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Osteoporosis is a systemic skeletal disease characterized by low bone mass and bone structural deterioration that may result in fragility fractures. Use of bone imaging modalities to accurately predict fragility fractures is always an important issue, yet the current gold standard of dual-energy X-ray absorptiometry (DXA) for diagnosis of osteoporosis cannot fully satisfy this purpose. The latest high-resolution peripheral quantitative computed tomography (HR-pQCT) is a three-dimensional (3D) imaging device to measure not only volumetric bone density, but also the bone microarchitecture in a noninvasive manner that may provide a better fracture prediction power. This systematic review and meta-analysis was designed to investigate which HR-pQCT parameters at the distal radius and/or distal tibia could best predict fragility fractures. A systematic literature search was conducted in Embase, PubMed, and Web of Science with relevant keywords by two independent reviewers. Original clinical studies using HR-pQCT to predict fragility fractures with available full text in English were included. Information was extracted from the included studies for further review. In total, 25 articles were included for the systematic review, and 16 articles for meta-analysis. HR-pQCT was shown to significantly predict incident fractures and/or major osteoporotic fractures (MOFs). Of all the HR-pQCT parameters, our meta-analysis revealed that cortical volumetric bone mineral density (Ct.vBMD), trabecular thickness (Tb.Th), and stiffness were better predictors. Meanwhile, HR-pQCT parameters indicated better performance in predicting MOFs than incident fractures. Between the two standard measurement sites of HR-pQCT, the non-weight-bearing distal radius was a more preferable site than distal tibia for fracture prediction. Furthermore, most of the included studies were white-based, whereas very few studies were from Asia or South America. These regions should build up their densitometric databases and conduct related prediction studies. It is expected that HR-pQCT can be used widely for the diagnosis of osteoporosis and prediction of future fragility fractures. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

This HR-pQCT study was conducted to examine bone properties of the distal tibia post-stroke and to identify clinical outcomes that were associated with these properties at this site. It was found that spasticity and gait speed were independently associated with estimated failure load in individuals with chronic stroke. Purpose (1) To examine the influence of stroke on distal tibia bone properties and (2) the association between these properties and clinical outcomes in people with chronic stroke. Methods Sixty-four people with stroke (age, 60.8 ± 7.7 years; time since stroke, 5.7 ± 3.9 years) and 64 controls (age: 59.4 ± 7.8 years) participated in this study. High-resolution peripheral quantitative computed tomography (HR-pQCT) was used to scan the bilateral distal tibia, and estimated failure load was calculated by automated finite element analysis. Echo intensity of the medial gastrocnemius muscle and blood flow of the popliteal artery were assessed with ultrasound. The 10-m walk test (10MWT), Fugl-Meyer Motor Assessment (FMA), and Composite Spasticity Scale (CSS) were also administered. Results The percent side-to-side difference (%SSD) in estimated failure load, cortical area, thickness, and volumetric bone mineral density (vBMD), and trabecular and total vBMD were significantly greater in the stroke group than their control counterparts (Cohen's d = 0.48-1.51). Isometric peak torque and echo intensity also showed significant within- and between-groups differences (p ≤ 0.01). Among HR-pQCT variables, the %SSD in estimated failure load was empirically chosen as one example of the strong discriminators between the stroke group and control group, after accounting for other relevant factors. The 10MWT and CSS subscale for ankle clonus remained significantly associated with the %SSD in estimated failure load after adjusting for other relevant factors (p ≤ 0.05). Conclusion The paretic distal tibia showed more compromised vBMD, cortical area, cortical thickness, and estimated failure load than the non-paretic tibia. Gait speed and spasticity were independently associated with estimated failure load. As treatment programs focusing on these potentially modifiable stroke-related impairments are feasible to administer, future studies are needed to determine the efficacy of such intervention strategies for improving bone strength in individuals with chronic stroke.

Background This study aimed to adjust and cross‐validate skeletal muscle mass measurements between bioimpedance analysis (BIA) and dual‐energy X‐ray absorptiometry (DXA) for the screening of sarcopenia in the community and to estimate the prevalence of sarcopenia in Hong Kong. Methods Screening of sarcopenia was provided to community‐dwelling older adults. Appendicular skeletal muscle mass (ASM) was evaluated by BIA (InBody 120 or 720) and/or DXA. Handgrip strength and/or gait speed were assessed. Diagnosis of sarcopenia was based on the 2019 revised Asian Working Group for Sarcopenia cut‐offs. Agreement analysis was performed to cross‐validate ASM measurements by BIA and DXA. Multiple regression was used to explore contribution of measured parameters in predicting DXA ASM from BIA. Results A total of 1587 participants (age = 72 ± 12 years) were recruited; 1065 participants were screened by BIA (InBody 120) with 18 followed up by DXA, while the remaining 522 participants were assessed by the BIA (InBody 720) and DXA. The appendicular skeletal muscle mass index (ASMI) evaluated by BIA showed a mean difference of 2.89 ± 0.38 kg/m2 (InBody 120) and 2.97 ± 0.45 kg/m2 (InBody 720) against DXA gold standard. A significant overestimation of muscle mass was measured by BIA compared with DXA (P

ObjectiveTo evaluate the effects of denosumab on erosion healing at 2–4 metacarpophalangeal (MCP) head as determined by high-resolution peripheral quantitative CT (HR-pQCT) in patients with rheumatoid arthritis (RA) with stable disease.MethodsThis was a randomised, placebo-controlled, double-blind study. Patients with RA with disease activity score 28 joints (DAS28) ≤5.1 were randomised (1:1) to subcutaneous denosumab 60 mg or placebo once every 6 months for 24 months. The primary outcome was erosion healing at MCP 2–4 on HR-pQCT at 12 months. The effects of denosumab on erosion and joint space parameters on HR-pQCT and radiographs, disease activity and health assessment questionnaire-disability index (HAQ-DI) were also examined.ResultsAt 24 months, HR-pQCT images were analysed in 98 patients. One-third of the patients achieved sustained low disease activity throughout the study. At 12 months, changes in erosion parameters on HR-pQCT were similar between the two groups. At 24 months, new erosions (19% vs 9%, p=0.009) and erosion progression (18% vs 8%, p=0.019) were more common in the placebo group than the denosumab group. Erosion healing was seen in a significantly higher proportion of patients in the denosumab group (20% vs 6%, p=0.045) at 24 months. No significant changes in joint space parameters on HR-pQCT, van der Heijde-Sharp erosion score, DAS28 and HAQ-DI were observed in the two groups at 12 and 24 months.ConclusionAlthough no differences in erosion parameters were observed at 12 months, denosumab was more efficacious than placebo in erosion repair on HR-pQCT after 24 months.Trial registration numberNCT03239080.

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. 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. 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. 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. 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.

The study procedure was conducted in accordance to guidelines approved by the institutional clinical research ethics committee (CREC No. 2016.722) and the Declaration of Helsinki. Written informed consent was obtained from all subjects and their parents before participating in this study. AbstractThis study aimed to characterize global sagittal alignment in adolescent idiopathic scoliosis (AIS) with normal kyphosis (NTK, kyphosis > 10°) and with thoracic hypokyphosis (THK, kyphosis 21). Biplanar radiographies were acquired at baseline, immediate post-operatively, 1-year and 2-year follow-up, and 3D reconstruction of the spine and pelvis was performed. NTK and THK showed different global sagittal alignment, as well as differences compared to controls. AIS with THK at baseline had higher SVA/SFD (2.0 ± 2.9 vs − 0.4 ± 1.9; P

This report is of a proximal femoral unicameral bone cyst in a patient presented at 3 years. Intra-lesional steroid injection was used to treat this large active lesion. The response to treatment was monitored with the use of dual-energy X-ray absorptiometry (DXA) scan as an indirect method of monitoring the activity of the bone cyst. The patient had developed stress fracture during the course of treatment which had remodelled fully after successful treatment with multiple injections; at 12-year follow-up, the patient reached skeletal maturity. The affected femur had remodelled back to normal radiological appearance without avascular necrosis. This has demonstrated that steroid injection is a safe and effective procedure to achieve regression of a large active bone cyst in the proximal femur. It is a minimal invasive procedure resulting in no scar. DXA scan is a useful method combining clinical assessment to monitor status of the bone cyst to allow timing of injection. 中文摘要: 本報告為3歲患者的股骨近端骨囊腫，以用病灶內類固醇注射來治療這個巨大的活性病灶。 使用雙能X射線吸收測定法 (DXA) 掃描作為間接方法監測骨囊腫活性對治療的反應。 患者在治療過程中出現了應力性骨折，經多次注射成功治療後已完全改型，隨訪12年，患者達到骨骼成熟。 受影響的股骨已經重新恢復正常的放射學外觀及沒有缺血性壞死。 這證明了類固醇注射是一種安全有效的方法，以實現股骨近端巨大活躍骨囊腫的消退。 這是微創手術，沒有疤痕。 DXA掃描結合臨床評估以監測骨囊腫狀態是有效的方法以允許注射時機。 Keywords: DXA, steroid injection, Unicameral Bone Cyst

Objective To compare the bone healing effects of denosumab and alendronate in female rheumatoid arthritis (RA) patients by high-resolution peripheral quantitative computed tomography (HR-pQCT). Methods This is a post-hoc analysis of a randomized-controlled trial (NCT01770106). 40 patients were randomized in a 1:1 ratio to receive either subcutaneous denosumab (60mg) once or oral alendronate (70mg) weekly for 6 months. The size of individual bone erosions and the presence and extent of erosion-associated sclerosis (marginal osteosclerosis) were measured in the second metacarpal head of the non-dominant hand at baseline, 3 and 6 months. Results 42 erosions were identified at baseline. After 6 months, the width, depth and volume of erosion significantly decreased in the denosumab group (-0.23mm, -0.16mm, -0.91mm3, respectively: all p

Background Although the short-term effects of tumor necrosis factor alpha (TNF-α) and interleukin-17A (IL-17A) inhibition on the structural changes in psoriatic arthritis (PsA) using high-resolution peripheral quantitative computed tomography (HR-pQCT) have been reported, no studies have investigated the long-term structural changes in PsA patients receiving routine care. We reported longitudinal changes of erosions and enthesiophytes using HR-pQCT and their relationship with treatments in PsA patients over a 5-year period. Methods HR-pQCT examination at the second and third metacarpal heads (MCH2 and MCH3) was performed in 60 PsA patients at baseline and after 5 years. The size of each individual lesion was quantified. Erosion and enthesiophyte progression were defined as change exceeding the smallest detectable change (SDC). Results A total of 108 bone erosions and 99 enthesiophytes were detected at baseline. Three new bone erosions but no new enthesiophytes were evident at 5 years. A significant increase in mean (±SD) erosion (0.58 ± 1.50 mm3, P 3, P P = 0.047) and the increased in enthesiophyte volume was significantly less (0.28 ± 0.67 vs 0.61 ± 0.80 mm3, P = 0.048) in the SDL group than in the non-SDL group. However, no significant difference between the TNFi and non-TNFi groups was detected in terms of the change in volume or progression of bone erosion and enthesiophyte. Conclusion Damage accrual in terms of bone erosion and enthesiophyte was observed in PsA patients over a period of 5 years despite receiving routine clinical care. Nonetheless, sustained control of disease activity may be able to prevent these bony damages.

Background: Psoriatic arthritis (PsA) is characterized by structural bone damage with bone erosions and enthesiophytes. Whether achieving low disease activity (LDA) according to Disease Activity in PSoriatic Arthritis (DAPSA-LDA) limits progression of structural bone damage, as assessed by high resolution-peripheral quantitative computed tomography (HR-pQCT), is uncertain. Objectives: To investigate the progression of structural bone abnormalities at the metacarpal head in patients with PsA over a 5-year period. Methods: HR-pQCT examination was were performed in 60 PsA patients at baseline and after 5 years. Baseline-indexed image registration and slice matching were performed to acquire precisely matched baseline and follow-up volumes of interest (VOI) at the 2nd and 3rd metacarpal heads (MCH2 & 3). A semi-automated method was used to calculate bone erosion and enthesiophyte volume [1]. Erosion and enthesiophyte progression was defined as change exceeding the smallest detectable change (SDC). The primary objective of this study was to investigate the degree of bone erosion and enthesiophyte progression in PsA patients receiving routine care. Secondary objectives were to compare changes in bone erosion and enthesiophyte volume between patients who 1) received (TNFi group) or did not receive TNF inhibitor (non-TNFi group); 2) achieved or did not achieve sustained DAPSA-LDA(sDAPSA-LDA) at both baseline and 5-year. Results: A total of 108 bone erosions and 99 enthesiophytes were detected at baseline. Three new bone erosions and no new enthesiophytes were evident at 5 years. Mean (±SD) individual bone erosion (4.23±4.15 mm3) and enthesiophyte (3.39±2.30 mm3) volume at baseline increased significantly (0.58±1.50 mm3, p Conclusion: Once DAPSA-LDA is achieved, it should be maintained for a long period so as to minimize progression of structural bone damage in patients with PsA. Reference [1] EULAR 2018 (OP0132) & ACR 2018 (865) Disclosure of Interests: None declared

Background Located inside the joint capsule,1 the entire metacarpal head (MCH) is directly exposed to intra-articular inflammatory milieu in patients with psoriatic arthritis (PsA). We hypothesise that bone loss and new bone formation in the MCH will be more prominent in PsA compared to healthy controls. Objectives To investigate structural (bone erosion and enthesiophyte) and microstructural intra-articular bone changes in patients with PsA at the second and third MCH (MCH 2 and 3) compared with controls. Methods 139 subjects (77PsA, 62 control) underwent HR CT scanning at the MCH 2 and 3 and distal radius. 15 patients with joint destruction2 were excluded from further analysis. An integrative CART-EBEE approach was developed to investigate the structural and microstructural bone changes. CART method (AB) was used to calculate volume of bone erosion and enthesiophyte [Crop of metacarpal bone(a,b); Automated segmentation of periosteal surface (c,e);Restoration of the missing cortical boundary based on anatomic curve(d,f);Three-dimensional calculation of volume(g)]; EBEE method was used to calculate volumetric bone mineral density (vBMD) and microstructure before and after exclusion of Bone Erosion (C) and Enthesiophyte (D). Results 62 patients with PsA and controls were comparable in age, gender and body mass index. PsA patients had a significantly increased number (mean ±SD/patient 2.4±1.4 vs 1.3±1.1, p Conclusions Intra-articular trabecular bone loss and entheseal new bone formation was more prevalent in the MCH of patients with PsA. References [1] Simon D, et al. J Bone Miner Res2017;32:722–730. [2] Stach CM, et al. Arthritis Rheum2010;62:330–9. Disclosure of Interest None declared

In this cross-sectional study, we investigated volumetric bone mineral density (vBMD), bone microstructure, and biomechanical competence of the distal radius in male patients with rheumatoid arthritis (RA). The study cohort comprised 50 male RA patients of average age of 61.1 years and 50 age-matched healthy males. Areal BMD (aBMD) of the hip, lumbar spine, and distal radius was measured by dual-energy X-ray absorptiometry. High-resolution peripheral quantitative computed tomography (HR-pQCT) of the distal radius provided measures of cortical and trabecular vBMD, microstructure, and biomechanical indices. aBMD of the hip but not the lumbar spine or ultradistal radius was significantly lower in RA patients than controls after adjustment for body weight. Total, cortical, and trabecular vBMD at the distal radius were, on average, –3.9% to –23.2% significantly lower in RA patients, and these differences were not affected by adjustment for body weight, testosterone level, or aBMD at the ultradistal radius. Trabecular microstructure indices were, on average, –8.1% (trabecular number) to 28.7% (trabecular network inhomogeneity) significantly inferior, whereas cortical pore volume and cortical porosity index were, on average, 80.3% and 63.9%, respectively, significantly higher in RA patients. RA patients also had significantly lower whole-bone stiffness, modulus, and failure load, with lower and more unevenly distributed cortical and trabecular stress. Density and microstructure indices significantly correlated with disease activity, severity, and levels of pro-inflammatory cytokines (interleukin [IL] 12p70, tumor necrosis factor, IL-6 and IL-1β). Ten RA patients had focal periosteal bone apposition most prominent at the ulnovolar aspect of the distal radius. These patients had shorter disease duration and significantly higher cortical porosity. In conclusion, HR-pQCT reveals significant alterations of bone density, microstructure, and strength of the distal radius in male RA patients and provides new insight into the microstructural basis of bone fragility accompanying chronic inflammation. © 2014 American Society for Bone and Mineral Research.

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. 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. 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. 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

SummaryWe conducted a cohort study to investigate if the vessel calcifications (VCs) found in the distal extremities are an index of low bone mass at multiskeletal sites. A total of 332 healthy women aged 41–80 years were recruited for bone mineral content (BMC) and bone mineral density measurement using peripheral quantitative computed tomography (pQCT) and dual-energy X-ray absorptiometry (DXA). Seven percent of the women showed VC at both upper and lower distal extremities based on pQCT images. Women who had VC were then compared with their age-matched non-VC counterparts. Results showed that peripheral VC was mainly formed at distal lower extremities, and the prevalence of VC increased with advancing age, with 0%, 5.6%, 9.3%, and up to 34.5% in the age groups of 41–50 years, 51–60 years, 61–70 years, and 71–80 years, respectively. Compared with the control group, the VC group showed a significantly higher body mass index (25.2 vs. 23.2, p

Osteopenia has been found to occur in about 30% of Adolescent Idiopathic Scoliosis (AIS) patients. This study aimed to investigate its prognostic value on the risk of curve progression to surgical threshold. Newly diagnosed AIS girls (N = 513) with Cobb angle 10°–40° were recruited with follow-up till maturity. Bilateral hips were assessed with dual-energy x-ray absorptiometry (DXA). Distal radius of a subgroup of 90 subjects was further assessed with high-resolution peripheral quantitative computed tomography (HR-pQCT). 55 patients progressed to surgical threshold or underwent spine surgery at the end of follow-up. Cox model with osteopenia status performed significantly better than the model without (p = 0.010). Osteopenic patients had significantly higher risk of surgery (HR2.25, p = 0.011), even after adjustment for menarche status, age and initial Cobb angle. The incremental predictive value of osteopenia was, however, not statistically significant. In the subgroup analysis, cortical bone density was identified as a better marker to improve the sensitivity of the prediction, but requires further larger study to validate this finding. These consistent results of bone density measured at different sites suggest a systemic effect, rather than local effect to the deformed spine, and support to the link of abnormal bone density to the etiopathogenesis in AIS patients.

We aimed to determine whether loss of volumetric bone mineral density (vBMD) and deterioration of microarchitecture imaged by high-resolution peripheral quantitative computed tomography at the distal radius/tibia provided additional information in fracture discrimination in postmenopausal women with recent hip fracture. This case-control study involved 24 postmenopausal Chinese women with unilateral femoral neck fracture (average [SD] age: 79.6[5.6]) and 24 age-matched women without any history of fracture. Each SD decrease in T-score at femoral neck (FN) was associated with a higher fracture risk (odds ratio: 6.905, p = 0.001). At the distal radius, fracture women had significantly lower total vBMD (−17.5%), fewer (−20.3%) and more unevenly spaced (81.4%) trabeculae and thinner cortices (−14.0%) (all p

We assessed the relationship of bone density and microarchitecture between hand, peripheral, and axial skeletal sites using high-resolution peripheral quantitative computed tomography (HR-pQCT) and dual-energy X-ray absorptiometry (DXA) in patients with rheumatoid arthritis (RA) and which factors influence these parameters. This was a cross-sectional study of 100 female patients (53.4 ± 9.3 years) with RA. HR-pQCT scans at distal radius and the second metacarpal head were performed to assess cortical and trabecular volumetric bone mineral density (vBMD) and microarchitecture. DXA scans at the hip, lumbar spine, and ultradistal radius were performed to assess areal BMD. There was significant correlation in vBMD and microarchitectural parameters between the second metacarpal head and distal radius (r = 0.201-0.628). Areal BMD at the axial skeleton was moderately associated with vBMD at the peripheral sites (r = 0.354-0.558). Factors related to disease severity/chronicity significantly correlated with vBMD and microarchitecture at the distal radius and the second metacarpal head. Factors related to disease activity were more likely to correlate with vBMD and microarchitecture at the second metacarpal head but not those at the distal radius. HR-pQCT is a promising technique that is capable of providing detailed quantitative assessment of disease-associated periarticular bone loss at both cortical and trabecular bone compartments in patients with RA. Future longitudinal studies will be needed to investigate whether assessment by HR-pQCT can be used as a marker of disease activity and a predictor of disease progression in RA.

Objective.To evaluate bone quality in patients with systemic lupus erythematosus (SLE) who were undergoing longterm glucocorticoid (GC) therapy, and to focus on the correlation between bone quality and organ damage.Methods.Seventy-eight female patients with SLE and organ damage taking longterm GC, and 72 age-matched SLE patients without damage taking longterm GC were recruited for study. Clinical variables of interest included disease activity, cumulative organ damage (by Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index; SDI), major organ involvement (musculoskeletal damage and neuropsychiatric damage, etc.), and use of medication. Areal bone mineral density (aBMD) was measured by dual-energy X-ray absorptiometry. Bone geometry, volumetric BMD (vBMD), microarchitecture, and biomechanical properties were measured by high-resolution peripheral quantitative computed tomography (HR-pQCT).Results.Patients were mean age of 45 years (SD 10) and 54% were postmenopausal. The median SDI score of the cohort was 1 (interquartile range 1−2, range 1−5). Compared with patients without damage, the prevalence of osteopenia at either total hip or lumbar spine was significantly higher, and there were trends of deterioration of bone geometry, vBMD, microarchitecture, and biomechanical properties in patients with organ damage. Potential risk factors for bone quality in patients with damage were screened by univariate analysis. During multiple regression analysis, SDI was the only clinical variable consistently associated with deterioration of vBMD and microarchitecture.Conclusion.Cumulative organ damage consistently correlated with deterioration of vBMD and bone microarchitecture in SLE patients with damage on longterm GC therapy. HR-pQCT provides an insight into the underlying mechanism of bone loss in SLE.

A case-control study comparing bone quality in Adolescent Idiopathic Scoliosis (AIS) with normal controls.To evaluate bone quality with quantitative ultrasound (QUS) in AIS and normal controls so as to detect any derangement in bone quality among AIS subjects.AIS is characterized by complex spinal deformities. Despite its high prevalence and clinical impact in adolescents, etiology of AIS remains unknown but one possible mechanism is related to derangement of bony mechanical stability, as quantified by bone mineral density (BMD) and bone quality. AIS is known for its association with osteopenia, but little is known about the bone quality in AIS. With technological advancement, QUS can provide objective measurement of bone quality. In this study, we sought to compare bone quality in AIS with normal controls using QUS in addition to the conventional BMD measurement.Six hundred thirty-five AIS girls and 269 age-matched normal girls were investigated. Broadband ultrasound attenuation (BUA), velocity of sound (VOS), and stiffness index (SI) were measured over the nondominant calcaneus using QUS. The results were correlated with anthropometric measurement, radiologic assessment, and BMD of both hips.The z-score of BMD at the femoral neck of AIS subjects (-0.47 ± 0.97) was significantly lower than that of normal controls (-0.12 ± 1.01, P0.001). Crude comparison showed that BUA, VOS, and SI of AIS group were 3.8% (P0.01), 0.5% (P = 0.042), and 6.9% (P0.01) lower than controls, respectively. After controlling confounding from maturity, body weight, body height, and BMD with multiple linear regression analysis for both mild (Cobb's angle ≤ 25°) and severe (Cobb's angle25°) curves, BUA and SI were found to be statistically significantly lower in AIS as compared with controls (P0.05).In addition to higher prevalence of osteopenia, AIS patients were also found to have deranged bone quality. These might contribute to the etiopathogenesis of spinal deformities in AIS.

Objective.We assessed the relationship between vertebral fracture and bone microarchitecture in patients with systemic lupus erythematosus (SLE) on chronic corticosteroid therapy using high-resolution peripheral quantitative computed tomography (HR-pQCT).Methods.Fifty-nine Chinese women with SLE taking corticosteroid were selected to participate in a cross-sectional study. Vertebral fracture was confirmed semiquantitatively by lateral radiographs of the thoracic and lumbar spine. Density and microarchitecture at the distal radius were measured with HR-pQCT. Areal bone mineral density (aBMD) at hip and lumbar spine was measured by dual-energy x-ray absorptiometry (DEXA).Results.Twelve patients had vertebral fractures. The aBMD of spine or hip did not differ between those with and without vertebral fractures. Measures by HR-pQCT revealed that patients with vertebral fractures had significantly lower level of average bone density (p = 0.007), cortical bone density (p = 0.029), trabecular bone density (p = 0.024), trabecular bone volume to tissue volume (p = 0.023), and trabecular thickness (p = 0.011) than those without vertebral fractures. Independent explanatory variables associated with higher risk of vertebral fractures were older age (p = 0.013) and lower average cortical bone density (p = 0.029).Conclusion.Vertebral fracture in patients with SLE on chronic corticosteroid treatment was associated with alterations of bone density and microarchitectures measured by HR-pQCT and DEXA. However, alterations were more pronounced in measurements by HR-pQCT. Low cortical bone density and old age were significant predictors of vertebral fracture risk.

High-resolution peripheral quantitative computed tomography (HR-pQCT) is a unique technology for assessing bone mineral density and bone microarchitecture. Currently, no universally accepted protocol for selecting the region of interest (ROI) at the distal radius has been established for growing subjects. This study aimed (1) to investigate the differences in HR-pQCT measurements of 2 different ROI protocols applied to the distal radius of healthy adolescents and (2) to identify the least common area of ROI (the least common ROI) between the protocols. Twenty-six boys and 26 girls aged between 13 and 16 yr old were recruited. Nondominant distal radius was scanned by 2 HR-pQCT protocols, namely, the "5-mm protocol," where the distal end of ROI started at 5 mm proximal to a reference line, and the "4% protocol," where the ROI started at 4% of the ulnar length proximal to another reference line. The least common ROI between the 2 protocols was identified and the slice numbering within the common ROI was determined. Bland-Altman plots were used to check the agreement of the least common ROIs between the 2 protocols. Paired t-test and Wilcoxon signed-rank test were used for analysis. In boys, significant differences between protocols were found in most parameters with the maximum difference observed in the cortical area (25.0%, p

Study design A genetic association study of estrogen receptor-[alpha] gene (ESR1) with adolescent idiopathic scoliosis (AIS) in Chinese. Objectives To investigate whether: 1) PvuII and XbaI polymorphisms in ESR1 are predisposition factor for AIS and 2) these polymorphisms correlate with the severity of curvature in AIS. Summary of background data A common single nucleotide polymorphism (SNP) in ESR1 (XbaI) was found to be associated with curve severity in Japanese AIS patients recently. The role of ESR1 as a predisposition gene using a case-control design in other ethnic groups is required to confirm the previous associations. Methods A total of 540 Chinese AIS girls with Cobb angle above 20 degrees were recruited as cases together with 260 healthy controls. The effect of ESR1 SNPs on severity of scoliosis was analyzed in a subgroup of AIS patients (n = 364) followed up until skeletal maturity with the maximum Cobb angle recorded. Two SNPs in ESR1 were genotyped by PCR-restriction fragment length polymorphism in all subjects. Results The allelic frequency of X allele was 23% in both case and control groups. The P allele was found at allelic frequency of 40% and 36% in the case and control groups, respectively. No association between the two ESR1 SNPs and the occurrence of AIS by both genotype and haplotype analysis could be established, suggesting that both SNPs were not predisposition alleles for AIS. AIS patients with different genotypes showed no difference in the maximum Cobb angle. No association was found between the genotype and anthropometric measurements in AIS patients. Conclusion The previously reported association with curve severity could not be replicated in our large series of Chinese AIS patients. The current study also did not show any association of the 2 SNPs with increased risk of having AIS.

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.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 progressedor =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.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 (p0.01).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.

BACKGROUND: Adolescent idiopathic scoliosis (AIS) is associated with low bone mineral density (BMD). The underlying etiology and how it may relate to the development of osteopenia remains unknown. Leptin has been postulated as one of the etiologic factors of AIS because of its profound effects on bone metabolism and pubertal growth. Its modulator, soluble leptin receptor (sOB-R), may affect leptin bioavailability and signaling. This study aimed to investigate whether serum leptin and sOB-R levels may be associated with bone quality, and whether these relationships may differ between young adolescent girls with and without AIS. METHODS: This was a case-control study involving 94 newly diagnosed AIS girls (Cobb angle 12-48°) aged 12 to 14 years old and 87 age and gender-matched normal controls. Subjects with BMI>23.0 Kg/m(2) were excluded. Anthropometric measurements including body weight, height, arm span and sitting height were taken. Serum total leptin and sOB-R were assayed with ELISA. Non-dominant distal radius was scanned with High Resolution pQCT for assessing bone quality in terms of bone morphometry, volumetric BMD (vBMD) and trabecular bone micro-architecture. RESULTS: Compared with normal controls, AIS girls had numerically higher sOB-R (p = 0.006), lower average vBMD (p = 0.048), lower cortical vBMD (p = 0.029), higher cortical bone perimeter (p = 0.014) and higher trabecular area (p = 0.027), but none remained statistically significant after the Hochberg-Benjamini procedure. Correlation analysis on serum leptin level indicated that distinctive correlations with trabecular bone parameters occurred only in AIS. CONCLUSION: This study showed that bone quality in AIS girls was deranged as compared with controls. In addition, the distinct differences in correlation pattern between leptin and trabecular bone parameters indicated possible abnormalities in bone metabolism and dysfunction of the leptin signaling pathway in AIS.

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. 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. 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. 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. 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.

The purpose of this work was to investigate the volumetric bone mineral density (vBMD), bone microstructure, and mechanical indices of the distal radius in female patients with rheumatoid arthritis (RA). We report a cross-sectional study of 66 middle-aged female RA patients and 66 age-matched healthy females. Areal BMD (aBMD) of the hip, lumbar spine, and distal radius was measured by dual-energy X-ray absorptiometry (DXA). High-resolution peripheral quantitative computed tomography (HR-pQCT) was performed at the distal radius, yielding vBMD, bone microstructure, and mechanical indices. Cortical and trabecular vBMD were 3.5% and 10.7% lower, respectively, in RA patients than controls, despite comparable aBMD. Trabecular microstructural indices were –5.7% to –23.1% inferior, respectively, in RA patients compared to controls, with significant differences in trabecular bone volume fraction, separation, inhomogeneity, and structural model index. Cortical porosity volume and percentage were 128% and 93% higher, respectively, in RA patients, with stress being distributed more unevenly. Fourteen RA patients had exaggerated periosteal bone apposition primarily affecting the ulnovolar aspect of the distal radius. These particular patients were more likely to have chronic and severe disease and coexisting wrist deformity. The majority of the differences in density and microstructure between RA patients and controls did not depend on menstrual status. Recent exposure to glucocorticoids did not significantly affect bone density and microstructure. HR-pQCT provides new insight into inflammation-associated bone fragility in RA. It detects differences in vBMD, bone microstructure, and mechanical indices that are not captured by DXA. At the distal radius, deterioration in density and microstructure in RA patients involved both cortical and trabecular compartments. Excessive bone resorption appears to affect cortical more than trabecular bone at distal radius, particularly manifested as increased cortical porosity. Ulnovolar periosteal apposition of the distal radius is a feature of chronic, severe RA with wrist deformity. © 2013 American Society for Bone and Mineral Research.

Recent familial segregation studies supported a multifactorial genetic model for the etiology of adolescent idiopathic scoliosis (AIS). However, the extent of quantitative genetic effects, such as heritability, have not been fully evaluated. This genetic epidemiology study examined the sibling recurrent risk and heritability of AIS in first-degree relatives of 415 Chinese female patients, which is up to now the largest cohort. They were first diagnosed by community screening program and compared to 203 age-matched normal controls. Out of the total 531 sibs of AIS cases, 94 sibs had scoliosis (sibling recurrence risk = 17.7%). The prevalence of AIS among male and female sibs of an index case were 11.5% (95% CI = 7.5–15.5) and 23.0% (95% CI = 18.1–27.9), respectively. Female sibs of an index case had an increased risk of 8.9-fold (95% CI = 3.2–34.4) for developing AIS. These recurrent risks were significantly higher than the risk in the control group (p

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.

Scoliosis is a three-dimensional (3D) structural spinal deformity characterized by both vertebral rotation and lateral curvature greater than 10°. Idiopathic scoliosis is the most common type of structural scoliosis and this chapter focuses on bone mineral and structure parameters in girls with adolescent idiopathic scoliosis (AIS) assessed using various bone densitometries, including dual-energy X-ray absorptiometry (DXA), peripheral quantitative computed tomography (pQCT), quantitative ultrasound (QUS), and micro-computed tomography (micro-CT). We found that systemic low bone mass was manifested in 30% of AIS girls. With the use of different modalities of bone densitometry, AIS girls were found to have a significantly lower areal and volumetric bone mineral density (BMD) at various skeletons including spine, proximal femur, and distal extremities. Moreover, poor bone quality re- flected by QUS technique was also found in AIS girls. Clinical application of bone densitometry in relation to the curve severity and prognostic value in predicting curve progression may enhance the clinical management and treatment planning for scoliosis patients.

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.

Background Patients with rheumatoid arthritis (RA) are associated with an increased risk of periarticular and generalized bone loss. A 3D high resolution peripheral quantitative computed tomography (HR-pQCT) system has been developed to perform in vivo human measurements of bone geometry, volumetric bone mineral density (vBMD) and microarchitecture on peripheral skeletal sites such as the radius and tibia. HR-pQCT also holds great potential to measure morphological, densitometric and microstructural changes of periarticular bones in RA. Objectives By using HR-pQCT, we aimed: 1) to investigate whether bone geometry, vBMD and microarchitectural measures of the distal radius are significantly associated with those of the 2nd metacarpal; 2) to investigate clinical factors influencing bone geometry, vBMD and microarchitectural measures of the distal radius and 2nd metacarpal. Methods This cross-sectional study involved 100 female RA patients. HR-pQCT at distal radius and 2nd metacarpal head, both of the non-dominant forearm, were performed to assess bone geometry, cortical and trabecular vBMD and microarchitecture. Results The cohort had a mean (SD) age of 53.4 (9.3) years old and a mean (SD) disease duration of 9.1 (7.8) years. Sixty-seven patients were post-menopausal. The cohort had mild disease activity, with mean (SD) Disease Activity Score in 28 Joint (DAS28) score of 3.7 (1.2), and mild disability, with median (range) of Health Assessment Questionnaire (HAQ) score of 0.38 (0-2.6). Forty-nine patients had erosive disease at wrists or hands. There were week correlations (range of r: 0.33-0.36) between total, cortical and trabecular area at distal radius and those at 2nd metacarpal. Moderate correlations were found between total ( r =0.63) and trabecular ( r =0.56), but not cortical ( r =0.38), vBMD at distal radius and those at 2nd metacarpal. There were also weak to moderate correlations between microarchitectural measures at distal radius and those at 2nd metacarpal, with the strongest correlation seen in the ratio of trabecular bone volume and tissue volume ( r =0.57) and the weakest one seen in trabecular thickness ( r =0.20). Clinical factors related to disease severity, including disease duration, the number of deformed joints, HAQ score, and erosive disease, significantly correlated with bone geometry, vBMD and microarchitecture at both distal radius and 2nd metacarpal. However, clinical factors related to disease activity, including the number of swollen joints, C-reactive protein level, and DAS28 score, were more likely to be correlated with bone geometry, vBMD and microarchitecture at 2nd metacarpal, but not those at distal radius. Conclusions Bone geometry, vBMD and microarchitectural measures of the distal radius significantly correlated with those of the 2nd metacarpal, but at a weak to moderate level of correlation. It appears that the clinical characteristics of RA contribute differently to bone quality at peripheral skeletal site and that at periarticular site. References Fouque-Aubert A, Boutroy S, Marotte H et al. Assessment of hand bone loss in rheumatoid arthritis by high-resolution peripheral quantitative CT. Ann Rheum Dis 2010;69(9):1671-6. Disclosure of Interest None Declared

Background Generalized bone loss at axial and peripheral bone is a common feature of rheumatoid arthritis (RA) and is one of the determinants of the fracture risk. The relationship between decreased areal bone mineral density (aBMD) and fracture is less clear in RA than in postmenopausal osteoporosis. High-resolution peripheral quantitative computed tomography (HR-pQCT) is an in vivo imaging technique capable of assessing volumetric BMD (vBMD) and microarchitecture of cortical and trebecular bone at the distal radius. Objectives To assess volumetric density, microarchitecture and bone strength at the distal radius in female patients with RA in comparison to healthy controls with HR-pQCT. Methods This cross-sectional study involved 66 female RA patients (age 48.9±8.2 years; disease duration 10.7±8.2 years) and 66 age-matched healthy females (age 48.8±8.2 years). aBMD of femoral neck, total hip, lumbar spine (L1-4) and forearm was measured by dual-energy X-ray absorptiometry (DXA). HR-pQCT at distal radius and image-based finite-element analyses (FEA) were performed to assess cortical and trabecular vBMD, microarchitecture and bone strength. Results There was no difference in age, body height and percentage of postmenopause between RA patients and controls. RA patients had significantly lower body weight (55.0±10.5kg vs. 58.3±7.3kg, p=0.038). aBMD at femoral neck, total hip, lumbar spine and forearm did not differ significantly between the 2 groups. However, at distal radius, compared with controls, RA patients had significantly lower volumetric cortical (p=0.004) and trabecular bone density (p=0.024), lower bone/tissue volume (p=0.023), higher trabecular separation (p=0.025), increased inhomogeneity of trabecular network (p=0.039), and increased structure model index (SMI). These alterations were independent of menstrual status. After adjusted for age, body weight, body height and aBMD of forearm by DXA, differences between RA and controls remained significant for cortical vBMD, trabecular separation, inhomogeneity of the trabecular network and SMI. Using FEA, there was no significant difference in stiffness, failure load and apparent modulus between RA and controls. Percentage difference in cortical and trabecular vBMD between RA and controls significantly correlated with disease activity (C-reactive protein, erythrocyte sedimentation rate, Disease Activity Score in 28 joints) and severity parameters (Health Assessment Questionnaire score and disease duration), while percentage difference in trabecular microarchitecture correlated with disease duration. Use of glucocorticoids did not influence vBMD or microarchitecture or bone strength in RA patients. Conclusions Patients with RA are associated with low vBMD and microarchitectural alterations of both cortical and trabecular bone at distal radius that are partially independent of demographics and aBMD assessed by DXA. Results from our study may increase understanding of the role of microarchitectural deterioration in bone fragility in patients with RA. References Haugeberg G et al. Bone mineral density and frequency of osteoporosis in female patients with rheumatoid arthritis: results from 394 patients in the Oslo County Rheumatoid Arthritis register. Arthritis Rheum 2000;43(3):522-30. Disclosure of Interest None Declared

Objectives Multiple studies have documented the presence of systemic osteopenia in AIS. Osteopenia was associated with severe curves and was reported to be one of the significant prognostic factors for curve progression in AIS. This study aimed to evaluate bone quality and bone strength parameters including rod-plate configuration and finite element analysis (FEA) with in vivo HighResolution Peripheral Quantitative Computed Tomography (HR-pQCT) and to investigate their relationship with osteopenia in AIS Vs normal controls.