A/Professor David Bossingham, James Cook University
Osteoporosis could be defined as “a loss of bone mass sufficient to allow fracture under minimal impact”. There are many forms but it is menopausal and senile osteoporosis which are numerically most important. It has been calculated that 87% of women in Australia will have suffered a fracture from osteoporosis by the age of 79 years. The number of deaths where osteoporosis plays a significant part is not counted but is considered to exceed those of breast, cervix and ovarian cancer combined at >4.500 p.a. The cost is in excess of $ 7.4 billion p.a. in Australia alone. In 2016 there were 26,400 NOF fractures nationally and it is predicted that by 2026 there will be 34,000 and > 60,000 by 2051.
Bone mass is maintained in youth by the combination of an appropriate diet, physical exercise and normal levels of oestrogenic and androgenic hormones. Bone growth is stimulated by these factors but the laying down of new bone by osteoblasts stimulates the development of osteoclasts able to absorb and remodel. Balance is maintained by a complex of peptides, cytokines most specifically osteoprotegerin, RANK and RANK-L (for ligand) a cytokine and its receptor on pre-osteoclastic cells play a central role.
With age the predominance of osteoclastic activity increases and bone mass falls especially quickly in women when the oestrogenic drive is lost. In advanced age there is still likely to be an overall male advantage. Peak bone mass occurs in the mid-twenties, slightly earlier in females, it is axiomatic that failure to achieve this potential will increase the risk of osteoporosis in later life.
The risk of fracture related to osteoporosis can be estimated by the use of simple demographic factors and by the use of bone densitometry using Dual Emission X-ray Absorptiometry (DEXA).
The major risk factors are:
- Family History of trivial trauma fracture
- Previous trivial trauma fracture
- BMI <22
- Smoking and regular alcohol intake
- Chronic Disease such as under treated rheumatoid arthritis
- Previous use of corticosteroid.
Taken together with the bone density of the femoral neck a fracture prediction can be made, there are various scales available personal preference is for www.sheffield.ac.uk › FRAX.
Bone density is assessed by two methods dependent on the patient’s age. For patients less than 45 years of age the “Z” score where the density is compared to the average for age is used and an abnormal result would be <-1.5 S.D below the norm. For all others the “T” score where Bone Mineral Density (BMD) is compared to a fixed point and osteoporosis is defined as a score of < -2.5 S.D. Conventionally density is measured at the femoral neck and the lumbar spine. This latter is less reliable for many reasons and the measurement for the former is used most, in special circumstances measurement at the distal radius can be appropriate. It is important that race relevant figures are compared, Asians are likely to be different to Negroes!
Osteoporosis does occur in men; fractures are much less common but when they do occur the outcome is far worse. After fracture of the neck of femur roughly 25% of women and 35% of men will die in the subsequent year. More than 50% will have severely limited independence and require social support. By any estimate osteoporosis is a major public health issue.
Osteoporosis could be reduced by ensuring that levels of dietary calcium and vitamin D from diet or modest U-V exposure (5 minutes per day between 10am and 4pm in Cairns) are maintained and that regular physical exercise is undertaken especially after school years. The cult of underweight in young women should be discouraged. There is evidence to support a bolus dose of parenteral vitamin D for all pensioners in the late autumn if U-V exposure is likely to be limited as in the southern states or by housing circumstances.
Treatment for osteoporosis is problematic; of the at risk population only about 0.1% will experience a fracture in the next 12 months but this will rise to possibly 2% if there has been one trivial trauma fracture and to 15% if there has been more than one. These figures explain the PBS regulations regarding treatment being made available to those most at risk. The use of calcium and vitamin D supplements is contentious, they are recommended for all requiring treatment, but evidence of benefit is limited and in the case of calcium possibly associated with coronary artery calcification. A conventional balanced diet seems most appropriate.
Active treatment can be directed towards anabolic agents or those which target the action of osteoclasts.
Oestrogens, with or without progesterone still have a place, short term use can give pain relief, they are most effective. The parathormone analogue teriparatide is highly effective but very expensive and reserved for the most severe situations. There is no place for the use of androgenic products or those mimicking the effect of growth hormone.
Bisphosphonates are a range of products whose action is to inhibit osteoclast maturation; they are all effective but when taken by mouth their benefits are reduced by poor absorption and reflux oesophagitis. Parenteral products are uniformly effective but like the oral formulations carry rare side effects such as an immediate cytokine storm and later problems of osteonecrosis of the jaw and diaphyseal fracture. These drugs are maintained in the body for many months and often years, their possible long term consequences are still unknown but are thought to be benign.
A similar effect on bone density can be achieved by using a monoclonal antibody directed against RANKL. Denosumab has the benefits and side effects of the bisphosphonates but has a half-life of just 4 months and can thus be given as a 6 monthly subcutaneous injection. Hypocalcaemia after the first injections can occur and requires blood calcium levels both before and after.
Other types of agent such as the selective oestrogenic receptor modulators (SERM’s), calcitonin and the mildly anabolic strontium products have proved disappointing because of relative inefficacy or side effects respectively. The search for new targets and agents is still active and developments can be expected in what is financially a very lucrative and attractive market.