Potency of a combined alfacalcidol-alendronate therapy to reduce the risk of falls and fractures in elderly patients with glucocorticoid-induced osteoporosis.

This is a preplanned subgroup analysis on 318 patients with glucocorticoid-induced osteoporosis (GIOP) from an open, prospective, multi-centered, uncontrolled study on a large cohort of elderly patients with a high risk of falls and fractures. The entire group of 2579 patients was recruited by 818 practicing physicians and treated for three months with a new combination package containing 4 or 12 self-explanatory one-week blisters, each with one tablet of 70 mg alendronate (CAS 260055-05-8) and 7 capsules of 1 pg alfacalcidol (CAS 41294-56-8) (Tevabone"). The average age of the GIOP patients was 71 years and the mean body mass index 26.7 kg/m2. 58% had a diagnosis of increased risk of falls, prevalent vertebral and non-vertebral fractures were documented in 70% and 65% of the patients, respectively, and a creatinine clearance (CrCl) below 65 ml/min was documented in 55 %. Main outcome parameters were the Chair Rising Test (CRT), Timed Up and Go Test (TUG), back pain and safety at onset and after 3 months. In addition, an evaluation of the package design was done at the end of the study. The percentage of patients able to perform the CRT within 10 sec increased from 21.1% to 39.4% after 3 months (increase 87%, p < 0.0001), while successful performance of TUG within 10 sec increased by 84% (p < 0.0001) from 23.1% at onset to 42.4% after 3 months. The mean time required to perform the CRT decreased after 3 months from an average of 15.92 to 14.02 sec (p = 0.0025) (difference of 1.9 sec) and for the TUG the mean time decreased from 16.86 sec to 14.64 sec (p = 0.0056) (difference of 2.2 sec). Mean back pain measured by a 0-10 visual analogue scale decreased significantly by 43% from 6.0 to 3.4 (p < 0.0001). Throughout the study 23 adverse events (AE) were reported in 11 of the 318 GIOP patients (incidence: 3.5 %). There were no patients who experienced serious AE. Patients using the new combined regimen of alfacalcidol plus alendronate for treating GIOP achieved significant improvements in CRT, TUG and back pain already after 3 months, with a high safety profile and good compliance. This may contribute to the previously shown significant effect on reducing falls and fractures with the same regimen during a controlled long-term trial in primary osteoporosis.

Treatment with alfacalcidol in elderly people significantly decreases the high risk of falls associated with a low creatinine clearance of <65 ml/min.

We previously observed that a creatinine clearance (CrCl) of <65 ml/min is a significant and independent risk factor for the number of fallers and falls in a community-dwelling elderly population and postulated that this increased risk is due to the associated significant lower D-hormone serum levels. To test our hypothesis, we investigated in a post hoc analysis of a double-blind randomized study whether treatment with alfacalcidol, a synthetic prodrug of the D-hormone, can reduce the high incidence of fallers and the high risk of falls associated with low CrCl. Of 378 Swiss community-dwelling women (n=191) and men (n=187), aged 70 years and older, 191 received randomly 1 microg capsules of alfacalcidol (AlphaD3: Teva), and 187 received one capsule of placebo daily. With the help of questionnaires we regularly assessed the incidence and frequency of falls. The risk of becoming a faller and the risk of falling were assessed in multivariate-controlled logistic regression models according to treatment groups and according to a CrCl cut-off of 65 ml/min. The presented results are from ITT analyses. In participants with a CrCl of <65 ml/min, the 36 weeks of treatment with alfacalcidol was, compared with placebo, associated with a significant reduction in the number of fallers (14/72 versus 25/70; OR 0.26, 95% CI 0.08-0.80, P=0.019), and a significant reduction of the number of falls (16/72 versus 28/70; OR 0.29, 95% CI 0.09-0.88, P=0.028). No such association was observed in participants with a CrCl of >or=65 ml/min (for fallers 26/120 versus 21/116; OR 0.92 95% CI 0.34-2.52, P=0.875; for falls 32/120 versus 23/116; OR 0.93 95% CI 0.34-2.54, P=0.885). In the placebo group frequency of falls was dependent on CrCl (P=0.006), whereas in the alfacalcidol treatment group frequency of falls was independent of CrCl (P=0.494). No cases of clinically relevant hypercalcemia were observed. In a community-dwelling population of elderly men and women with a CrCl of <65 ml/min, treatment with alfacalcidol can significantly and safely reduce the low CrCl associated increased number of fallers and the high risk of falls.

A new significant and independent risk factor for falls in elderly men and women: a low creatinine clearance of less than 65 ml/min.

OBJECTIVES: Because impaired renal function is detrimental for the conversion of calcidiol to calcitriol (D-hormone) and since D-hormone analogues have been shown to decrease the risk of falls, we investigated whether creatinine clearance (CrCl) is associated with the number of fallers and falls in elderly men and women. METHODS: Within a randomized controlled study, we observed for 36 weeks 186 placebo-treated community-dwelling elderly men and women over 70, in an attempt to determine the influence of baseline CrCl on calcitropic hormone serum levels, as well as the influence of baseline CrCl on the number of fallers and falls over time. With the help of questionnaires, we regularly assessed fall incidence and frequency. The risk of falls and the risk of becoming a faller were assessed in multivariate-controlled logistic regression models according to a cutoff value of the CrCl set at 65 ml/min. RESULTS: At baseline, serum levels of 1.25(OH)(2)D(3) and iPTH were, in multivariate-controlled analyses, significantly associated with CrCl (p<0.0001, p=0.001, respectively), whereas serum levels of 25(OH)D(3) were not associated with CrCl. Below a CrCl of 65 ml/min, 1.25(OH)(2)D(3) serum levels steadily declined. We therefore chose a CrCl of 65 ml/min as cutoff for further analyses. During the 36 weeks of observation, elderly people with a CrCl of < 65 ml/min had, in multivariate controlled analyses, compared with elderly with a CrCl of > or =65 ml/min, a significantly higher incidence of number of fallers (25/70 vs 21/116; OR=4.01; 95% CI, 1.48-10.98; p=0.006), and a significantly higher incidence of falls (28/70 vs 23/116; OR=3.68; 95% CI, 1.38-9.82; p=0.009). CONCLUSIONS: For the first time we showed that in a community-dwelling population of elderly men and women, a CrCl of less than 65 ml/min is a significant and independent risk factor for fallers and falls.