Background: Reducing bisphosphonate dosing frequency may improve suboptimal adherence to treatment and therefore therapeutic outcomes in postmenopausal osteoporosis. Once-monthly oral ibandronate has been developed to overcome this problem. Objective: To confirm the 1 year results and provide more extensive safety and tolerability information for once-monthly dosing by a 2 year analysis. Methods: MOBILE, a randomised, phase III, non-inferiority study, compared the efficacy and safety of once-monthly ibandronate with daily ibandronate, which has previously been shown to reduce vertebral fracture risk in comparison with placebo. Results: 1609 postmenopausal women were randomised. Substantial increases in lumbar spine bone mineral density (BMD) were seen in all treatment arms: 5.0%, 5.3%, 5.6%, and 6.6% in the daily and oncemonthly groups (50 + 50 mg, 100 mg, and 150 mg), respectively. It was confirmed that all once-monthly regimens were at least as effective as daily treatment, and in addition, 150 mg was found to be better (p,0.001). Substantial increases in proximal femur (total hip, femoral neck, trochanter) BMD were seen; 150 mg produced the most pronounced effect (p,0.05 versus daily treatment). Independent of the regimen, most participants (70.5-93.5%) achieved increases above baseline in lumbar spine or total hip BMD, or both. Pronounced decreases in the biochemical marker of bone resorption, sCTX, observed in all arms after 3 months, were maintained throughout. The 150 mg regimen consistently produced greater increases in BMD and sCTX suppression than the 100 mg and daily regimens. Ibandronate was well tolerated, with a similar incidence of adverse events across groups. Conclusions: Once-monthly oral ibandronate is at least as effective and well tolerated as daily treatment. Once-monthly administration may be more convenient for patients and improve therapeutic adherence, thereby optimising outcomes.

SummaryThis post-hoc analysis queried whether women experiencing fracture on denosumab indicates inadequate treatment response or whether the risk of subsequent fracture remains low with continuing denosumab. Results showed that denosumab decreases the risk of subsequent fracture and fracture sustained while on denosumab is not necessarily indicative of inadequate treatment response.IntroductionThis analysis assessed whether a fracture sustained during denosumab therapy indicates inadequate treatment response and if the risk of a subsequent fracture decreases with continuing denosumab treatment.MethodsIn FREEDOM, a clinical trial to evaluate the efficacy and safety of denosumab, postmenopausal women with osteoporosis were randomized to placebo or denosumab for 3 years. In the 7-year FREEDOM Extension, all participants were allocated to receive denosumab. Here we compare subsequent osteoporotic fracture rates between denosumab-treated subjects during FREEDOM or the Extension and placebo-treated subjects in FREEDOM.ResultsDuring FREEDOM, 438 placebo- and 272 denosumab-treated subjects had an osteoporotic fracture. Exposure-adjusted subject incidence per 100 subject-years was lower for denosumab (6.7) vs placebo (10.1). Combining all subjects on denosumab from FREEDOM and the Extension for up to 10 years (combined denosumab), 794 (13.7%) had an osteoporotic fracture while on denosumab. Of these, one or more subsequent fractures occurred in 144 (18.1%) subjects, with an exposure-adjusted incidence of 5.8 per 100 subject-years, similar to FREEDOM denosumab (6.7 per 100 subject-years) and lower than FREEDOM placebo (10.1 per 100 subject-years). Adjusting for prior fracture, the risk of having a subsequent on-study osteoporotic fracture was lower in the combined denosumab group vs placebo (hazard ratio [95% CI]: 0.59 [0.43–0.81]; P = 0.0012).ConclusionsThese data demonstrate that denosumab decreases the risk of subsequent fracture and a fracture sustained while on denosumab is not necessarily indicative of inadequate treatment response.Electronic supplementary materialThe online version of this article (10.1007/s00198-018-4687-2) contains supplementary material, which is available to authorized users.

Tiludronate (T) is a new generation bisphosphonate which was previously shown to be safe and effective in treatment of Page's disease of bone. Due to its anti-osteoclastic properties, T was successfully used to reduce vertebral bone loss in late postmenopansal women. The present trial was designed to evaluate the ability of T to reduce poamaenopansal bone loss in early postmenopausal women. For this purpose, 421 Caucasian women, menopaused from 6 to 48 months, were randomized in a double-blind, placebo controlled, prospective, 18month trial. They were randomly assigned to 4 therapeutic groups receiving respectively placebo (n=141) (P), 12.5 mg/day T (12.5) (n=94), 50 nag/day (50 T) (n=91) or 200 me/day (200 T) (n=93) of oral sodium tiludronate for 6 months. No calcium supplementation was administered during this trial. Bone mineral density of the lumbar spine (sBMD) and femoral neck (hBMD) were evaluated by dual energy X-ray absorptinmetry (Hologic QDR 1000) prior (M0) and at the end of (M6) of the treatment period and, subsequently, 6 months (MI2) and 12 months (MIS) after the completion of the treatment. At MIS, mean losses in sBMD from baseline were 2.8 % ~or P, 2.6 % for 12.5 T, 2.2 % for 50 T and 1.9 % for 200 T. The difference between patients receiving P and those treated with 200 rag/day of T was bordedine significant (p=0.065). In terms of hBMD, patients treated with 200 me/day of T had a significantly (p=0.014) lower decrease over the 18 months (1.0 %) compared to the placebo group (2.g %). Premature discontinuation from adverse event was observed in 3 %inthe P, 3 %in 12.5 T, 9 %in 50 Tand 7 %in 200 T. The global distribution of premature withdrawal was not significantly different between the groups. We conclude that daily administration, of 200 mg of T tablets may significantly reduce bone loss in early postmenopausal women. The optimal therapeutic regimen remains to be evaluated.

Using a discrete choice experiment, we aimed to assess patients' preferences with regard to adopting lifestyle behaviours to prevent osteoporotic fractures. Overall, the 1042 patients recruited from seven European countries were favourable to some lifestyle behaviours (i.e., engaging in moderate physical activity, taking calcium and vitamin D supplements, reducing their alcohol consumption and ensuring a normal body weight). Introduction Alongside medical therapy, healthy lifestyle habits are recommended for preventing osteoporotic fractures. In this study, we aimed to assess patients' preferences with regard to adopting lifestyle changes to prevent osteoporotic fractures. Methods A discrete choice experiment was conducted in seven European countries. Patients with or at risk of osteoporosis were asked to indicate to what extent they would be motivated to adhere to 16 lifestyle packages that differed in various levels of 6 attributes. The attributes and levels proposed were physical activity (levels: not included, moderate or high), calcium and vitamin D status (levels: not included, taking supplements, improving nutrition and assuring a minimal exposure to sunlight daily), smoking (levels: not included, quit smoking), alcohol (levels: not included, moderate consumption), weight reduction (levels: not included, ensure a healthy body weight) and fall prevention (levels: not included, receiving general advice or following a 1-day fall prevention program). A conditional logit model was used to estimate a patient's relative preferences for the various attributes across all participants and per country. Results In total, 1042 patients completed the questionnaire. Overall, patients were favourable to lifestyle behaviours for preventing osteoporotic fractures. However, among the lifestyle behaviours proposed, patients were consensually not prone to engage in a high level of physical activity. In addition, in Ireland, Belgium, the Netherlands and Switzerland, patients were also not inclined to participate in a 1-day fall prevention program and Belgian, Swiss and Dutch patients were not prone to adhere to a well-balanced nutritional program. Nevertheless, we observed globally that patients felt positively about reducing their alcohol consumption, engaging in moderate physical activity, taking calcium and vitamin D supplements and ensuring a normal body weight, all measures aimed at preventing fractures. Conclusions In a patient-centred approach, fracture prevention should take these considerations and preferences into account.

No abstract