Browsing by Subject "Alendronate"

Now showing 1 - 3 of 3
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    Antiremodeling Agents Influence Osteoblast Activity Differently in Modeling and Remodeling Sites of Canine Rib
    (Calcified Tissue International, 2006-10-10) Allen, Matthew R.; Follet, Helene; Khurana, M.; Sato, M.; Burr, David B.; Department of Anatomy & Cell Biology, IU School of Medicine
    Antiremodeling agents reduce bone loss in part through direct actions on osteoclasts. Their effects on osteoblasts and bone formation activity are less clear and may differ at sites undergoing modeling vs. remodeling. Skeletally mature intact beagles, 1–2 years old at the start of the study, were treated daily with clinically relevant doses of alendronate (0.10 or 0.20 mg/kg), risedronate (0.05 or 0.10 mg/kg), raloxifene (0.50 mg/kg), or vehicle (1 mL/kg). Dynamic bone formation parameters were histologically assessed on periosteal, endocortical/trabecular, and intracortical bone envelopes of the rib. Raloxifene significantly increased periosteal surface mineral apposition rate (MAR), a measure of osteoblast activity, compared to all other treatments (+108 to +175%, P < 0.02), while having no significant effect on MAR at either the endocortical/trabecular or intracortical envelope. Alendronate (both 0.10 and 0.20 doses) and risedronate (only the 0.10 dose) significantly (P ≤ 0.05) suppressed MAR on the endocortical/trabecular envelope, while none of the bisphosphonate doses significantly altered MAR at either the periosteal or intracortical envelopes compared to vehicle. Based on these results, we conclude that (1) at clinically relevant doses the two classes of antiremodeling agents, bisphosphonates and selective estrogen receptor modulators, exert differential effects on osteoblast activity in the canine rib and (2) this effect depends on whether modeling or remodeling is the predominant mechanism of bone formation.
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    The Effect of Alendronate and Risedronate on Bone Remodeling in the Canine Maxilla
    (1999) Callegari, Brent Joseph; Garetto, Lawrence P.; Hartsfield, James K., Jr.; Katona, Thomas R.; Turner, Charles H.; Shanks, James C.
    Bisphosphonates, effective inhibitors of bone resorption, are used in the treatment of postmenopausal osteoporosis. At present, the effects of bisphosphonate therapy on the maxilla have not been quantitatively studied. As part of the masticatory system, dentate alveolar bone is exposed to a unique pattern of loading. As such, data obtained from bisphosphonate studies of other bones may not be applicable to the cortical bone of the dentate maxilla. The objective of this study is to histomorphometrically quantify the effects of alendronate and risedronate therapy on alveolar bone of the dog maxilla (MX) and to determine if this site is affected differently than the cortical bone in the rib (R) from these same animals. Twenty-two female dogs were divided into three treatment groups of 1 mg/kg/day alendronate, 0.5 mg/kg/day risedronate, and a saline vehicle control. Fluorochrome labels were used to mark sites of bone formation. Maxillary and rib specimens from each dog were prepared for analysis of static and dynamic histomorphometric parameters. MX cortical bone surrounding the third premolar was further analyzed by side (buccal vs. lingual) and region (coronal vs. apical). Mineralizing surface (MS/BS) and bone formation rate (BFR) in the coronal maxilla of the control group is significantly (p < 0.05) higher than that of the bisphosphonate groups. In bisphosphonate treated animals, MS/BS, BFR, and activation frequency (AcF) were significantly (p < 0.05) higher in the R than in the MX. In all treatment groups, very little osteoid was detected, and no significant difference in the mineral apposition rate (MAR) was noted. These results indicate that: (1) bisphosphonate dosages used in this study effectively inhibited remodeling within the dog maxilla; (2) alveolar bone remodeling was decreased more than remodeling in rib cortical bone; (3) within the dentate maxilla, alveolar bone remodeling was decreased more in the coronal than in the apical region, and (4) none of the groups appears to show inhibition of mineralization.
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    Osteoblastic protein tyrosine phosphatases inhibition and connexin 43 phosphorylation by alendronate
    (Elsevier, 2014) Lezcano, V.; Bellido, T.; Plotkin, L. I.; Boland, R.; Morelli, S.; Anatomy, Cell Biology and Physiology, School of Medicine
    Bisphosphonates (BPs), potent inhibitors of bone resorption which inhibit osteoclasts, have also been shown to act on osteocytes and osteoblasts preventing apoptosis via connexin (Cx) 43 hemichannels and activating the extracellular signal regulated kinases ERKs. We previously demonstrated the presence of a saturable, specific and high affinity binding site for alendronate (ALN) in osteoblastic cells which express Cx43. However, cells lacking Cx43 also bound BPs. Herein we show that bound [(3)H]-alendronate is displaced by phosphatase substrates. Moreover, similar to Na3VO4, ALN inhibited the activity of transmembrane and cytoplasmic PTPs, pointing out the catalytic domain of phosphatases as a putative BP target. In addition, anti-phospho-tyrosine immunoblot analysis revealed that ALN stimulates tyrosine phosphorylation of several proteins of whole cell lysates, among which the major targets of the BP could be immunochemically identified as Cx43. Additionally, the transmembrane receptor-like PTPs, RPTPµ and RPTPα, as well as the cytoplasmic PTP1B, are highly expressed in ROS 17/2.8 cells. Furthermore, we evidenced that Cx43 interacts with RPTPµ in ROS 17/2.8 and ALN decreases their association. These results support the hypothesis that BPs bind and inhibit PTPs associated to Cx43 or not, which would lead to the activation of signaling pathways in osteoblasts.