The beneficial effect of intravenous zoledronic acid therapy following an acute stroke in rats.
OBJECTIVE
Changes of bone metabolism begin from the initial stages of stroke; therefore, early prevention of these changes has become important. The most appropriate target for preventive therapy is to restrict the profound increase in osteoclastic bone resorption that occur soon after stroke. Oral bisphosphonates, which selectively target osteoclasts and their precursors, are appropriate drugs, but dysphagia or drowsiness after acute stroke can make it difficult to easily administer these compounds to stroke patients. The intravenous (IV) administration of bisphosphonates is an alternative method that can overcome these limitations. In order to determine the effect of IV bisphosphonates at the initial stages of stroke for preventing bone loss, an experiment using ischemic stroke rats was conducted.


METHODS
Female Sprague-Dawley rats (n = 100) were randomly divided into four separate groups; sham surgery and vehicle-treated group (sham-vehicle), stroke and vehicle-treated group (stroke-vehicle), stroke with low-dose zoledronic acid treatment group (stroke-low) and stroke with high-dose zoledronic acid treatment group (stroke-high). Permanent occlusion of the left middle cerebral artery was performed, resulting in right hemiplegia. The bone mineral density (BMD) of the 4th and 5th lumbar vertebrae and the femur on the stroke side were measured in vivo on the day before stroke and on the 10th and 21st day after stroke. The osteocalcin and carboxy-terminal telopeptide blood levels were measured on the 10th and 21st day after stroke. The BMD of the excised proximal tibia and the maximum load of femoral neck were measured on the 21st day after stroke.


RESULTS
After 21 days of stroke, the BMD of the lumbar vertebrae, femur, and excised tibia and the maximum load of the femoral neck in the sham-vehicle, stroke-low, and stroke-high groups were significantly higher than those in the stroke-vehicle group (P < 0.05). The carboxy-terminal telopeptide levels in the sham-vehicle and stroke-high groups were significantly lower than those in the stroke-vehicle group (P < 0.05).


CONCLUSIONS
The results suggest that IV zoledronic acid treatment might prevent bone loss during the initial stages of stroke.
Lee
Jong In
JI
Department of Rehabilitation Medicine, College of Medicine, The Catholic University of Korea, 505 Banpo-Dong, Seocho-Gu, Seoul 137-701, Korea.
Kim
Hye Won
HW
Rhee
Won Ihl
WI
Park
Joo Hyun
JH
Lim
Seong Hoon
SH
Im
Sun
S
Ko
Young Jin
YJ
D015502:Absorptiometry, Photon; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001696:Biomechanical Phenomena; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004164:Diphosphonates / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005269:Femur / Q000000981:diagnostic imaging / Q000187:drug effects / Q000502:physiology; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D007275:Injections, Intravenous; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000187:drug effects; D015675:Osteocalcin / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D011347:Procollagen / Q000097:blood; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000209:etiology*; D013977:Tibia / Q000000981:diagnostic imaging / Q000187:drug effects; D000077211:Zoledronic Acid
D015415:Biomarkers; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D010446:Peptide Fragments; D011347:Procollagen; C042813:procollagen type I carboxy terminal peptide; D015675:Osteocalcin; D000077211:Zoledronic Acid