Risk communication about oral BP-related ONJ in Japan

Date*	Organization	Content
Oct. 2006	PMDA†, pharmaceutical manufacturers	Measure: revised package insert for alendronate and risedronate
		“ONJ has been reported in patients receiving bisphosphonates. The majority of reported cases have been associated with dental procedures, such as tooth extraction, or with local infection. Physicians should fully disclose the adverse reactions to their patients and observe them closely.”
Jan. 2007	pharmaceutical manufacturers	Notices to hospitals and “Dear Health Professional” letters to inform them about the content of the revised package insert
June 2007	academic association	Publication of a case report33
		There was one case of osteoporosis diagnosed with oral BP-related ONJ; the other case, a case of multiple myeloma, was diagnosed with iv BP-related ONJ.
Sep. 2007	PMDA, pharmaceutical manufacturers	Measure: revised package insert for etidronate
Oct. 2007	academic association	Publication of an observational study34
		Questionnaires were sent to 239 institutions, and 30 patients with osteonecrosis were reported. Of them, 20 patients received iv BPs, eight received oral BPs and one received both.
Jan. 2008	academic association	News article entitled “osteonecrosis of the jaws induced by anti-osteoporosis treatment”
		“Patients on BP therapy requiring dental procedures should tell their dentists that they are being treated with BPs, and physicians should fully explain the adverse reactions to their patients when prescribing BPs.”
Jan. 2008	academic association, pharmaceutical manufacturers	Announcement of a guidance publication, entitled “Bisphosphonates and osteonecrosis of the jaw”
		A 20-page pamphlet, with the diagnostic criteria, clinical manifestations, risk factors and epidemiology of iv and oral BP-related osteonecrosis of the jaw and instructions for physicians, pharmacists, dentists and oral surgeons
Mar. 2008	academic association	Announcement of guidance publication, entitled “management of patients on BP therapy”
		A four-page pamphlet with the diagnostic criteria, management, risk factors, epidemiology of iv and oral BP-related osteonecrosis of the jaw and instructions for physicians, dentists and oral surgeons
Apr. 2008	academic association	Public meeting for citizens: “The state of osteonecrosis of the jaw related to BPs”
Sep. 2008	academic association	A pamphlet, entitled “Bisphosphonates and osteonecrosis of the jaw: clinical manifestations and guidelines for management, 2008”
Feb. 2009	academic association	Training session for dentists, entitled “The state of osteonecrosis of the jaw related to BPs”
Feb. 2009	academic association	News article, entitled “Bisphosphonates and osteonecrosis of the jaws”
May 2009	PMDA, academic association	Announcement of a guidance publication, entitled “Bisphosphonate-Related Osteonecrosis of the Jaws”35
		This official therapeutic manual for severe adverse reactions included the diagnostic criteria, clinical manifestations, risk factors and management methods for iv and oral BP-related osteonecrosis of the jaw for citizens and health care professionals
June 2009	academic association	Public meeting for citizens, entitled “The state and the management of osteonecrosis of the jaws related to BPs”
July 2009	academic association	Training meeting regarding BP-related osteonecrosis of the jaw for health care professionals
Nov. 2009	academic association	Publication of an observational study36
		The follow-up survey showed that surgical treatment might be useful for BRONJ when performed at the appropriate time, and BRONJ was shown to be refractory because only nine of 17 cases were cured in these 2 years.
May 2010	academic association, pharmaceutical manufacturers	Publication of a position paper37
June 2010	PMDA	Measure: revised package inserts for alendronate, risedronate and etidronate
		“ONJ has been reported in patients receiving bisphosphonates, regardless of the route of administration. Treating physicians should advise their patients to undergo dental examinations and to finish any invasive dental procedures, such as tooth extraction, if necessary, prior to treatment with BPs. While on treatment with BPs, these patients should have regular dental consultations and avoid invasive dental procedures.”
Sep. 2010	academic association	Publication of a book, entitled “The utility and osteonecrosis of the jaw of BPs”
Sep. 2010	PMDA	Release of safety measures (“The progress of assessments and measures regarding BP-related osteonecrosis of the jaw”), including a survey of the number of cases of BP-related osteonecrosis of the jaw and an outline of the individual case reports reported to PMDA

^*The date indicates the first dissemination of safety information.

^†PMDA: Pharmaceuticals and Medical Devices Agency.