The influence of dichloromethylene bisphosphonate on the healing of a long bone fracture, composition of bone mineral and histology of bone in the rat.
The effects of dichloromethylene bisphosphonate (clodronate) on the composition of bone mineral, morphology and histology of a long bone with an artificial femoral fracture were studied in a 22 week experiment. Two hundred twenty-four female rats were allocated to dose groups of 0, 3, 10, and 30 mg/kg clodronate daily subcutaneously. Bone calcium, phosphorus and magnesium concentrations remained stable and fluoride concentration rose with time. There were no statistical differences between different groups. Clodronate did not alter the histology of the callus nor delayed the healing of the fracture. It caused mild to moderate prominence of the metaphyseal area in the fractured bone in a dose- and time-dependent manner. Serum osteocalcin levels were lowered in the treated animals dose-dependently. Other serological as well as haematological values were within normal range. Clodronate seems in this experimental arrangement to be a safe agent to administer in different pathological conditions of bone even when they are complicated by fractures of long bones.
Hyvönen
P M
PM
Department of Pharmacology and Toxicology, University of Kuopio, Finland.
Karhi
T
T
Kosma
V M
VM
Liimola-Luoma
L
L
Hanhijärvi
H
H
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D004002:Clodronic Acid / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000187:drug effects; D005260:Female; D005264:Femoral Fractures / Q000188:drug therapy*; D005269:Femur / Q000187:drug effects / Q000473:pathology; D005459:Fluorides / Q000378:metabolism; D017102:Fracture Healing / Q000187:drug effects*; D006801:Humans; D007279:Injections, Subcutaneous; D008274:Magnesium / Q000378:metabolism; D015675:Osteocalcin / Q000097:blood; D015663:Osteoporosis, Postmenopausal / Q000473:pathology; D010758:Phosphorus / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D004002:Clodronic Acid; D015675:Osteocalcin; D010758:Phosphorus; D008274:Magnesium; D005459:Fluorides; D002118:Calcium