title: Calcium supplementation does not reproduce the pharmacological efficacy of alfacalcidol for the treatment of osteoporosis in rats.
abstract: The purpose of this study was to assess whether a nutritional supply of calcium (Ca) could be substituted for alfacalcidol (ALF) administration in preventing bone loss due to estrogen deficiency. Female Wistar-Imamichi rats (8 months old) were ovariectomized (OVX) or sham-operated. OVX rats received ALF administration (0.025, 0.5, or 0.1 microg/kg, p.o., 5 times a week) with standard rodent chow [Ca 1.2%, phosphorus (P) 1.04%], a Ca-enriched diet containing 2%, 4%, or 6% Ca (Ca/P ratio of 2, 4, and 6, respectively), or a Ca/P-enriched diet (Ca/P ratio of 1.2). After 12 weeks of treatment, all rats were killed to harvest the spine, serum, and urine samples. Neither the ALF treatment nor the Ca supplement caused hypercalcemia. In the spine, ALF prevented decreases in bone mineral density (BMD) and compressive strength of lumbar spine induced by OVX. Micro-computed tomographic analysis confirmed that ALF significantly improved the trabecular bone pattern factor and the structure model index and suppressed bone destruction. In contrast, of particular interest, high-dose Ca administration did not have marked effects on bone fragility. Also, when both Ca and P were administered in high doses, BMD and mechanical strength decreased dose-dependently, urinary P excretion significantly increased, and serum parathyroid hormone level increased. Together, it is difficult to adjust the Ca supply through diet alone without disrupting the balance between serum Ca and P levels. Consequently, we conclude that ALF is beneficial for the treatment of osteoporosis, which is not achieved by the use of a Ca supplement.
authors.affiliation: Product Research Department, Chugai Pharmacological Co., 1-135 Komakado, Gotemba, Shizuoka 412-8513, Japan. shiraishiayk@chugai-pharm.co.jp
authors.forename: A
authors.initials: A
authors.lastname: Shiraishi
authors.forename: M
authors.initials: M
authors.lastname: Ito
authors.forename: N
authors.initials: N
authors.lastname: Hayakawa
authors.forename: N
authors.initials: N
authors.lastname: Kubota
authors.forename: N
authors.initials: N
authors.lastname: Kubodera
authors.forename: E
authors.initials: E
authors.lastname: Ogata
mesh_terms: D000596:Amino Acids / Q000652:urine; D000818:Animals; D001806:Blood Urea Nitrogen; D015519:Bone Density / Q000187:drug effects / Q000502:physiology*; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D002118:Calcium / Q000097:blood / Q000652:urine; D002136:Calcium, Dietary / Q000008:administration & dosage* / Q000627:therapeutic use; D019245:Compressive Strength; D003404:Creatinine / Q000032:analysis / Q000652:urine; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006887:Hydroxycholecalciferols / Q000494:pharmacology*; D010024:Osteoporosis / Q000188:drug therapy*; D010052:Ovariectomy; D010281:Parathyroid Hormone / Q000097:blood; D010758:Phosphorus / Q000097:blood / Q000652:urine; D051381:Rats; D017208:Rats, Wistar; D014057:Tomography, X-Ray Computed
chemical_list: D000596:Amino Acids; D050071:Bone Density Conservation Agents; D002136:Calcium, Dietary; D006887:Hydroxycholecalciferols; D010281:Parathyroid Hormone; D010758:Phosphorus; C036020:deoxypyridinoline; D003404:Creatinine; D002118:Calcium; C008088:alfacalcidol