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.

Objectives: Progressive and generalized loss of skeletal muscle mass (SMM) and strength are characteristics of sarcopenia. However, the impact of appendicular and trunk SMM and back extensor strength (BES) on spinal sagittal alignment remains unclear. Herein, we investigate the relationship between these factors and spinal sagittal alignment. Methods: In total, 202 women without vertebral fractures (median age, 66.9 years; interquartile range, 61.4–71.9 years) were analyzed at an orthopedic outpatient clinic. Pelvic incidence (PI), lumbar lordosis (LL), sagittal vertical axis (SVA), and pelvic tilt (PT) were measured on whole spine radiographs. Body mass index (BMI), appendicular and trunk relative SMM index, and BES were also evaluated. These measurements were compared between spinal sagittal alignment groups using the Mann–Whitney U test. Finally, the factors contributing to abnormal alignment were analyzed using multiple logistic regression analysis. Results: BES was significantly lower in all abnormal sagittal alignment groups, as defined by PI-LL (≥ 10°), SVA (≥4 cm), and PT (≥20°) (all P < 0.001). On multivariate analysis, BES was a contributing factor for abnormal PI-LL (P < 0.001), SVA (P = 0.001), and PT (P < 0.001). Conversely, a decrease in appendicular and trunk relative SMM index did not statistically affect abnormal spinal sagittal alignment. Conclusions BES was associated with changes in spinal sagittal alignment; however, SMM, which is often used for diagnosing sarcopenia, did not affect spinal sagittal alignment.

Objectives: Progressive and generalized loss of skeletal muscle mass (SMM) and strength are characteristics of sarcopenia. However, the impact of appendicular and trunk SMM and back extensor strength (BES) on spinal sagittal alignment remains unclear. Herein, we investigate the relationship between these factors and spinal sagittal alignment. Methods: In total, 202 women without vertebral fractures (median age, 66.9 years; interquartile range, 61.4–71.9 years) were analyzed at an orthopedic outpatient clinic. Pelvic incidence (PI), lumbar lordosis (LL), sagittal vertical axis (SVA), and pelvic tilt (PT) were measured on whole spine radiographs. Body mass index (BMI), appendicular and trunk relative SMM index, and BES were also evaluated. These measurements were compared between spinal sagittal alignment groups using the Mann–Whitney U test. Finally, the factors contributing to abnormal alignment were analyzed using multiple logistic regression analysis. Results: BES was significantly lower in all abnormal sagittal alignment groups, as defined by PI-LL (≥ 10°), SVA (≥4 cm), and PT (≥20°) (all P < 0.001). On multivariate analysis, BES was a contributing factor for abnormal PI-LL (P < 0.001), SVA (P = 0.001), and PT (P < 0.001). Conversely, a decrease in appendicular and trunk relative SMM index did not statistically affect abnormal spinal sagittal alignment. Conclusions BES was associated with changes in spinal sagittal alignment; however, SMM, which is often used for diagnosing sarcopenia, did not affect spinal sagittal alignment.

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.

STUDY DESIGN: Retrospective and comparative study. PURPOSE: We assessed surgical treatment outcomes in patients with thoracic myelopathy due to ossification of the ligamentum flavum (OLF), and OLF combined with ossification of the posterior longitudinal ligament (OPLL) or vertebral fracture (VF) at the same level. OVERVIEW OF LITERATURE: OLF and OPLL cause severe thoracic myelopathy. Osteoporotic VF commonly occurs at the thoracolumbar junction. There have been no investigations of thoracic myelopathy due to OLF and VF. METHODS: Forty patients were divided among three groups: the OLF group (n=23): myelopathy due to OLF, the OLF+OPLL group (n=12): myelopathy due to OLF and OPLL, and the OLF+VF group (n=5): myelopathy due to OLF and VF. We recorded OLF, OPLL, and VF sites and operative procedures. Each patient’s neurological status, according to the Japanese Orthopaedic Association (JOA) score, and walking ability were evaluated pre- and postoperatively. RESULTS: Patients in the OLF+OPLL group were significantly younger than those in the other two groups. The preoperative JOA score was significantly lower in the OLF+VF than OLF group. The final JOA score was significantly lower in the OLF+VF than OLF and OLF+OPLL groups. The JOA score recovery rate was significantly lower in the OLF+VF than OLF group. Final walking ability was significantly worse in the OLF+OPLL and OLF+VF groups than in the OLF group and significantly worse in the OLF+VF than OLF+OPLL group. CONCLUSIONS: Thoracic myelopathy due to OLF+VF occurs primarily in older females, who also exhibit worse preoperative and postoperative neurological status, and worse walking ability, than patients with thoracic myelopathy due to OLF or OLF+OPLL.

OBJECTIVES: The purpose of this study is to evaluate the effects of teriparatide (TPTD) on bone mineral density (BMD), bone strength, and bone quality in Akita mouse models of diabetes mellitus. METHODS: Twelve-week-old female Akita mice and control mice (C57/BL/6NCrSlc) were divided into 4 groups: control mice treated with vehicle (n = 7) or TPTD (n = 6); and Akita mice treated with vehicle (n = 6) or TPTD (n = 7). TPTD or vehicle was administered subcutaneously 3 times a week for 8 weeks. Blood glucose, serum sclerostin, total tibial BMD, femoral shaft bone strength, and bone quality using Fourier-transform infrared spectroscopy imaging were evaluated. RESULTS: No significant differences in serum sclerostin levels were evident among these groups after 8 weeks of treatment. TPTD significantly increased BMD in control mice (+12.7%, P = 0.02) and Akita mice (+29.2%, P = 0.001) compared with vehicle. Maximum load and stiffness were significantly higher in Akita mice treated with TPTD than in Akita mice treated with vehicle (+56.6%, P = 0.03 and + 90.5%, P = 0.02, respectively). On Fourier-transform infrared spectroscopy imaging, the mineral/matrix ratio was significantly lower in Akita mice treated with vehicle than in control mice (−12.2%, P = 0.02), and TPTD treatment significantly increased the mineral/matrix ratio (P = 0.003). CONCLUSIONS TPTD thus improved BMD and bone strength in both control mice and Akita mice, with improvements in the mineral/matrix ratio among Akita mice.

OBJECTIVES: Rheumatoid arthritis (RA) is characterized by chronic inflammation of the synovium, progressive erosion of the articular cartilage, and joint destruction. RA also causes secondary osteoporosis and muscle wasting. We investigated the effects of ibandronate (IBN), a bisphosphonate; eldecalcitol (ELD), an active vitamin D3 derivative; and combination treatment with both agents on secondary osteoporosis and muscle wasting using adjuvant-induced arthritis rats. METHODS: Arthritis was induced in 8-week-old male Lewis rats. Rats were randomized into 4 treatment groups and an untreated normal control group: IBN (subcutaneously, once every 2 weeks, 10 µg/kg), ELD (orally, once daily, 30 ng/kg/day), IBN + ELD, vehicle, and control. Paw thickness measurements were performed for evaluation of arthritis. The femur was scanned using dual-energy X-ray absorptiometry. Cross-sectional areas of left tibialis and anterior muscle fibers and the expression of MuRF1, atrogin-1, MyoD, and myogenin in the gastrocnemius muscle were measured to evaluate muscle wasting. RESULTS: IBN and/or ELD increased bone mineral density (BMD) in the femur. In addition, there was an additive effect of combination treatment compared with single treatments for BMD. However, IBN and/or ELD did not inhibit muscle wasting in adjuvant-induced arthritis rats. CONCLUSIONS: Combination treatment with IBN and ELD may be effective for secondary osteoporosis associated with RA. Other treatments are necessary for muscle wasting associated with RA. Studies in humans are needed to confirm these findings.
Absorptiometry, Photon ; Animals ; Arthritis ; Arthritis, Rheumatoid ; Bone Density ; Cartilage, Articular ; Cholecalciferol ; Femur ; Humans ; Inflammation ; Joints ; Male ; Muscle, Skeletal ; Myogenin ; Osteoporosis ; Rats ; Synovial Membrane ; Vitamin D

STUDY DESIGN: A retrospective comparative study. PURPOSE: To compare perioperative medical complications after posterior approach spinal instrumentation surgery for osteoporotic vertebral collapse (OVC) between patients with primary osteoporosis and those with secondary osteoporosis. OVERVIEW OF LITERATURE: With increased aging of society, the demand for instrumentation surgery for an osteoporotic spine has been increasing. However, no studies have compared the rates or severities of perioperative complications after spinal instrumentation surgery between patients with primary osteoporosis and those with secondary osteoporosis. METHODS: Ninety-one patients with OVC aged ≥50 years (23 males and 68 females) who underwent posterior approach vertebral replacement with cages or posterior spinal fusion combined with vertebroplasty were divided into primary (n=56) and secondary (n=35) osteoporosis groups. Bone mineral density (BMD), osteoporosis treatment prior to OVC, operative invasiveness, and perioperative medical complications were compared. RESULTS: Diabetes mellitus (51.4%) was the most common cause of secondary osteoporosis, followed by glucocorticoid use (22.9%). No significant differences were seen in terms of age, gender, BMD, osteoporosis treatment, or operative invasiveness, including the number of levels fused, estimated blood loss, and number of patients requiring transfusion. No significant difference in the incidence of perioperative complications were observed between the primary and secondary osteoporosis groups (16.1% vs. 22.9%). However, surgical site infection (SSI) was significantly more frequently seen in the secondary osteoporosis group (11.4%) than in the primary osteoporosis group (1.8%; p<0.05). One patient in the secondary osteoporosis group developed methicillin-resistant Staphylococcus aureus infection that ultimately required instrument removal. CONCLUSIONS: The overall incidence of perioperative medical complications after posterior approach spinal instrumentation surgery for OVC was comparable between the primary and secondary osteoporosis groups under conditions of similar background characteristics and operative invasiveness. However, SSI (particularly more severe cases) occurred more frequently in patients with secondary osteoporosis.
Aging ; Bone Density ; Diabetes Mellitus ; Humans ; Incidence ; Male ; Methicillin-Resistant Staphylococcus aureus ; Osteoporosis* ; Retrospective Studies ; Spinal Fusion ; Spine ; Surgical Wound Infection ; Vertebroplasty

OBJECTIVES: Glucocorticoid (GC) treatment inhibits activation of runt-related transcription factor 2 (Runx2), which is essential for osteoblast differentiation from stem cells. As a result, GC treatment results in bone loss, GC-induced osteoporosis (GIO), elevated fracture risk, and delayed bone healing. Bisphosphonates such as alendronate (ALN) are recommended for treating or preventing GIO, and lowintensity pulsed ultrasound (LIPUS) facilitates fracture healing and maturation of regenerated bone. Combined therapy with ALN and LIPUS may stimulate cancellous bone healing in GIO rats. Here, we examined the effect of ALN and LIPUS on cancellous bone osteotomy repair in the proximal tibia of GIO rats. METHODS: Prednisolone (10 mg/kg body weight/day) was administered for 4 weeks to induce GIO in 6-month-old female Sprague-Dawley rats. Tibial osteotomy was then performed and daily subcutaneous injection of ALN (1-µg/kg body weight) was subsequently administered alone or in combination with LIPUS (20 min/day) for 2 or 4 weeks. RESULTS: ALN significantly increased bone mineral density (BMD) at 2 and 4 weeks, and ALN + LIPUS significantly increased BMD at 4 weeks. Bone union rates were significantly increased after 2 and 4 weeks ALN and ALN + LIPUS treatment. Lastly, ALN and ALN + LIPUS significantly increased the proportion of Runx2 positive cells at 4 weeks. CONCLUSIONS: ALN monotherapy and combined ALN and LUPUS treatment augmented BMD and stimulated cancellous bone repair with increased Runx2 expression at the osteotomy site in GIO rats. However, the combined treatment had no additional effect on cancellous bone healing compared to ALN monotherapy.
Alendronate* ; Animals ; Bone Density ; Bone Diseases, Metabolic* ; Diphosphonates ; Female ; Fracture Healing ; Humans ; Infant ; Injections, Subcutaneous ; Osteoblasts ; Osteoporosis ; Osteotomy* ; Prednisolone ; Rats* ; Rats, Sprague-Dawley ; Stem Cells ; Tibia* ; Transcription Factors ; Ultrasonic Waves*