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The 2013 ISCD consensus recommended a Caucasian female reference database for T-score calculation in men, which says "A uniform Caucasian (non-race adjusted) female reference database should be used to calculate T-scores for men of all ethnic groups." However, this statement was recommended for the US population, and no position was taken with respect to BMD reference data or ethnicity matching outside of the USA. In East Asia, currently, a Japanese BMD reference database is universally adopted in Japan for clinical DXA diagnosis, while both local BMD and Caucasian BMD reference databases are in use in Mainland China, South Korea, Taiwan, and Singapore. In this article, we argue that an ethnicity- and gender-specific BMD database should be used for T-score calculations for East Asians, and we list the justifications why we advocate so. Use of a Caucasian BMD reference database leads to systematically lower T-scores for East Asians and an overestimation of the prevalence of osteoporosis. Using a female BMD reference database to calculate T-scores for male patients leads to higher T-score values and an underestimation of the prevalence of osteoporosis. Epidemiological evidence does not support using a female BMD reference database to calculate T-scores for men. We also note that BMD reference databases collected in Asia should be critically evaluated for their quality., (© 2023. The Author(s), under exclusive licence to International Skeletal Society (ISS).)

Objectives: To investigate the efficacy of two tight-control treatment strategies aimed at simplified disease activity score [SDAI] remission (SDAI ≤ 3.3) compared to DAS28 remission (DAS28 < 2.6) on progression of bone erosions in early rheumatoid arthritis (ERA) patients using high-resolution peripheral quantitative computed tomography (HR-pQCT)., Methods: This was an open-label study in which 80 early RA patients were randomized to receive 1-year of tight-control treatment. Group 1 (n = 37) aimed at SDAI ≤ 3.3 and group 2 (n = 43) aimed at DAS28-CRP < 2.6. The number and size of bone erosions, as well as the bone mineral density (BMD) surrounding bone erosion at the second metacarpophalangeal joint (MCP2), were measured at baseline and 12 months., Results: After 12 months, images were analyzed in 63 patients. Changes in clinical parameters, number and size of bone erosions as well as the BMD surrounding bone erosion between the two treatment groups were similar. Therefore, a post-hoc analysis including all 63 patients was performed to elucidate the independent predictors of erosion progression and repair. Multivariate analysis revealed that not achieving sustained SDAI remission at month 6, 9 and 12 (p = 0.034) and rheumatoid factor >16U (p = 0.021) were independent predictors associated with an increase in erosion volume. Logistic regression analysis showed that achieving sustained SDAI remission (p = 0.043) was associated with partial erosion repair., Conclusions: Although more stringent treatment target did not notably affect clinical treatment outcome and erosion progression at 1 year, achieving sustained SDAI remission was found to be associated with partial erosion repair., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Context: Measurement of areal bone mineral density (aBMD) by dual-energy x-ray absorptiometry (DXA) was able to predict fracture risk. High-resolution peripheral quantitative computed tomography (HR-pQCT) yields additional information about volumetric bone mineral density (vBMD), microarchitecture, and strength that may increase our understanding of fracture susceptibility., Objective: To ascertain whether vBMD, microarchitecture, and estimated bone strength derived from HR-pQCT can discriminate vertebral fractures in patients with glucocorticoid-induced osteoporosis (GIOP) independent of aBMD., Design: A cross-sectional case-control study., Setting: Seven regional hospitals in Hong Kong., Patients: A total of 110 patients on long-term glucocorticoids with vertebral fracture, determined radiographically, and 110 patients on long-term glucocorticoids without fracture., Main Outcome Measures: We assessed vBMD, microarchitecture, and bone strength; aBMD; and fracture risk assessment tool (FRAX)., Results: Patients with vertebral fracture had lower total vBMD and a thinner cortex at the distal tibia after adjustment for age, sex, and aBMD or FRAX. In the antiresorptive treatment-naive subgroup, patients with vertebral fracture also had lower total vBMD at both the distal radius and the tibia after adjustment for covariates. Lower total vBMD and a thinner cortex were also noticed in the nonosteoporotic or FRAX score of <10% subgroups with vertebral fracture and were also associated with increasing prevalence of vertebral fracture., Conclusion: Patients with GIOP and vertebral fracture have a significant reduction in total vBMD and cortical thinning independent of aBMD and FRAX. These changes may help identify high-risk patients in the subgroups currently considered to have low fracture risk as assessed by DXA or FRAX.

Objective: To compare the bone healing effects of denosumab and alendronate in female rheumatoid arthritis (RA) patients by high-resolution peripheral quantitative computed tomography., Methods: This is a post hoc analysis of a randomized controlled trial. Forty patients were randomized in a 1:1 ratio to receive either subcutaneous denosumab (60 mg) once or oral alendronate (70 mg) 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 nondominant hand at baseline, 3 months, and 6 months., Results: Forty-two erosions were identified at baseline. After 6 months, the width, depth, and volume of erosion significantly decreased in the denosumab group (-0.23 mm, -0.16 mm, -0.91 mm 3 , respectively; all P < 0.01), whereas these parameters significantly increased in the alendronate group (0.19 mm, 0.32 mm, and 1.38 mm 3 , respectively; all P < 0.01; between-group differences, P < 0.01 for all). Quantitative analysis showed that the bone mineral density of the erosion margin significantly increased only after treatment by denosumab (19.75 mg/cm 3 ; P < 0.05 for denosumab, and -5.44 mg/cm 3 ; P = 0.51 for alendronate; P < 0.05 for between-group differences)., Conclusion: Inhibition of receptor activator of NF-κB ligand by denosumab can induce partial repair of erosions in patients with RA, while erosions continued to progress in patients treated with alendronate. Combining denosumab with disease-modifying antirheumatic drugs may be considered for RA patients with progressive bone erosions., (© 2016, American College of Rheumatology.)

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.

Objective: To determine changes of bone mineral density (BMD) over a 5-year period in a cohort of female patients with systemic lupus erythematosus (SLE) and to identify factors predictive of BMD loss., Methods: Our longitudinal study involved 125 female patients with SLE with a mean (SD) age of 46.5 years (10.1) and a median disease duration of 10.4 years. Demographics and clinical data were collected and BMD at the femoral neck, total hip, and lumbar spine (L1-4) was performed by using dual-energy x-ray absorptiometry at baseline and followup., Results: Average percentage changes of BMD over a mean followup of 5 years were -2.41% at the femoral neck, -1.63% at the total hip, and -0.62% at the lumbar spine, with significant changes at both the femoral neck (p < 0.0001) and total hip (p < 0.0005), but not at the lumbar spine (p = 0.128). Disease flare, new organ damage, and use of glucocorticoids during followup were significantly associated with larger decreases in BMD. BMD loss was arrested at the femoral neck and BMD increased at the total hip and lumbar spine in patients receiving antiosteoporosis therapy. In multivariate analyses, use of antiosteoporosis therapy was independently associated with increased BMD at any site and new organ damage was an independent predictor of BMD loss at the femoral neck., Conclusion: Significant BMD loss at the hip over a period of 5 years was found in patients with SLE. Disease activity, disease damage, and use of glucocorticoids are the disease-specific variables that contribute to bone loss in SLE.

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.)

Summary: This study used the "functional muscle-bone unit" concept to investigate muscle-bone interaction of the lumbar spine in subjects of varying bone mineral density. It was found that unit bone mass corresponded to a relatively more muscle mass in subjects with reduced bone mineral density, indicating a relatively higher mechanical load from muscles exerted on trabecular bone., Introduction: Bone is an architecturally adaptive tissue which responds to mechanical loading. This study is proposed to use "functional muscle-bone unit" to reflect this muscle-bone interaction at spine in subjects with different bone mineral density., Methods: The study was carried out in young normal subjects (21 females; age, 29 ± 3) and elderly subjects (155 females; age, 73 ± 3.9) with varying bone mineral density. Cross-sectional area of paravertebral muscle groups was measured in MR images to indicate the muscle mass, while the bone mineral content by dual X-ray absorptiometry was used to represent the bone mass. The functional muscle-bone unit was calculated as the ratio between the bone mass to muscle mass., Results: It showed that with aging, the muscle mass decreased with the bone mass losing. However, more pronounced reduction was found in bone mass than in muscle mass in the subjects with lower bone mineral density., Conclusions: Muscle-bone interaction was changed in elderly, especially in those with osteoporosis. Unit bone mass corresponded to a higher muscle mass in subjects with reduced bone mineral density than those normal subjects. This may be contributory to the occurrence of nontraumatic vertebral fractures in elderly subjects with reduced bone mineral density.

This study examined the BOLD effect on calf muscles in elderly subjects with different bone mineral density. The purpose was to investigate the oxygenation characteristics in different calf muscle groups for the elderly females and compare the muscle oxygenation among groups with different bone mineral density. Temporary vascular occlusion was induced with air-cuff compression of the thigh and BOLD-MRI data curve was fitted to derive quantitative parameters. Three muscle groups, gastrocnemius muscle (lateral head), soleus muscle, and tibialis anterior muscle, were investigated individually. Quantitative CT measurement was conducted on each subject, based on which subjects were classified into normal, osteopenia, and osteoporosis groups. The BOLD signal in soleus muscle showed the lowest minimum ischemic value during ischemia and the steepest slope during hyperemia. As soleus muscle is mainly composed by slow-twitch oxidative muscle fibers, current results may be due to a higher vascular bed density and better endothelial function in such muscle. By t-test, the half-life of the BOLD signal decay during ischemia in both gastrocnemius and soleus muscles was significantly prolonged in osteoporosis group, indicating a degenerated muscular oxygen metabolic capacity in osteoporotic patients.

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.

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.

Objective: Osteoporotic Fractures in Men (Hong Kong) and Osteoporotic Fractures in Women (Hong Kong) represent the first large-scale prospective population-based studies on bone health in elderly (age≥65 years) Chinese men (n=2,000) and women (n=2,000). We undertook the current study to investigate the prevalence of lumbar disc space narrowing in these subjects, and to identify the potential relationship between disc space narrowing and sex, bone mineral density (BMD), and other demographic and clinical data., Methods: On lumbar lateral radiographs, L1/L2-L4/L5 disc space was classified into 4 categories: 0=normal; 1=mild narrowing; 2=moderate narrowing; 3=severe narrowing. We compared demographic and clinical data between subjects with and those without total disc space narrowing scores≥3., Results: Disc space narrowing was more common in elderly women than in elderly men. The mean±SD disc space narrowing score for the 4 discs was 2.71±2.21 for men and 3.08±2.50 for women (P<0.0001). For the 3 age groups of 65-69 years, 70-79 years, and ≥80 years, the average disc space narrowing score increased with increasing age in both men and women, and to a greater degree in women than in men. The average disc space narrowing score differences between women and men were 0.12, 0.40, and 0.90, respectively, in the 3 age groups. For both men and women, a disc space narrowing score≥3 was associated with older age, higher spine and hip BMD, low back pain, and restricted leg mobility., Conclusion: The prevalence and severity of disc space narrowing are higher in elderly women than in elderly men. With increasing age, disc space narrowing progresses at a greater rate in women than in men. A disc space narrowing score≥3 is associated with higher spine and hip BMD., (Copyright © 2013 by the American College of Rheumatology.)

Objective: To investigate sex hormone deficiency related osteoporosis and efficacy of different therapies., Methods: Orchiectomized and ovariectomized rat models are used to investigate sex hormone deficiency related osteoporosis and efficacy of different therapies. A rat vertebral body can be longitudinally divided into central portion, which contain more trabecular bone, and para-endplate portions which contain more compact bone. In matured male and female Wistar and Sprague-Dawley rat lumbar spines, we investigated baseline bone mineral density (BMD) characteristics and the differential segmental responses in bone loss within the lumbar vertebral body post gonadal surgery with clinical multidetector computed tomography., Results: Para-endplate sections had a higher BMD than central sections. The cephalad para-endplate sections had a higher BMD than the caudad para-endplate sections. Eight weeks after gonadal removal, there was more bone loss in central sections than para-endplate sections. The relative difference of bone loss between para-endplate and central sections was more apparent in male rats than in female rats. There was more bone loss in caudad sections than cephalad sections; this lead to a further increase of BMD difference between caudad para-endplate sections and cephalad para-endplate sections post gonadal surgery., Conclusion: The approach described in this study provided a consistent way to study BMD change within predominantly compact bone portion and trabecular bone portion of the vertebral body., (Copyright © 2012 The Editorial Board of Biomedical and Environmental Sciences. Published by Elsevier B.V. All rights reserved.)

Study Design: Cross-sectional study., Objective: To investigate changes in the morphology of the lumbar vertebrae and intervertebral discs associated with osteoporosis of the spine in elderly subjects., Summary of Background Data: Osteoporosis is a common condition that primarily affects the elderly with significant impact on quality of life. How exactly osteopenia and osteoporosis influence vertebral and intervertebral disc morphology remains unknown and needs exploration., Methods: A total of 395 community-dwelling ambulatory adults from 67 to 89 years of age were studied. The lumbar bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry. T2-weighted sagittal images of the lumbar spine were obtained using a 1.5-T magnet. For each subject, the anterior height (Ha), middle height (Hm), posterior height (Hp), and anterior-posterior (AP) dimension of the 5 lumbar vertebrae (L1-L5) and 6 intervertebral discs (T12-L1 to L5-S1) were measured. To minimize the age effect, volume of these vertebrae and discs was measured in subgroups of 47 men (mean age = 74 yr, range: 73-75 yr) and 67 women (mean age = 72 yr, range: 71-73 yr). Continuous variables were examined by analysis of covariance after adjustment of height and age., Results: There was no significant age difference between the groups of normal BMD, osteopenia, and osteoporosis. For the vertebral bodies, lower BMD was associated with a decrease of Ha, Hm, and Hp but not AP in both sexes, leading to an increased biconcavity index. For the discs, lower BMD was associated with a decrease of Ha and Hp, as well as AP, and an increase in Hm in both men and women. The disc biconvexity index was increased. Lower BMD is associated with an overall decrease in both vertebral volume and disc volume., Conclusion: Lower BMD is associated with a decreasing trend in both lumbar vertebral and disc volumes in elderly subjects but an increase in the Hm of the intervertebral discs.

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.

Purpose: To investigate vertebral bone marrow fat content in elderly subjects related to sex, age, and bone mineral density (BMD) and relate these findings to published data in younger subjects., Materials and Methods: A total of 259 healthy subjects (145 females, 114 males; age range, 62-90 years) underwent proton ((1) H) MR spectroscopy of L3 vertebral body and BMD of the lumbar spine with results stratified according to age. Ninety age- and BMD-matched subjects were selected to determine sex differences in marrow fat content and BMD., Results: In females, vertebral marrow fat content rose sharply between 55 and 65 years of age while in males vertebral marrow fat content rose gradually throughout life. Vertebral marrow fat content in females more than 60 years was approximately 10% higher in females than males, i.e., a reversal of sex difference reported in marrow fat content for subjects less than 60 years., Conclusion: Marrow fat content increases sharply in female subjects between 55 and 65 years of age while male subjects continue to increase marrow fat at a more gradual steady rate. Females older than 60 years have a higher marrow fat content than males. This increased deposition in marrow fat concurs with recognized changes in extraosseous fat distribution in postmenopausal females., (Copyright © 2012 Wiley Periodicals, Inc.)

The objective of this study is to characterize perfusion and bone mineral density (BMD) in the lumbar spine as a function of level and anatomic location. Fourteen male subjects with healthy vertebral endplates were selected to avoid gender and endplate disease influence. The bone perfusion and BMD of different vertebral level (L1-L4) were measured by the dynamic contrast enhancement MRI (DCE MRI) and the dual-energy X-ray absorptiometry (DXA) respectively. Perfusion parameters showed a significant negative correlation with upper to lower vertebral levels while inverse observation was found for BMD. The results indicated that the perfusion and BMD are as function of vertebral level and anatomic location at lumbar spine. The BMD varying with vertebral level may be determined by the biomechanical usage at the lumbar spine, where the lower levels sustain more mechanical forces. Perfusion changes along the lumbar spine level suggested that the bone marrow component could be different when BMD varies, which needs further histological verification.

A reduced bone perfusion has been found for osteoporotic subjects in previous studies. However, the physiological changes underlying the varied perfusion function is not well known yet. Tofts model is one of the most frequently used pharmacokinetic models in analyzing perfusion process. This study modified the Tofts model by replacing the arterial input function (AIF) by a new algorithm. The modified model was then employed to analyze vertebral bone marrow perfusion in subjects with different bone mineral density (BMD). Eighty-two male subjects were involved in this study and classified into three groups (normal, osteopenia, and osteoporosis) according to T-score. BMD was measured by dual-energy X-ray absorptiometry (DXA). The quantitative parameters derived from the pharmacokinetic model, K(trans) (extravasation transfer efficiency for blood perfusion) and v(e) (extravascular extracellular space for blood perfusion), showed a significant reduction in subjects with lower BMD, respectively. The results suggested that with the bone mineral content lost, the vascular wall properties as well as the bone marrow content may also vary. The resultant perfusion change may also influence the bone nutrition supply in reverse.

Voxel-based morphometry (VBM) is a computational technique that has been used to analyze statistical differences between groups of MR brain images. This study outlines a new VBM pipeline, designed for determining statistical variation in bone mineral density (BMD). CT images of proximal sesamoid bone (PSB) specimens from the right forelimb of six racehorses that had suffered PSB fractures were compared with six age-matched control specimens. Following segmentation, masked gray-scale images were co-aligned to a statistical template generated with all 12 CT datasets iteratively. Student t-tests were performed voxel-by-voxel on spatially aligned 3D images to reveal significant differences in the spatial variation of bone density between the fracture and control groups. Overall density and densities from the axial and abaxial areas of PSBs were compared between groups. The BMD in abaxial regions of the medial and lateral PSBs of the fracture group were 12.7% (p = 0.044) and 13.5% (p = 0.047) higher, respectively, than controls. The overall mean density of paired PSB and the medial and lateral PSBs separately were higher in the fracture group. The VBM pipeline facilitates detailed comparison of density variation between bone groups at the voxel level., (Copyright © 2011 Orthopaedic Research Society.)

Objective: To determine whether MR perfusion indices or marrow fat content at baseline can predict areal bone mineral density (BMDa) loss., Methods: Repeat dual x-ray absorptiometry (DXA) of the hip was performed in female subjects at 2 years (n = 52) and 4 years (n = 45) following baseline MR perfusion imaging and spectroscopy of the hip., Results: Percentage reduction in femoral neck BMDa at 4 years post-baseline was greater in subjects with below median acetabulum enhancement slope (E(slope)) (-5.6 ± 1.2 Vs -1.1 ± 1.2 (mean ± standard error) p = 0.014) or muscle maximum enhancement (E(max)) (-5.7 ± 1.2 Vs -0.23 ± 1.2, p = 0.009) after adjusting for baseline co-variables. Baseline MR parameters correlated with reduction in BMDa at 4 years (acetabulum E(slope) r = 0.517, p = 0.0003; muscle E(max) r = 0.306, p = 0.043) as well as traditionally applied clinical risk factors. Acetabulum E(slope), femoral neck E(max) and marrow fat content at baseline had sensitivities of 89%, 81% and 72% respectively at distinguishing between fast (>1%/annum) (n = 18) and slow (<1%/annum) (n = 27) BMD losers., Conclusion: Elderly female subjects with reduced perfusion indices at baseline had increased femoral neck bone loss at 4 years. Selected perfusion indices and marrow fat content have a moderate to high sensitivity in discriminating between fast and slow bone losers.

Purpose: To study the relationship between hip bone mineral density (BMD), lumbar disc degeneration, and lumbar disc space narrowing in elderly subjects., Materials and Methods: The study cohort comprised 196 females and 163 males (age range, 67-89 years) with no age difference between the two groups. Anteroposterior total hip areal BMD was measured with DXA and lumbar spine MRI was acquired using a 1.5 Tesla scanner. Lumbar disc degeneration was assessed using an eight-level grading system wherein each grade represents a stepwise progression from normal disc to severe disc degeneration and disc space narrowing., Results: After controlling for the age effect, no significant relationship was observed between total hip T-score status and severity of disc degeneration. There was no significant difference in total hip BMD in the subjects with or without the disc space narrowing (P < 0.05). Female subjects are more likely to have a narrowed disc space than males at all levels, and being statistically significant at L3/4 and L4/5 levels, and with an overall significance of P = 0.007., Conclusion: There was no association observed between hip BMD and lumbar disc degeneration. Elderly females were more likely to have a narrowed lumbar disc space than elderly males., (Copyright © 2011 Wiley-Liss, Inc.)

Unlabelled: The study cohort comprised 196 females and 163 males. Lumbar spine bone mineral density (BMD) and magnetic resonance imaging (MRI) were acquired. Females had more severe disc degeneration than males. Lumbar spine lower BMD was associated with less severe disc degeneration. Lumbar disc spaces were more likely to be narrower when vertebral BMD was higher., Introduction: The purpose of this paper is to study the relationship between gender, BMD, and disc degeneration in the lumbar spine., Methods: The study cohort comprised 196 females and 163 males (age range 67-89 years) with no age difference between the two groups. Lumbar spine BMD was measured with dual X-ray densitometry, and MRI was acquired at 1.5 T. A subgroup of 48 males had additional lumbar vertebral quantitative computerized tomography densitometry. Lumbar disc degeneration was assessed using a MRI-based eight-level grading system., Results: Female subjects had more severe disc degeneration than male subjects. After removing age effect, a positive trend was observed between T-score and severity of lumbar disc degeneration. This was significant in female subjects while not significant in male subjects. Lumbar disc spaces were more likely to be narrowed when vertebral BMD was higher. These observations were more significant in the midlumbar region (L3/4 and L4/5) and less so at the thoracolumbar junction., Conclusion: Female subjects tended to have slightly more severe lumbar disc degeneration than male subjects. Lower lumbar spine BMD was associated with less severe disc degeneration.

High-resolution peripheral quantitative computed tomography (HR-pQCT) is a new noninvasive bone imaging technology that generates high-resolution 3-D images for quantitatively analysis of the bone microarchitecture in human. To enable quantitative evaluation of bone changes, either bone gain or loss, accurate alignment between the baseline and follow-up scans of the same individual is necessary. The major difficulties in achieving efficient and automatic registration of the HR-pQCT data are the large data size, deformations in the nonskeletal structures, and the complexity of the trabecular bone geometry. In this paper, we propose an automatic surface-based approach for fast and accurate registration of the HR-pQCT data, where the rigid registration is applied on the surfaces of the bony structures extracted from the grayscale HR-pQCT. The bony structure segmentation is performed via an automatic method that can adaptively determine the thresholds for separating the bony structure from the background and nonskeletal tissues. Experimental results performed on ten pairs of baseline and follow-up wrist scans of five adolescents and five elderly patients with osteoporosis showed the advantage of the proposed method in the high degree of automation, while the resultant parameters describing bone mineral density and trabecular architecture after registration were comparable with the outputs of the scanner's software. This automatic and accurate matching procedure may contribute to the clinical application and research of HR-pQCT.

Purpose: To apply pharmacokinetic modeling to the investigation of bone perfusion in subjects of varying bone mineral density., Materials and Methods: This study re-analyzed previous experimental data. A modified pharmacokinetic model was applied to data obtained from two prior studies of dynamic contrast-enhanced MR imaging of L3 vertebral body in 165 subjects (65 males, 100 females), classified into three groups (normal, osteopenia, and osteoporosis) according to bone mineral density. Three parameters, amplitude A, exchange rate (k(ep)), and elimination rate (k(el)), were obtained by fitting the signal intensity to the pharmacokinetic model. These parameters were compared across the three groups for males and females, respectively., Results: Perfusion parameters, amplitude A was found to be reduced in osteoporotic subjects with additional, though less pronounced, reductions found in the permeability constant (A*k(ep)) and the elimination rate (k(el)). Increased marrow fat content was found in osteoporotic bone, which helped to partially explain the observed reduction in interstitial space., Conclusion: By pharmacokinetic model, bone perfusion can be quantitatively analyzed with alteration in functional parameters related to microcirculation in subjects of varying bone mineral density. Developing bone marrow specific pharmacokinetic models should help to deepen knowledge of physiological and pathological perfusion changes occurring in bone., (Copyright 2010 Wiley-Liss, Inc.)

Bone fracture is related to bone strength. In current clinical practice, bone mineral density (BMD) is used as the prime indicator of bone strength, not infrequently at the neglect of an even more pertinent measure of reduced bone strength, namely the radiographic presence of an insufficiency fracture. Bone strength depends not just on BMD but also on bone quality, which relates to such factors as bone architecture, turnover, mineralization, and cellularity. The high resolution available from current imaging techniques, particularly computed tomography and magnetic resonance imaging, along with advanced analytical software has greatly enhanced evaluation of bone architecture and strength. This has improved our knowledge of the pathophysiological processes behind osteoporosis and its treatment beyond that provided by BMD measurement alone. Although still in the experimental stage, these techniques will no doubt be incorporated into clinical practice, leading to a more tailored approach to the screening, monitoring, and treatment of osteoporosis.

Introduction: The purpose of this research is to assess the effects of oral ibandronate on bone microarchitecture by using high-resolution peripheral quantitative computed tomography (HR-pQCT) in patients with systemic lupus erythematosus (SLE) taking a long-term glucocorticoid., Methods: In this double-blind placebo-controlled study, 40 Chinese female SLE patients taking prednisolone were randomly assigned to receive either monthly oral ibandronate (150 mg) or placebo with daily 1-hydroxycholecalciferol (Alfacalcidol; 1 μg) and calcium supplement for 12 months. Assessments of bone microarchitecture by using HR-pQCT and area bone mineral density (aBMD) of the lumbar spine and hip with dual-energy x-ray absorptiometry (DXA) were performed at baseline and 12 months., Results: No differences in baseline characteristics were found between the two groups. After 12 months, no statistical differences were noted in any of the bone densities, microarchitectural parameters, or percentage changes of these parameters, as measured with HR-pQCT or DXA between the two groups. However, within the active group, the percentage improvement was significant in cortical bone density (P = 0.023) which was absent in the placebo group. Improvement was also seen in the aBMD of both the lumbar spine (P < 0.0001) and the hip (P < 0.005). In the placebo group, the percentage increase in trabecular separation was significant (P = 0.04), and the percentage improvement in aBMD in the spine also was significant (P = 0.049)., Conclusions: Oral ibandronate treatment improves microarchitecture in SLE patients taking long-term glucocorticoid assessed with HR-pQCT, and this new technology may have a role in assessing bony changes in future longitudinal studies in SLE patients., Trial Registration: ClinicalTrials.gov identifier: NCT00668330.

Using dynamic contrast enhanced MR imaging, this study investigated perfusion of the proximal femur in subjects with normal BMD, low bone mass and osteoporosis. Study cohort comprised healthy elderly Hong Kong Chinese volunteers consisting of 107 males (74.4+/-4.2 years, mean+/-SD) and 135 females (73.9+/-4.3 years). Right proximal femur BMD measurement by DXA and MR perfusion imaging (maximum enhancement, E(max) and enhancement slope, E(slope)) of the femoral head, neck, and proximal shaft were carried out within a one month interval. Normal BMD, low bone mass and osteoporotic subjects accounted for 46.7%, 44.9%, and 8.4% of males; and 32.6%, 43.7%, and 23.7% of females. Perfusion indices showed that femoral head perfusion was less perfused compared to the femoral shaft (E(max) and E(slope) indices of head region=28% of shaft region). Compared with normal BMD subjects, E(max) of femoral head, neck, and proximal femur shaft were reduced by 15+/-5% (mean+/-standard error); 40+/-4%; 15+/-5% respectively for low bone mass subjects, and 36+/-4%; 50+/-6%; 47+/-6% respectively for osteoporotic subjects. E(slope) of femoral head, neck, and proximal femur shaft were reduced by 17+/-7%; 41+/-5%; 4+/-7% for low bone mass subjects and 50+/-5%, 62+/-5%, 34+/-8% for osteoporotic subjects. In low bone mass and osteoporotic subjects there was a tendency for perfusion in the femoral neck to reduce to a greater degree relative to that in the femoral head and shaft.

Osteoporosis is associated with an increase in marrow fat. Fats, particularly polyunsaturated fats, either in co-cultures or diet, have been shown to significantly influence bone remodeling. Whether the increase in marrow fat seen in osteoporosis is also associated with a change in fatty acid composition is not known. This study was undertaken to investigate the fatty acid composition in subjects of varying bone mineral density (BMD). Samples of marrow fat and subcutaneous fat from 126 subjects (98 females, 34 males, mean age 69.7+/-10.5 years) undergoing orthopedic surgery were analyzed for fatty acid composition by gas chromatography. These results were correlated with BMD assessed by DXA. A total of 22 fatty acids were identified in marrow and subcutaneous fat. Significant differences in fatty acid composition existed between marrow and subcutaneous fat as well as between marrow fat samples obtained from the proximal femur and proximal tibia. Other than cis-7-hexadecenoic acid [C16:1 (n=9)] and docosanoic acid [C22:0], no difference in marrow fatty acid composition was evident between subject groups of varying BMD (normal, low bone mass, and osteoporosis). In conclusion, there exists a wide range of individual fatty acids in marrow fat. Marrow fatty acid composition differs from that of subcutaneous fat and varies between predominantly erythropoetic and fatty marrow sites. Other than cis-7-hexadecenoic acid [C16:1 (n=9)] and docosanoic acid [C22:0], no difference in marrow fatty acid composition was evident between subjects of varying BMD.

Quantitative examination of iliac crest bone biopsies shows that as subjects become older bone and functional marrow are replaced by adipose tissue. Studies of vertebral marrow fat using nuclear magnetic resonance spectroscopy ((1)H-MRS) show that subjects with lower spine T-scores have significantly higher marrow fat content. These findings suggest that the ability of DXA scans to determine fracture risk may be partly explained by the effect of increased marrow fat on BMD. However, a proper evaluation of the relationship between WHO spine T-score status and marrow fat content requires that the BMD data are first corrected for the bias caused by a selection effect in which subjects with higher marrow fat are more likely to be identified as having osteoporosis. In this study we have therefore reanalysed previously published data for 185 elderly Hong Kong Chinese subjects (103 women, mean age 73 y; 82 men, mean age 73 y) who had spine DXA scans and (1)H-MRS measurements of L3 marrow fat. The effect of varying marrow fat on BMD was modelled using vertebral body thicknesses measured in 50 men and women. Spine T-scores in each individual were adjusted for the measured marrow fat. Subjects were assigned to WHO categories based on their corrected T-scores, and the relationship between marrow fat and T-score status evaluated using regression analysis and analysis of variance. The average change in percent marrow fat per T-score unit was used to infer the fraction of the spine BMD fracture discrimination explained by marrow composition. The mean (SD) of the L1-L4 vertebral body thickness was 30.2 (2.1) mm for Hong Kong women and 33.4 (2.5) mm for men. A change in marrow fat content from 0 to 100% was estimated to produce a BMD decrease of 0.14 g/cm(2) (1.3 T-score units) in women and 0.16 g/cm(2) (1.3 T-score units) in men. Although adjusting spine BMD for marrow fat reduced the significance of the correlation, there was still a trend for marrow fat to increase with decreasing T-score with a slope of -1.2+/-0.7% per T-score unit (p=0.078) for women and -1.4+/-0.6% per T-score unit (p=0.023) for men. When the effect of marrow composition on fracture discrimination was evaluated the results showed that the higher vertebral marrow fat content found in osteoporotic subjects made a negligible contribution to the ability of spine BMD measurements to predict fracture risk.

Purpose: To investigate the relationship between vertebral blood perfusion and vertebral bone mineral density (BMD) in a rat orchiectomy (ORX) model., Materials and Methods: Nine 6-month-old male Wistar-Kyoto rats were used. Computed tomography (CT) bone densitometry and dynamic MRI were performed at baseline and four weeks post-ORX. MRI was performed on a 1.5 T clinical MR scanner with a small surface coil placed under the rat lumbar spine region. A sagittal midsection of the lumbar spine was prescribed. Dynamic MRI was performed after a bolus injection of gadolinium-tetraazacyclododecane tetraacetic acid (Gd-DOTA) (0.3 mmol/kg) administered through a tail vein cannula. At a temporal resolution of 0.6 seconds, 800 images were acquired. Regions-of-interest were drawn comprising the medullary component of lumbar vertebrae L3-L6. Maximum enhancement was analyzed., Results: Satisfactory CT and MRI data for analysis was obtained in all animals. Vertebral BMD decreased by 16.6% at four weeks post-ORX (1.134 +/- 0.035 vs. 0.946 +/- 0.027 g/cm(3), P = 0.008). MRI maximum enhancement decreased by 17% at four weeks post-ORX (151.5 +/- 12.0% vs. 125.8 +/- 9.9%, P = 0.015)., Conclusion: Vertebral blood perfusion reduction is associated with vertebral BMD reduction in a male rat osteoporosis model. Perfusion MRI provides a new investigative technique for osteoporosis experimental research., ((c) 2008 Wiley-Liss, Inc.)

Bone fracture occurs when the bone strength (i.e. the ability of the bone to resist a force) is less than the force applied to the bone. In the elderly, falls represent the more severe forces applied to bone. Bone density is a good marker of bone strength, and has been used widely in this respect. Nevertheless, many aspects of bone strength cannot be explained by bone density alone. For this reason there has been increasing interest in studying architectural parameters of bone, beyond bone density, which may affect bone strength. Macro-architectural parameters include e.g. bone size and geometry assessed with techniques such as radiography, dual-energy x-ray absorptiometry (DXA), peripheral quantitative computed tomography (QCT), computed tomography (CT) and magnetic resonance imaging (MRI). Micro-architectural parameters include fine cortical and trabecular structural detail which can be evaluated using high-resolution imaging techniques such as multidetector CT, MRI, and high-resolution peripheral QCT. These techniques are providing a great deal of new information on the physiological architectural responses of bone to aging, weightlessness, and treatment. This will ultimately lead to the prediction of fracture risk being improved through a combined assessment of bone density and architectural parameters.

Correlation between kinematics and morphological characteristics of lumbar spine was studied in subjects with varying bone mineral density. Effect of morphological characteristics and bone mineral density on the lumbar spine movement was investigated. Morphology parameters were measured from radiographs and a high-frequency motion tracking device were employed to detect surface movement of lumbar spine. Multiple regression analysis identified factors influencing lumbar kinematics while ANOVA examined differences in morphology with normal bone mineral density, osteopenia and osteoporosis. The results show that morphological characteristics, such as wedging deformity, are indeed influential to the kinematics. Related to our previous report, abnormal lumbar kinematic pattern in the subjects with osteoporosis, this study shows although morphological characteristics were found significantly different among normal, osteopenia, and osteoporosis subjects, the change in lumbar kinematic pattern could not be fully explained by the altered vertebral or disc morphology.

Purpose: To prospectively study the relationship among vertebral marrow fat content, marrow diffusion indexes, and marrow and erector spinae muscle perfusion indexes in female subjects with varying bone mineral density., Materials and Methods: Institutional study approval and informed consent were obtained. Dual x-ray absorptiometry, proton magnetic resonance (MR) spectroscopy, diffusion-weighted MR imaging, and dynamic contrast material-enhanced MR imaging of the lumbar spine and erector spinae muscle were performed in 110 women (mean age, 73 years; range, 67-84 years). Marrow fat content, marrow apparent diffusion coefficient (ADC), and perfusion indexes (maximum enhancement and enhancement slope) of marrow and erector spinae muscle were compared among three bone density groups (normal, osteopenic, and osteoporotic). The t test comparisons and Pearson correlations were applied., Results: Seven subjects were excluded, which yielded a final cohort of 103 subjects: 18 with normal bone density, 30 with osteopenia, and 55 with osteoporosis. Vertebral marrow fat content was significantly increased in the osteoporotic group (67.8% +/- 8.5 [standard deviation]) when compared with that of the normal bone density group (59.2% +/- 10.0, P = .002). Vertebral marrow perfusion indexes were significantly decreased in the osteoporotic group (enhancement slope, 1.10%/sec +/- 0.51) compared with those of the osteopenic group (1.45%/sec +/- 0.51, P = .01) and normal bone density group (1.70%/sec +/- 0.52, P < .001). Erector spinae muscle perfusion indexes did not decrease as bone density decreased. The ADC of vertebral marrow did not change with bone density., Conclusion: The subjects experienced a decrease in vertebral marrow maximum enhancement and enhancement slope and an increase in marrow fat content as bone density decreased. The reduction in perfusion indexes occurred only within the vertebral body and not in the paravertebral tissues supplied by the same artery., ((c) RSNA, 2006.)

Previous population studies have demonstrated an association between peripheral vascular disease and bone mineral density in women, but not in men. In a large prospective cohort of 3,998 Chinese men and women aged 65 to 92 years of age in Hong Kong, the association between peripheral vascular disease and bone mineral density was explored. Demographic and lifestyle information was obtained from face to face interviews using a standardized questionnaire. This included demographic information, medical history and lifestyle factors. Physical examination measurements included anthropometry and tibial and brachial systolic blood pressures. The ratio of the posterior tibial and brachial systolic blood pressures, the ankle/arm index, was used as a measure of peripheral arteriosclerosis in the lower extremities. Bone mineral density (BMD) at the total hip and spine (L1-L4) was measured by Hologic QDR-4500 W densitometers (Hologic, Inc., Waltham, Mass.). In this cross-sectional analysis, the ankle brachial index (ABI) was positively correlated with hip BMD (correlation coefficient=0.27; P<0.001). However, after adjustment for confounders, the correlation became much weaker (correlation coefficient=0.03; P<0.05). This showed that much of the relationship between ABI and BMD could be explained by other confounders. In multiple regression analysis, an increase in ABI of 1 SD of ABI was associated with an increase of 0.5% (95% CI: 0.02%, 0.9%) in hip BMD after adjusting for age, sex, body weight, smoking status, history of diabetes, cardiovascular diseases, use of thiazide diuretics, grip strength and physical activity. Although our study shows that peripheral vascular disease in the lower extremities may be associated with decreased bone mineral density, the association is weak especially after adjustment was made for confounders. This indicates that other factors may be contributing to the association between peripheral vascular disease and osteoporosis.

Purpose: To prospectively use hydrogen 1 (1H) magnetic resonance (MR) spectroscopy and dynamic contrast material-enhanced MR imaging to measure vertebral body marrow fat content and bone marrow perfusion in older men with varying bone mineral densities as documented with dual x-ray absorptiometry (DXA)., Materials and Methods: This study had institutional review board approval, and all participants provided informed consent. DXA, 1H MR spectroscopy, and dynamic contrast-enhanced MR imaging of the lumbar spine were performed in 90 men (mean age, 73 years; range, 67-101 years). Vertebral marrow fat content and perfusion (maximum enhancement and enhancement slope) were compared for subject groups with differing bone densities (normal, osteopenic, and osteoporotic). The t test was used for comparisons between groups, and the Pearson test was used to determine correlation between marrow fat content and perfusion indexes., Results: Eight subjects were excluded, yielding a final cohort of 82 subjects (mean age, 73 years; range, 67-101 years) that included 42 subjects with normal bone density (mean T score, 0.8 +/- 1.1 [standard deviation]), 23 subjects with osteopenia (mean T score, -1.6 +/- 0.4), and 17 subjects with osteoporosis (mean T score, -3.2 +/- 0.5). Vertebral marrow fat content was significantly increased in subjects with osteoporosis (mean fat content, 58.23% +/- 7.8) (P = .002) or osteopenia (mean fat content, 55.68% +/- 10.2) (P = .034) compared with that in subjects with normal bone density (50.45% +/- 8.7). Vertebral marrow perfusion indexes were significantly decreased in osteoporotic subjects (mean enhancement slope, 0.78%/sec +/- 0.3) compared with those in osteopenic subjects (mean enhancement slope, 1.15%/sec +/- 0.6) (P = .007) and those in subjects with normal bone density (mean enhancement slope, 1.48%/sec +/- 0.7) (P < .001)., Conclusion: Subjects with osteoporosis have decreased vertebral marrow perfusion and increased marrow fat compared with these parameters in subjects with osteopenia. Similarly, subjects with osteopenia have decreased vertebral marrow perfusion and increased marrow fat compared with these parameters in subjects with normal bone density.

The article presents a study which investigates the risk factors and incidence of non-vertebral and vertebral fracture in female Chinese patients with systemic lupus erythematosus (SLE). Topics discussed include the measurement of bone mineral density (BMD), the prevalence of osteoporosis, and the use of dual-energy X-ray absorptiometry.