Osteoparesis 9/7/12 Ive been working on GMS Medicines 6&10 but those projects are progressing adequately so I was

prompted by this weeks BMJ to return to some work Id been doing on osteoporosis. The leader by Cooper and Harvey (Cooper & Harvey 2012) made me look again at FRAX (Frax 2012) and also alerted me to QFracture (QFracture 2012) (Hippisley-Cox & Coupland 2012) which I hadnt known and was able to study in an updated version. I was struck by the opening sentence of the leader: The management of osteoporosis has been transformed over the past quarter century. That seems an overstatement. Theres been a lot of activity but, while there might have been benefit for a small number of severely affected patients, Im not aware of any benefit at primary care or population level. The risk assessment tools are interesting. Both of them are web-based and easy to use. FRAX incorporates fewer risk factors which makes it quicker to use and less prone to input error but QFractures incorporation of many specified risk factors is educational and theoretically more discriminating. QFracture presents risk of fracture as smileys squares of 10x10 smiley and snarly coloured faces which is clear and easy for the lay person and non-specialist to understand. FRAX does something different and strange. It has a chart like a Joint British Society vascular risk chart showing age on the horizontal axis and 10-year risk of fracture on the vertical axis with coloured bands indicating what are called low, intermediate and high risk. However, whereas a vascular risk chart has more red (indicating high risk) with increasing age, a FRAX chart has less red at extreme old age. I think the reason is that the very old wont live long enough to have the fractures that theyd be at risk of having if they lived long enough. I wonder if presenting and labelling the risk thus is logical. Bisphosphonates dont necessarily work beyond 5 years so 10 years seems too long for a risk estimate. If prevention works within a year then a one-year estimate of risk would be appropriate. Clinically evident vertebral fracture isnt specifically incorporated into the calculation for either FRAX or QFracture even though - as the FRAX website acknowledges it confers a high risk. FRAX has the advantage over QFracture of a specific Read Code so that data entry and retrieval are easier and more reliable. A month or two ago, when I started working on osteoporosis, I identified patients with a history of fracture and studied the notes of the oldest patients. Now, Ive used the two tools to estimate these patients risks. The FRAX estimates range from 4% to 33% and the QFracture estimates from 2% to 20%: the discrepancy between the two tools is bigger than I expected from the BMJ paper. None of the risks are high. Several patients have intermediate risk and Ive experimented on paper and screen to find out how their risks vary with input data. In FRAX the intermediate-risk zone (before bone density is known and where densitometry is suggested) is about 10-20% for 70-year-olds and about 20-40% for 85-year-olds. Patients aged 70y or 85y are unlikely to have t-scores higher than -1 or -2 so lets assume that densitometry doesnt move any or many of the these patients into the low-risk zone. 70-year-olds with risks of 10% and 20% will have risks after a densitometry t-score of -5 of 40% and 66% respectively. 85-year-olds with risks of

20% and 40% will have risks after a densitometry t-score of -5 of 48% and 62% respectively. So densitometry increases risk by a maximum of 3-4 fold in 70-year-olds and 2-3 fold in 85-year-olds. If we convert these 10-year risks to 1-year risks the percentages are small. If bisphosphonates produce a relative risk reduction of 50% we have a minimum number needed to treat after densitometry of 30 a year. For drugs with known and still to be discovered toxicity and an outcome this is unimpressive. Cooper, C. & Harvey, N.C., 2012. Osteoporosis risk assessment. BMJ (Clinical research ed.), 344, p.e4191. Frax, 2012. FRAX Calculation Tool UK. Available at: http://www.shef.ac.uk/FRAX/tool.jsp? country=1#notes [Accessed July 8, 2012]. Hippisley-Cox, J. & Coupland, C., 2012. Derivation and validation of updated QFracture algorithm to predict risk of osteoporotic fracture in primary care in the United Kingdom: prospective open cohort study. BMJ (Clinical research ed.), 344, p.e3427. QFracture, 2012. QFracture 2012 risk calculator. Available at: http://www.qfracture.org/.