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Short report on the Clinical Update Session: Management of osteoporosis
By Bo Abrahamsen
This session provided a thorough and systematic update on fundamental aspects of diagnosis and
management of osteoporosis for clinicians and allied health professionals.
Make the right diagnosis and understand risk assessment tools
Professor Juliet Compston introduced secondary causes of osteoporosis and differential diagnoses,
along with a presentation of the panel of clinical and paraclinical investigations available to the
clinician and their respective limitations. A broad laboratory work-up aimed at ruling out vitamin D
deficiency, genetic, endocrine and malignant diseases may be warranted, especially perhaps in
younger patients who present with osteoporosis in the absence of strong risk factors.
A presentation on risk factors, the extent of prescription of osteoporosis drugs relative to the
expected burden of osteoporosis in various European countries and the development of FRAX was
given by Dr Helena Johansson. There was a lot of interest from the audience and a number of
critical questions about potential limitations to FRAX and gaps in the evidence base when it comes to
selecting patients for treatment based on FRAX score, evidence that mainly builds on post-hoc
analyses of trials that were designed before the development of FRAX. However, it was also argued
that a high FRAX risk score is strongly associated with low BMD, the inclusion criterion generally
used in the RCTs. The justification of the built-in mortality adjustment or death function in FRAX was
also commented upon, in particular if this meant that FRAX was ageist and if the possibility that
osteoporosis treatment could reduce mortality, as suggested by a number of recent studies, should
perhaps count in favour of targeting treatment to patients at high risk of dying rather than the
opposite.
Consider new strategies for inhibiting the osteoblast yet allowing formation of new bone
After the discussions on diagnosis and risk stratification, the session moved on to cover antiresorptive treatment (Professor Lorenz Hofbauer) and anabolic treatment (Professor Östen
Ljunggren). The kinetics of anti-resorptives differ; some have only a short stay and bone while others
are strongly bound and cleared very slowly. It is possible that the mechanism by which osteoclasts
are made unavailable or unable to resorb bone may have an impact even on osteoblast activity.
Professor Hofbauer proposed that kathepsin K inhibitors could be viewed as “uncoupling antiresorptives” with the capacity to maintain normal backcoupling from the osteoclast to the
osteoblast, permitting continued bone formation despite the reduction in bone resorption. Taking
up from there, Professor Ljunggren suggested that we should think about the possibility that we may
have hit the ceiling with bisphosphonates, whereas we may still be able to obtain additional
reductions in fracture risk with bone anabolic agents. After all, it is unclear how long we should be
using anti-resorptives for in the individual patient, and the only other options seem to be building
new bone and/or tackling sarcopenia and falls. Professor Juliet Compston commented that we
should bear in mind that no evidence is available to demonstrate that anabolic treatment reduces
the risk of hip fractures and that there is a loss of cortical BMD, at least in the early stages of
treatment with PTH analogues.
Though treatment is effective at group level, it may still need to be individualized to be effective in
some patients.
In the last lecture of the update session, Professor Richard Eastell discussed the concept of
personalized osteoporosis treatment. The efficacy of osteoporosis drugs in preventing fractures have
been clearly demonstrated at group level in RCTs, but how do we select the best treatment for the
individual patient and how can we determine – if possible at an early stage – if treatment works in
the patient and that fracture risk will be reduced? The currently available bone markers offer many
advantages over the first generation markers. They have much better precision and can be used to
identify suboptimal treatment responses or poor adherence to treatment. In future, we may be able
to tailor individual treatment duration from bone turnover markers, perhaps giving long acting
bisphosphonates such as zoledronic acid at much longer intervals so long as turnover markers
remain in the therapeutic range. There is clearly a lack of good data on the optimum treatment
duration and this is likely to be different for different medications as their half life in bone and
duration of action is not the same.