Surface-bound bisphosphonates enhance screw fixation in rats—increasing effect up to 8 weeks after insertion

Figures & data

Table 1.  Ellipsometric film thicknesses and surface mass densities of fibrinogen and the two bisphosphonates pamidronate and ibandronate on silicon

	Film thickness, Å		Surface mass
	mean	SD	density, μg/cm2
Fibrinogen	840	68	10.1
Pamidronate	30	18	0.36
Ibandronate	10	4	0.12

Table 2.  Biomechanical data for the study on the effect of acid etching

	Treatment	n	Mean	SD
Force (N)	Blank	12	38	7
	Acid etched	11	38	4
	Bisphosphonates	10	50	15
Stiffness (N/mm)	Blank	12	65	23
	Acid etched	11	79	15
	Bisphosphonates	10	113	21
Energy (Nmm)	Blank	12	23	7
	Acid etched	11	21	5
	Bisphosphonates	10	24	10

Table 3.  The effects of acid etching and bisphosphonate coating of the screws, expressed as 95% confidence intervals for the difference between mean values in group comparisons. P-values are based on unpaired t-tests

	Acid etched vs. blank			Bisphosphonates vs. blank			Bisphosphonates vs. acid etched
	mean	(95% CI)	P-value	mean	(95% CI)	P-value	Mean	(95% CI)	P-value
Force (N)	0	(–12 to 12)	1.0	32	(5 to 58)	0.01	32	(6.3 to 57)	0.01
Stiffness (N/mm)	22	(–2.7 to 46)	0.1	74	(46 to 102)	< 0.001	43	(23 to 63)	< 0.001
Energy (Nmm)	–8.7	(–33 to 14)	0.5	4.3	(–28 to 36)	0.8	14	(–18 to 47)	0.4

Table 4.  Biomechanical data for each group in the study on cancellous vs. cortical bone

		Biomechanical data
Bone structure	Treatment	n	mean	SD
Force (N)
Cancellous	Control	9	40	4.8
	Bisphosphonates	9	46	6.3
Cortical	Control	7	56	16
	Bisphosphonates	7	73	9.1
Stiffness (N/mm)
Cancellous	Control	9	84	34
	Bisphosphonates	9	85	32
Cortical	Control	7	114	54
	Bisphosphonates	7	141	48
Energy (Nmm)
Cancellous	Control	9	20	6.5
	Bisphosphonates	9	27	8.8
Cortical	Control	7	29	7.8
	Bisphosphonates	7	37	12

Table 5.  The effect of bisphosphonate-coated screws in cancellous vs. cortical bone described as the 95% confidence interval for the difference between means, expressed as percentage increase from controls. The p-values are based on unpaired t-tests

Bone structure		Percentage increase as a result of bisphosphonate treatment,		P-value	Treatment × bone structure a
		mean	(95% CI)
Force (N)	Cancellous	15	(2.1 to 28)	0.02	0.2
	Cortical	30	(6.0 to 55)	0.03
Stiffness (Nmm)	Cancellous	1.2	(–35 to 38)	0.9	0.6
	Cortical	24	(–23 to 71)	0.3
Energy (Nmm)	Cancellous	35	(–0.8 to 71)	0.09	0.6
	Cortical	28	(–9 to 64)	0.2

aP-values for the interrelationship between effect of treatment and bone structure were calculated with unpaired t-test on the bisphosphonate/control ratio in bilateral experiments in a cancellous bone group vs. the same ratio in a cortical bone group.

Table 6.  The effect of bisphosphonate and the effect of time in cancellous bone, described with p-values based on 2-way ANOVA (ln-transformed)

	Time	Treatment	Time × treatment a
Force (N)	< 0.001	< 0.001	0.02
Stiffness (N/mm)	< 0.001	0.004	0.4
Energy (Nmm)	< 0.001	< 0.001	< 0.001

aP-values for the interrelationship between treatment and time (i.e. whether effect of treatment changed significantly changed with time).

Table 7.  Biomechanical data for the study on time sequence in cancellous bone

		Biomechanical data			Percentage increase as a result of bisphosphonate
Time	Treatment	N	mean	SD	mean	(95% CI)
Force (N)
1	B	10	32	13	19	(–13 to 50)
1	C	11	27	4.9
2	B	8	62	21	27	(–5.7 to 59)
2	C	9	49	9.4
4	B	6	120	37	79	(31 to 127)
4	C	7	67	17
8	B	8	170	53	102	(50 to 154)
8	C	10	84	38
Stiffness (N/mm)
1	B	10	55	17	3.8	(–19 to 26)
1	C	11	53	9
2	B	8	90	17	20	(–5.5 to 46)
2	C	9	75	23
4	B	6	122	19	25	(–2.4 to 51)
4	C	7	98	29
8	B	8	144	19	30	(12 to 48)
8	C	10	111	24
Energy (Nmm)
1	B	10	16	4.8	6.7	(–19 to 32)
1	C	11	15	4.1
2	B	8	35	14	25	(–13 to 63)
2	C	9	28	6.3
4	B	6	45	34	32	(–49 to 114)
4	C	7	34	6.6
8	B	8	113	34	197	(122 to 273)
8	C	9	38	25

B – Bisphosphonates; C – Control

Table 8.  The effect of bisphosphonate and the effect of time in the cortical bone study, described with p-values based on 2-way ANOVA (ln transformed)

	Time	Treatment	Time × treatment a
Force (N)	< 0.001	< 0.001	< 0.001
Stiffness (N/mm)	< 0.001	0.03	< 0.001
Energy (Nmm)	< 0.001	< 0.001	< 0.001

aP-values show the interrelationship between treatment and time (i.e. whether effect of treatment changed significantly with time).

Table 9.  Biomechanical data for the study on time sequence in cortical bone

		Biomechanical data			Percentage increase as a result of bisphosphonate
Time	Treatment	n	Mean	SD	mean	(95% CI)
Force (N)
0.5	B	10	51	5.6	6.3	(–10 to 23)
0.5	C	9	48	11
1	B	10	59	14	–11	(–27 to 6.1)
1	C	10	66	11
2	B	11	94	16	29	(9.3 to 48)
2	C	11	73	18
4	B	5	132	23	69	(32 to 106)
4	C	6	78	26
8	B	9	133	26	43	(16 to 70)
8	C	7	93	25
Stiffness (N/mm)
0.5	B	10	91	15	–5.2	(–17 to 6.5)
0.5	C	9	96	9.7
1	B	10	90	21	–4.3	(–20 to 11)
1	C	10	94	14
2	B	11	104	19	24	(7.2 to 40)
2	C	11	84	14
4	B	5	151	8.2	43	(32 to 53)
4	C	6	106	11
8	B	9	140	22	–4.8	(–17 to 7.6)
8	C	7	147	15
Energy (Nmm)
0.5	B	10	22	5.2	10	(–17 to 37)
0.5	C	9	20	6.5
1	B	10	29	8.0	–6.5	(–28 to 16)
1	C	10	31	7.5
2	B	11	61	13	45	(19 to 71)
2	C	11	42	13
4	B	5	97	30	126	(52 to 199)
4	C	6	43	22
8	B	9	90	52	114	(26 to 203)
8	C	7	42	20

B – Bisphosphonates; C – Control

Table 10.  Biomechanical data for the study on long-term effects

	Treatment	n	Mean	SD
Force (N)	Bisphosphonate	9	229	52
	Control	10	184	40
Stiffness (N/mm)	Bisphosphonate	9	320	36
	Control	10	285	47
Energy (Nmm)	Bisphosphonate	9	109	42
	Control	10	80	24

Table 11.  95% confidence intervals for the difference between mean values in group comparison in the longterm effect study. P-values are based on unpaired ttests

	Bisphosphonates versus control
	mean	(95% CI)	P-value
Force (N)	25	(1.6 to 47)	0.05
Stiffness (N/mm)	12	(–0.9 to 25)	0.09
Energy (Nmm)	36	(–3 to 75)	0.08