The effects of abaloparatide on hip geometry and biomechanical properties in Japanese osteoporotic patients assessed using DXA-based hip structural analysis: results of the Japanese phase 3 ACTIVE-J trial.

Daily subcutaneous injection of 80 µg abaloparatide increased bone mineral density in Japanese patients with osteoporosis at high fracture risk in the ACTIVE-J trial. Dual-energy X-ray absorptiometry-based hip structural analysis from ACTIVE-J data showed improved hip geometry and biomechanical properties with abaloparatide compared with placebo. PURPOSE: Abaloparatide (ABL) increased bone mineral density (BMD) in Japanese patients with osteoporosis at high fracture risk in the ACTIVE-J trial. To evaluate the effect of ABL on hip geometry and biomechanical properties, hip structural analysis (HSA) was performed using ACTIVE-J trial data. METHODS: Hip dual-energy X-ray absorptiometry scans from postmenopausal women and men (ABL, n = 128; placebo, n = 65) at baseline and up to week 78 were analyzed to extract bone geometric parameters at the narrow neck (NN), intertrochanteric region (IT), and proximal femoral shaft (FS). Computed tomography (CT)-based BMD and HSA indices were compared between baseline and week 78. RESULTS: ABL treatment showed increased mean percent change from baseline to week 78 in cortical thickness at the NN (5.3%), IT (5.3%), and FS (2.9%); cross-sectional area at the NN (5.0%), IT (5.0%), and FS (2.6%); cross-sectional moment of inertia at the NN (7.6%), IT (5.1%), and FS (2.5%); section modulus at the NN (7.4%), IT (5.4%), and FS (2.4%); and decreased mean percent change in buckling ratio (BR) at the IT (- 5.0%). ABL treatment showed increased mean percent change in total volumetric BMD (vBMD; 2.7%) and trabecular vBMD (3.2%) at the total hip and decreased mean percent change in BR at femoral neck (- 4.1%) at week 78 vs baseline. All the changes noted here were significant vs placebo (P < 0.050 using t-test). CONCLUSION: A 78-week treatment with ABL showed improvement in HSA parameters associated with hip geometry and biomechanical properties vs placebo. TRIAL REGISTRATION: JAPIC CTI-173575.

Differential effects of jump versus running exercise on trabecular bone architecture and strength in rats.

PURPOSE: This study compared differences in trabecular bone architecture and strength caused by jump and running exercises in rats. METHODS: Ten-week-old male Wistar rats (n=45) were randomly assigned to three body weight-matched groups: a sedentary control group (CON, n=15); a treadmill running group (RUN, n=15); and a jump exercise group (JUM, n=15). Treadmill running was performed at 25 m/min without inclination, 1 h/day, 5 days/week for 8 weeks. The jump exercise protocol comprised 10 jumps/day, 5 days/week for 8 weeks, with a jump height of 40 cm. We used microcomputed tomography to assess microarchitecture, mineralization density, and fracture load as predicted by finite element analysis (FEA) at the distal femoral metaphysis. RESULTS: Both jump and running exercises produced significantly higher trabecular bone mass, thickness, number, and fracture load compared to the sedentary control group. The jump and running exercises, however, showed different results in terms of the structural characteristics of trabecular bone. Jump exercises enhanced trabecular bone mass by thickening the trabeculae, while running exercises did so by increasing the trabecular number. FEA-estimated fracture load did not differ significantly between the exercise groups. CONCLUSION: This study elucidated the differential effects of jump and running exercise on trabecular bone architecture in rats. The different structural changes in the trabecular bone, however, had no significant impact on trabecular bone strength.

Radiculopathy Contralateral to the Side of Disc Herniation -Microendoscopic Observation.

INTRODUCTION: There are patients with lumbar disc herniation (LDH) having contralateral sciatic symptoms although the mechanisms of this clinical feature are still not well understood. The purpose of this study was to investigate these mechanisms by microendoscopic findings. METHODS: Patients were performed microendoscopic surgery using over-the-top approach (ME-OTT), with laminoplasty, extirpation of herniation, and observation of the contralateral nerve root. The over-the-top approach was applied through the same incision from the herniation side. Clinical results were assessed according to the clinical scoring system established by the Japanese Orthopedic Association (JOA) score. RESULTS: This study consisted of five patients, with the average age of 55.6 years old. The mean preoperative JOA score was 13 points. Three cases were Grade II and two were Grade III degrees of disc herniation. Levels of herniation were one at L3-4 and four at L4-5. Remission of sciatic symptoms was obtained in all cases after surgery. The average and percent improvements (%IP) of JOA scores at 2 months after surgery were 27.8 points and 92%, respectively. By the approach from the herniation side using ME-OTT, image around the contralateral nerve root was obtained without radical intervention. By ME-OTT, redness of the nerve root and fibrosis around the symptomatic nerve root were identified, whereas inflammatory changes were not apparent on the ipsilateral nerve root. CONCLUSIONS: Operative treatment of LDH with contralateral symptoms by ME-OTT was a useful procedure for decompression and observation of the affected nerve root. Asymptomatic disc herniation, "silent disc herniation," was considered at the herniation side since there were less inflammatory changes around the ipsilateral nerve root. In contrast, compression of dura toward the opposite side by disc herniation could have led to mechanical stress against the contralateral nerve root and triggered inflammation at lateral recess, resulting in radicular pain.

Effect of swimming exercise on three-dimensional trabecular bone microarchitecture in ovariectomized rats.

Swimming is generally considered ineffective for increasing bone mass in humans, at least compared with weight-bearing sports. However, swimming exercise has sometimes been shown to have a strong positive effect on bone mass in small animals. This study investigated the effects of swimming on bone mass, strength, and microarchitecture in ovariectomized (OVX) rats. OVX or sham operations were performed on 18-wk-old female Fisher 344 rats. Rats were randomly divided into four groups: sham sedentary (Sham-CON), sham swimming exercised (Sham-SWI), OVX sedentary (OVX-CON), and OVX swimming exercised (OVX-SWI). Rats in exercise groups performed swimming in a water bath for 60 min/day, 5 days/wk, for 12 wk. Bone mineral density (BMD) in right femurs was analyzed using dual-energy X-ray absorptiometry. Three-dimensional trabecular architecture at the distal femoral metaphysis was analyzed using microcomputed tomography (µCT). Geometrical properties of diaphyseal cortical bone were evaluated in the midfemoral region using µCT. The biomechanical properties of femurs were analyzed using three-point bending. Femoral BMD was significantly decreased following ovariectomy. This change was suppressed by swimming. Trabecular bone thickness, number, and connectivity were decreased by ovariectomy, whereas structure model index (i.e., ratio of rod-like to plate-like trabeculae) increased. These changes were also suppressed by swimming exercise. Femurs displayed greater cortical width and maximum load in SWI groups than in CON groups. Together, these results demonstrate that swimming exercise drastically alleviated both OVX-induced decreases in bone mass and mechanical strength and the deterioration of trabecular microarchitecture in rat models of osteoporosis.

Effects of different types of jump impact on trabecular bone mass and microarchitecture in growing rats.

Substantial evidence from animal studies indicates that jumping increases bone mass and strength. However, most studies have focused on the take-off, rather than the landing phase of jumps. Thus, we compared the effects of landing and upward jump impact on trabecular bone mass and microarchitecture. Male Wistar rats aged 10 weeks were randomly assigned to the following groups: sedentary control (CON), 40-cm upward jumps (40UJ); 40-cm drop jumps (40DJ); and 60-cm drop jumps (60DJ) (n = 10 each). The upward jump protocol comprised 10 upward jumps/day, 5 days/week for 8 weeks to a height of 40 cm. The drop jump protocol comprised dropping rats from a height of 40 or 60 cm at the same frequency and time period as the 40UJ group. Trabecular bone mass, architecture, and mineralization at the distal femoral metaphysis were evaluated using microcomputed tomography. Ground reaction force (GRF) was measured using a force platform. Bone mass was significantly higher in the 40UJ group compared with the DJ groups (+49.1% and +28.3%, respectively), although peak GRF (-57.8% and -122.7%, respectively) and unit time force (-21.6% and -36.2%, respectively) were significantly lower in the 40UJ group. These results showed that trabecular bone mass in growing rats is increased more effectively by the take-off than by the landing phases of jumps and suggest that mechanical stress accompanied by muscle contraction would be more important than GRF as an osteogenic stimulus. However, the relevance of these findings to human bone physiology is unclear and requires further study.

Hip structural analysis: a comparison of DXA with CT in postmenopausal Japanese women.

Geometry of the proximal femur is one determinant of fracture risk, and can be analyzed by a simple method using dual-energy X-ray absorptiometry (DXA). The aim of the present study was to investigate the accuracy of hip structural analysis (HSA) using clinical data in postmenopausal Japanese women. A total of 184 postmenopausal women aged 51-88 years (mean, 70.5 ± 8.7 years) who underwent artificial joint replacement surgery for osteoarthrosis of the hip or knee joint were included. Computed tomography (CT) data from preoperative assessment were utilized for analysis of proximal femoral geometry (CT-HSA) using QCTPro Software (Mindways Software Inc., Austin, TX) and compared with HSA results based on DXA (DXA-HSA). The results of femoral geometry were further compared with a CT-based finite-element method (CT/FEM). There was moderate to high correlation between DXA-HSA and CT-HSA (r=0.60-0.90, p<0.001), except for the buckling ratio in the intertrochanteric region. Moreover, the correlation of HSA with CT/FEM was similar between DXA-HSA and CT-HSA. The present results suggest that the geometry of proximal femoral cross sections can be reasonably well characterized using DXA.

[Advances in bone densitometry equipment].

Techniques in bone densitometry have made remarkable progress in the past quarter-century and are now widely used in the daily practice of osteoporosis. Since the skeletal site and the method of measurement differ among the type of equipments, several types are adopted to suit the situation of each medical institute. Central DXA is used to provide a thorough examination of osteoporosis in large hospitals, whereas in general clinics the radial DXA or radiographic photodensitometry of metacarpus is mainly used. Quantitative ultrasound of calcaneus is mostly used for screening osteoporosis. DXA is also going to be applied to vertebral fracture assessment, hip structural analysis and micro-architectural analysis of vertebral trabecular bone.

Jump exercise during hindlimb unloading protect against the deterioration of trabecular bone microarchitecture in growing young rats.

Three-dimensional femoral trabecular architecture was investigated in tail-suspended young growing rats and the effects of jump exercise during the period of tail-suspension were also examined. Eight-week-old male Wistar rats (n = 24) were randomly assigned to three body weight-matched groups: a tail suspended group (SUS, n = 8); a sedentary control group (CON, n = 8) and rats primed with jump exercise during the period of tail suspension (JUM, n = 8). The jump exercise protocol consisted of 30 jumps/day, five days/week with a 40 cm jump height. After 3 weeks of jump exercise, bone mineral density (BMD) of the entire right femur was measured using dual energy X-ray absorptiometry. Three-dimensional trabecular bone architecture at the distal femoral metaphysis was evaluated using microcomputed tomography (micro-CT). Tail suspension caused a decrease in femoral BMD (-5%, p < 0.001) and trabecular bone architectural deterioration. Deterioration in the trabecular network during hindlimb unloading was mostly attributed to the reduction of trabecular number (-32%, p < 0.001) in the distal femoral metaphysis. Jump exercise during the tail suspension period increased trabecular thickness (14%, p < 0.001) and the reduction of trabecular number was suppressed. The present data indicate that jump exercise applied during hindlimb unloading could be able to inhibit bone loss and trabecular bone architectural deterioration caused by tail suspension.

Differential effects of jump versus running exercise on trabecular architecture during remobilization after suspension-induced osteopenia in growing rats.

High-impact exercise is considered to be very beneficial for bones. We investigated the ability of jump exercise to restore bone mass and structure after the deterioration induced by tail suspension in growing rats and made comparisons with treadmill running exercise. Five-week-old male Wistar rats (n = 28) were randomly assigned to four body weight-matched groups: a spontaneous recovery group after tail suspension (n = 7), a jump exercise group after tail suspension (n = 7), a treadmill running group after tail suspension (n = 7), and age-matched controls without tail suspension or exercise (n = 7). Treadmill running was performed at 25 m/min, 1 h/day, 5 days/wk. The jump exercise protocol consisted of 10 jumps/day, 5 days/wk, with a jump height of 40 cm. Bone mineral density (BMD) of the total right femur was measured by dual-energy X-ray absorptiometry. Three-dimensional trabecular bone architecture at the distal femoral metaphysis was evaluated using microcomputed tomography. After 5 wk of free remobilization, right femoral BMD, right hindlimb muscle weight, and body weight returned to age-matched control levels, but trabeculae remained thinner and less connected. Although both jump and running exercises during the remobilization period increased trabecular bone mass, jump exercise increased trabecular thickness, whereas running exercise increased trabecular number. These results indicate that restoration of trabecular bone architecture induced by jump exercise during remobilization is predominantly attributable to increased trabecular thickness, whereas running adds trabecular bone mass through increasing trabecular number, and suggest that jumping and running exercises have different mechanisms of action on structural characteristics of trabecular bone.