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Purpose: The effects of daily teriparatide (D-PTH, 20 μg/day), weekly high-dose teriparatide (W-PTH, 56.5 μg/week), or bisphosphonate (BP) on the vertebra and proximal femur were investigated using quantitative computed tomography (QCT)., Methods: A total of 131 postmenopausal women with a history of fragility fractures were randomized to receive D-PTH, W-PTH, or bisphosphonate (oral alendronate or risedronate). QCT were evaluated at baseline and after 18 months of treatment., Results: A total of 86 participants were evaluated by QCT (Spine: D-PTH: 25, W-PTH: 21, BP: 29. Hip: PTH: 22, W-PTH: 21, BP: 32. Dropout rate: 30.5 %). QCT of the vertebra showed that D-PTH, W-PTH, and BP increased total vBMD (+34.8 %, +18.2 %, +11.1 %), trabecular vBMD (+50.8 %, +20.8 %, +12.2 %), and marginal vBMD (+20.0 %, +14.0 %, +11.5 %). The increase in trabecular vBMD was greater in the D-PTH group than in the W-PTH and BP groups. QCT of the proximal femur showed that D-PTH, W-PTH, and BP increased total vBMD (+2.8 %, +3.6 %, +3.2 %) and trabecular vBMD (+7.7 %, +5.1 %, +3.4 %), while only W-PTH and BP significantly increased cortical vBMD (-0.1 %, +1.5 %, +1.6 %). Although there was no significant increase in cortical vBMD in the D-PTH group, cortical bone volume (BV) increased in all three treatment groups (+2.1 %, +3.6 %, +3.1 %)., Conclusions: D-PTH had a strong effect on trabecular bone of vertebra. Although D-PTH did not increase cortical BMD of proximal femur, it increased cortical BV. W-PTH had a moderate effect on trabecular bone of vertebra, while it increased both cortical BMD and BV of proximal femur. Although BP had a limited effect on trabecular bone of vertebra compared to teriparatide, it increased both cortical BMD and BV of proximal femur., Competing Interests: Declaration of competing interest This study was supported by Asahi Kasei Pharma Corporation and Eli Lilly Japan K.K., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: The effects of daily teriparatide (20 μg) (D-PTH), weekly high-dose teriparatide (56.5 μg) (W-PTH), or bisphosphonates (BPs) on areal bone mineral density (aBMD), bone turnover markers (BTMs), volumetric BMD (vBMD), microarchitecture, and estimated strength were investigated in postmenopausal osteoporosis patients., Methods: The study participants were 131 women with a history of fragility fractures. They were randomized to receive D-PTH, W-PTH, or BPs (alendronate or risedronate) for 18 months. Dual-energy X-ray absorptiometry (DXA), BTMs, and high-resolution peripheral quantitative CT (HR-pQCT) parameters were evaluated at baseline and after 6 and 18 months of treatment. The primary endpoint was the change (%) in cortical thickness (Ct.Th) after 18 months' treatment compared with baseline., Results: DXA showed that D-PTH, W-PTH, and BPs increased lumbar spine aBMD (+12.0%, +8.5%, and +6.8%) and total hip aBMD (+3.0%, +2.1%, and +3.0%), but D-PTH and W-PTH decreased 1/3 radius aBMD (-4.1%, -3.0%, -1.4%) after 18 months. On HR-pQCT, D-PTH increased trabecular vBMD (Tb.vBMD) at the distal radius and tibia after 18 months (+6.4%, +3.7%) compared with the BPs group, decreased cortical volumetric tissue mineral density (Ct.vTMD) (-1.8%, -0.9%) compared with the other groups, increased Ct.Th (+1.3%, +3.9%), and increased failure load (FL) (+4.7%, +4.4%). W-PTH increased Tb.vBMD (+5.3%, +1.9%), maintained Ct.vTMD (-0.7%, +0.2%) compared with D-PTH, increased Ct.Th (+0.6%, +3.6%), and increased FL (+4.9%, +4.5%). The BPs increased Tb.vBMD only in the radius (+2.0%, +0.2%), maintained Ct.vTMD (-0.6%, +0.3%), increased Ct.Th (+0.5%, +3.4%), and increased FL (+3.9%, +2.8%)., Conclusions: D-PTH and W-PTH comparably increased Ct.Th, the primary endpoint. D-PTH had a strong effect on trabecular bone. Although D-PTH decreased Ct.vTMD, it increased Ct.Th and total bone strength. W-PTH had a moderate effect on trabecular bone, maintained Ct.vTMD, and increased Ct.Th and total bone strength to the same extent as D-PTH., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: The primary purpose of this cross-sectional study was to investigate the characteristics of age-related changes in bone microstructure on high-resolution peripheral quantitative computed tomography (HR-pQCT), areal bone mineral density (aBMD) on dual-energy X-ray absorptiometry (DXA), and bone-related biochemical markers in men. The secondary purpose of this study was to examine how bone microstructure is related to aBMD and biochemical markers., Methods: The subjects were 128 healthy Japanese men (20-97 years old). Bone microstructure was measured in the distal radius and tibia using second-generation HR-pQCT; aBMD in the proximal femur and lumbar spine was measured with DXA; and tartrate-resistant acid phosphatase-5b (TRACP-5b), type I procollagen-N-propeptide (P1NP), 25(OH) vitamin D, and pentosidine concentrations were measured by blood tests., Results: In trabecular bone, the trabecular volumetric BMD (Tb.vBMD) and trabecular number (Tb.N) were lower with age (r = -0.23, -0.35) (r = -0.36,-0.33), and trabecular separation (Tb.Sp) and the star volume of marrow space (V*ms) were higher with age (r = 0.29, 0.41) (r = 0.34, 0.38) in both the radius and tibia. In cortical bone, cortical volumetric BMD (Ct.vBMD) was lower with age (r = -0.25, -0.52), and cortical porosity (Ct.Po) was higher with age (r = 0.67, 0.62) in both the radius and tibia. In the tibia, cortical thickness (Ct.Th) and cortical area (Ct.Ar) were lower with age (r = -0.40) (r = -0.43), whereas, in the radius, they were maintained, and periosteal perimeter (Ct.Pm) was higher with age (r = 0.35). aBMD in the proximal femur and P1NP were lower, and pentosidine was higher with increased age, whereas aBMD in the lumbar spine, TRACP-5b, and 25(OH) vitamin D had no relationships with age. DXA and HR-pQCT showed strong correlations particularly with femoral aBMD and tibial Tb.vBMD and Ct.Ar (r = 0.61) (r = 0.61), whereas no DXA parameters were related with Ct.Po. In correlations between biochemical markers and HR-pQCT, TRACP-5b and total P1NP were negatively correlated with Ct.vBMD (r = -0.31) (r = -0.35), but almost no other correlations were seen., Conclusions: Age-related changes of the bone microstructure in men were characterized by decreases in trabecular and cortical vBMD associated with decreased trabecular number, cavitation of the trabecular structure, and increased cortical porosity. Femoral aBMD was strongly related to bone microstructure in the tibia, whereas both lumbar aBMD and femoral aBMD were not related to Ct.Po, and biochemical markers showed almost no relationships with bone microstructure., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: High-resolution peripheral quantitative computed tomography (HR-pQCT), which enables in vivo analysis of bone morphometry, is widely used in osteoporosis research. The scan position is usually determined by the fixed offset method; however, there are concerns that the scan position can become relatively proximal if limb length is short. The present study compared bone mineral density and morphometry measured using the fixed and relative offset methods, in which the scan position is determined based on the lengths of the forearm and lower leg, and investigated factors responsible for measurement differences between the two methods., Methods: A total of 150 healthy Japanese subjects, comprising 75 men and 75 women, with a mean age of 45.1 years, were enrolled in this study. The distal radius and tibia were scanned using the fixed and relative offset methods; the fixed offset method involved scanning the radius and tibia at 9 mm and 22 mm, respectively, proximal to their distal articular surfaces. By contrast, the relative offset method entailed scanning the radius at 4% of the forearm length and the tibia at 7.3% of the lower leg length, proximal to their respective distal articular surfaces. The percent overlap between the scan positions of the two methods was measured using the scout views. Measurement values obtained with the two methods were compared. The correlation between the differences in the values among the two methods and forearm length, lower leg length, and body height was examined., Results: The subjects had a mean height of 164.3 ± 14.3 cm, mean forearm length of 252.9 ± 17.3 mm, and mean lower leg length of 346.7 ± 22.3 mm. The mean percent overlap was 85.0 ± 9.1% (59.2-99.6%) for the radius and 79.8 ± 12.5% (48.3-99.8%) for the tibia. Fixed offset scanning yielded higher total volumetric bone mineral density (Tt.vBMD) and cortical vBMD (Ct.vBMD) and greater cortical thickness (Ct.Th) (all p < 0.001). The differences between the two methods in terms of Tt.vBMD, Ct.vBMD and Ct.Th were significantly greater with shorter forearm length, lower leg length, and body height (radius: 0.51 < |r| < 0.63, tibia: 0.61 < |r| < 0.95)., Conclusion: Measurements of bone mineral density and morphometry obtained using the fixed offset method differed from those obtained using the relative offset method, which takes body size into account. Shorter body height, forearm length, and lower leg length were found to correlate with greater measurement differences. In populations with smaller stature, use of the fixed offset method results in relatively proximal images; thus, caution should be exercised when comparing groups of different height., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: To investigate the effects of sequential therapy with monthly intravenous ibandronate on bone mineral density (BMD) and microstructure in patients with primary osteoporosis who received teriparatide treatment., Methods: Sixty-six patients with primary osteoporosis who had undergone teriparatide treatment for more than 12 months (mean 18.6 months) received sequential therapy with 1 mg/month intravenous ibandronate for 12 months. The patients were evaluated using dual-energy X-ray absorptiometry (DXA), quantitative ultrasound, bone turnover markers, and high-resolution peripheral quantitative computed tomography (HR-pQCT) at baseline and 6 and 12 months after beginning administration., Results: At 12 months after beginning sequential therapy, the bone resorption marker, tartrate-resistant acid phosphatase-5b, decreased by 39.5%, with 82.3% of the patients exhibiting levels within the normal limit. DXA revealed that the BMD of the lumbar spine increased by 3.2%, with 79.0% of the patients exhibiting a response, and 40.3% experiencing an increase in BMD over 5%. HR-pQCT revealed that the cortical thickness of the distal tibia was increased by 2.6%. The cortical area increased by 2.5%, and the buckling ratio (an index of cortical instability) decreased by 2.5%. Most parameters of the trabecular bone showed no significant changes. These changes in the cortical bone were observed in both the distal radius and tibia and appeared beginning 6 months after treatment initiation., Conclusions: Sequential therapy with monthly intravenous ibandronate increased the BMD and improved the cortical bone microstructure of osteoporotic patients who had undergone teriparatide treatment., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: Subchondral bone plays an important role in the pathological mechanisms of knee osteoarthritis (OA). High-resolution peripheral quantitative computed tomography (HR-pQCT) is an imaging modality allowing noninvasive microstructural analysis of human bone, and the second generation enables scanning of the knee. The purpose of this study was to perform in vivo analysis of subchondral trabecular bone in patients with medial knee OA, to elucidate features of bone microstructure in medial knee OA, and to investigate relationships between bone microstructure and both stage of disease and lower limb alignment., Methods: Subjects were 20 women, including both patients with medial knee OA (Kellgren-Lawrence (KL) grade 2, n = 5, KL grade 3, n = 7, and KL grade 4, n = 4; mean age: 63.0 years; body mass index (BMI): 23.8 kg/m 2 ) and volunteers without knee OA (KL grade 1, n = 4, mean age: 66.0 years; BMI: 23.8 kg/m 2 ). The proximal tibia (20-mm length) was scanned by second-generation HR-pQCT at a voxel size of 60.7 μm. A subchondral trabecular bone volume of 5 mm length was extracted from the medial and lateral plateaus. They were then divided into 4 regions: anterior, central, medial or lateral, and posterior. Finally, subchondral bone microstructure parameters were analyzed and compared, between each plateau and region. Relationships between microstructural parameters and disease stage (KL grade, minimum joint space width), and between those parameters and lower limb alignment (femorotibial angle: FTA, mechanical axis deviation: MAD) were also investigated., Results: In the medial plateau, volumetric bone mineral density (vBMD), bone volume fraction (BV/TV), and trabecular thickness were significantly higher and structure model index (SMI) was significantly lower than in the lateral plateau, particularly in the anterior, central, and medial regions (p < .01 each). In the anterior region of the medial plateau, vBMD, BV/TV, and connectivity density showed strong positive correlations with KL grade, FTA, and MAD (r-range: 0.61 to 0.83), while trabecular separation and SMI exhibited strong negative correlations with KL grade, FTA, and MAD (r-range: -0.60 to -0.83)., Conclusions: Higher bone volume, trabecular thickness, and a more plate-like structure were observed in the medial tibial plateau than in the lateral. Subchondral bone microstructure at the anterior region in the medial plateau showed strong relationships with KL grade and lower limb alignment. These results indicate that subchondral bone microstructure in this region may provide representative indices, particularly in medial knee OA. Although this study involved a specifically Asian cohort with a lower BMI distribution than other ethnic groups, the technique presented may be useful in studying the pathogenesis of OA or evaluating treatment effects., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: High-resolution peripheral quantitative computed tomography (HR-pQCT) has enabled us to observe changes of bone microstructure during fracture healing. However, a method of analyzing the healing process after osteosynthesis has yet to be established due to implant artifacts. The purpose of this study was to investigate the effects of volar locking plates for distal radius fractures on the image quality of HR-pQCT., Methods: Four different types of plates for distal radius fractures were evaluated. The scan region of HR-pQCT was the center of each plate, not including the screw insertion sites. To assess plate-generated noise, each plate was fixed to the top of a water-filled rubber glove, scanned by HR-pQCT, and the signal-to-noise ratio (SNR) of the region under the plates was calculated. To investigate accuracy, 12 cadaveric radii with and without each plate were scanned by HR-pQCT, and differences between the measured values with and without the plate were evaluated. Differences between the measurements of the entire circumference and of the dorsal third of the radius were also compared. Reproducibility of the in vivo measurement was investigated by repeated scans of 10 patients with distal radius fractures who had undergone surgery with a volar locking plate., Results: The SNR was significantly higher away from the plate than immediately below the plate. Percentage differences of the measurement values between with and without the plate were 1.4%-3.2% for cortical bone mineral density (Ct.BMD) and 7.2%-9.8% for cortical bone thickness (Ct.Th) when the entire circumference was measured. When the dorsal third was measured, they were 0.3%-1.7% for Ct.BMD and 1.8%-2.7% for Ct.Th. The root-mean-square coefficient of variation (RMS%CV) was 1.12% for Ct.BMD and 4.18% for Ct.Th., Conclusions: The accuracy and reproducibility of cortical bone measurements with a volar locking plate on HR-pQCT were acceptable when the dorsal third of the Ct.BMD was analyzed, and this method would be useful for in vivo analysis of the fracture healing process after osteosynthesis., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: A vertebral fracture is the most common complication of osteoporosis, and various factors are involved in its occurrence. The purpose of this study was to investigate the role of trabecular and cortical bone microstructure on vertebral strength using high-resolution peripheral quantitative computed tomography (HR-pQCT)., Methods: Three female cadaveric spines were investigated (average age: 80.3 years). The whole spine (T1-L4) was scanned by second-generation HR-pQCT at a voxel size of 60.7 μm. Bone microstructure analysis and micro finite element analysis were performed after excluding the upper and lower endplates and posterior elements of a total of 48 vertebrae. Correlations between trabecular and cortical bone microstructure parameters and estimated vertebral strength were analyzed by univariate and multivariate regression models., Results: Cortical thickness (Ct.Th) and trabecular thickness (Tb.Th) were strongly correlated with estimated failure load on univariate analysis (r = 0.89, 0.82). Trabecular volumetric bone mineral density (Tb.vBMD), bone volume fraction (BV/TV), trabecular number (Tb.N), and Ct.Th were correlated with estimated failure load on multivariate regression analysis., Conclusions: It was suggested that, in addition to trabecular bone (Tb.vBMD, BV/TV, Tb.N), cortical bone (Ct.Th) contributed significantly to vertebral strength in elderly women., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Trabecular bone microfracture pathogenesis and associated healing processes are not well understood. We analyzed the microcalluses that form subsequent to microfractures in patients with osteoporosis (OP) using synchrotron radiation micro CT (SRCT). Subchondral bone columns were extracted from the femoral heads of 11 female patients with a femoral neck fracture. SRCT scanning was performed with 5.9×5.9×5.9 μm3 voxel size and the microcallus number was measured in a 5-mm cubic subchondral bone region. The trabecular bone microstructure was measured and its relationship to the microcallus number was analyzed. In addition, the degree of mineralization of the microcallus region and that of the rest of the trabecular bone were measured and compared. Microcallus formations were detected in all cases, with a mean microcallus number of 4.9 (range, 2-11). The microcallus number had a significantly negative correlation with bone volume fraction (BV/TV), trabecular thickness (Tb.Th), and degree of mineralization, and had a positive correlation with specific bone surface (BS/BV). The degree of mineralization of the microcallus region was lower than that of the rest of the trabecular bone and had a wider range of values. Microcallus formations were frequently detected in patients with OP, and more prevalent in the bone with thinner trabeculae, suggesting microfractures might occur due to activities of daily living as the OP progresses. The degree of mineralization of microcallus might represent the process of bone healing from immature woven bone to mature trabecular bone., (Copyright © 2014 Elsevier Inc. All rights reserved.)