title: Effects of raloxifene and alendronate on non-enzymatic collagen cross-links and bone strength in ovariectomized rabbits in sequential treatments after daily human parathyroid hormone (1-34) administration.
abstract: This study investigated the effects of raloxifene and alendronate to follow parathyroid hormone (PTH) on bone collagen and biomechanical properties in ovariectomized rabbits. Sequential treatments of raloxifene and alendronate after hPTH(1-34) treatment improved biomechanical properties with and without bone collagen improvement, respectively.
  
  
  
  The standard sequential treatment to follow human parathyroid hormone (hPTH) (1-34) therapy for osteoporosis has yet to be determined. The objective of this study was to compare the effects of raloxifene and alendronate treatments to follow daily hPTH(1-34) treatment on non-enzymatic collagen cross-links, bone mass, and bone strength in ovariectomized (OVX) rabbits.
  
  
  
  From 3 months after ovariectomy, seven month-old female New Zealand white rabbits were given either vehicle or hPTH(1-34) (8 μg/kg/day), once daily for 5 months. After hPTH(1-34) treatment, the hPTH(1-34)-treated animals were divided into two groups, and given raloxifene (10 mg/kg, daily) orally or alendronate (100 μg/kg, twice weekly) subcutaneously for 5 months. We evaluated bone mineral density (BMD), bone structural parameters, advanced glycation end product (AGE) content in collagen, and bone mechanical parameters including intrinsic parameters in the femur.
  
  
  
  Raloxifene (hPTH/RLX) and alendronate (hPTH/ALN) to follow hPTH(1-34) increased cortical thickness, maximum load, and maximum stress and decreased endocortical surface in the diaphysis, in addition to increasing total BMD in the distal metaphysis. Decreased trabecular AGE, pentosidine, and homocysteine contents and increased toughness and breaking energy were noted with hPTH/RLX treatment only. With hPTH/ALN treatment, no effects on non-enzymatic collagen cross-link AGEs were noted although increases in stiffness and elastic modulus were observed.
  
  
  
  These results suggest that sequential treatments with hPTH(1-34) and antiresorptive drugs (raloxifene and alendronate) have a beneficial effect on bone mass and biomechanical properties in OVX rabbits.
authors: Medical Science, Medicines Development Unit Japan, Eli Lilly Japan KK, Sannomiya Plaza Building 7-1-5 Isogami-dori, Chuo-ku, Kobe, 651-0086, Japan. kimura_shuichi@lilly.com.
authors: S
authors: S
authors: Kimura
authors: Department of Orthopaedic Surgery, Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato-ku, Tokyo, 105-8461, Japan.
authors: M
authors: M
authors: Saito
authors: Department of Orthopaedic Surgery, Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato-ku, Tokyo, 105-8461, Japan.
authors: Y
authors: Y
authors: Kida
authors: Hamri Co., Ltd., 2638-2, Osaki, Koga, Ibaraki, 306-0101, Japan.
authors: A
authors: A
authors: Seki
authors: Medical Science, Medicines Development Unit Japan, Eli Lilly Japan KK, Sannomiya Plaza Building 7-1-5 Isogami-dori, Chuo-ku, Kobe, 651-0086, Japan.
authors: Y
authors: Y
authors: Isaka
authors: Department of Orthopaedic Surgery, Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato-ku, Tokyo, 105-8461, Japan.
authors: K
authors: K
authors: Marumo
mesh_terms: D019386:Alendronate / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001696:Biomechanical Phenomena; D015519:Bone Density / Q000187:drug effects* / Q000502:physiology; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000494:pharmacology*; D003094:Collagen / Q000187:drug effects* / Q000378:metabolism; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical; D004359:Drug Therapy, Combination; D005260:Female; D005269:Femur / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D017127:Glycation End Products, Advanced / Q000187:drug effects / Q000378:metabolism; D010052:Ovariectomy; D011817:Rabbits; D020849:Raloxifene Hydrochloride / Q000008:administration & dosage / Q000494:pharmacology; D013314:Stress, Mechanical; D019379:Teriparatide / Q000494:pharmacology; D016474:Weight-Bearing
chemical_list: D015415:Biomarkers; D050071:Bone Density Conservation Agents; D017127:Glycation End Products, Advanced; D019379:Teriparatide; D020849:Raloxifene Hydrochloride; D003094:Collagen; D019386:Alendronate
keywords: Advanced glycation end products; Alendronate; Collagen cross-links; OVX rabbit; Raloxifene; hPTH(1-34)