title: The effects of bone remodeling inhibition by alendronate on three-dimensional microarchitecture of subchondral bone tissues in guinea pig primary osteoarthrosis.
abstract: We assessed whether increase of subchondral bone density enhances cartilage stress during impact loading, leading to progressive cartilage degeneration and accelerated osteoarthrosis (OA) progression. Sixty-six male guinea pigs were randomly divided into six groups. During a 9-week treatment period, four groups received twice-weekly subcutaneous injections of alendronate (ALN) in two doses: two groups received 10 microg/kg and two groups received 50 microg/kg. The two control groups received vehicle. After 9 weeks, one 10 microg/kg ALN group, one 50 microg/kg ALN group, and one control group were killed. The remaining three groups (17-week groups) were left for an additional 8 weeks, receiving the same treatment regimen before death. The left proximal tibiae were scanned by micro-computed tomography to quantify the microarchitecture of subchondral bone, followed by mechanical testing and determination of collagen and mineral. The control groups had typical OA-related cartilage degeneration at 9 and 17 weeks, whereas the 50 microg/kg ALN group had even worse degeneration in the medial condyle. It is unclear whether there is a direct or a secondary effect of ALN on the cartilage. The 9-week ALN group had significantly greater subchondral plate thickness. The 9- and 17-week groups had similar changes of cancellous bone microarchitecture, with greater volume fraction and connectivity and an extremely plate-like structure. The 9-week ALN group had greater bone mineral concentration, and the 17-week ALN group had reduced collagen concentration and greater mineral concentration. Treatment with ALN did not significantly change the mechanical properties of the cancellous bone.
authors.affiliation: Orthopedic Research Laboratory, Department of Orthopedics, Aarhus University Hospital, Aarhus, Denmark. ming.ding@ouh.regionsyddanmark.dk
authors.forename: Ming
authors.initials: M
authors.lastname: Ding
authors.forename: Carl Christian
authors.initials: CC
authors.lastname: Danielsen
authors.forename: Ivan
authors.initials: I
authors.lastname: Hvid
mesh_terms: D019386:Alendronate / Q000494:pharmacology*; D000818:Animals; D015519:Bone Density / Q000187:drug effects / Q000502:physiology; D050071:Bone Density Conservation Agents / Q000494:pharmacology; D016723:Bone Remodeling / Q000187:drug effects* / Q000502:physiology; D001842:Bone and Bones / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D002358:Cartilage, Articular / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D003094:Collagen / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D004334:Drug Administration Schedule; D006168:Guinea Pigs; D007596:Joints / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D007719:Knee Joint / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008297:Male; D010003:Osteoarthritis / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D013314:Stress, Mechanical; D013977:Tibia / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D016474:Weight-Bearing / Q000502:physiology
chemical_list: D050071:Bone Density Conservation Agents; D003094:Collagen; D019386:Alendronate