You are using an outdated browser. Please upgrade your browser to improve your experience.
Become a Fellow
ACP offers a number of resources to help members make sense of the MOC requirements and earn points.
Understanding MOC Requirements
Earn MOC points
The most comprehensive meeting in Internal Medicine.
April 11-13, 2019
Internal Medicine Meeting 2019
Prepare for the Certification and Maintenance of Certification (MOC)
Exam with an ACP review course.
Board Certification Review Courses
MOC Exam Prep Courses
Treating a patient? Researching a topic? Get answers now.
Visit AnnalsLearn More
Visit MKSAP 18Learn More
Visit DynaMed Plus
Ensure payment and avoid policy violations. Plus, new resources to help you navigate the Medicare Access and CHIP Reauthorization Act of 2015 (MACRA).
Access helpful forms developed by a variety of sources for patient charts, logs, information sheets, office signs, and use by practice administration.
ACP advocates on behalf on internists and their patients on a number of timely issues. Learn about where ACP stands on the following areas:
© Copyright 2018 American College of Physicians. All Rights Reserved. 190 North Independence Mall West, Philadelphia, PA 19106-1572
Toll Free: (800) 523.1546 · Local: (215) 351.2400
First Author: Caroline M. Lewis, Georgia Regents University,
Class of 2016
Bisphosphonates are a class of drugs that inhibit the resorption
of bone by osteoclasts to increase bone mass. They are commonly
prescribed to increase bone mass in patients with osteoporosis,
cancerous tumors of bone, and other bone disorders. Unfortunately,
bisphosphonates are associated with the poorly understood side
effect of bisphosphonate related osteonecrosis of the jaw (BRONJ).
This side effect is initiated by a traumatic injury to the jaw,
such as a tooth extraction.
Traumatic tissue injury produces tears or disruptions in the
plasma membranes of resident cells, and a previous study indicated
that bisphosphonates interact with the protein machinery that
mediates repair of this type of cell injury. Here we have tested
whether the most commonly prescribed bisphosphonate with the
highest incidence of the BRONJ side effect, zoledronate, inhibits
the membrane repair process, and might thereby contribute to
Monkey kidney epithelial cells (BSC1) and mouse myoblasts
(C2C12) were treated with zoledronate and plasma membrane
disruptions such as those that occur in traumatic injury. Membrane
disruptions were created with a microscope laser in the presence of
FM1-43, a fluorescent dye that rushes into the cell and brightly
illuminates its interior when repair fails. When, however, the
integrity of the boundary is restored by successful repair, FM1-43
dye entry into the cell interior is minimal: the cell interior
remains dark except for a small, peripheral, spot-weld scar of
fluorescence where the injury and subsequent repair occurred. This
uptake of fluorescence can be quantitated by image analysis.
Both BSC1 and C2C12 cells incubated 24 hours with 1µM
zoledronate in this laser assay exhibited significant ( p <
0.05, one way ANOVA Tukey post hoc comparison) increases in uptake
of dye over time compared to untreated, control cells.
Zoledronate-treated cells filled rapidly with dye, whereas controls
did not. Thus, zoledronate strikingly inhibits cell membrane repair
in two distinct cell types.
Zoledronate-induced inhibition of cell membrane repair and
consequent cell death may be an important factor in BRONJ. Wound
healing requires frequent membrane repairs since membranes are torn
as cells glide past one another. Without proper cell membrane
repair, these cells die, and complete wound healing cannot occur.
Further study of BRONJ and the involvement of zoledronate-induced
inhibition of cell membrane repair is warranted. Recently, a
non-toxic compound, vitamin E, was found to promote membrane
repair. The results of this study suggest a simple and inexpensive
possible prophylactic treatment for BRONJ: administration of
vitamin E supplements prior to dental work.
October 2014 Issue of IMpact