Decreased cortical bone density and mechanical strength with associated elevated bone turnover markers at peri-pubertal peak height velocity: a cross-sectional and longitudinal cohort study of 396 girls with adolescent idiopathic scoliosis.

Decreased cortical bone density and bone strength at peak height velocity (PHV) were noted in girls with adolescent idiopathic scoliosis (AIS). These findings could provide the link to the previously reported observation that low bone mineral density (BMD) could contribute as one of the prognostic factors for curve progression that mostly occurs during PHV in AIS. INTRODUCTION: As part of the studies related to aetiopathogenesis of AIS, we assessed bone qualities, bone mechanical strength and bone turnover markers (BTMs) focusing at the peri-pubertal period and PHV in AIS girls. METHODS: 396 AIS girls in two separate cohorts were studied. Skeletal maturity was assessed using the validated thumb ossification composite index (TOCI). Bone qualities and strength were evaluated with high-resolution peripheral quantitative computed tomography (HR-pQCT) and finite element analysis (FEA). RESULTS: Cohort-A included 179 girls (11.95 ± 0.95 years old). Girls at TOCI-4 had numerically the highest height velocity (0.71 ± 0.24 cm/month) corresponding to the PHV. Subjects at TOCI-4 had lower cortical volumetric BMD (672.36 ± 39.07 mg/mm3), cortical thickness (0.68 ± 0.08 mm) and apparent modulus (1601.54 ± 243.75 N/mm2) than: (a) those at TOCI-1-3 (724.99 ± 32.09 mg/mm3 (p < 0.001), 0.79 ± 0.11 mm (p < 0.001) and 1910.88 ± 374.75 N/mm2 (p < 0.001), respectively) and (b) those at TOCI-8 (732.28 ± 53.75 mg/mm3 (p < 0.001), 0.84 ± 0.14 mm (p < 0.001), 1889.11 ± 419.37 N/mm2 (p < 0.001), respectively). Cohort-B included 217 girls (12.22 ± 0.89 years old). Subjects at TOCI-4 had higher levels of C-terminal telopeptide of type 1 collagen (1524.70 ± 271.10 pg/L) and procollagen type 1 N-terminal propeptide (941.12 ± 161.39 µg/L) than those at TOCI-8 (845.71 ± 478.55 pg/L (p < 0.001) and 370.08 ± 197.04 µg/L (p < 0.001), respectively). CONCLUSION: AIS girls had decreased cortical bone density and bone mechanical strength with elevated BTMs at PHV. Coupling of PHV with decreased cortical and FEA parameters could provide the link to the previously reported observation that low BMD could contribute as one of the prognostic factors for curve progression that mostly occurs during PHV in AIS.

Comparison of bone structure and microstructure in the metacarpal heads between patients with psoriatic arthritis and healthy controls: an HR-pQCT study.

Human cadaveric study has indicated that the metacarpal head (MCH) is intracapsular in location. We hypothesized that exposure to the intra-articular inflammatory milieu in psoriatic arthritis (PsA) will lead to bone loss in the MCH. INTRODUCTION: To compare the bone structure and microstructure in the MCH between patients with PsA and healthy controls by high-resolution peripheral quantitative CT (HR-pQCT), and to ascertain factors associated with bone loss in PsA patients. METHODS: Sixty-two PsA patients without joint destruction and 62 age-, gender-, and body mass index-matched healthy subjects underwent HR-pQCT imaging of the second and third MCH (MCH 2&3). The number and volume of bone erosion and enthesiophytes, as well as volumetric bone mineral density (vBMD) and microstructure at the MCH 2&3, were recorded. Correlation analysis and multivariable linear regression models were used to determine the association of demographic and disease-specific variables with compromised bone structure and microstructure in PsA. RESULTS: At the MCH 2&3, bone erosion (p = 0.003) and enthesiophyte (p = 0.000) volumes in PsA patients were significantly larger than healthy controls. In PsA patients, older age was associated with a larger erosion and enthesiophyte volume. Concerning the mean vBMD and microstructure at the MCH 2&3, PsA patients had significantly lower mean vBMD (average vBMD - 6.9%, trabecular vBMD - 8.8%, peri-trabecular vBMD - 7.7%, meta-trabecular vBMD - 9.8%), trabecular bone volume fraction (- 8.8%), and trabecular thickness (- 8.1%) compared with control subjects. Multivariable regression analysis revealed that older age and a higher C-reactive protein level were associated with trabecular bone loss. CONCLUSIONS: PsA patients had a higher burden of bone damages (erosions and enthesiophytes) and trabecular bone loss compared with healthy control at the MCH. Inflammation contributed to the deterioration in trabecular microstructure in these patients.

Impaired bone microarchitecture in distal interphalangeal joints in patients with primary hypertrophic osteoarthropathy assessed by high-resolution peripheral quantitative computed tomography.

This study aimed to investigate the bone impairment in finger joints in PHO patients by HR-pQCT. Results showed distinguished differences in bone architecture and biomechanics parameters at DIPs between PHO patients and healthy controls using HR-pQCT assessment. Besides, serum PGE2, hsCRP and ESR levels were found negatively correlated with total vBMD. INTRODUCTION: This study aimed to investigate the bone impairment in finger joints in primary hypertrophic osteoarthropathy (PHO) patients firstly by high-resolution peripheral quantitative computed tomography (HR-pQCT). METHODS: Fifteen PHO patients and 15 healthy controls were enrolled in this study. Bone erosions in hands at distal interphalangeal joints (DIPs) in both PHO patients and controls were evaluated by X-ray. Bone geometry, vBMD, microstructure parameters, and size of individual bone erosion were also measured at the 3rd DIP by HR-pQCT as well. Blood biochemistry levels between the two groups were also compared. RESULTS: Compared to X-ray, HR-pQCT assessment were more sensitive for detection of bone erosions, with 14 PHO patients by HR-pQCT versus ten PHO patients by X-ray judged at the 3rd DIP. The average depth, width, and volume of erosions size in PHO patients were 1.38 ± 0.80 mm, 0.79 ± 0.27 mm, and 1.71 ± 0.52 mm3, respectively. The bone cross-areas including total area (+ 25.3%, p ≤ 0.05), trabecular area (+ 56.2%, p ≤ 0.05), and cortical perimeter (+ 10.7%, p ≤ 0.05) at the defined region of interest of 3rd DIP was significantly larger than controls. Total vBMD was 11.9% lower in PHO patients compared with the controls (p ≤ 0.05). Biochemical test results showed the increased levels of inflammatory cytokines, bone resorption markers, and joint degeneration markers in PHO patients. Serum prostaglandin PGE2, high-sensitive C-reactive protein (hsCRP) and erythrocyte sedimentation rate (ESR) levels were found negatively correlated with total vBMD. CONCLUSIONS: This study demonstrated higher sensitivity of the HR-pQCT measurement at DIPs by showing the differences in architecture and biomechanics parameters at DIPs between the PHO patients and healthy controls, which would be of interest clinically to investigate bone deterioration in PHO patients.

Prevalence of vitamin D insufficiency among adolescents and its correlation with bone parameters using high-resolution peripheral quantitative computed tomography.

UNLABELLED: Vitamin D deficiency and insufficiency are highly prevalent among adolescents in Hong Kong, which is a sub-tropical city with ample sunshine. Vitamin D level is significantly correlated with key bone density and bone quality parameters. Further interventional studies are warranted to define the role of vitamin D supplementation for improvement of bone health among adolescents. INTRODUCTION: The relationship between bone quality parameters and vitamin D (Vit-D) status remains undefined among adolescents. The aims of this study were to evaluate Vit-D status and its association with both bone density and bone quality parameters among adolescents. METHODS: Three hundred thirty-three girls and 230 boys (12-16 years old) with normal health were recruited in summer and winter separately from local schools. Serum 25(OH) Vit-D level, bone density and quality parameters by Dual Energy X-ray Absorptiometry (DXA) and High-Resolution peripheral Quantitative Computed Tomography (HR-pQCT), dietary calcium intake, and physical activity level were assessed. RESULTS: Sixty-four point seven percent and 11.4 % of subjects were insufficient [25 ≤ 25(OH)Vit-D ≤ 50 nmol/L] and deficient [25(OH)Vit-D < 25 nmol/L] in Vit-D, respectively. The mean level of serum 25(OH)Vit-D in summer was significantly higher than that in winter (44.7 ± 13.6 and 35.9 ± 12.6 nmol/L, respectively) without obvious gender difference. In girls, areal bone mineral density (aBMD) and bone mineral content (BMC) of bilateral femoral necks, cortical area, cortical thickness, total volumetric bone mineral density (vBMD), and trabecular thickness were significantly correlated with 25(OH)Vit-D levels. In boys, aBMD of bilateral femoral necks, BMC of the dominant femoral neck, cortical area, cortical thickness, total vBMD, trabecular vBMD, BV/TV, and trabecular separation were significantly correlated with 25(OH)Vit-D levels. CONCLUSION: Vit-D insufficiency was highly prevalent among adolescents in Hong Kong with significant correlation between Vit-D levels and key bone density and bone quality parameters being detected in this study. Given that this is a cross-sectional study and causality relationship cannot be inferred, further interventional studies investigating the role of Vit-D supplementation on improving bone health among adolescents are warranted.

Abnormal Bone Mechanical and Structural Properties in Adolescent Idiopathic Scoliosis: A Study with Finite Element Analysis and Structural Model Index.

Previous studies found adolescent idiopathic scoliosis (AIS) is associated with low bone mineral density (BMD) and abnormal bone quality, whilst the association between AIS and their bone strength is unknown. From high-resolution peripheral quantitative computed tomography-generated images, bone mechanical properties can be evaluated with finite element analysis (FEA), and trabecular rod-plate configuration related to trabecular bone strength can be quantified by structure model index (SMI). This study aimed to compare trabecular configuration and bone mechanical properties between AIS and the controls. 95 AIS girls aged 12-14 years and 97 age- and gender-matched normal controls were recruited. Bilateral femoral necks and non-dominant distal radius were scanned by dual-energy X-ray absorptiometry for areal BMD and HR-pQCT for SMI and FEA, respectively. Subjects were further classified into osteopenic and non-osteopenic group based on their areal BMD. Bone mechanical properties (stiffness, failure load and apparent modulus) were calculated using FEA. Linear regression model was used for controlling age, physical activity and calcium intake. AIS was associated with lower failure load and apparent modulus after adjusting for age, whereas AIS was associated with lower apparent modulus after adjusting for all confounders. Osteopenic AIS was associated with more rod-like trabeculae when compared with non-osteopenic AIS, whereas no difference was detected between osteopenic and non-osteopenic controls. This might be the result of abnormal regulation and modulation of bone metabolism and bone modelling and remodelling in AIS which will warrant future studies with a longitudinal design to determine the significance of micro-architectural abnormalities in AIS.

Cortical thinning and progressive cortical porosity in female patients with systemic lupus erythematosus on long-term glucocorticoids: a 2-year case-control study.

UNLABELLED: In this study, we characterized longitudinal changes of volumetric bone mineral density and cortical and trabecular microstructure at the distal radius using HR-pQCT in female systemic lupus erythematosus (SLE) patients on long-term glucocorticoids. Cortical thinning and increased cortical porosity are the major features of longitudinal microstructural deterioration in SLE patients. INTRODUCTION: The study aims to characterize longitudinal changes of volumetric bone mineral density (vBMD) and bone microstructure at distal radius in female systemic lupus erythematosus (SLE) patients on long-term glucocorticoids. METHODS: This 2-year case-control study consisted of 166 premenopausal subjects (75 SLE patients and 91 controls) and 79 postmenopausal subjects (44 SLE patients and 35 controls). We obtained areal BMD (aBMD) by dual-energy X-ray absorptiometry at multiple skeletal sites and indices of vBMD and microstructure at distal radius by high-resolution peripheral quantitative computed tomography (HR-pQCT) at baseline, 12 and 24 months. RESULTS: In either premenopausal or postmenopausal subjects, changes in aBMD did not differ between patients and controls except that decrease in aBMD at total hip at 24 months in premenopausal patients was significantly higher. In premenopausal subjects, decrease in cortical area (-0.51 vs. -0.06 %, p = 0.039) and thickness (-0.63 vs. 0.02 %, p = 0.031) and increase in cortical porosity (21.7 vs. 7.16 %, p = 0.030) over study period were significantly larger in patients after adjustment of age and body mass index. Decreased in trabecular vBMD was significantly less (-0.63 vs. -2.32 %, p = 0.001) with trabecular microstructure better maintained in patients. In postmenopausal subjects, decrease in cortical vBMD (-2.66 vs. -1.56 %, p = 0.039) and increase in cortical porosity (41.6 vs. 16.3 %, p = 0.021) were significantly higher in patients, and there was no group-wise difference in change of trabecular microstructure. CONCLUSION: Longitudinal microstructural deterioration in SLE is characterized by cortical thinning and increased cortical porosity. Cortical bone is an important source of bone loss in SLE patients on glucocorticoids.

Lifelong bound feet in China: a quantitative ultrasound and lifestyle questionnaire study in postmenopausal women.

OBJECTIVE: The phenomenon of foot binding, also known as 'lotus feet', has an enduring and influential history in China. To achieve a man-made smaller foot size, lifelong foot binding may have had adverse effects on the skeleton. We investigated bone properties in postmenopausal women with bound feet, which may provide new information for developing countermeasures for prevention of fragility fractures. DESIGN: Population-based cohort study. PARTICIPANTS: This study involved 254 postmenopausal women aged 65-80, including 172 with bound feet and 82 age- and gender-matched control subjects, living in a remote region of China. OUTCOMES: Anthropometric, SF-36 Lifestyle Questionnaire and heel quantitative ultrasound (QUS) data were collected for the whole study population. A small subset of two cases was also invited for assessment of bone mineral density and microarchitecture at the distal tibia using high-resolution peripheral quantitative CT (HR-pQCT) and gait and balance tests. RESULTS: Women with bound feet had significantly lower QUS values than age-matched women with normal feet; this was supported by HR-pQCT data. However, SF-36 Questionnaire results did not reveal any statistically significant differences in any categorical responses, including physical functioning, general health vitality and physical component summary score, and number of previous fractures. No impairment of body balance was found in the small subset. CONCLUSIONS: The man-made changes caused by foot binding led to reduced physical activity, making the subjects prone to osteoporosis. Women with bound feet and osteoporosis did not have a higher incidence of fragility fractures than controls. This might be explained by compensation in physical activity to improve body balance, implying the importance of improving or maintaining body balance in overall prevention strategies against fragility fractures.

Age-related differences in volumetric bone mineral density, microarchitecture, and bone strength of distal radius and tibia in Chinese women: a high-resolution pQCT reference database study.

UNLABELLED: In a cohort of 393 Chinese women, by using high-resolution peripheral quantitative computed tomography (HR-pQCT), we found that significant cortical bone loss occurred after midlife. Prominent increase in cortical porosity began at the fifth decade but reached a plateau before the sixth decade. Trabecular bone loss was already evident in young adulthood and continued throughout life. INTRODUCTION: This study aimed to investigate age-related differences in volumetric bone mineral density (vBMD), microarchitecture, and estimated bone strength at peripheral skeleton in Chinese female population. METHODS: In a cross-sectional cohort of 393 Chinese women aged 20-90 years, we obtained vBMD, microarchtecture, and micro-finite element-derived bone strength at distal radius and tibia using HR-pQCT. RESULTS: The largest predictive age-related difference was found for cortical porosity (Ct.Po) which showed over four-fold and two-fold differences at distal radius and tibia, respectively, over the adulthood. At both sites, cortical bone area, vBMD, and thickness showed significant quadratic association with age with significant decrease beginning after midlife. Change of Ct.Po became more prominent between age of 50 and 57 (0.26 %/year at distal radius, 0.54 %/year at distal tibia, both p ≤ 0.001) but thereafter, reached a plateau (0.015 and 0.028 %/year, both p > 0.05). In contrast, trabecular vBMD and microarchitecture showed linear association with age with significant deterioration observed throughout adulthood. Estimated age of peak was around age of 20 for trabecular vBMD and microarchitecture and Ct.Po and age of 40 for cortical vBMD and microarchitecture. Estimated stiffness and failure load peaked at mid-30s at the distal radius and at age 20 at distal tibia. CONCLUSIONS: Age-related differences in vBMD and microarchitecture in Chinese women differed by bone compartments. Significant cortical bone loss occurred after midlife. Prominent increase in Ct.Po began at the fifth decade but appeared to be arrested before the sixth decade. Loss of trabecular bone was already evident in young adulthood and continued throughout life.

Density, structure, and strength of the distal radius in patients with psoriatic arthritis: the role of inflammation and cardiovascular risk factors.

UNLABELLED: We investigated the densitometric and microstructural features of the distal radius in psoriatic arthritis (PsA) patients using high-resolution peripheral quantitative computed tomography. PsA patients have unique bone microstructural deficits, manifested as lower cortical bone density and higher cortical porosity, which are associated with a propensity to bone fragility. INTRODUCTION: The aim of this study was to investigate the densitometric, geometric, microstructural, and biomechanical features of the distal radius in psoriatic arthritis (PsA) patients. METHODS: This study cohort consisted of 53 PsA patients (24 males and 29 females), with an average age of 53.1 years and 53 gender- and age-matched controls. Areal bone mineral density (aBMD) of the hip, lumbar spine, and ultradistal radius was measured by dual-energy X-ray absorptiometry. High-resolution peripheral quantitative computed tomography (HR-pQCT) was performed at the distal radius to obtain measures of volumetric BMD (vBMD), microstructure, and derived biomechanical indices. RESULTS: There were no significant between-group differences in aBMD at the femoral neck, total hip, and ultradistal radius, while aBMD at the lumbar spine was significantly higher in patients. The only indices indicating compromised bone quality in PsA patients were related to cortical bone quality. Cortical vBMD were -3.8% significantly lower, while cortical pore volume, porosity index, and pore diameter were 108, 79.5, and 8.6%, respectively, significantly higher in patients. Cortical stress was marginally lower (-1.3%, p = 0.077) in patients with stress significantly more unevenly distributed (4.9%, p = 0.035). Endocortical perimeter and cortical pore volume were significantly higher in patients with vertebral fracture. Deficits in cortical bone quality were associated with indices of disease activity/severity and were more prominent in patients with type 2 diabetes mellitus or hypertension. CONCLUSIONS: There is an intertwined relationship between chronic inflammation, cardiovascular risk factors, and bone loss in PsA. PsA patients seem to have unique bone microstructural deficits which are associated with a propensity to bone fragility.

Effects of 18-month low-magnitude high-frequency vibration on fall rate and fracture risks in 710 community elderly--a cluster-randomized controlled trial.

UNLABELLED: This study is a prospective cluster-randomized controlled clinical trial involving 710 elderly subjects to investigate the long-term effects of low-magnitude high-frequency vibration (LMHFV) on fall and fracture rates, muscle performance, and bone quality. The results confirmed that LMHFV is effective in reducing fall incidence and enhancing muscle performance in the elderly. INTRODUCTION: Falls are direct causes of fragility fracture in the elderly. LMHFV has been shown to improve muscle function and bone quality. This study is to investigate the efficacy of LMHFV in preventing fall and fractures among the elderly in the community. METHODS: A cluster-randomized controlled trial was conducted with 710 postmenopausal females over 60 years. A total of 364 participants received daily 20 min LMHFV (35 Hz, 0.3 g), 5 days/week for 18 months; 346 participants served as control. Fall or fracture rate was taken as the primary outcome. Also, quadriceps muscle strength, balancing abilities, bone mineral density (BMD), and quality of life (QoL) assessments were done at 0, 9, and 18 months. RESULTS: With an average of 66.0% compliance in the vibration group, 18.6% of 334 vibration group subjects reported fall or fracture incidences compared with 28.7% of 327 in the control (adjusted HR = 0.56, p = 0.001). The fracture rate of vibration and control groups were 1.1 and 2.3 % respectively (p = 0.171). Significant improvements were found in reaction time, movement velocity, and maximum excursion of balancing ability assessment, and also the quadriceps muscle strength (p < 0.001). No significant differences were found in the overall change of BMD. Minimal adverse effects were documented. CONCLUSION: LMHFV is effective in fall prevention with improved muscle strength and balancing ability in the elderly. We recommend its use in the community as an effective fall prevention program and to decrease related injuries.

SLE disease per se contributes to deterioration in bone mineral density, microstructure and bone strength.

OBJECTIVE: The objective of this report is to assess the effect of systemic lupus erythematosus (SLE) disease itself on deterioration of bone mineral density (BMD), microstructure and bone strength. METHOD: Thirty age-matched SLE patients on long-term glucocorticoids (GC) (SLE/GC), 30 SLE patients without GC (SLE/non-GC) and 60 healthy controls were examined. Areal BMD (aBMD) was measured by dual-energy X-ray absorptiometry. Bone geometry, volumetric BMD (vBMD), and architectural parameters at the nondominant distal radius were assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT). Bone strength was estimated by HR-pQCT-based micro-finite element analysis. RESULTS: Adjusted for menopausal status and adjusted calcium level, when compared with controls, SLE/non-GC patients had significantly lower aBMD at femoral neck and total hip, and diminished radial total vBMD, cortical area, vBMD and thickness, respectively, by 8.3%, 8%, 2.7% and 9.2%, as well as significant compromised bone strength (stiffness, failure load and apparent modulus) by 8.3%, 9.1% and 9.5%, respectively. Similar alterations were also found in SLE/GC patients when compared to controls. In the premenopausal subgroup analysis, when compared with controls, total hip aBMD and radial cortical area were significantly lower in SLE/non-GC patients, and cortical area and thickness were significantly deficit in SLE/GC patients. However, no significant difference in any bone variables was present between SLE/GC and SLE/non-GC patients in the entire cohort or in the premenopausal subgroup. CONCLUSION: SLE disease per se contributes to the deterioration in bone density, cortical microstructure and bone strength. This might help to explain the considerably higher fracture risk seen in SLE patients.

Alterations of bone geometry, density, microarchitecture, and biomechanical properties in systemic lupus erythematosus on long-term glucocorticoid: a case-control study using HR-pQCT.

UNLABELLED: Compared to controls, HR-pQCT at distal radius of SLE patients on chronic glucocorticoid (SLE/GC) revealed reduced bone area, vBMD, deteriorated microarchitecture, and unevenly distributed stresses limited to cortical bone. Despite similar trabecular quality, whole bone strength decreased in patients. These alterations may partly explain high fracture rates in SLE/GC. INTRODUCTION: To assess bone geometric, densitometric, microarchitectural, and biomechanical properties in patients with systemic lupus erythematosus (SLE) on long-term glucocorticoid (GC) (SLE/GC) as compared with healthy controls. METHODS: A total of 180 female SLE patients and 180 healthy controls were in this cross-sectional study to assess areal bone mineral density (aBMD) by dual-energy X-ray absorptiometry. High-resolution peripheral quantitative computed tomography (HR-pQCT) and microfinite element analysis (µFEA) was performed at distal radius. RESULTS: In addition to significantly lower aBMD at femoral neck, total hip and lumbar spine, cortical area, average volumetric BMD (vBMD) and cortical vBMD also significantly reduced by 5.3, 5.7, to 1.9 % in SLE patients, respectively. Deteriorations of cortical microarchitecture were pronounced in patients, with 6.3 % reduction in cortical thickness and 13.6 % higher in cortical porosity. Local stresses were more unevenly distributed through cortical bone in patients. SLE/GC patients had decreased whole bone stiffness, estimated failure load, and apparent modulus. Parameters related to trabecular bone density and microarchitecture were comparable between patients and controls. CONCLUSION: In SLE/GC patients, despite a reduction in bone area, vBMD and deteriorated microarchitecture and unevenly distributed stresses limited to the cortical compartment, whole bone strength decreased. HR-pQCT and µFEA were promising in elucidating the potential underlying pathophysiology of bone loss and propensity to fracture in SLE/GC and provide us additional information about alterations of bone quality which might better predict fracture risk beyond aBMD in SLE/GC.

Impaired bone healing in rabbits with steroid-induced osteonecrosis.

Corticosteroids are prescribed for the treatment of many medical conditions and their adverse effects on bone, including steroid-associated osteoporosis and osteonecrosis, are well documented. Core decompression is performed to treat osteonecrosis, but the results are variable. As steroids may affect bone turnover, this study was designed to investigate bone healing within a bone tunnel after core decompression in an experimental model of steroid-associated osteonecrosis. A total of five 28-week-old New Zealand rabbits were used to establish a model of steroid-induced osteonecrosis and another five rabbits served as controls. Two weeks after the induction of osteonecrosis, core decompression was performed by creating a bone tunnel 3 mm in diameter in both distal femora of each rabbit in both the experimental osteonecrosis and control groups. An in vivo micro-CT scanner was used to monitor healing within the bone tunnel at four, eight and 12 weeks postoperatively. At week 12, the animals were killed for histological and biomechanical analysis. In the osteonecrosis group all measurements of bone healing and maturation were lower compared with the control group. Impaired osteogenesis and remodelling within the bone tunnel was demonstrated in the steroid-induced osteonecrosis, accompanied by inferior mechanical properties of the bone. We have confirmed impaired bone healing in a model of bone defects in rabbits with pulsed administration of corticosteroids. This finding may be important in the development of strategies for treatment to improve the prognosis of fracture healing or the repair of bone defects in patients receiving steroid treatment.

Genetic association study of insulin-like growth factor-I (IGF-I) gene with curve severity and osteopenia in adolescent idiopathic scoliosis.

UNLABELLED: IGF-I has a pivotal role in bone growth and could be one of the putative disease-modifier genes in AIS. Two SNPs in IGF-I gene promoter region were studied for any association with occurrence of AIS and for their effect on the curve severity among AIS. METHODS: 506 AIS girls (Cobb>20 degrees) and 227 age-matched Chinese girls were recruited. The spine (L2-L4) and hip BMD of the subjects were measured by DXA. A subgroup of AIS patients (N=340) who were followed-up to skeletal maturity and the maximum Cobb's angle was recorded. Two SNPs were genotyped by PCR-RFLP (rs5742612 and rs2288377). The chi-square test and one-way ANOVA were used to test the association between genotypes and quantitative parameters, respectively. RESULTS: No association was between the genotypes and the occurrence of AIS and the BMD of the spine and hip. The allelic frequency of T allele was 0.69 in AIS and control. However, the Cobb's angle was higher in patients with the homozygous T allele (Mean Cobb's angle: 38.1 degrees in TT vs 35.9 degrees in TC vs 33.2 degrees in CC group; p=0.04). DISCUSSION: Interestingly, IGF-I polymorphism affects the curve severity of AIS though it was not associated with onset of AIS per se. It indicates that IGF-I may be a disease modifying gene. The importance of IGF-I in skeletal growth makes it a good candidate gene which would play a role in the documented association of rapid growth with curve progression in AIS.

Persistent osteopenia in adolescent idiopathic scoliosis--longitudinal monitoring of bone mineral density until skeletal maturity.

The aim of this study was to monitor BMD changes occurring during periods of rapid growth and to investigate whether osteopenia was a persistent phenomenon in skeletally matured AIS girls. 196 AIS Chinese girls and 122 healthy controls, aged 11-16, were follow-up for 3.5 years. Bilateral femoral neck bone mineral density (BMD) and volumetric BMD (vBMD) of the distal tibia were obtained by dual energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT). Osteopenia was defined if the age-adjusted BMD was below or equal to -1 standard deviation (SD). The average age at the final follow-up was 16.8 years old. The median initial Cobb angle for this group of patients was 26 degrees. The prevalence of osteopenia at the baseline measurement was 35.9%. Longitudinal BMD results demonstrated that 86.0% of osteopenic AIS girls had persistently low BMD at the time of skeletal maturity (age of 16). vBMD of distal tibia of AIS was significantly lower than that of the controls throughout the age of 13 to 17 during the period of rapid growth. In addition, there were also significant differences in vBMD among AIS (moderate and severe group) and the controls by one-way ANOVA (p<0.05). The present study for the first time revealed that over 86% of osteopenic AIS patients had persistently low BMD, at both distal tibia and femoral neck regions, at the time of skeletal maturity. Early detection and treatment of AIS-related osteopenia might help in maximizing peak bone mass during peripubertal growth that thereby minimizing risks of developing osteoporotic fractures later in life.

Lower degree of mineralization found in cortical bone of adolescent idiopathic scoliosis (AIS).

UNLABELLED: A lowered bone mineral density (BMD) was observed in trabecular bone in a significant number of AIS patients. The present study aims at investigating whether lower BMD is a systemic phenomenon, which would also be present in the cortical component of long bone. SUBJECTS AND METHODS: 78 AIS girls (age:15-18y.o) with either moderate (Cobb: 20-40) or severe (Cobb: >40) curve and 44 age-matched controls were recruited. The BMD of the distal region and the mid-shaft of radius were measured with a multi-layer peripheral quantitative computed tomography (pQCT). The trabecular bone and cortical bone BMD and the morphology of mid-shaft were compared. RESULTS: Both trabecular and cortical BMD in severe AIS group was significantly lower than the control by 8.7% and 1.7% (p<0.05 for both), respectively. However, the cortical bone area of the mid-shaft did not show any differences from the normal control subjects. DISCUSSION: This study demonstrates a systemic low BMD including the cortical bone. It is suggested that AIS girls may have disturbance in mineralization and ossification during peripubertal growth.

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.

Effects of weight bearing and non-weight bearing exercises on bone properties using calcaneal quantitative ultrasound.

OBJECTIVE: This study was designed to investigate bone properties using heel quantitative ultrasound (QUS) in young adults participating in various sports. METHODS: A cross sectional study was performed on Chinese male students (n = 55), aged 18-22 years. Subjects with previous fractures or suffering from any diseases known to affect bone metabolism or taking any medication with such an effect, were not included. The subjects were categorised according to their main sporting activities, including soccer (n = 15) (a high impact, weight bearing exercise), dancing (n = 10) (a low impact, weight bearing exercise), and swimming (n = 15) (non-weight bearing exercise). A sedentary group acted as controls (n = 15). A reproducibility study of the velocity of sound (VOS) and the broadband ultrasound attenuation (BUA) measurement was performed and analysed using the intraclass correlation coefficient (ICC). RESULTS: There was good intra-investigator and inter-investigator agreement (ICC > or = 0.8; p < 0.05) in the measurement of BUA and VOS. No significant differences in BUA and VOS (p > 0.05) were found between the dominant and non-dominant heel. Soccer players (137 +/- 4.3 dB/MHz; 1575 +/- 56 m/s; 544.1 +/- 48.4) and dancers (134.6 +/- 3.7 dB/MHz; 1538 +/- 46 m/s; 503.0 +/- 37.0) had significantly higher BUA, VOS, and stiffness index (SI) scores (p < 0.05), respectively, than swimmers (124.1 +/- 5.1 dB/MHz; 1495 +/- 42 m/s; 423.3 +/- 46.9) and the sedentary control group (119.9 +/- 6.1 dB/MHz; 1452 +/- 41 m/s; 369.9 +/- 46.4). A trend of a significant linear increase with the weight bearing and high impact exercise was revealed in all QUS parameters (p < 0.05). CONCLUSION: This cross sectional study indicated that regular participation in weight bearing exercise in young people might be beneficial for accruing peak bone mass and optimising bone structure.

Regional differences in cortical bone mineral density in the weight-bearing long bone shaft--a pQCT study.

This study used a multislice peripheral quantitative computed tomography (pQCT) to measure volumetric BMD (vBMD) and cortical thickness for investigating regional adaptation in lower tibial shaft in 72 healthy postmenopausal women aged 47-60. Tomographic slices were analysed on four distinct cortical regions: the anterior, posterior, medial and lateral cortical wall. One-way analysis of variance (ANOVA) test was used to compare the vBMD in the four regions. The results showed that the posterior cortex had the highest vBMD (1923 +/- 135.3 mg/cm(3)), significantly (P < 0.001) higher than the anterior cortex (1805 +/- 110.6 mg/cm(3)), medial cortex (1863 +/- 103.6 mg/cm(3)) and lateral cortex (1815 +/- 111.6 mg/cm(3)); whereas there was no significant difference (P > 0.05) between the medial and lateral cortices located near the neutral plane of bending. The anterior cortex had the greatest thickness (2.56 +/- 0.47 mm), significantly (P < 0.001) greater than that of the posterior cortex (2.11 +/- 0.27 mm), medial cortex (2.20 +/- 0.39 mm) and lateral cortex (2.03 +/- 0.29 mm). The vBMD of the posterior cortex was a significant 6.5% higher than that of the anterior cortex (P < 0.001); whereas the anterior cortical thickness was a significant 21.3% greater than that of the posterior cortex (P < 0.001). There was no linear relationship found between cortical vBMD and cortical thickness measured at the four cortical regions (r = 0.086, P > 0.05). In conclusion, the regional differences, with higher vBMD found in posterior cortex, might be a result of mechanical adaptation, which caused the posterior cortex to sustain higher compressive loading than the anterior tensile cortex during the landing phase in the gait cycles of individuals. Nevertheless, regional geometric adaptation in anterior cortical thickness might be adapted to accommodate for the reduced vBMD and to reduce the bending stress in this region.

The effect of vertebral rotation of the lumbar spine on dual energy X-ray absorptiometry measurements: observational study.

OBJECTIVE: To estimate how axial rotation of lumbar vertebrae quantitatively affects bone mineral density, as measured by dual energy X-ray absorptiometry in the anteroposterior plane. DESIGN: Observational study. SETTING: University teaching hospital, Hong Kong. PATIENTS: Cadaver lumbar vertebrae (L2 to L4) were removed from four adults. MAIN OUTCOME MEASURES: Using dual energy X-ray absorptiometry, the bone mineral content, bone area, and bone mineral density were measured in the neutral position and with vertebral axial rotation in increments of 7.5 degrees, up to a maximum of 45 degrees. RESULTS: Correlation analysis showed a significant positive correlation between the degree of rotation and measured bone area, a significant negative correlation between degree of rotation and bone mineral density measurements, but no significant correlation between degree of rotation and measured bone mineral content. The measured bone area increased approximately 24% and the bone mineral density decreased approximately 19% when the vertebrae were rotated by 45 degrees. CONCLUSIONS: These results suggest that for patients with rotational deformity of the spine, such as scoliosis, measurements of lumbar spine bone mineral content by dual energy X-ray absorptiometry is not affected, while bone mineral density measurements are not reliable.