Osteoporosis, available treatment and ONJ

What is osteoporosis?

Osteoporosis is a systemic condition characterized by low bone mass and deterioration of the microarchitecture of the bone. This can lead to bone fragility and the increase risk of fractures.

Figure 1 Comparing the microarchitecture of bone in normal vs osteoporosis patients.

How to diagnose and measure osteoporosis

One thing doctors can do is to measure the Bone Mineral Density (BMD) of the bone using dual energy X-ray absorptiometry (DXA). The lower a person’s BMD means a higher risk of fractures.

T-scores and Z-scores are used to express and measure a person’s severity of  bone loss and thus used to diagnose osteoporosis. The T-score is the number of standard deviations(SD) away from the mean BMD of an adult aged 30 years old. According to the World Health Organization(WHO) criteria, diagnosis of osteoporosis can be made based on a patient’s T-score.

Table 1 Interpretation of T-scores according to the WHO criteria

T score	Interpretation
-1 and or above	Normal
Between -1 and -2.5	Osteopenia
-2.5 or lower	Osteoporosis

Z-scores are used to assess patients younger than 50 years of age as the score represents the number of SD away the patient is from age and sex matched mean BMD.  Prompt investigation is required with a Z-score under -2.

Risk factors for Osteoporosis and what can you do to reduce it

There have been a multitude of risk factors that contribute to osteoporosis. It has been established that some medications can increase a patient’s risk of bone fractures and cause osteoporosis. On the other hand, some constitutional factors such as the female gender, aging as well as race increase patient’s risks too.

Fortunately there are also life style and nutritional factors one can modify to help reduce the risk of osteoporosis and fractures. Studies have shown that smoking, excessive alcohol consumption and lack of physical activity increases the risk of patients getting fractures.

Therefore by exercising more, smoking less and drinking less one can reduce the risk of fractures. Patients can improve their hand eye co-ordination, balance and muscle strength through exercising. This greatly reduces the risk of falls and thus is a great preventer for fractures. Weight bearing exercises have also demonstrated to increase BMD in some instances.

Health supplements such as calcium and vitamin D are essential for bone health. According to the Australian Therapeutic Guidelines (TG), approximately 1300mg of calcium as well as maintaining a level of 25-OH vitamin D above 75nmol/L is crucial for the prevention and maintenance treatment of osteoporosis.

Treatments available for osteoporosis in Australia

Table 2 Summary of available treatment for osteoporosis in Australia

Medication	How it works	Benefits	Cons	Special consideration
Bisphosphonate    Alendronate (oral)    Risedronate (oral)    Zoledronic Acid (IV)	Decrease bone resorption(bone loss)	First line therapy to treat osteoporosis. Flexible dosing schemes such as once daily, weekly or monthly. IV bisphosphonates are only a once yearly dose	Associated with oesophagitis and in worse cases of oesophagel ulceration. Osteonectrosis of the jaw (ONJ) is a rare but serious documented side effect of bisphosphonates.	Oral bisphosphonate therapy requires the patient to stay upright for 30 mins after ingesting to reduce risk of oesophagitis. See your dentist before starting bisphosphonates.
Raloxifene	Selective Oestrogen Recptor Modulator that provides the benefits of oestrogen to the bones while reducing the risk of breast cancer associated with oestrogen supplementation	Less risk of breast cancer compared to HRT.	Equal risk of DVT compared to HRT supplementation. Less beneficial than bisphosphonates and HRT individually. Only effective in reducing fractures on the vertebrae.
Strontium ranelate	Increase bone formation and decrease bone resorption	Well established evidence in reducing vertebral fractures in women.	Increase risk of VTE.	Previously only approved for female patients, now approved for both men and women. Take at night time. Avoid taking strontium and calcium together as it affects its absorption.
Denosumab	Decrease bone resorption and loss by inhibiting RANKL.	New therapy with a completely new mechanism of action. Injections come once every 6 months. Great results directly comparable to alendronate.	Not much evidence is documented regarding its side effect. Long term safety profile is not well established.	One case reporting of ONJ. Consult dentist for checkup before starting therapy.
Hormone Replacement Therapy (HRT)	Oestrogen effects from HRT helps reduce bone loss.		Increases the risk of breast cancer as well as stroke, heart diseases and blood clots	Lacking evidence of long term benefits past 5 years of HRT.
Teriparatide	Increases bone formation.	Only therapy that actively increases bone formation.	Only reserved for patients who cannot tolerate all the other therapies. Increases the chance of getting bone sarcoma (cancer). Never use in patients under 25 years old.	Maximum life time exposure of 18 months (1.5 years) Only a specialist may initiate this therapy.

What is Osteonecrosis of the Jaw (ONJ)? What can be done about it?

Osteonecrosis of the Jaw (ONJ) is a rare but serious complication associated with bisphosphonate usage. Although it is prevalently warned to all patients on bisphosphonates, it has mainly been seen in patients receiving intravenous bisphosphonates who also underwent dental surgery during the treatment.

It seems that ill fitting dentures as well as performing dental extractions during bisphosphonate treatment are major risk factors of developing ONJ.

It is recommended to patients to have a thorough dental examination prior to commencing bisphosphonates. Doctors should also ensure patients have all necessary extractions and surgery performed prior to commencing bisphosphonates to reduce the risk of bisphosphonate related osteonecrosis of the jaw (BRONJ).

The reason why this is recommended is because the drug is absorbed into the bone and can have lasting effects from 1 to 10 years. It is unclear if stopping bisphosphonates before planned dental extractions would reduce the risk of BRONJ, but it is prudent to do so.

If dental extraction is absolutely necessary, the C-terminal telopeptide (CTX) concentration is a good indicator to determine whether it is safe to perform dental surgery. CTX is a breakdown product of bone resorption, and thus its concentration give doctors a good idea of bone turnover. A normal concentration of CTX is around 400-500 picograms/mL.

If the CTX concentration in the patient is more than 150 picograms/mL, dental surgery can safely proceed. If it is less than 150 picograms/mL, the patient will need to cease bisphosphonates temporarily. Usually CTX levels increase by 25 picograms/mL every month after ceasing bisphosphonates. By monitoring CTX levels, practitioners can determine the length of time the bisphosphonate needs to be ceased before starting dental surgery.

Bisphosphonates can then be resumed 10 days after the extraction.

Note: While the new medicine denosumab is not a bisphosphonate, there has been an incidence of ONJ occurring during treatment. Prescribers are also recommended to exercise the same level of caution and recommendations as for patients on bisphosphonate therapy, and ensure all necessary dental work is completed before starting denosumab.

References:

1. Therapeutic Guidelines - Endocrinology. 4th edition. Melbourne: Therapeutic Guideline limited; 2009.
2. Osteoporosis microarchitechture comparison [image on the Internet]. 2013 [updated 15 Sep 2013; cited 16 Sep 2013]. Available from: http://physioworks.com.au/injuries-conditions-1/osteoporosis#
3. Australian Medicines Handbook. 2013 edition. Adelaide: Pharmaceutical Society of Australia; 2013. pg 419-435
4. Denosumab (Prolia) for postmenopausal osteoporosis. NPS RADAR[serial online]. 2010 Dec [cited 16 Sep 2013]; Available from http://www.nps.org.au/publications/health-professional/nps-radar/2010/december-2010/denosumab
5. Therapeutic Guidelines - Oral and Dental. 2nd edition. Melbourne: Therapeutic Guideline limited; 2012. pg.152-156