Effects of teriparatide and low-intensity aerobic exercise on osteopenia in type 2 diabetes mellitus rats.

INTRODUCTION: In patients with type 2 diabetes mellitus (T2DM), bone fragility increases fracture risk. Teriparatide (TPTD) improves bone strength, and exercise therapy suppresses blood glucose levels in T2DM. In this study, the combined effects of TPTD and exercise therapy on trabecular and cortical bone were examined in advanced T2DM model rats. MATERIALS AND METHODS: Thirty-week-old Otsuka Long-Evans Tokushima Fatty rats were divided into four groups (n = 9-10 in each group at two time points): Cont group (vehicle-treated control), TPTD group (TPTD 30 µg/kg injected subcutaneously, 3 times/week), Exe group (treadmill exercise, 10 m/min, 60 min/day, 5 times/week), and Comb group (TPTD-treated and treadmill exercise combined). Five and 10 weeks after treatment, bone mineral density (BMD), bone strength, and bone micro-architecture were measured. RESULTS: TPTD and combined treatment significantly increased BMDs of the lumbar spine and femur compared to the Cont group (p < 0.05 to p < 0.01). In the three-point bending test of the femur, only combined treatment increased the maximum load at 5 weeks compared with the Cont and Exe groups (p < 0.01). In the compression test of the distal femoral metaphysis, both TPTD and combined treatment increased the trabecular bone strength compared with the Cont and Exe groups (p < 0.05 to p < 0.01). Although TPTD and combined treatment improved the micro-architecture of trabecular bone (p < 0.05 to p < 0.01), only combined treatment improved the micro-structures of cortical bone from 5 weeks of treatment (p < 0.05 to p < 0.01). CONCLUSION: The combination of TPTD and treadmill exercise increased BMD and trabecular and cortical bone strength of the femur with improved micro-architecture in T2DM model rats.

Teriparatide and exercise improve bone, skeletal muscle, and fat parameters in ovariectomized and tail-suspended rats.

INTRODUCTION: Although teriparatide (TPTD) and exercise may improve osteoporosis, muscle atrophy, and fat metabolism during ageing, the effects of treatment with a combination of TPTD and exercise on these factors remain unclear. Therefore, this study examined the effects of TPTD and exercise on bone, skeletal muscle, and fat in ovariectomized and tail-suspended rats. MATERIALS AND METHODS: Seven-month-old female Wistar rats were ovariectomized and subjected to tail suspension. The rats were then randomized into one of the following four groups (n = 20/group) after 4 weeks: control group, treated with TPTD vehicle and no exercise; TPTD group (30 µg/kg TPTD, 3 days/week); Exercise group (treadmill at 12 m/min, 60 min/day, 5 days/week); and Combined group treated with TPTD and treadmill exercise. After 1 and 8 weeks of treatment, bone, skeletal muscle, and fat tissue parameters were evaluated. RESULTS: TPTD improved bone mineral density (BMD), bone structure, bone strength at the femoral metaphysis, and the percentage of skeletal muscle mass, and decreased the percentage of fat mass and the adipose volume in the bone marrow. Treadmill exercise increased BMD, bone strength of cancellous bone, and the percentage of skeletal muscle mass, and decreased the percentage of fat mass as seen on dual-energy X-ray absorptiometry. Furthermore, combined treatment significantly affected BMD, bone structure, and bone strength of cortical bone at the femoral diaphysis. CONCLUSION: TPTD or treadmill exercise improved bone, skeletal muscle, and fat mass. Combination therapy with TPTD and exercise had synergistic effects on BMD, structure, and bone strength in ovariectomized, tail-suspended rats.

Teriparatide and etelcalcetide improve bone, fibrosis, and fat parameters in chronic kidney disease model rats.

Objectives: Chronic kidney disease (CKD) complicated by secondary hyperparathyroidism (SHPT) is associated with an increased risk of fragility fractures. Etelcalcetide (EC) is a treatment for SHPT that reduces serum parathyroid hormone (PTH) levels. However, the effects of combined treatment with osteoporosis drugs such as teriparatide (TPTD) remain unclear. This study investigates the combined effects of EC and TPTD on bone in CKD model rats. Methods: The CKD model was established in 8-week-old male Wistar rats by feeding them a 0.75% adenine diet for 4 weeks. At 20 weeks of age, the rats were divided into 4 groups (N = 9-10 in each group): CKD group (vehicle administration), TPTD group (30 µg/kg, 3 times/week), EC group (0.6 mg/kg, daily), and Comb group (TPTD and EC combined). EC was injected for 12 weeks starting at 20 weeks of age, and TPTD was injected for 8 weeks starting at 24 weeks of age. After treatment, the followings were evaluated: bone mineral density, bone strength, biochemical tests, bone and fat histomorphometry, and micro-computed tomography. Results: In CKD model rats, the combination of EC and TPTD was more effective in increasing cortical bone thickness and bone strength and inhibiting porosity. In addition, the combined treatment decreased bone marrow adiposity and fibrosis, and it increased bone mass and improved bone microstructure in trabecular bone. Conclusions: With the observed benefits such as improved bone mass, bone strength, structural properties, and bone marrow adiposity, combination therapy may be a potential way to improve bone fragility in CKD.

Intravascular Administration of Acridine Orange and Zoledronate in a Bone Metastasis Model of Breast Cancer.

BACKGROUND/AIM: This study evaluated the effect of haematogenous administration of acridine orange (AO) alone and in combination with zoledronate (ZOL) on bone metastases. MATERIALS AND METHODS: E0771 cells (1.0×105 cells/10 µl) were injected directly into the right femur of female mice. The mice were divided into five groups according to treatment (drugs and irradiation) and were reared and sacrificed after 6 weeks. Micro-computed tomography (µCT) was performed to calculate the destruction rate of the femur bone. We measured tumour weight and volume at sacrifice and performed terminal deoxynucleotidyl transferase dUTP Nick-End Labelling staining of tumours. RESULTS: At 4 weeks, the bone destruction rate was lower in the AO+ZOL group than in the radiation group. At 6 weeks, the AO+ZOL group had a lower bone destruction rate than the control and radiation groups; the ZOL group had a lower rate than the radiation group. The AO and AO+ZOL groups had suppressed tumour weight and volume compared to the control and radiation groups. The number of extraosseous apoptotic cells was higher in the AO+ZOL group than in all other groups except the AO group. CONCLUSION: In a model of local bone metastasis of breast cancer, haematogenous administration of AO reduced tumour size and more so when combined with ZOL.

Analysis of bone in adenine-induced chronic kidney disease model rats.

OBJECTIVES: The purpose of this study is to investigate the stage of chronic kidney disease (CKD) in adenine-induced CKD model rats by serum analyses, and to examine bone mineral density (BMD), bone strength, and microstructure of trabecular and cortical bone in these rats. METHODS: Eight-week-old, male Wistar rats (n = 42) were divided into 2 groups: those fed a 0.75% adenine diet for 4 weeks until 12 weeks of age to generate CKD model rats (CKD group); and sham rats. The CKD and sham groups were sacrificed at 12, 16, and 20 weeks of age (n = 7 in each group and at 12, 16, and 20 weeks), and various parameters were evaluated, including body weight, renal wet weight, muscle wet weight, renal histology, biochemical tests, BMD, biomechanical testing, and micro-computed tomography (CT). The parameters were compared between the 2 groups at the various time points. RESULTS: In the CKD model rats, at 20 weeks of age, serum creatinine, phosphorus, and intact-PTH levels were elevated, and serum calcium levels were normal, indicating that the CKD was stage IV and associated with secondary hyperparathyroidism. Decreased BMDs of the whole body and the femur were observed as bone changes, and micro-CT analysis showed deterioration of bone microstructure of the cortical bone that resulted in decreased bone strength in the cortical and trabecular bone. CONCLUSIONS: These CKD model rats showed stage IV CKD and appear appropriate for evaluating the effects of several treatments for CKD-related osteoporosis and mineral bone disorder.

Surgical treatment of complete fifth lumbar osteoporotic vertebral burst fracture: A retrospective case report of three patients.

BACKGROUND: Due to its rarity, surgical treatments for a complete fifth lumbar osteoporotic vertebral burst fracture (L5 OVBF) have yet to be well documented as compared to that for osteoporotic vertebral fractures of the thoracolumbar spine. The current case report discusses details of the surgical outcomes following posterior decompression and fusion for a complete L5 OVBF. CASE DESCRIPTION: Three women, ranging in age from 69 years to 82 years, were surgically treated for a complete L5 OVBF. Two of these patients were being treated for rheumatoid arthritis. Surgery was performed using the L5 shortening osteotomy or vertebroplasty, with one- or two-level posterior lumbar interbody fusion, and posterior spinal fixation for the L2 or L3 to the pelvis. Although the spinal alignment parameters, which included lumbar lordosis (LL), pelvic incidence-lumbar lordosis, T1 pelvic angle, and sagittal vertical axis, were better as compared to that observed before the surgery, these worsened at the final follow-up due to clinical fractures that occurred at the adjacent vertebral body and proximal junctional kyphosis. Compared to preoperative Japanese Orthopaedic Association (JOA) scores, postoperative JOA scores were improved and maintained at the final follow-up. CONCLUSION: Posterior surgery of a complete L5 OVBF led to improvement of both the JOA score and spinal alignment after the surgery. Despite a worsening of the spinal alignment parameters, the JOA score was maintained at the final follow-up.