ECCEO 9-IOF | ATHENS | GREECE | March 18 - 21, 2009 | Megaron Athens International Conference Centre

Daily News 2

HIGHLIGHTS OF THE MEETING

The morning session of Friday March 20 started with the Lecture of Professor Roux who reminded us that because osteopenia is more common than osteoporosis, the majority of fractures occur in patients with osteopenia. However physicians are facing two problems. First, a low BMD in the range of osteopenia is not enough to discriminate patients who will fracture and those who will not. Second, the level of evidence for efficacy of anti-osteoporotic treatments in this population is low. Professor Roux stressed that fact that FRAX is a convenient tool to assess the individual fracture risk and that patients with osteopenia must have a careful assessment of all concomitant risk factors. Those with a high calculated risk must receive the highest priority. He concluded that, in the majority of cases, patients with osteopenia should be encouraged for lifestyle modifications with reassessment in 3-4 years.

In relation with this lecture, it has been shown, from a 24-month, Phase 3, double-blind, placebo-controlled, multicenter trial, that in postmenopausal women with normal to low bone mass, arzoxifene 20mg/day increased BMD at the spine and hip, and had a neutral effect on the uterus and endometrium (OC26).

Fractures are a major cause of pain and disability, and are associated with a high mortality rate, particularly in elderly people who have suffered hip fractures. Professor Cooper presented the results of a study assessing the self-perceived risk of osteoporotic fracture among women 55 years and older with reported risk factors (OC25). From the Global Longitudinal Study of Osteoporosis in Women, he showed that out of the women with no risk factors, 89% believed their risk was the same as or lower than that of women of the same age, whereas the majority of women with risk factors failed to appreciate their increased risk of fracture. Among women diagnosed with osteoporosis, 55% believed they were not at increased risk. He concluded that most women at elevated likelihood of osteoporotic fracture do not perceive themselves to be at increased risk.

Pharmacoeconomic analyses have also been highlighted yesterday. For example, it has been shown, with a Markow model incorporating the FRAX algorithm, that cost-effectiveness of bazedoxifene improved with higher 10-year risk and bazedoxifene was cost-effective in 70-year old women at the threshold of osteoporosis (OC27). Interestingly, when an effect was also modelled for non-vertebral fractures or breast cancer the cost-effectiveness improved further. Another study, using a validated Markov microsimulation model with a Belgian payer’s perspective, showed that denosumab is cost-effective for postmenopausal Belgian women with low bone mass and who are similar to patients included in the FREEDOM Trial (OC34).

Some treatments, approved in osteoporosis, could also have other beneficial effects for health. Raloxifene, for example, is also approved in the US for reduction in risk of invasive breast cancer in postmenopausal women with osteoporosis or
at high risk for invasive breast cancer. Analysis of the effects of these treatments on mortality is critical to assessment of the overall risk and benefit. Yesterday the pooled analysis of mortality data from large placebo-controlled clinical trials
(>1000 participants) of raloxifene 60mg/d was presented (OC28). The authors showed that all-cause mortality was 10% lower in women receiving raloxifene 60mg/d compared to placebo, due primarily to a reduction in non-cardiovascular, particularly non-cancer, death.

Clinical management of osteoporosis was also taken into account during this second day of the meeting. For example, it has been shown that in women with postmenopausal osteoporosis, a 5-year treatment with 150mg once-monthly oral ibandronate was generally well tolerated and continuously improved lumbar spine BMD while maintaining the improvements in total hip, femoral neck and trochanter BMD achieved after 2 years of initial treatment (OC32). Another study showed that, compared with placebo, women assigned to denosumab had a 68% (95% CI, 59 to 74%) reduced risk of new vertebral fractures decreased the risk of non-vertebral fracture by 20% (95% CI [5%, 33%]) (OC33). An original study assessed the efficacy of bazedoxifene on fracture outcomes and presented subgroup analysis by examining efficacy as a function of fracture risk based on the FRAX tool (OC35). This study showed that bazedoxifene (20 and 40mg doses combined) significantly decreases the risk of all clinical fractures and morphometric vertebral fractures in women at or above a FRAX® based fracture probability threshold. As a matter of fact, in this study, efficacy increased with increasing fracture probability.

As on the first day of the meeting, yesterday’s communications provided a lot of new comparative studies. For example, in women with post-menopausal osteoporosis followed for one year, a study suggests that strontium ranelate had significantly higher effects than alendronate on distal tibia microstructure including cortical and trabecular variables (OC31). On the other hand, in a phase 3, double-blind, 12-month study, arzoxifene treatment increased BMD and suppressed bone turnover to a greater extent than raloxifene, and resulted in a lower incidence of new/worsening hot flushes (OC30).

On Friday March 20, some communications related to the management of osteoarthritis were also presented. It started with the plenary lecture of Professor Pelletier that reminded us that osteoarthritis is the most common musculoskeletal disease and its clinical management largely relies on symptomatic interventions (Pl6). He pointed out the fact that new insights from clinical studies have enhanced our understanding of the management of risk and predisposing factors which could yield significant rewards in the fight against this disease. Those include excessive weight, knee misalignment, acute knee injury particularly anterior cruciate ligament damage, and meniscal lesions. Professor Pelletier
believes that with major advances in our understanding of the osteoarthritis process complemented with recently developed imaging technologies that assess and quantify the evolution of joint tissue changes in osteoarthritis, all of the elements to successfully develop new and effective DMOADs are now in place. In an oral communication related to his lecture, Professor Pelletier presented the results of an open-label 12-month pilot study evaluating the disease modifying effect of continuous treatment with celecoxib 200mg daily compared to a modelized historical control cohort in the treatment of knee osteoarthritis (OC37). Interestingly, he showed that although celecoxib was demonstrated to be safe and effective for knee osteoarthritis symptom relief at a daily dose of 200mg, it did not demonstrate a structural protective effect on knee cartilage.

In relation to the plenary lecture, and of primary importance for the methodology of phase III trial in osteoarthritis, Dr Gensburger presented the results of a study investigating whether knowledge of sequence of radiographs impacts inter- and intra-reader reproducibility for reading joint space width (JSW) in patients with knee osteoarthritis (OC36). She showed that intra- and inter-reader reproducibility was high with or without blinding of the X-ray sequence. She concluded that in longitudinal studies in osteoarthritis, X-rays can be read with known sequence.

In the field of the management of osteoarthritis, an interesting study has been presented yesterday. We know from previous work that health-utility measures, which may be implemented as a stand-alone assessment of health-related quality of life or incorporated into health economic analyses, can be used to quantitatively value relief of pain and improvement in physical function in studies of interventions for osteoarthritis. From 2 randomised, double-blind, placebo-controlled 3-year trials of glucosamine sulfate, utility values have been estimated from the WOMAC score (OC38). Using these data, the authors have shown that glucosamine sulphate induces a statistically significant benefit compared to placebo when considering health utility measures. The authors believe that such data could be useful for economic evaluation of glucosamine sulphate in osteoarthritis.

Today, you will have the privilege, during the oral communications, to hear scientists about the clinical management of osteoporosis, the clinical use of FRAX and even pharmacovigilance. You will also have the opportunity to attend the symposium organized by the European Society on Clinical and Economic aspects of Osteoporosis (ESCEO) on the “Management of the patient after a hip fracture” and to attend the Meeting of the Greek National Scientific Societies on the management of osteoporosis and osteoarthritis.