Abdy, S.

Aspray, T.

Statham, Louise

Sunderland University Institutional Repository

Statham, Louise, Aspray, T. and Abdy, S. (2016) Can bone turnover markers help to define the duration of biphosphonate drug holidays? In: 43rd Annual European Calcified Tissue Society, 15 May 2016, Rome, Italy. Downloaded from: http://sure.sunderland.ac.uk/6354/Usage guidelinesPlease  refer  to  the  usage guidelines  at  http://sure.sunderland.ac.uk/policies.html  or  alternatively contact sure@sunderland.ac.uk.Review (32%)• Adherence• Renal	function• Recent	fracture• AbsorptionConsider	restart(28%)Delay	restart(72%)N	Consider	restart(53%)Delay	restart(47%)At	Baseline	CTX	≤	pre-menopausal	mean*	(68%)4	month	Review	CTX	supressed?(i.e.	≤	mean	or	LSC	not	achieved)	12	month	ReviewCTX	supressed?(i.e.	≤	mean	or	LSC	not	achieved)	N	 N	Total	Patients	=158	• Patients on BP drug holiday via outpatient Bone Clinic identified from monitoringrecords• Data extracted; patient age, sex, serum CTX levels 0, 4, 12 months, bisphosphonate andduration of use• Excluded if baseline (0m) CTX ≥0.51 ug/L (higher fracture risk)• Data analysis using Stata Statistics software.• Offset of action defined as• a rise by the Least Significant Change (LSC=33%*) in CTX and CTX above thepre-menopausal mean (0.19ug/L)*LSC=2.33x√(CVa2)+(CVi2): CVa is analytical coefficient of variation, CVi is intra-individual CVCan	bone	turnover	markers	help	to	define	the	duration	of	bisphosphonate	drug	holidays?Louise	Statham1,2,	Sharon	Abdy1,	Terry	Aspray1,31	The	Newcastle	upon	Tyne	Hospitals	NHS	Foundation	Trust,	Newcastle	upon	Tyne,	NE7	7DN,	UK2 University	of	Sunderland,	Dept.	of	Pharmacy,	Health	&	Well-being,	Sunderland,	SR1	3SD,	UK	3	Newcastle	University,	Institute	of	Cellular	Medicine,	Newcastle	upon	Tyne,	NE2	4HH,	UKBackgroundMethodsCTX	0m	 =138CTX	4	m	=136CTX	12	m	=100Results	Conclusion		Figure	4:	CTX	monitoring	outcomesat	baseline,	4	and	12	months*Mean	premenopausal	CTX	0.19	ug/L(0.05-0.63)4Figure 1: All patient characteristics• After	at	least	5	years	of	treatment,	CTX	may	not	be	adequately	suppressed	in	a	third	of	patients.	Drug	adherence	and	therapy	choice	should	be	reviewed	in	this	group.	• Less	significant	changes	in	CTX	seen	if	levels	not	adequately	suppressed	at	baseline																		?adherence• Treatment	effects	can	wear	off	as	quickly	as	4	months,	but	may	also	be	maintained	for	12	months• Monitoring	of	CTX	can	potentially	be	used	to	identify	these	patients,	some	of	whom	may	need	to	re-start	treatment	earlierMean Patient	Age 71	yearsGender 83%	female;	17%	maleMean	Duration	BP 8	years	(range 3-15	years)Alendronicacid 59%Risedronate 33%Other	Bisphosphonate8%1.Sorensen	OH	et	al	(2003)	Long-term		efficacy	of	risedronate:	a	5-year	placebo-controlled	clinical	experience.	Bone;32(2):120-6.;	2.Black	DM	et	al	(2006)	Effects	of	continuing	or	stopping	alendronate	after	5	years	of	treatment:	the	Fracture	Intervention	Trial	Long-term	Extension	(FLEX):	a	randomized	trial.	JAMA	;	296;	24;2927-2938;	3.MHRA	Drug	Safety	Update	June	2011,	vol 4	issue	11:	A1;	4.	Gossiel F	et	al	(2014)	Establishing	reference	intervals	for	bone	turnover	markers	in	healthy	postmenopausal	women	in	a	nonfasting state.	BoneKEy Reports	3,	article	no:	573.	BPs	impair	Bone	Turnover;	CTX	bone	turnover	marker	(bone	resorption)• Start	BP	→	↓CTX• Stop	BP	&	CTX	rises2Local	practice	since	late	2012• Review	BP	after	5	yrs• Drug	holiday• Routine	monitoring	CTX	at	baseline,	4	months	and	12	monthsOur	aim	was	to	analyse	changes	in	CTX	on	stopping	long	term	bisphosphonate	treatment	to	guide	clinical	decision-making	on	the	duration	of	treatment	cessationPotential	for	harm• Atypical	fractures,	osteonecrosis	of	the	jaw	(ONJ)• Rare	occurrence,	↑risk	with	increasing	duration3Good	evidence	for	5	years	bisphosphonate	(BP)	treatment1,2 but	beyond	this	less	clear	• BP	long	half-life;	stopping	treatment	→	wears	off	gradually2Drug	holidays increasingly	common	- stop	BP	for	period	of	timePost menopausalMean (0.31 ug/L)Pre menopausalMean (0.19 ug/L)Figure	3:	CTX	at	0,	4,	12	months	for	defined	populationsDelta	CTXMedian	[IQR]	in	ug/LMean	(SD)	in	ug/L%+0.04	[0.01-0.08]+0.04	(0.06)	+42%+0.09	[0.04-0.12]	+0.08	(SD	0.06)	+80%Significant	rise	(>LSC) 47% 69%n	=136n	=117n	=	89a)	≤	pre-menopausal	mean	at	baseline b)	>	pre-menopausal	mean	at	baselineKey:Figure	2:	CTX	at	0,	4,	12	months	all	patients	(<0.51	at	baseline)a)	*0-4m	mean	CTX	+	0.05ug/L	(95%	CI	0.04-0.06)		**0-12m	mean	CTX	+0.09ug/L	(95%	CI	0.07-0.10)b)	*0-4m	mean	CTX	+	0.01ug/L	(95%	CI	-0.01-0.04)		**0-12m	mean	CTX	+0.05ug/L	(95%	CI	0.01-0.09)Overall	population	(figure	2):	•Detectable	rise	in	CTX		seen	from	as	early	as	4	months	in	47%	patients;	69%	at	12	months	Subpopulations	(figure	3):•If	CTX	≤	pre-menopausal	mean	(i.e.	treatment	target)		at	baseline,		statistically	significant	increases	in	CTX	seen	at	4	and	12	months•If	CTX	>	pre-menopausal	mean	at	baseline,	no	significant	change	at	4	months,	significant	by	12	months•No	significant	difference	between	Alendronic	acid	and	Risedronate	seen	(data	not	shown)Monitoring	outcomes	using	population	data	(figure	4):•Baseline	CTX	not	suppressed	to	premenopausal	mean	level	after	5	yrs	of	BP	use	in	32%	patients•Where	CTX	suppressed	at	baseline:-At	4	months	28%	had	significant	rise	in	CTX		that	was	also	above	mean	level	(?consider	re-start)-At	12	months	this	had	risen	to	53%;		47%	CTX	still	suppressed	at	this	stageReferences	Conflicts	of	interest:	None	declared

Can bone turnover markers help to define the duration of biphosphonate drug holidays?

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