured by 3H-proline incorporation from 40 ± 2 cpm/1000 cells to 27 ± 4 cpm/1000 cells. The suppressed human tenocyte cellular activity and reduced collagen production may lead to disturbed tendon structure and predispose the tendon to subsequent spontaneous rupture.

Expression of VEGF and MMP-9 in giant cell tumor of bone and other osteolytic lesions.

This study aims to investigate the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) in giant cell tumor of bone (GCT) and other osteolytic lesions in bone. By using semi-quantitative RT-PCR, we showed that three major isoforms of VEGF (121, 165 and 189) were expressed in GCTs, with isoform 121 being the most abundant. The expression levels of VEGF and MMP-9 mRNA were significantly higher in advanced GCTs (stage II/III) than in stage I GCTs. We further elucidated the cellular localization of VEGF and MMP-9 gene transcripts in GCT and other osteolytic lesions using an in situ hybridization assay. The results showed that stromal tumor cells and osteoclast-like giant cells of GCT, fibrous stromal cells in anuerysmal bone cysts and fibrous dysplasia, and Langerhans-type giant cells as well as histocytes in eosinophillic granuloma, were all strongly positive for VEGF and MMP-9 mRNA expression. In a prospective study, we performed VEGF and MMP-9 immuno-staining on paraffin sections of pathological tissues harvested from 48 patients (14 GCT, 10 anuerysmal bone cysts, 10 eosinophillic granuloma, 4 fibrous dysplasia, 2 simple bone cyst, 2 osteomyelitis and 6 patients with fractured femoral head as control). The results showed that the differences in VEGF and MMP-9 expression between Stage I and other advanced Stages (II, III and recurrent) were highly significant (p<0.001), with advanced stages showing a higher mean expression. The difference between recurrent and Stage II and III lesions, was also statistically significant (p=0.03 for VEGF, and p=0.01 for MMP-9 expression), with recurrent lesions showing a higher mean expression of both VEGF and MMP-9. In conclusion, VEGF and MMP-9 expression in osteolytic lesions of bone co-relates well with the extent of bone destruction and local recurrence. Their expression may therefore provide some prognostic indication of the possible aggressive behavior of the underlying pathology.

The roles of bone morphogenetic protein (BMP) 12 in stimulating the proliferation and matrix production of human patellar tendon fibroblasts

Recombinant human (rh) bone morphogenetic protein 12 (BMP12) is proved to induce the formation of tendon and ligament tissues in animal experiments. But the roles of BMP12 on tissue regeneration in human tendons remain unexplored. In the present study, healthy human patellar tendon samples were collected for histological examination and preparation of tendon fibroblast culture. Immunohistochemical staining showed that BMP12 was detected on healthy patellar tendon samples, only located on active tenoblasts and perivascular mesenchymal cells but not in interstitial tenocytes. The expression of PCNA and procollagen type I also exhibited a similar distribution. It indicates that BMP12 may be involved in matrix remodeling process in adult tissues. In vitro studies showed that rhBMP12 could increase proliferation of tendon fibroblasts and increase the gene expression of procollagen type I and type III, but decrease the gene expression of decorin in tendon fibroblasts culture. Our findings suggest that BMP12 may play a role in early phases of tissue regeneration in tendons.

Generalized osteopenia in adolescent idiopathic scoliosis--association with abnormal pubertal growth, bone turnover, and calcium intake?

Study Design. A cross-sectional study in girls with adolescent idiopathic scoliosis (AIS) and healthy counterparts of similar age. Objectives. To study the association of bone mass with anthropometric parameters, bone turnover, and calcium intake in 621 girls with AIS, aged 11–6-years, and compare the results with 300 healthy girls of similar age. Summary of Background Data. Generalized low bone mass has been documented in AIS, yet the cause of low bone mineral density in AIS is unknown. Methods. Corrected height and arm span, bone mineral density and bone mineral content of proximal femur, lumbar spine, and distal tibia, and bone turnover markers (bone alkaline phosphatase [bALP] and deoxypyridinoline) were evaluated. Results. From age 13 years and older, the AIS group had longer anthropometric parameters (P < 0.05), generalized lower bone mass (P < 0.035), and 38.6% higher in bALP (P < 0.004) when compared with controls. A stronger inverse correlation between bALP and bone mass was noted in the AIS group. The bALP was positively correlated with bone area of tibia (P = 0.013) in the AIS group only. Deoxypyridonine of the AIS group was not different from the controls until age 15 years. The mean calcium intake of the AIS group was very low (only 361 mg/day), and calcium intake was significantly associated with bone mass in the AIS group. Low bone mass in AIS could be explained by faster anthropometric bone growth, higher bone turnover, and lower calcium intake in multiple regression analysis. Conclusions. Results from the current study showed that an abnormally faster growth rate and higher bone turnover in the patient with AIS might lead to increased bone dimensions. Calcium intake in patients with AIS was very low and likely to be insufficient for normal bone mineralization. Therefore, low bone mass in AIS may result from abnormal bone mineralization qualitatively and quantitatively and, thus, fails to catch up with increased bone growth during the peripubertal period.

Histomorphometric study of the spinal growth plates in idiopathic scoliosis and congenital scoliosis

Background: Previous studies have suggested that the relative anterior spinal overgrowth may play an important role in the etiopathogenesis of spinal deformity in adolescent idiopathic scoliosis (AIS). Little is known about the histomorphometry of the anterior and posterior spinal growth plates.