The combination therapy with alfacalcidol and risedronate improves the mechanical property in lumbar spine by affecting the material properties in an ovariectomized rat model of osteoporosis
Open Access
- 15 June 2009
- journal article
- research article
- Published by Springer Science and Business Media LLC in BMC Musculoskeletal Disorders
- Vol. 10 (1), 66
- https://doi.org/10.1186/1471-2474-10-66
Abstract
We conducted the present study to investigate the therapeutic effects of a combination treatment of alfacalcidol (ALF) and risedronate (RIS) on the bone mechanical properties of bone and calcium (Ca) metabolism using an ovariectomized (OVX) rat model of osteoporosis. Female Wistar rats were OVX- or sham-operated at 40 weeks of age. Twelve weeks post-surgery, rats were randomized into seven groups: 1) sham + vehicle, 2) OVX + vehicle, 3) OVX + ALF 0.025 μg/kg/day, 4) OVX + ALF 0.05 μg, 5) OVX + RIS 0.3 mg, 6) OVX + RIS 3.0 mg, 7) OVX + ALF 0.025 μg + RIS 0.3 mg. Each drug was administered orally five times a week for 12 weeks. After treatment, we evaluated the mechanical properties of the lumbar vertebra and femoral midshaft. In the lumbar vertebra, structural and material analyses were performed using micro-computed tomography (micro-CT) and microbeam X-ray diffraction (micro-XRD), respectively. Biochemical markers in serum and urine were also determined. (1) With respect to improvement in the mechanical strength of the lumbar spine and the femoral midshaft, the combination treatment of ALF and RIS at their sub-therapeutic doses was more effective than each administered as a monotherapy; (2) In the suppression of bone resorption and the amelioration of microstructural parameters, the effects of ALF and RIS were considered to be independent and additive; (3) The improvement of material properties, such as microstructural parameters and the biological apatite (Bap) c-axis orientation, contributed to the reinforcement of spinal strength; and (4) The combination treatment of ALF and RIS normalized urinary Ca excretion, suggesting that this treatment ameliorated the changes in Ca metabolism. These results demonstrate that the combination treatment of ALF and RIS at their sub-therapeutic doses can improve the mechanical properties of the spine as well as the femur and ameliorate changes in Ca metabolism in an animal model of osteoporosis, suggesting that the combination treatment of ALF and RIS has a therapeutic advantage over each monotherapy for the treatment of osteoporosis.Keywords
This publication has 40 references indexed in Scilit:
- Alendronate treatment promotes bone formation with a less anisotropic microstructure during intramembranous ossification in ratsJournal of Bone and Mineral Metabolism, 2008
- Areal Distribution of Preferential Alignment of Biological Apatite (BAp) Crystallite on Cross-Section of Center of Femoral Diaphysis in Osteopetrotic (op/op) MouseMATERIALS TRANSACTIONS, 2007
- Bone Fragility and Collagen Cross-LinksJournal of Bone and Mineral Research, 2004
- Effect of Combined Risedronate and Hormone Replacement Therapies on Bone Mineral Density in Postmenopausal WomenJournal of Clinical Endocrinology & Metabolism, 2001
- Alfacalcidol Inhibits Bone Resorption and Stimulates Formation in an Ovariectomized Rat Model of Osteoporosis: Distinct Actions from EstrogenJournal of Bone and Mineral Research, 2000
- Direct Three-Dimensional Morphometric Analysis of Human Cancellous Bone: Microstructural Data from Spine, Femur, Iliac Crest, and CalcaneusJournal of Bone and Mineral Research, 1999
- Pharmacokinetics of AlendronateClinical Pharmacokinetics, 1999
- Intermittent cyclical etidronate treatment maintains the mass, structure and the mechanical property of bone in ovariectomized ratsJournal of Bone and Mineral Research, 1995
- Direct stereological estimation of three-dimensional connectivity in rat vertebrae: Effect of estrogen, etidronate and risedronate following ovariectomyBone, 1995
- The effect of aging and ovariectomy on the vertebral bone mass and biomechanical properties of mature ratsBone, 1993