Clinical study of correlation between C-terminal cross-linking telopeptide of type I collagen and risk assessment, severity of disease, healing after early surgical intervention in patients with bisphophonate-related osteonecrosis of the jaws

Jin-Woo Song; Ki-Hyun Kim; Jae-Min Song; Byung-Do Chun; Yong-Deok Kim; Uk-Kyu Kim; Sang-Hun Shin

doi:10.5125/jkaoms.2011.37.1.1

Journal List > J Korean Assoc Oral Maxillofac Surg > v.37(1) > 1032453

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Song, Kim, Song, Chun, Kim, Kim, and Shin: Clinical study of correlation between C-terminal cross-linking telopeptide of type I collagen and risk assessment, severity of disease, healing after early surgical intervention in patients with bisphophonate-related osteonecrosis of the jaws

Original Article

J Korean Assoc Oral Maxillofac Surg 2011;37(1):1-8.

Published online: 10 January 2011

DOI: https://doi.org/10.5125/jkaoms.2011.37.1.1

Clinical study of correlation between C-terminal cross-linking telopeptide of type I collagen and risk assessment, severity of disease, healing after early surgical intervention in patients with bisphophonate-related osteonecrosis of the jaws

Jin-Woo Song, Ki-Hyun Kim, Jae-Min Song, Byung-Do Chun, Yong-Deok Kim, Uk-Kyu Kim, Sang-Hun Shin

Department of Oral and Maxillofacial Surgery, School of Dentistry, Pusan National University, Yangsan, Korea

Sang-Hun Shin Department of Oral and Maxillofacial Surgery, School of Dentistry, Pusan National university Beomeo-ri, Mulgeum-eup, Yangsan, 626-770, Korea TEL: +82-55-360-5100 FAX: +82-55-360-5104 E-mail: ssh8080@pusan.ac.kr

Received 19 October 2010 Revised 18 January 2011 Accepted 7 February 2011

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Introduction

The utility of the C-terminal cross-linking telopeptide test (CTX) as a method for staging Bisphosphonate-related osteonecrosis of the jaws (BRONJ) and its healing process was examined.

Materials and Methods

A total 19 patients who were diagnosed with BRONJ underwent a fasted morning CTX test, were enrolled in this study. The serum CTX values ranged from 50 to 630 pg/mL (mean 60). The risk assessment was rated according to the CTX values of the individual patient (minimal risk, ≥150 pg/mL, moderate, 100 to 150 pg/mL, high, ≤100 pg/mL). The BRONJ scores were then calculated according to the number of BRONJ lesions and their stage. The operation was done as soon as possible, regardless of BORNJ stage.

Results

The mean duration of bisphosphonate therapy was 4.1 years. Of the 19 patients, 15, 2 ans 2 received alendronate, risedronate and zoledronate, respecively. Of the 19 patients who underwent a sequestrectomy, saucerization and smoothing, 15 healed after the initial surgery, 1 patient healed after one more surgical procedure, 3 patients did not heal completely but showed improvement in symptoms. Therefore, 17 out of the 19 patients healed completely with complete mucosal coverage and the elimination of pain. The risk assessment using the CTX value and disease severity were not correlated (r=-0.264, P=0.275). In addition, the risk assessment using CTX value and healing after surgery were not correlated (r=-0.147, P=0.547).

Conclusion

The serum CTX should be considered carefully by clinicians as part of overall management. Early surgical intervention is of benefit in the treatment of stage II BRONJ.

Keywords: Bisphosphonates, Osteonecrosis, Bisphosphonate-related osteonecrosis of the jaws (BRONJ), Jaw diseases, Collagen type I trimeric cross-linked peptide

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Fig. 1.

Structures of bisphosphonate and pyrophosphonate.

Fig. 2.

The lamina dura remains after extraction.

Fig. 3.

Bone sequestration on mandible after extraction.

Fig. 4.

Bone sequestration on left maxilla with purulent sinusitis.

Fig. 5.

Scatter graph of preoperative BRONJ score and CTX values.(pg/mL) (BRONJ: bisphosphonate-related osteonecrosis of the jaw, CTX: C-terminal cross-linking telopeptide test)

Fig. 6.

Scatter graph of BRONJ score change after operation and CTX values.(pg/mL) (BRONJ: bisphosphonate-related osteonecrosis of the jaw, CTX: C-terminal cross-linking telopeptide test)

Table 1.

Staging and treatment strategies of BRONJ according to the American Association of Oral and Maxillofacial Surgeons

BRONJ stage	Treatment strategy
At risk category No apparent exposed/necrotic bone in patients who have been treated with either oral or IV bisphosphonates	∙No treatment indicated
	∙Patient education
Stage 1 Exposed/necrotic bone in patients who are asymptomatic and have no evidence of infection	∙Antibacterial mouth rinse
	∙Clinical follow-up on a quarterly basis
	∙Patient education and reveiw of indications for continued bisphosphonate therapy
Stage 2 Exposed/necrotic bone associated with infection as evidenced by pain and erythema in the region of the exposed bone	∙Symptomatic treatment with broad-spectrum oral anbiotics with or without purulent drainage (penicillin, cephalexin, clindamycin, or 1st generation fluoro quinolone)
	∙Oral antibacterial mouth rinse
	∙Pain control
	∙Only superficial debridments to relieve soft tissue irritation
Stage 3 Exposed/necrotic bone in patients with pain, infection, and one or more of the following: pathologic fracture, extra-oral fistula, or osteolysis extending to the inferior border	∙Antibacterial mouth rinse
	∙Antibiotic therapy and pain control
	∙Surgical debridment/resection for longer term palliation of infection and pain

(BRONJ: bisphosphonate-related osteonecrosis of the jaw)

Table 2.

Patients treated with BRONJ

Pt No.	Age (yr)	Sex	Indication	Medical comorbidities	Dental comorbidities	Bisphosphonate	Duration (yr)	Lesions (n) Mn. /Mx.	CTX (pg/mL)/ risk assessment	Stage	BRONJ score
1	77	F	osteoporosis	RA	ext.	alendronate	3	1/0	156/mi	II	2
2	72	F	osteoporosis	HT, DM	ext.	alendronate	10	1/0	167/mi	II	2
3	86	F	osteoporosis	HT	ext.	risedronate	3	1/0	122/mo	II	2
4	75	F	osteoporosis	HT, DM	ext.	alendronate	8	1/0	193/mi	II	2
5	78	F	osteoporosis	AP	ext.	alendronate	3	0/1	89/h	II	3
6	66	F	osteoporosis	none	ext.	alendronate	7	1/0	84/h	II	2
7	77	F	osteoporosis	none	ext.	alendronate	3	1/0	110/mo	II	2
8	76	F	osteoporosis	DM, HT	ext.	alendronate	5	0/1	50/h	II	3
9	62	F	osteoporosis	DM	ext.	alendronate	3	1/0	60/h	II	2
10	73	F	osteoporosis	CVA, Hyperthyroidism	imp.	alendronate	10	0/1	210/mi	II	3
11	67	F	osteoporosis	DM	ext.	alendronate	3	1/0	130/mo	II	2
12	76	F	osteoporosis	RA, AP	ext.	alendronate	6	0/1	120/mo	II	3
13	79	F	osteoporosis	HT, Hypothyroidism	ext.	alendronate	6	1/0	100/mo	II	2
14	72	F	osteoporosis	HT, DM	ext.	alendronate	4	1/1	270/mi	II/II	5
15	75	F	osteoporosis	AP, HT, CVA	ext.	risedronate	6	0/1	570/mi	II	3
16	73	M	prostate cancer	none	ext.	zoledronate	2	1/0	630/mi	III	3
17	53	F	breast cancer	none	ext.	zoledronate	6	2/1	270/mi	I/I	3.5
18	71	F	osteoporosis	DM	ext.	alendronate	5	1/0	40/h	III	3
19	79	F	osteoporosis	HT, DM	ext.	alendronate	1	1/0	60/h	II	2

(BRONJ: bisphosphonate-related osteonecrosis of the jaw, Pt No: patient number, CTX: C-terminal cross-linking telopeptide test, Mn.: mandible, Mx.: maxilla, RA: rheumatoid arthritis, HT: hypertension, DM: diabetic melitus, AP: angina pectoris, CVA: central vascular accident, ext: extraction, imp: implant, mi: minimal, mo: moderate, h: high)

Table 3.

BRONJ management outcome

Patient No.	Risk assessment	Preoperation BRONJ score	Postoperation BRONJ score
1	minimal	2	0
2	minimal	2	0
3	moderate	2	0
4	minimal	2	0
5	high	3	1.5
6	high	2	0
7	moderate	2	0
8	high	3	0
9	high	2	0
10	minimal	3	3
11	moderate	2	0
12	moderate	3	1.5
13	moderate	2	2
14	minimal	5	0
15	minimal	3	0
16	minimal	3	0
17	minimal	3.5	0
18	high	3	0
19	high	2	0

(BRONJ: bisphosphonate-related osteonecrosis of the jaw)

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