Relationships between QUS and HR-pQCT, DXA, and bone turnover markers.

INTRODUCTION: Relationship of quantitative ultrasound (QUS) with high-resolution peripheral quantitative computed tomography (HR-pQCT), dual-energy X-ray absorptiometry (DXA), and bone-related biochemical markers was analyzed. MATERIALS AND METHODS: The subjects were 480 individuals. Speed of sound (SOS) was measured by calcaneal QUS. Volumetric bone mineral density (vBMD) and microarchitecture of trabecular and cortical bone in the distal radius and tibia were assessed by HR-pQCT. Areal bone mineral density (aBMD) in the lumbar spine and proximal femur were measured by DXA. TRACP-5b, P1NP, 25 (OH) vitamin D, and pentosidine were evaluated by biochemical tests. The correlation of each parameter was analyzed for all subjects and by sex and age group. RESULTS: QUS was moderately correlated with Tb.vBMD and Tb.BV/TV in the radius and tibia. No correlation was seen with Ct.vBMD or cortical porosity (Ct.Po). Although a correlation was seen with cortical thickness (Ct.Th) in the tibia in all subjects, no correlation was seen in women aged ≥ 60 years. QUS showed moderate correlations with aBMD in the proximal femur. Although moderate correlation was seen with aBMD in the lumbar spine in all subjects, no correlation was seen in subjects aged ≥ 60 years. No significant correlations were seen between QUS and biochemical markers. CONCLUSIONS: Moderate correlations were seen between QUS and Tb.vBMD and microarchitecture in the radius and tibia and aBMD of the proximal femur. On the other hand, practically no correlations were seen with Ct.vBMD or Ct.Po and the bone-related biochemical markers. Only in middle age, moderate correlations were seen with Ct.Th in the tibia and with aBMD of the lumbar spine.

Cortical thickness mapping at segmented regions in the distal radius using HR-pQCT.

INTRODUCTION: An advanced method of analyzing the cortical bone microarchitecture of the distal radius using high-resolution peripheral quantitative computed tomography (HR-pQCT) was developed. MATERIALS AND METHODS: The subjects were 60 women (20: aged 30-49, 20: aged 50-69, and 20: aged 70-89 years). The distal radius was scanned by HR-pQCT, and its cortical volumetric bone mineral density (Ct.vBMD), cortical porosity (Ct.Po), and cortical thickness (Ct.Th) were measured. The cortical bone was also divided into three areas according to whether its thickness was < 0.5 mm, 0.5-1.0 mm, or > 1.0 mm, and the percentage of each surface area in the total surface area of cortical bone was calculated (Ct.Th (<0.5), Ct.Th (0.5-1.0), Ct.Th (>1.0), respectively). The cortical bone at the distal radius was further segmented into dorsal, palmar, radial, and ulnar sides, and the above-described parameters were measured in these regions. RESULTS: Integral analysis showed that Ct.vBMD and Ct.Th decreased and Ct.Po increased with age (R = - 0.62, - 0.55, and 0.54). Ct.Th (< 0.5) expanded with age (R = 0.49), with the rate of change between those aged 30-49 years and those aged 50-69 years being 106.7%. On regional analysis, the expansion of Ct.Th (< 0.5) with age was particularly marked on the dorsal and palmar side (R = 0.51 and 0.49), where the rate of change between those aged 30-49 years and those aged 50-69 years was the highest, at 196.1 and 149.6%. CONCLUSION: The method to identify areas of cortical bone thinning in the segmented regions of the dorsal, palmar, radial, and ulnar sides of the distal radius using HR-pQCT may offer a sensitive assessment of age-related deterioration of cortical bone.

Comparison of bone microstructures via high-resolution peripheral quantitative computed tomography in patients with different stages of chronic kidney disease before and after starting hemodialysis.

Chronic kidney disease (CKD) negatively affects bone strength; however, the osteoporotic conditions in patients with CKD are not fully understood. Moreover, the changes in bone microstructure between pre-dialysis and dialysis are unknown. High-resolution peripheral quantitative computed tomography (HR-pQCT) reveals the three-dimensional microstructures of the bone. We aimed to evaluate bone microstructures in patients with different stages of CKD. This study included 119 healthy men and 40 men admitted to Nagasaki University Hospital for inpatient education or the initiation of hemodialysis. The distal radius and tibia were scanned with HR-pQCT. Patient clinical characteristics and bone microstructures were evaluated within 3 months of initiation of hemodialysis (in patients with CKD stage 5 D), patients with CKD stage 4-5, and healthy volunteers. Cortical bone parameters were lower in the CKD group than in healthy controls. Tibial cortical and trabecular bone parameters (cortical thickness, cortical area, trabecular volumetric bone mineral density, trabecular-bone volume fraction, and trabecular thickness) differed between patients with CKD stage 5 D and those with CKD stage 4-5 (p < 0.01). These differences were also observed between patients with CKD stage 5 and those with CKD stage 5 D (p < 0.017), but not between patients with CKD stage 4 and those with CKD stage 5, suggesting that the bone microstructure rapidly changed at the start of hemodialysis. Patients with CKD stage 5 D exhibited tibial microstructural impairment compared with those with CKD stage 4-5. HR-pQCT is useful for elucidation of the pathology of bone microstructures in patients with renal failure.

Precision of 3D Registration Analysis for Longitudinal Study of Second-Generation HR-pQCT.

OBJECTIVE: The objective of this research was to develop 3D registration analysis method in longitudinal studies of high-resolution peripheral quantitative computed tomography (HR-pQCT), to analyze ranges of bone microstructure parameters in addition to standard parameters, and to test the precision of these measurements. METHODS: Scans of HR-pQCT and analysis of bone microstructure were performed at 3 times in 15 subjects. The 3 images were matched 3-dimensionally, and bone microstructures were analyzed in the common region. In addition to standard measurement parameters of geometry, bone mineral density (BMD), trabecular bone, and cortical bone, parameters showing plate to rod-like structure, connectivity, cavity formation of trabecular bone, and bending stability of cortical bone were also measured. Precision was evaluated with the root mean square percent coefficient variance (RMS%CV). RESULTS: RMS%CV was 0.1%-1.3% for geometry, 0.6%-1.9% for BMD, 0.8%-3.3% for trabecular bone, 2.1%-9.8% for additionally measured trabecular bone, 1.0%-3.4% for cortical bone excluding Ct.Po, 6.0%-6.1% for Ct.Po, and 0.8%-1.5% for additionally measured cortical bone. Precision was higher for 3D registration than for 2D registration in geometry, BV/TV, and Ct.Po. CONCLUSIONS: 3D registration analysis of a range of bone microstructural parameters in longitudinal analysis of HR-pQCT showed good precision, offering potential for contributing to future research on osteoporosis and bone metabolic diseases.

Development of a QUS Device to Evaluate Deterioration of Cortical Bone: Verification by HR-pQCT and Measurements in Healthy Individuals and Dialysis Patients.

INTRODUCTION: The objectives of this study were to identify what is reflected in cortical speed of sound (cSOS) measured by a cortical quantitative ultrasound (cortical QUS) device we have developed, and to investigate cSOS measurements in healthy individuals and dialysis patients. METHODS: The cSOS and the SOS were measured by cortical QUS and conventional QUS in 20 volunteers, and the correlations between these measurements and areal bone mineral density measured by dual-energy X-ray absorptiometry and bone microstructural parameters on high-resolution peripheral quantitative computed tomography were analyzed. The cSOS and the SOS were measured in 91 young adults (47 men, 44 women), 64 elderly people (30 men, 33 women), and 64 dialysis patients (33 men, 31 women). The period of hemodialysis and intact parathyroid hormoneevels were also investigated in the dialysis patients. RESULTS: cSOS was correlated with cortical tissue mineral density (tibia: r = 0.74, radius: r = 0.72) on high-resolution peripheral quantitative computed tomography, reflecting the degree of minaralization and microporosity of cortical bone. There was no correlation with the thickness of cortical bone, suggesting that it measured the bone quality rather than bone mass. Elderly women had lower cSOS than young adults (3865 ± 74 vs 3971 ± 63 m/s, p < 0.01). Many of dialysis patients showed very low cSOS and it was related to higher intact parathyroid hormone levels (male: ß = -0.67, female: ß = -0.60). CONCLUSIONS: Our cortical QUS device is capable of evaluating the qualitative degradation of cortical bone, which cannot be assessed by conventional QUS, and its use in combination with conventional QUS may provide a better understanding of fracture risk.

Analysis of fracture healing process by HR-pQCT in patients with distal radius fracture.

INTRODUCTION: High-resolution peripheral quantitative computed tomography (HR-pQCT) has enabled us to observe the changes in bone microarchitecture over time in vivo. In this study, the process of fracture healing was analyzed using HR-pQCT in patients with distal radius fracture who underwent osteosynthesis. MATERIALS AND METHODS: A total of 10 fracture sites identified from four patients with a distal radius fracture who underwent internal fixation with a volar locking plate (mean age 68.8 years, all women) were investigated. HR-pQCT was performed within a week (baseline) 4, 12, and 24 weeks after fracture. Rectangular region of interest (ROI) was established in the fracture site, inner callus, and external callus area, and the changes in bone mineral density (BMD) in each region were analyzed. RESULTS: From baseline to 24 weeks post-fracture, the BMD changed from 105.5 (95% CI 98.6-113) to 428.0 (331-554) mgHA/ccm at the fracture site, from 111.0 (104-119) to 375.3 (290-486) mgHA/ccm at the inner callus area, and from 98.5 (91.6-106) to 171.6 (132-222) mgHA/ccm at the external callus area. The BMD increased at the fracture site and inner callus area, but increased only slightly at the external callus area. At 24 weeks post-fracture, the BMD at the fracture site and inner callus area was significantly higher than the external callus area. CONCLUSION: In the healing process of postoperative distal radius fractures, increased BMD at the inner surface of the fracture site was confirmed in all fractures. Bone formation on the endosteal side may be a necessary condition for bone union of distal radius fractures.

Deterioration of bone microstructure by aging and menopause in Japanese healthy women: analysis by HR-pQCT.

INTRODUCTION: Second-generation high-resolution peripheral quantitative computed tomography (HR-pQCT) has provide higher quality of bone images with a voxel size of 61 µm, enabling direct measurements of trabecular thickness. In addition to the standard parameters, the non-metric trabecular parameters such as trabecular morphology (plate to rod-like structures), connectivity, and anisotropy can also be analyzed. The purpose of this study is to investigate deterioration of bone microstructure in healthy Japanese women by measuring standard and non-metric parameters using HR-pQCT. MATERIALS AND METHODS: Study participants were 61 healthy Japanese women (31-70 years). The distal radius and tibia were scanned using second-generation HR-pQCT, and microstructures of trabecular and cortical bone were measured. Non-metric trabecular parameters included structure model index (SMI), trabecular bone pattern factor (TBPf), connectivity density (Conn.D), number of nodes (N.Nd/TV), degree of anisotropy (DA), and star volume of marrow space (V*ms). Estimated bone strength was evaluated by micro finite element analysis. Associations between bone microstructure, estimated bone strength, age, and menopause were analyzed. RESULTS: Trabecular number declined with age, and trabecular separation increased. SMI and TBPf increased, Conn.D and N.Nd/TV declined, and V*ms increased. Cortical BMD and thickness declined with age, and porosity increased. Stiffness and failure load decreased with age. Cortical thickness and estimated bone strength were affected by menopause. Cortical thickness was most associated with estimated bone strength. CONCLUSIONS: Trabecular and cortical bone microstructure were deteriorated markedly with age. Cortical thickness decreased after menopause and was most related to bone strength. Non-metric parameters give additional information about osteoporotic changes of trabecular bone.

Epidemiological survey and risk factor analysis of dialysis-related amyloidosis including destructive spondyloarthropathy, dialysis amyloid arthropathy, and carpal tunnel syndrome.

The RDT population, initially at 215 patients, exceeded 300,000 in 2011, with a total of 329,609 patients at the end of December 2016. In our Institute, the number of patients with destructive spondylosis is increasing with the increase in the number of dialysis patients in Japan. We had 14 Cases in the 1990s, and then 82 cases in the 2000s and have already had 131 cases in the 2010s. The purpose of this study was to investigate the incidence of dialysis-related amyloidosis (DRA) such as destructive spondyloarthropathy (DSA), dialysis amyloid arthropathy (DAA), and carpal tunnel syndrome (CTS). In addition, another purpose was to examine the risk factors of the DRA. DAA made its own assessment on radiographs based on stage. Survey items were patient's basic data, laboratory data and X-ray view. Patient's basic data included such as sex, age, height, and weight and RDT-related factors such as kidney disease that led to RDT, age at start of RDT, RDT history, medical history (past and present), and history of surgery. The frequency of DRA was examined by medical history and radiological examination in 199 dialysis patients who obtained informed consent. The patients were divided into two groups according to the presence or absence of DRA, and risk factors of DRA were investigated from the medical history, basic data of patients, and blood tests. Of the 199 patients on regular dialysis therapy, 41 (20.6%) showed DRA. Based on the X-ray images, 21 patients (10.6%) showed DSA, while 22 patients (11.1%) showed DAA. Sixteen patients (8.0%) had CTS, determined through a history of surgery. Regarding overlap of conditions, 14 had both DSA and DAA, 3 had both DSA and CTS, and 2 had both DAA and CTS. There were statistically significant differences between the two groups in the cause of disease in Chronic glomerulonephritis and Diabetic Nephropathy, age at the start of RDT, period of RDT, body weight, blood platelet count, and blood Ca level. When multivariate analysis was performed on these items, statistical differences were recognized only during the dialysis period. In conclusion, long dialysis period was a risk factor for DRA.

Bone Mineral Density and Microstructure of the Elbow in Baseball Pitchers: An Analysis by Second-Generation HR-pQCT.

BACKGROUND: Baseball pitchers' elbows are exposed to repeated overloading during the throwing motion, which causes bone structural changes such as bone sclerosis and osteophyte formation. They have been observed by clinical CT and MRI, while the bone microstructural change has not yet been studied in vivo. The aims of this study were to establish a method of imaging the elbow joint using second-generation high-resolution peripheral quantitative CT and to investigate the bone microstructural change in baseball pitchers' dominant elbows. METHODS: The subjects were 17 baseball pitchers. The elbow was fixed using a custom-made cast and scanned by second-generation high-resolution peripheral quantitative CT. The scan conditions were as follows: voxel size 60.7 µm, integration time 43 ms, scan length 30.6 mm, and total scan time 8 min. Volumetric bone mineral density (vBMD) and trabecular bone microstructure were analyzed in the 6.5-mm3 cubic regions set in the capitellum and trochlea, and the dominant and nondominant elbows were compared. RESULTS: vBMD, bone volume fraction (BV/TV), and trabecular thickness (Tb.Th) at the capitellum were significantly higher in the dominant elbow than in the nondominant elbow. On the other hand, no parameters at the trochlea were significantly different. CONCLUSIONS: Higher vBMD accompanied by thicker trabecular bone was observed at the capitellum. These bone microstructural changes would reflect the valgus stress generated by the pitching motion in the elbow joint.

Precision of Second-Generation High-Resolution Peripheral Quantitative Computed Tomography: Intra- and Intertester Reproducibilities and Factors Involved in the Reproducibility of Cortical Porosity.

High-resolution peripheral quantitative computed tomography (HR-pQCT) was upgraded to a second generation in 2014 with higher spatial resolution, faster scan time, and a different measurement algorithm. The purpose of this study was to investigate the precision of the second-generation HR-pQCT. The distal radius and tibia of 15 healthy men and women (age range of 20-74 yr, 8 men and 7 women) were scanned by second-generation HR-pQCT, and their geometry, bone mineral density (BMD), and the microstructure of trabecular and cortical bones were evaluated. Scans and measurements were performed by tester 1 at baseline and at 1 and 4 wk to evaluate intratester reproducibility, and by testers 2 and 3 one time each to evaluate intertester reproducibility. Reproducibility was evaluated by root mean square percent coefficient of variance (RMS%CV). Factors involved in the reproducibility of cortical porosity (Ct.Po) were also investigated. The ranges of RMS%CV were 0.2%-2.5% for geometry, 0.6%-1.7% for BMD, 0.7%-2.4% for trabecular bone, and 1.1%-1.3% for cortical thickness, showing excellent reproducibility. The range of RMS%CV for Ct.Po was 11.0%-13.3%, relatively higher than those for the other parameters. There was no apparent difference between intra- and intertester reproducibilities. There was no clear correlation between the percent coefficient of variance of Ct.Po and the subjects' background characteristics, motion artifact, and cortical bone structure. The reproducibility of the second-generation HR-pQCT was excellent in geometry, BMD, trabecular bone, and cortical thickness, with no apparent difference between intra- and intertester reproducibilities. Compared with the first-generation HR-pQCT, the reproducibility of trabecular bone was improved. The reproducibility of Ct.Po was insufficient and needed to be improved, and factors that influence its reproducibility were not clear.

Characterization of cartilage defects detected by MRI in Kellgren-Lawrence grade 0 or 1 knees.

INTRODUCTION: Osteoarthritis of the knee is generally evaluated by plain X-rays, which are incapable of detecting small cartilage damage. There are some patients who have small cartilage defects on MRI with no abnormal findings on plain X-rays. In this study, the prevalence and regional characteristics of cartilage defects detected by MRI were studied in cases with normal X-ray findings (Kellgren-Lawrence grade 0 and 1). Relationships between the cartilage defects and OA risk factors such as obesity and leg alignment were also investigated. METHODS: A total of 51 knees of Kellgren-Lawrence grade 0 or 1 without knee joint pain were included. Fat-suppressed spoiled-gradient recalled (SPGR) sagittal images were scanned by 3 T MRI, and the presence of cartilage damage was confirmed. Cartilage damage was visualized three-dimensionally, and its location and morphology were analyzed. On a full length standing radiograph of the lower extremities, leg alignment and other parameters were measured, and their associations with cartilage damage were analyzed. RESULTS: Cartilage defects were detected in 26% of women aged >50 years. Cartilage damage was located on the medial femoral condyle near the intercondylar notch, and was mostly elliptically shaped in the anteroposterior direction. Subjects with damaged cartilage were not obese and did not have abnormal leg alignment. CONCLUSION: It should be borne in mind that some elderly women may have damaged cartilage on the intercondylar notch side of the medial joint, even though plain X-rays appear normal, and this cannot be predicted by obesity or leg alignment.

Effects of daily teriparatide, weekly high-dose teriparatide, or bisphosphonate on cortical and trabecular bone of vertebra and proximal femur in postmenopausal women with fragility fracture: Sub-analysis by quantitative computed tomography from the TERABIT study.

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.

High risk of elevated metal concentrations with 9/10-mm stem trunnions and highly cross-linked polyethylene grafted with poly(2-methacryloyloxyethyl phosphorylcholine) in total hip arthroplasty.

BACKGROUND: The risks of metal release due to fretting and corrosion at the head-neck junction and consequent adverse local tissue reaction (ALTR) have concerns in metal-on-polyethylene (MoP) total hip arthroplasty (THA). Although trunnions have become thinner in diameter to increase the range of motion, it has remained unclear whether this change affects metal release and ALTR in vivo. This study aimed to investigate serum metal concentrations and the prevalence of ALTR in MoP THA with a 9/10-mm stem trunnion. PATIENTS AND METHODS: A consecutive series of 37 hips that underwent THA using MoP grafted with poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) with a 9/10-mm trunnion stem were retrospectively reviewed. Serum metal levels were assessed and compared with those in MoP THA with a 10/12-mm trunnion stem. ALTR was diagnosed with serum metal levels and cross-sectional images. The factors associated with serum metal levels were also assessed. RESULTS: The median serum cobalt and chromium levels were 1.5 µg/L and 1.0 µg/L in the 9/10-mm group and 0.2 µg/L and 0.4 µg/L in the 10/12-mm group, respectively. ALTR was found in 5 hips of 3 patients. Revision surgery was performed in 4 hips, and all stem trunnions and femoral heads showed severe corrosion. Postoperative walking ability was associated with serum metal levels. CONCLUSION: It was found that a 9/10-mm stem trunnion with MoP grafted with PMPC had high risks of metal release in primary THA. Careful follow-up and cross-sectional imaging are needed to detect ALTR for early revision.

Differences in the flexion and extension phases during kneeling investigated by kinematic and contact point analyses: a cross-sectional study.

BACKGROUND: Kneeling is necessary for certain religious and ceremonial occasions, crouching work, and gardening, which many people take part in worldwide. However, there have been few reports about kneeling activities. The purpose of this study was to clarify the kinematics of kneeling. METHODS: The subjects were 15 healthy young males. Kneeling activity was analysed within a knee flexion angle from 100° to maximum flexion (maxflex, mean ± SD = 161.3 ± 3.2°). The kinematic and contact point (CP) analyses were performed using a 2D/3D registration method, in which a 3D bone model created from computed tomography images was matched to knee lateral fluoroscopic images and analysed on a personal computer. RESULTS: In the kinematic analysis, the femur translated 37.5 mm posteriorly and rotated 19.8° externally relative to the tibia during the knee flexion phase. During the knee extension phase, the femur translated 36.4 mm anteriorly, which was almost the same amount as in the knee flexion phase. However, the femur rotated only 7.4° internally during the knee extension phase. In the CP analysis, the amount of anterior translation of the CP in the knee extension phase was greater in the medial CP and smaller in the lateral CP than that of posterior translation in the knee flexion phase. CONCLUSIONS: In kneeling, there was a difference in the rotational kinematics between the flexion phase and the extension phase. The kinematic difference between the flexion and extension phases may have some effect on the meniscus and articular cartilage.

Bone microstructure in healthy men measured by HR-pQCT: Age-related changes and their relationships with DXA parameters and biochemical markers.

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.

Randomized controlled trial of daily teriparatide, weekly high-dose teriparatide, or bisphosphonate in patients with postmenopausal osteoporosis: The TERABIT study.

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.

Differences in bone mineral density and morphometry measurements by fixed versus relative offset methods in high-resolution peripheral quantitative computed tomography.

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.

Effects of monthly intravenous ibandronate on bone mineral density and microstructure in patients with primary osteoporosis after teriparatide treatment: The MONUMENT study.

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.

Hoxa10 mediates positional memory to govern stem cell function in adult skeletal muscle.

Muscle stem cells (satellite cells) are distributed throughout the body and have heterogeneous properties among muscles. However, functional topographical genes in satellite cells of adult muscle remain unidentified. Here, we show that expression of Homeobox-A (Hox-A) cluster genes accompanied with DNA hypermethylation of the Hox-A locus was robustly maintained in both somite-derived muscles and their associated satellite cells in adult mice, which recapitulates their embryonic origin. Somite-derived satellite cells were clearly separated from cells derived from cranial mesoderm in Hoxa10 expression. Hoxa10 inactivation led to genomic instability and mitotic catastrophe in somite-derived satellite cells in mice and human. Satellite cell-specific Hoxa10 ablation in mice resulted in a decline in the regenerative ability of somite-derived muscles, which were unobserved in cranial mesoderm-derived muscles. Thus, our results show that Hox gene expression profiles instill the embryonic history in satellite cells as positional memory, potentially modulating region-specific pathophysiology in adult muscles.

A Modified Pre-plating Method for High-Yield and High-Purity Muscle Stem Cell Isolation From Human/Mouse Skeletal Muscle Tissues.

Primary culture of skeletal muscle stem cells (MuSCs) is indispensable to study the dynamics of muscle regeneration and homeostasis. Here we describe the modified pre-plating method for isolating MuSCs in culture with greatly improved purity, yield, and procedure time. The protocol is based on the distinct adhesion characteristics of MuSCs. We reduced the procedure time to 2.5 days to obtain highly purified MuSCs through a newly employed re-plating step, which repeats incubation and cell-suspension. The re-plating step efficiently traps remaining fibroblastic cells, but not MuSCs, on a collagen-coated dish. Additionally, we confirmed that MuSCs can be isolated from small amounts of human/mouse muscle tissues, enabling us to perform experiments with amount-limited specimens. Thus, our method can be performed with basic laboratory equipment suitable for most facilities and without sophisticated MuSC handling techniques.