Peer-review started: May 6, 2019
First decision: September 2, 2019
Revised: November 26, 2019
Accepted: December 14, 2019
Article in press: December 14, 2019
Published online: January 8, 2020
Endochondral ossifying constitutes the fundamental model for the development of appendicular skeletal formation. This process requires well-organized changes on the cartilage morphological aspects that includes the resting, proliferative, prehypertrophic, hypertrophic segments which it is followed by replacement of mineralized hypertrophic cartilage with osteoprogenitor cells, and the calcified cartilage is subsequently replaced by bone. Under pathological situation this usual development does not occur, promoting growth deficiencies. Since alendronate may contribute either for chondrogenic or osteogenic development, herein we evaluated the likely effect of alendronate in epiphyseal plate of newborn rats, in order to verify the real effect of alendronate during earlier development of appendiclar bones.
The fundamental topics adressesd in the present study were: (1) Would be alendronate a drug that should be able to improve the chondrogenic and osteogenic in eralier stage of development; and (2) Alendronate alters the correlation between transforming growth factor-β1 (TGF-β1) and bone morphogenetic protein-2 (BMP2) during endochondral ossification? The answer of this question, could give us a direction between for a likely therapy apporach in child that possess congenital deficies of growth.
Thus, the main objective of this study was to verify how alendornate acts on the epifeaseal developmental plaque. In addition, we evaluated which region of endochondral development is most stimulated or inhibited by alendronate, as well as whether the drug may cause early ossification.
Thus, we analyzed the evaluation of femoral bone growth of neonatal rats by measuring the distance between the apex of the greater trochanter until the lower intercondylar midlle face. We also measured the area of each stratification of the endochondral histological zones, as well as where the ossifications occurred - late or early. We also evaluated by immunohistochemistry, the immunopresence of TGF-β1 and BMP-2 in each of these endochondral zones.
Here we reveal that specimens given alednroanto developed greater cartilage hypertrophy while the reserve zone was decreasing. These results also coincide with changes in co-immunolocation between TGF-β1 and BMP-2. Here we demonstrate a greater presence of osteoprotein in areas where endochondral proliferation and endochondral diphonication should occur, triggering early ossification. These results also coincide with lower bone growth.
In this study we may conclude that: (1) Alendronate may compromise the usual development and growth of epiphyseal plaque. (2) This pathological event may occur as alednronate provides prior expression of BMP-2, while TGF-1 immunolocation decreases. And (3) the fundamental result found here indicates that alendronate does not induce appendicular bone growth. Thus, it may indicate that the use of this drug is not a plausible conduct for children suffering from endochondral growth disorders.
Here we suggest the perspective that alendronate compromises the development of long bones. There is a need for research using other drugs to try to promote greater growth of endochondral zones, ossification in suitable areas, conditions that are important for appendicular bone growth.