James a

JAMES A. SIMON, M.D. Infertility Menopause/Osteoporosis Gynecology Reproductive Endocrinology
Clinical Professor

Bisphosphonates and ONJ: Risks, Benefits, and Prevention
Carol J. Mack, MPH, PA-C Patricia M. DeHof, CRNP, MS A few years ago, several major news publications published articles regarding the risk of osteonecrosis of the jaw (ONJ) for patients taking drugs called James A. Simon, MD PC
1850 M Street, NW
bisphosphonates. These articles, along with several lawsuits filed against the pharmaceutical companies manufacturing these drugs, purport the dangerous nature of bisphosphonates and exaggerate the likelihood of ONJ. This, in turn, has raised concern among many patients taking bisphosphonates. ONJ is a condition affecting the bones of the jaw - usually the lower jaw. The
condition may resemble other types of dental disease, and often causes symptoms
such as: pain in the teeth and jaw, loosening of teeth, infection, swelling, and
draining. ONJ may initially show no symptoms for several months.
The estimated occurrence of ONJ in persons taking oral bisphosphonates {Fosamax®
(Alendronate), Actonel® (Risedronate), Boniva® (Ibandronate)} is extremely low,
roughly 0.7 cases per 100,000 person-years exposure. These cases represent only 6%
of all bisphosphonate related ONJ occurrences. Cancer patients receiving intravenous
bisphosphonates have a reported 6-10% rate of developing ONJ, and these cases
make up 94% of all reported bisphosphonate related instances of ONJ. When
considering these risks, it is important to note that osteoporosis, left untreated, is
estimated to cause at least one fracture (wrist, hip, or spine) in one of every two
women during their lifetimes. These osteoporotic fractures can be debilitating and
contribute to a significant number of hospitalizations, institutionalizations, and
deaths. Furthermore, a recent analysis on data from the Women’s Health Initiative
(WHI) demonstrated a 32% decrease in breast cancer cases in women taking oral
bisposphonates compared to women not taking the drugs. Although this data is
preliminary and must be confirmed with further studies, it is an encouraging and
possibly important development.
Oral bisphosphonates are used to prevent bone loss and fractures. Bisphosphonates
improve bone health by reducing bone turnover, a process by which the bone
“remodels” itself, allowing elasticity of the bone, repair of microfractures and proper
distribution of calcium. During the bone remodeling cycle, the collagen and mineral
in the bone are first broken down, a process called resorption, and then the bone is
reformed and restored to its normal mass. In osteoporosis, too much bone is resorbed
and not enough synthesized/formed. This results in thin, brittle, fragile bones, which
fracture easily. Bisphosphonates limit the entire process of bone turnover, by
inhibiting resorption.
The risk for ONJ is highest for patients who have been treated for metastatic breast
cancer and multiple myeloma as these patients are likely to receive high doses of
intravenous bisphosphonates. This allows a very large amount of bisphosphonate -
50% of the administered dosage – to be absorbed directly into the bone. In contrast,
the percentage absorbed from oral doses is only about 1%. The small absorption rate
lowers the overall impact of the drug and appears to decrease the risk of developing
ONJ. An individual’s risk may be increased by certain factors, including age (over 65
years), use of glucocorticoids (cortisone-like medications) and/or estrogen, previous periodontal disease, other causes of poor oral hygiene, and invasive recent dental procedures (i.e. tooth extractions).
While the risk for developing ONJ is already extremely low, this risk can be lowered
by simply maintaining good oral hygiene and seeing a dentist regularly. It is also
recommended that patients who are about to begin oral bisphosphonate treatment
should obtain a thorough oral evaluation by a dentist. Once taking bisphosphonates,
if dental treatment, other than routine check-ups, is required, alternative or non-
surgical treatment should be considered above surgical or invasive procedures, if
possible. Using antibiotics before and after dental procedures may also reduce the
risk of dangerous infections. While some dentists may advise stopping
bisphosphonate treatment in the months before a dental procedure, it has not been
proven that this has any effect on the risk of developing ONJ.
Total numbers ONJ cases reported (as of 7/1/06) in association with orally
administered nitrogen-containing bisphosphonates:
170 cases with Alendronate (Fosamax®, Merck and Co., inc.)
20 cases with risedronate (Actonel®, Procter and Gamble)
1 case with ibandronate (Boniva®, Roche)
Rosen, Clifford J. and Tenenhouse, Alan. “Biochemical Markers of Bone Turnover: A Look at
Laboratory Tests that Reflect Bone Status”. Available at: http://www.postgradmed.com/issues/1998/10_98/rosen.htm. (06/29/06). Van Staa, T.P. et al. “Use of Oral Corticosteroids and Risk of Fracture”. Van Staa, T.P. et al. Journal of Bone and Mineral Research. Vol. 15: 6. 2000. Sook-Bin Woo, Hellstein, John W., and Kalmar, John R. “Systematic Review: Bisphosphonates and Ostonecrosis of the Jaw”. Annals of Internal Medicine. May, 2006 Vol. 144: 753-761. Edwards, Beatrice J, et al. “Expert Panel Recommendations: Dental Management of Patients on Oral Bisphonate Therapy”. Report of the Council on Scientific Affairs, American Dental Association. June, 2006. Carreyrou, John. “Fosamax Drug Could Become Next Merck Woe”. The Wall Street Journal. April Kolata, Gina. “Drug for Bones Is Newly Linked to Jaw Disease”. The New York Times. June 2, 2006. Rabin, Roni Caryn. “Bone Drugs Taken by Some Women May Lower Breast Cancer Risk, Studies Say”. The New York Times. December 10, 2009. Kendra Smith James A. Simon, MD, CCD

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