Preventive effect of doxycycline sponge against bisphosphonate-related osteonecrosis of the jaws: an animal study

Figures & data

Table 1. Comparison of CTx, TRACP 5b and ALP levels between the groups.

	Control	Group I	Group II	Group III
	*Mean ± SD (median)	Mean ± SD (median)	Mean ± SD (median)	Mean ± SD (median)	**P value
CTx (ng/ml)	11.86 ± 6.09 (10.7)	12.73 ± 5.29 (11.3)	12.34 ± 9.77 (10.5)	14.2 ± 7.28 (10.8)	0.901
ALP (U/L)	50.15 ± 20.03 (45.7)	49.12 ± 26.27 (41.3)	51.21 ± 37.7 (44.6)	55.04 ± 44.22 (31)	0.927
TRACP 5b (ng/ml)	19.93 ± 9.0 (16.8)	18.24 ± 11.82 (14.2)	15.31 ± 5.97 (15.1)	14.68 ± 12.5 (12.5)	0.233

*SD: Standard deviation.

**Kruskal–Wallis test (p < 0.05).

Table 2. Evaluation of serum biomarkers levels between non-ONJ and ONJ groups.

	ONJ group	Non-ONJ group
	Mean ± SD (median)	Mean ± SD (median)	*P value
CTX (ng/ml)	11.96 ± 7.89 (9.8)	13.48 ± 6.12 (12.06)	0.401
ALP (U/L)	40.94 ± 22.71 (29.8)	60.21 ± 35.47 (53.03)	0.139
TRACP 5b (ng/ml)	15.4 ± 10.54 (14.03)	18.43 ± 9.17 (15.37)	0.258

*Mann–Whitney U-test (p < 0.05).

Table 3. Evaluation of clinical findings among the groups.

	Control	Group I	Group II	Group III
Clinical findings	n (%)	n (%)	n (%)	n (%)	*P value
Grade 0	6 (100%)	0 (0%)	3 (50%)	4 (66.7%)	0.022*
Grade 1	0 (0%)	4 (66.7%)	1 (16.7%)	2 (33.3%)
Grade 2	0 (0%)	2 (33.3%)	2 (33.3%)	0 (0%)

*Chi-square test (p < 0.05).

Figure 1. Clinical appearance of extraction sites: control group; complete mucosal healing, Group I; osteonecrosis with swelling and hyperaemia, Group II; osteonecrosis, Group III; complete mucosal healing.

Figure 2. Histopathological view showing the normal and necrotic bone areas on the jaws: (A) control, normal bone cellularity, (B and C) Groups I and II, large necrotic areas (stars) bone, apoptotic osteoclasts with condensate nuclei (arrowhead), (D) Group III, small amounts of necrotic bone, control like histological features (HE, 100×).

Figure 3. Evaluation of the ratio of necrotic bone area to the total bone area among the groups.

Figure 4. Histopathological view showing the osteoblastic activity: cuboidal and dense stained osteoblasts (arrow) reflected osteoid formation. Basophilic reversal lines (arrowhead) were considered to identify the bone remodelling (A) control, moderate osteoblastic activity, (B and C) Groups I and II, mild to moderate osteoblastic activities along with small amounts of reversal lines, (D) Group III, an increased osteoblastic activity (Toluidin blue 400x).

Figure 5. Histopathological view showing the severity of inflammation among the groups: (A) control, normal appearance, (B and C) Groups I and II, focal inflammation areas, neutrophils and foamy histiocytes surrounding the extraction sites, severe inflammation, (D) Group III, similar with control group, mild inflammation (PAS + HL 200×).

Table 4. Evaluation of severity of inflammation among the groups.

	Control	Group I	Group II	Group III
Inflammation	n (%)	n (%)	n (%)	n (%)	*P value
Normal	5 (83.3%)	0 (0%)	0 (0%)	3 (50%)	0.004*
Mild	1 (16.7%)	0 (0%)	1 (16.7%)	3 (50%)
Moderate	0 (0%)	4 (66.7%)	4 (66.7%)	0 (0%)
Severe	0 (0%)	2 (33.3%)	1 (16.7%)	0 (0%)

*Chi-square test (p < 0.01).

Table 5. Evaluation of osteoclast number among the groups.

	Control	Group I	Group II	Group III
Osteoclast numbers	Mean ± SD (median)	*Mean ± SD (median)	*Mean ± SD (median)	*Mean ± SD (median)	*P value
Attached to the bone	3.83 ± 0.98 (3.5)	3 ± 0.89 (3)	4 ± 0.89 (4)	4.33 ± 0.52 (4)	0.106
Detached	0.67 ± 0.82 (0.5)	2.67 ± 1.03 (3)	2.17 ± 0.41 (2)	1.83 ± 0.41 (2)	0.006*
Giant cell	0.67 ± 0.82 (0.5)	2.5 ± 0.55 (2.5)	3.3 ± 0.52 (3)	4.17 ± 0.41 (4)	0.001*
Apoptotic	0.33 ± 0.52 (0)	3.83 ± 0.98 (3.5)	3 ± 0.89 (3)	1.67 ± 0.82 (1.5)	0.001*

*Kruskall–Wallis test (p < 0.01).

Figure 6. Histopathological view showing the osteoclast density: (A) control, osteoclasts (arrowhead) were shown associated with bone surface in their active pole in the control group. (B) Detached (arrowhead) and apoptotic (star) osteoclasts were marked in Group I. (C and D) Osteoclast number with normal appearance was increased in Groups II and III. Giant type osteoclasts were characteristics of that groups (Mallory Triple 400x)