Micro-CT imaging analysis for the effects of ibandronate and eldecalcitol on secondary osteoporosis and arthritis in adjuvant-induced arthritis rats.

We investigated the effects of ibandronate, a bisphosphonate; eldecalcitol, an active vitamin D3 analogue; and combination treatment with both agents on secondary osteoporosis and arthritis using rats with adjuvant-induced arthritis. Arthritis was induced in 8-week-old male Lewis rats. Rats were randomized into four treatment groups and an untreated normal control group: ibandronate, eldecalcitol, ibandronate + eldecalcitol, vehicle, and control. Paw thickness was measured to evaluate arthritis. Joint destruction was evaluated histomorphometrically by the ankle joint stained with Fast Green and safranin O. The femur and lumbar spine were scanned using dual-energy X-ray absorptiometry, and the distal femur was scanned using micro-computed tomography for bone mineral density (BMD) and trabecular microstructural evaluations. Ibandronate and/or eldecalcitol increased BMD in both the lumbar vertebrae and femur and improved several microstructural parameters (bone volume/total volume, structure model index, trabecular number, and trabecular separation of the distal femur). In addition, there was an additive effect of combination treatment compared with single treatments for most trabecular parameters, including BMD and bone volume. However, ibandronate and/or eldecalcitol did not inhibit arthritis and joint destruction. Combination treatment with ibandronate and eldecalcitol may be effective for secondary osteoporosis associated with arthritis.

Effects of eldecalcitol and ibandronate on secondary osteoporosis and muscle wasting in rats with adjuvant-induced arthritis.

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.

Combined treatment with minodronate and vitamin C increases bone mineral density and strength in vitamin C-deficient rats.

OBJECTIVES: Reduced bone quality caused by vitamin C deficiency in older persons may lead to incidental fragility fractures during bisphosphonate treatment, although bisphosphonate increases bone mineral density (BMD). This study aimed to evaluate the effects of minodronate and ascorbic acid (Aa) on BMD, bone quality, and bone strength in Aa-deficient osteogenic disorder Shionogi (ODS) rats. METHODS: Six-month-old ODS rats were divided into four groups (n = 20 per group): (1) Aa supplementation (Aa+); (2) Aa-deficient (Aa-); (3) Aa supplementation and minodronate administration (Aa+ + Mino); and (4) Aa-deficient and minodronate administration (Aa- + Mino). BMD, bone strength, bone histomorphometry, and bone quality determined using Fourier transform infrared spectroscopy imaging (FTIRI) were evaluated after 4 and 8 weeks. RESULTS: BMD was significantly higher in the Aa+ + Mino group than in the Aa- group (p < 0.05). Bone strength was significantly higher in the Aa+ and Aa+ + Mino groups than in the Aa- group (p < 0.05). Furthermore, bone strength was significantly higher in the Aa+ + Mino group than in the Aa- + Mino group (p < 0.05). Minodronate treatment irrespective of Aa supplementation significantly decreased bone resorption compared with the Aa+ and Aa- groups (p < 0.05). No significant differences in the parameters evaluated by FTIRI were observed between the groups. CONCLUSIONS: Aa supplementation improved bone strength in ODS rats. Combined treatment with minodronate and Aa, but not minodronate alone, improved bone strength and increased BMD. Aa is required for bone health because it is essential for osteoblast differentiation.

High prevalence of abdominal aortic aneurysm in patients with chronic low back pain.

Low back pain (LBP) is one of the most common symptoms in outpatient clinics, and abdominal aortic aneurysm (AAA) is one of the causes of LBP. In the present study, we examined the prevalence of chronic LBP in patients with aortic aneurysm. The study included 23 patients with AAA and 23 patients with thoracic aortic aneurysm (TAA); all of them visited a regional center hospital in Akita, Japan. A total of 207 hypertension patients were also enrolled as a control. Chronic LBP was defined in patients who visited the orthopedic outpatient clinic for the LBP treatment for more than three months. The prevalence of chronic LBP in the AAA group (52.2%) was significantly higher than that in the TAA (17.4%, P < 0.05) or hypertension patients (11.6%, P < 0.01). The rate of a trigger point (TP) injection was significantly higher in the AAA group or the TAA group than that in hypertension patients (P < 0.01, P < 0.05), but there was no significant difference between the AAA and TAA groups. The TP injection represents an injection of local anesthesia to the low back muscles. We also evaluated the involvement of various factors in LBP caused by AAA, such as age, gender, blood pressure, the existence of dissection, and the maximum diameter of AAA, but none of them showed significant relationship to LBP. The prevalence of LBP is high in AAA patients, and doctors who treat chronic LBP should be aware of AAA as a potential cause of LBP.