One of the most important recent advances in osteoporosis has been in the development and application of fracture risk assessment tools to guide pharmacotherapy.
As well as FRAX, QFracture is also in use particularly in primary care. NICE short clinical guidance 146, published last year, describes the use of these tools in clinical practice, including some of their limitations. These tools are continually being refined, with for example, advice about how to modify the output of FRAX in patients receiving higher doses of glucocorticoids, and in those with preferential reductions in bone mineral density at the lumbar spine.
Whereas fracture risk tools are based on ascertainment of established risk factors, additional risk factors for osteoporosis continue to be described. These include neurological disorders such as Parkinson's disease, which is now recognised as having a high risk of fracture presumably due to the associated increase in risk of falls; there is also an increasing array of drugs thought to affect fracture risk including serotonin reuptake inhibitors and H2 antagonists. Conversely, other agents have been suggested to exert previously unknown benefits for fracture risk, such as b1 selective beta blockers.
There have also been important advances recently in terms of the use of drug therapy for osteoporosis. Probably the most significant has been the emergence of new safety concerns in relation to drugs that have been used to treat osteoporosis for many years. For example, there are now concerns that patients who have received prolonged treatment with bisphosphonates are at increased risk of so-called atypical hip fractures, which primarily affect the sub-trochanteric region. This has led to recommendations to re-evaluate the need for further treatment in patients who have received oral bisphosphonates for more than five years, possibly considering a "drug holiday" of between one and three years. Another recent safety concern is that strontium ranelate may be associated with an increased risk of cardiac events including non-fatal myocardial infarction, based on re-analysis of previous clinical trial data. This has led to the interim recommendation that strontium should be avoided in patients at increased risk of cardiovascular disease.
In terms of more effective therapy, one approach has been to combine anti-resorptive and anabolic (ie. bone-forming) treatment. Recent evidence suggests that combined use of teriparatide and denosumab may be particularly effective in this regard. As far as new treatments are concerned, odanacatib is a cathepsin K inhibitor, which acts to suppress bone resorption, and may also have a separate anabolic action, for reasons which are currently unclear.
Following the identification of sclerostin as an endogenous inhibitor of bone formation, sclerostin antibodies are being developed as a novel anabolic agent for osteoporosis. Whether these newer agents offer advantages over existing therapies in terms of efficacy and/or safety is an important question, which will hopefully be answered from results of phase III trials which are currently on-going.
Dr Tobias will be speaking at the BGS Falls and Postural Stability conference in September