title: High concentrations of pamidronate in bone weaken the mechanical properties of intact femora in a rat model.
abstract: OBJECTIVE
  Bisphosphonates have been used to treat osteoporosis for more than ten years. However, complications associated with long-term administration of bisphosphonates, such as nonunion after pelvic insufficiency fracture or osteonecrosis of the jaw, have been recently reported in the literature. We investigated the relationships among the mechanical properties of the intact rat femur as well as healing fracture calluses and the intraosseous concentration of pamidronate (ICP), after long-term administration of pamidronate in a rat osteoporosis model.
  
  
  METHODS
  We performed bilateral ovariectomy in 25 3-month-old female Sprague-Dawley rats. Beginning three months after ovariectomy, disodium pamidronate (0.5 mg/kg) was injected every month. After the six-month administration period, the left femoral shaft was fractured using the closed fracture technique. Five weeks after fracture, 23 rats were euthanized and both femora were removed. We checked the mechanical properties of the intact (right) and fractured (left) femora using a three-point bending technique. Intraosseous concentration of pamidronate was checked by high-performance liquid chromatography.
  
  
  RESULTS
  The mean ICP was 61.8+/-15.7 ng/mg of bone. High ICP decreased the ultimate load to failure, stiffness, and ultimate stress of the intact femora (p=0.015, 0.027, 0.039, respectively). There was a tendency to decrease the ultimate load to failure in the healing callus when the ICP increased (p= 0.183). High ICP decreased the bone mineral density of the femoral head (p=0.005).
  
  
  CONCLUSIONS
  High concentrations of pamidronate in intact bone decreased the bone mineral density and weakened the mechanical strength of the rat femora. The mechanical strength of the early healing callus was not correlated with concentration of pamidronate in the bone.
authors.affiliation: Department of Orthopaedic Surgery, Yongdong Severance Hospital, Yonsei University College of Medicine, 146-92 Dokok-dong, Kangnam-gu, Seoul 135-720, Korea. kyang@yuhs.ac
authors.forename: Kyu Hyun
authors.initials: KH
authors.lastname: Yang
authors.forename: Jung Hoon
authors.initials: JH
authors.lastname: Won
authors.forename: Han Kook
authors.initials: HK
authors.lastname: Yoon
authors.forename: Jong Hyeon
authors.initials: JH
authors.lastname: Ryu
authors.forename: Kyo Seok
authors.initials: KS
authors.lastname: Choo
authors.forename: Jae Shin
authors.initials: JS
authors.lastname: Kim
mesh_terms: D000818:Animals; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D004164:Diphosphonates / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D005269:Femur / Q000187:drug effects* / Q000502:physiology; D017102:Fracture Healing / Q000502:physiology; D010024:Osteoporosis / Q000378:metabolism*; D000077268:Pamidronate; D051381:Rats; D017207:Rats, Sprague-Dawley; D013314:Stress, Mechanical
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D000077268:Pamidronate