The influence of alendronate on bone formation and resorption in a rat ectopic bone development model.
BACKGROUND
Most bone grafting techniques that include bone marrow, alloplastic materials, and extracellular bone matrix produce new bone mass, filling bone defects unpredictably. In most cases, the new bone undergoes resorption due to low local strains, resulting in significant bone loss. Recently, it was shown that alendronate and other bisphosphonates reduce bone loss when administered systemically or locally. The aim of this study was to investigate whether alendronate is effective on bone formation or bone resorption.


METHODS
A total of 64 rats were divided into 2 main groups. In all the rats, fresh bone marrow removed from DA young rats was placed into demineralized rat femur cylinders (DBMC) and implanted into subcutaneous sites of host DA rats, to form new bone. Group A served as an alendronate treatment group, and group B served as a non-treated control. Group A received 100 microl of 1.5 mg/ml alendronate solution at 1, 2, and 3 weeks (group A1) and at 3, 4, and 5 weeks (group A2). At designated times, the rats were sacrificed, and the implanted DBMC was dissected out of the thorax and processed for histological and microradiography image analysis.


RESULTS
Alendronate given at 1, 2, and 3 weeks (during the bone formation phase) did not increase the amount of bone or the visual bone density in comparison to the time-matched control, after 4 and 8 weeks. When alendronate was injected at 3, 4, and 5 weeks, the bone mass increased by 70% and by 166% after 6 and 10 weeks, respectively, in comparison to the untreated control. The visual bone density in group A2 was maintained at the level of 140 +/- 15 at 6 weeks and 152 +/- 15 at 10 weeks. The matched, non-treated control group B2 was significantly lower, 106 +/- 20 and 108 +/- 15, respectively. The histological sections showed that alendronate treatment at 3, 4, and 5 weeks maintained the normal appearance of the ossicle at 6 and 10 weeks in comparison to the osteopenic bone appearance in the matched controls.


CONCLUSIONS
This study suggests that alendronate is effective in inhibiting bone loss, but ineffective during the bone formation phase. We suggest, therefore, that alendronate should be administered in procedures where bone resorption is expected.
Yaffe
Avinoam
A
Department of Prosthodontics, Hebrew University Hadassah School of Dental Medicine, Jerusalem, Israel. yaffeavi@netvision.net.il
Kollerman
Ron
R
Bahar
Hila
H
Binderman
Itzhak
I
D019386:Alendronate / Q000008:administration & dosage / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D001851:Bone Diseases, Metabolic / Q000473:pathology / Q000503:physiopathology; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology; D001862:Bone Resorption / Q000473:pathology / Q000503:physiopathology* / Q000517:prevention & control; D062109:Dermatologic Surgical Procedures; D004195:Disease Models, Animal; D007091:Image Processing, Computer-Assisted; D007275:Injections, Intravenous; D008297:Male; D008852:Microradiography; D009999:Ossification, Heterotopic / Q000503:physiopathology*; D010006:Osteoblasts / Q000473:pathology; D010012:Osteogenesis / Q000187:drug effects*; D011897:Random Allocation; D051381:Rats; D011919:Rats, Inbred Strains; D013223:Statistics as Topic; D013997:Time Factors
D019386:Alendronate