Mronj and Coagulation cascade Flashcards
Whchronic enchat is MRONJ?
Medication-related osteonecrosis of the jaws is a condition whereby there is an area of the exposed jaw bone that persists for more than 8 weeks in a patient on bisphosphonates or monoclonal antibodies targeting bone resorption and in some instaces other medications though less rare.
The important aspect is the absence of cancer in the site and no history of radiotherapy to the head and neck region.
What are some of the other causes of osteonecrosis of the jaws?
- Anatomical
- Smoking
- Diabetes
- Othe rmedications
What is mechanism of action of oral bisphosphonates?
Bisphosphonates are antiresorptive agents that inhibit osteoclast-mediated bone resorption, thereby helping to prevent pathological bone loss in conditions such as osteoporosis, Paget’s disease, and metastatic bone disease.
Structurally, bisphosphonates are analogues of pyrophosphate with a high affinity for hydroxyapatite in bone. They are preferentially incorporated into sites of active bone turnover. Once internalized by osteoclasts during bone resorption, bisphosphonates exert their effects via two main mechanisms:
- Non-nitrogen-containing bisphosphonates (e.g. etidronate, clodronate) are metabolized into cytotoxic ATP analogues within osteoclasts, leading to cellular apoptosis.
- Nitrogen-containing bisphosphonates (e.g. alendronate, zoledronate) inhibit farnesyl pyrophosphate synthase (FPPS) in the mevalonate pathway. This blocks prenylation of small GTPase signaling proteins (e.g. Ras, Rho, Rac), disrupting osteoclast cytoskeletal organization, vesicular trafficking, and survival, ultimately leading to apoptosis.
By suppressing osteoclast function and survival, bisphosphonates reduce pathological bone resorption and promote skeletal stability.
What is the mode of function of IV bisphosphonates?
They work similarly to oral bisphosphonates but are more potent and thus are prescribed to people who show no progress towards improvement of their bone condition.
What is Denosumab and what is it’s function?
Denosumab is a human monoclonal antibody that binds the cytokine RANKL thus de-activating it. RANKL inhibition blocks osteoclast maturation, function and survival, thus reducing bone resorption. Unlike oral or IV bisphosphonates, Denosumab does not bind to bone minerals.
What is Romosozumab and what it’s function?
Romosozumab is a humanized monoclonal antibody that targets endogenous cytokine that inhibits bone formation and stimulates bone resorption. By blocking, romosozumab has a “dual effect” of increasing bone formation and decreasing bone resorption.
What is the management advice for patients at risk of medication-related osteonecrosis of the jaw undergoing a bone-invasive dental procedure?
- Inform the patient about risk of MRONJ and obtain consent
- See advice on drug holidays and scheduling of procedures
- Do not use antibiotic prophylaxis to reduce the risk of MRONJ. If an active infection occurs - it should be treated with antibiotics.
- Ensure optimal oral hygiene before and after the procedure
- Reduce the plaque load with mechanical debridement and pre- and post-procedural CHx mouthwash
- Minimise trauma and periosteum stripping
- Monitor the oral wound until it heals
- Do not debride nonhealing wounds
- Refer to a specialist if the bone is still visible at 8 weeks post-op
What are the drug holiday recommendations for anti-resorptive therapy?
- Oral and IV bisphosphonates - although stopping bisphosphonates for a short period is unlikely to cause harm in a patient at low risk of fracture, there is no evidence that this approach reduces the risk of medication-related osteonecrosis of the jaw.
- Denosumab is a reversible antiresorptive administered every 6 months for osteoporosis. If it is possible to delay a bone-invasive dental procedure in a patient taking denosumab for osteoporosis, ideally schedule the procedure just before the next dose of denosumab. It is never appropriate to interrupt or delay the dose of denosumab; withdrawal of denosumab has been associated with an increased risk of spontaneous vertebral fractures.
- Remosozunab should not be discontinued
What is ORN?
Osteo-radio necrosis is an exposed irradiated bone that fails to heal over three months in the absence of residual or recurrent tumour.
What are the clinical findings related to ORN?
Clinical:
1. Small areas of exposed bone
2. Orocutaneous fistula, pathologic fracture secondary to devitalised/necrotic bone
Radiographic:
1. Osteolytic mandibular lesion
2. Sequestreum
3. Pahologic fracture
What is the triple H response to radiotherapy?
- Hypovascularity
- Hypocellularity
- Hypoxia
What is the potential treatment for the triple H response?
Hyperbaric oxygen:
- Stimulates angiogenesis
- Corrects hypoxia
- Allow for cellular proliferation
What is the Marx Osteoradionecrosis protocol?
- Patient receives 30 sessions of HBO at 2.4 ATA for 90 minutes. Patients who respond are Stage 1 and undergo 10 sessions to continue healing
- Patients who have not improved in 30 sessions receive transoral debridement with primary wound closure
- Stage I or II nonresponders or those patients who present
with pathologic fracture, cutaneous fistula, or osteolysis
involving inferior border of the mandible. Patients undergo
segmental resection, stabilization of segments, and 10
postsurgical HBO sessions followed by delayed
reconstruction.
What are the oral complications of radiotherapy to head and neck?
- Oral pain
- Mucositis
- Reduced salivary flow
- Oral infection
- Trismus
- Altered taste
What are the clinical differences between mronj and orn?
MRONJ - soft tissues are not affected, effects the entire bone, resection with soft tissue replacement or free vascularised flap
ORN - soft and hard tissue affected, non-surgical management possible, resection of radiated bone can effect cure, often need to replace blood supply and tissues both soft and hard.
What is a normal platelet count?
150,000-350,000
What patients require anticoagulation or antiplatelet therapy?
- Patients with DVT and pulmonary emboli
- Patient with artificial heart valves
- Patient with congenital thrombophilia
- Patients with atrial fibrilation
- Patients with drug eluting coronary artery stents
- Patient with hypercoagulation
What are some local measures for haemostasis?
- Gauze pressure
- Gelatin sponges
- Absorbable oxycellulos (Surgicell)
- Collagen
- Bone wax
- Suturing
- Activated toppical human thrombin
- Fibrin glue
- Rinse with tranexamic acid hold 10 mL in mouth for 2.5 minutes preop
How can we determine stroke risk?
CHA2DS2VASc score. This stands for:
C - Congestive heart failure y=1
H - Hypertension y=1
A2 - Age 75 or more y=2
D - Diabetes mellitus y=1
S2 Stroke y=2
V - vascular disease y=1
A - Age 65-74 y=1
Sc - Sex Female y=1
Maximum score is 9
How do you assess major bleeding risk?
HAS-BLED:
Hypertention
Abnormal liver/renal function
Stroke history
Bleeding predisposition
Labile INR
Elderly more than 65
Drug/alcohol usage
What do you do after every extraction?
WRITTEN POSTOPERATIVE INSTRUCTIONS
What is the difference between NOACs and warfarin in terms of clotting cascade and oral implication of use of tranexamic acid after extractions?
Clotting Cascade:
Warfarin inhibits vitamin K epoxide reductase, reducing activation of factors II, VII, IX, X (extrinsic and common pathways). This impairs thrombin formation and fibrin clot stability. Onset is slow (36–72 hrs), and INR monitoring is required.
NOACs act directly on active clotting factors:
Dabigatran: inhibits thrombin (IIa)
Rivaroxaban, Apixaban, Edoxaban: inhibit factor Xa
NOACs have rapid onset, predictable effects, and do not require monitoring.
Oral Implications – Tranexamic Acid Post-Extraction:
Tranexamic acid inhibits plasminogen activation, preserving fibrin clots locally.
Warfarin patients (INR ≤3.5): continue therapy; apply tranexamic acid mouthwash (4.8%) QID for 2–5 days, or soaked gauze to reduce bleeding.
NOAC patients: time extraction ≥12–24 hrs after last dose; resume NOAC 24–48 hrs post-op. Use tranexamic acid similarly to aid haemostasis.
