Osteoporosis and its management, in particular, are of major importance in patient dental care.

The condition is more common in women, as the calcium in the bones is lost mainly as a result of menopause, making the bones more brittle and increasing the likelihood that they will fracture easily.

Osteoporosis:

• Important cause of morbidity and mortality
• Fractures – Increased costs for medical care
• Bisphosphonates reduce fracture risk by 50%
• Other issues
• Low diagnosis rate
• Mismatch

Preventing osteoporosis with drugs that prevent the normal bone physiology of removing calcium from the bone skeleton (bone turnover) has revolutionised the care process and greatly reduced the number of fractures. These drugs are also used to prevent bone destruction by tumours, e.g. prostate, breast and lung cancer.

Osteoporosis prevention

Osteoporosis – Diagnosis

Bone fracture due to osteoporosis

• A current or past osteoporotic fracture
• Occurrence of minor fractures
• Low bone mass in the absence of a fracture
• Osteoporosis – BMD deficiency of 2.5 or greater deviations
• standard up to young adulthood in the Caucasian population
• after menopause
• Osteopenia – BMD deficiency of 1 – 2.5 standard deviations by young adulthood

Risk of fracture

Bone mineral density

Each standard deviation decreases BMD:

• Increases the risk of fracture 2-fold(Marshall et al, 1996)
• Osteoporotic fractures, 1:2 women and 1:3 men over 60 years of age
• Vertebral fractures – the cascade effect
• (#1) risk due to vertebral fractures – x4
• (#3) risk due to vertebral fractures – x11

Klotzbuecher et al, 2000

Other risk factors

Risk – Osteoporotic fractures(Nguyen et al, 2004) – includes:

• Family history of fractures
• Sedentary lifestyle or physical inactivity
• Smoking / excessive alcohol consumption
• Late onset menstruation / early menopause
• Low weight / anorexia
• Hyperthyroidism / low testosterone levels – in men / corticosteroids / Ca++ and vitamin D deficiency / GRH therapy

Osteoporosis – why oral drug treatment (pills) does not give results…

When patients feel well, they often stop taking their medication…

Frequently, drugs from the bisphosphonate class are prescribed to treat osteoporosis. These reduce the rate of fractures by 50%. But for these drugs to be effective in tablet form, they need to have a dose rate of 80%. This means that the patient needs to take 80% of the tablets for the drug to take effect.

In reality, only 19-40% of patients take daily medicines as prescribed, and the percentage rises to 31-55% for long-term, weekly medicines.

Bisphosphonates are a BUSINESS OF PROPORTIONS. In a multi-billion dollar global industry, perhaps 80% of patients taking these oral bisphosphonates experience no improvement in health. This was a shocking revelation. So Mega Pharmacy has fought back by changing the way the drugs are administered, so that they are given in injectable form, to ensure that the drugs are actually administered and can work in the bones. This seems like a rational option, but it needs to be looked at more closely.

Why are bisphosphonates important in dentistry?

The mandible or jaw bones are 15 times more prone to biochemical turnover (remodelling) compared to other areas of the skeleton. This increased turnover rate allows teeth to move in the bone and the oral cavity to change shape. If this biology is affected by drugs such as bisphosphonates, if a tooth is extracted when oral surgery is performed on the jaw or mandible, such as the insertion of a dental implant, the bone may not heal. 

It is also possible that dental infections and abscesses will not heal, even if endodontic treatment is applied and the dental nerve dies.

This condition was originally known as osteonecrosis maxillaris (ONJ), but is now associated with a number of drugs that affect bone turnover. It has therefore been renamed medication-associated osteonecrosis of the jaw (MRONJ).

MRONJ can become life-threatening.

The risk of jaw osteonecrosis is reported to be low. One of the reasons for this is that 80% of patients who take medication by routeoral, are not taking the correct treatment, and the actual incidence is likely to be much higher than reported.

However, the shift from oral to injectable treatment is worrying:

• The risk of MRONJ is 10 times higher for injectable bisphosphonates than for oral medicines;
• The risk of MRONJ being irreversible is higher (injectable drugs are more potent);
• The risk of developing MRONJ is higher with prolonged drug treatment;
• The risk of developing MRONJ is higher in patients taking steroids;
• The risk of MRONJ is higher in periodontal diseases;
• MRONJ can be bilateral and multifocal, especially in cancer patients;
• MRONJ Tori and other bone exostoses (growths) may increase the risk;

Tori (bull horns) are benign bony growths of the jaw bones. Patients suffering from Tori are less likely to develop osteoporosis and more likely to develop jaw osteonecrosis if given bisphosphonate treatments.

How do bisphosphonates work?

Bone contains a soft gelatinous substance, like a collagen matrix, which is calcified by cells called osteoblasts, derived from stem cells.

The transcription factor(Cbfa1) is the main gene that controls osteoblast differentiation.

Once formed, the bone is constantly changing and reshaping itself. They manage the forces applied to the bone and its elongation and help fractures heal. The cells that destroy bone tissue are called osteoclasts.

Osteoclasts are important in osteoporosis because they are responsible for extracting calcium from the bones and releasing it into the bloodstream.

If the balance of the calcium deposit does not correspond to the amount of calcium extracted from the bone, then problems occur; bones become brittle (osteoporosis) and fractures can occur.

Therefore, the most important aspect of treatment is to stop osteoblasts from functioning.

The understanding of osteoclast formation and activation increased considerably with the discovery of the RANKL/RANK/OPG system in the mid-1990s.

Pre-osteoblast cells contain a RANKL receptor (receptor activator of nuclear factor kappa ligand receptor) in their membrane that binds to its RANK receptor on the surface of osteoclasts and precursor cells. This binding regulates the rate of osteoclast formation and calcium loss from bone.

Osteoprotegerin (OPG) is secreted by binding of osteoblasts to RANKL.

RANK (receptor activator of nuclear factor kappa) cannot bind because the receptor is now occupied and osteoclast formation is slowed/stopped. This prevents bone resorption and calcium extraction from the skeleton.

Bisphosphonates act in the same way as OPG. The drug blocks the RANKL receptor and bone resorption stops.

Calcium stays in the bones, they become stronger and the likelihood of fractures decreases.

Therefore, how can we solve this problem for patients who take bisphosphonates and need dental treatment.

CTX Test (Cross Laps Test)

C-terminal Telopeptide is a protein released when osteoclasts resorb bone, thus being a measure of bone remodelling and indicating how active osteoblasts are when the blood sample is taken.

Professor Alistair Goss of Adelaide has calculated that a CTX level > 200 pg/ml present in a pre-prandial blood sample indicates a somewhat safe level for performing oral surgery procedures involving bone, e.g. dental extractions, placement of dental implants, apicoectomy, etc.

The test is not completely error-free, but it is probably the best indicator of a “safe area for intervention”.

If patients have a low CTX level, after a discussion with the family doctor and/or hospital specialist and a mutual decision, a temporary suspension of the drug treatment may be established. The patient stops bisphosphonate treatment and a blood sample is taken monthly before eating until the Safe Zone is reached.

So, if the initial CTX level is 100 pg/ml, we can expect unchanged CTX levels to reach 200 pg/ml in 4 months.

If the CTX level was 50 pg/ml, we can expect CTX levels on an unanchored basis to reach 200 pg/ml in 8 months.

can the intervention be performed if the CTX level is below 200 pg/ml?

Yes!

But it could be riskier, especially if the drugs are given by injection.

Example of MRONJ

Conclusion

Medication-associated osteonecrosis of the jaw can occur with various drugs that affect bone remodelling, in osteoporosis (bisphosphonates and denosumab) and in cancers that spread to the bone. Drugs that prevent the development of blood vessels in cancers also cause MRONJ.

This aspect is crucial in dentistry and it is important that patients understand the reasons why special care is needed and why treatment can be particularly difficult. If an operation is to be carried out, e.g. in an emergency, it should be gentle and as atraumatic as possible and followed by medical care and careful supervision.

For patients who are about to start treatment with a risk of MRONJ, a rigorous dental check-up is essential and the treatment plan should try to exclude the need for future surgery. The start of drug treatment may be delayed until your doctor considers that the tooth socket has healed completely following extraction.

By working together, we can make the treatment as safe as possible, but there are no 100% guarantees.

We can only do our best.

Thank you for your attention.