Microsurgical Reconstruction of the Jaws Using Vascularised Free Flap Technique in Patients with Medication-Related Osteonecrosis: A Systematic Review

Received Jan 21, 2018; Revised Apr 2, 2018; Accepted May 9, 2018

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1. Introduction

Bisphosphonates (BP) are antiresorptive drugs used in the management of conditions as diverse as osteoporosis and metastatic bone diseases. These drugs are widely administered and generally well tolerated by patients. In 2003, Marx et al. [1] first reported a nonhealing necrosis of the maxillofacial region in some patients taking BPs.

In the last decade researchers have discovered that BPs not exclusively cause osteonecrosis of jaws, as other drugs, such as antiresorptive (bone-targeted) agents like denosumab, but also were found to cause it. In addition, monoclonal antibodies able to bind and selectively inhibit VEGF-A, specifically mTOR inhibitors, can also cause osteonecrosis of the jaw [2–6].

For this reason, in 2014 the bisphosphonate-related osteonecrosis of the jaw (BRONJ) nomenclature was changed by the position paper of the American Association of Oral and Maxillofacial Surgeons (AAOMS) special committee on Medication-Related Osteonecrosis of the Jaws (MRONJ) [7]. The term “medication-related osteonecrosis of the jaws” (MRONJ) refers to a complication associated with groups of medications, such as antiangiogenic or antiresorptive drugs [8]. These medications can have different indications depending on their mode of administration (Tables 1 and 2) [9, 10].

Table 1

Antiresorptive drugs used in oncologic and nononcologic patients. Btl: bottle; IM: intramuscular; IV: intravenous; MM: multiple myeloma; PO: orally; SC: subcutaneous; SRE: skeletal-related event; Tab: tablet.

Pharmacologic active ingredient	Formulation	Route of administration	Indication and frequency
Alendronic acid (sodium salt)	Tab 70 mgTab 10 mg	PO	Treatment of postmenopausal osteoporosis (70 mg/week) Treatment of osteoporosis in men (70 mg/week)Treatment and prevention of osteoporosis induced by glucocorticoids (70 mg/week)
Alendronic acid + cholecalciferol	Tab 70 mg/5600 UI	PO	Treatment of postmenopausal osteoporosis in patients with unsupplemented vitamin D deficit (70 mg/week)
Ibandronic acid (monosodium salt monohydrate)	Tab 50 mgBtl 6 mg/6 mlTab 150 mgBtl 3 mg/3 ml	POIVPOIV	Prevention of SREs in breast cancer patients with bone metastases (50 mg/day p.o. or 6 mg every 3–4 weeks iv.)Treatment of hypercalcemia of malignancyTreatment of postmenopausal osteoporosis...