Efficacy and safety of a novel delayed-release risedronate 35 mg once-a-week tablet

Dosing regimens of oral bisphosphonates are inconvenient and contribute to poor compliance. The bone mineral density response to a once weekly delayed-release formulation of risedronate given before or following breakfast was non-inferior to traditional immediate-release risedronate given daily before breakfast. Delayed-release risedronate is a convenient regimen for oral bisphosphonate therapy

Using clinical risk factors and bone mineral density to determine who among patients undergoing bone densitometry should have vertebral fracture assessment

Vertebral fracture assessment (VFA) is a new method for imaging thoracolumbar spine on bone densitometer. Among patients referred for bone densitometry, the selection of patients for VFA testing can be optimized using an index derived from clinical risk factors and bone density measurement. VFA, a method for imaging thoracolumbar spine on bone densitometer, was developed because vertebral fractures, although common and predictive of future fractures, are often not clinically diagnosed. The study objective was to develop a strategy for selecting patients for VFA. A convenience sample from a university hospital bone densitometry center included 892 subjects (795 women) referred for bone mineral density (BMD) testing. We used questionnaires to capture clinical risk factors and dual-energy X-ray absorptiometry to obtain BMD and VFA. Prevalence of vertebral fractures was 18% in women and 31% in men (p = 0.003 for gender difference). In women, age, height loss, glucocorticoid use, history of vertebral and other fractures, and BMD T-score were significantly and independently associated with vertebral fractures. A multivariate model which included above predictors had an area under the receiver operating curve of 0.85 with 95% confidence interval (CI) of 0.81 to 0.89. A risk factor index was derived from the above multivariate model. Using a level of 2 as a cut-off yielded 93% sensitivity (95% CI 87, 96) and 48% specificity (95% CI 69, 83). Assuming a 15% prevalence of vertebral fractures, this cut-off value had a 24% positive and 97% negative predictive value and required VFA scanning of three women at a cost of $60 (assuming a$20 cost/VFA scan) to detect one with vertebral fracture(s). Selecting patients for VFA can be optimized using an index derived from BMD measurement and easily obtained clinical risk factors

Treatment with intravenous pamidronate is a good alternative in case of gastrointestinal side effects or contraindications for oral bisphosphonates

<p>Abstract</p> <p>Background</p> <p>In case of contraindications or intolerance during treatment with oral bisphosphonates (OB), administration of pamidronate intravenously is a widely used alternative.</p> <p>In this study we compared the effect on change in bone mineral density (BMD) of the spine and hip during long term treatment with pamidronate iv in comparison to OB.</p> <p>Methods</p> <p>We studied 61 patients receiving treatment for at least two years. In case of contraindications or intolerance (within 3 months) of an OB, pamidronate iv was started. BMD was measured on a Hologic 4500 and a Lunar DPX-IQ at the spine (L1-L4) and total hip.</p> <p>Results</p> <p>Thirty-one patients were enrolled in the OB group and 30 in the intravenous pamidronate group. Mean follow-up duration (SD) was 4.3 (1.3) years. We observed a significant increase (p < 0.001) in spinal BMD, both in the OB group (8.3%) as well as in the pamidronate iv group (6.1%), but no significant difference in BMD change between the OB and pamidronate iv groups. At the hips, we observed a tendency to increased BMD in both groups, 1.1% in the OB and 1.4% in the pamidronate iv group.</p> <p>Conclusion</p> <p>We conclude that intravenous pamidronate is a good alternative for oral bisphosphonates in the treatment of osteoporosis in patients with contraindications or intolerance during treatment with oral bisphosphonates.</p

Evaluation of the clinical value of bone metabolic parameters for the screening of osseous metastases compared to bone scintigraphy

BACKGROUND: Bone metastases are common in many types of cancer. As screening methods different imaging modalities are available. A new approach for the screening of osseous metastases represents the measurement of bone metabolic markers. Therefore aim of this study was to evaluate the usefulness of the determination of bone metabolic markers aminoterminal propeptide of type I procollagen (PINP, osteoblastic activity) and the carboxyterminal pyridinoline cross-linked telopeptide of type I collagen (ICTP, osteoclastic activity) for the detection of bone metastases associated with other malignancies. METHODS: 88 patients aged 21 – 82 years with malignant tumors were prospectively studied. The serum concentrations of PINP and ICTP were measured and compared to the results of bone scintigraphy, radiological bone series, CT, MRI and clinical follow-up. RESULTS: Osseous metastases were found in 21 patients. 19 of them were correctly identified by bone scintigraphy (sensitivity: 90%). For bone metabolic markers results were as follows: ICTP sensitivity: 71%, specificity: 42%; PINP sensitivity: 24%, specificity: 96%. CONCLUSIONS: As markers of bone metabolism PINP and ICTP showed low sensitivity and/or specificity for the detection of osseous metastases. The presented markers did not seem to be sufficient enough to identify patients with bone metastases or to replace established screening methods

Ethnic difference of clinical vertebral fracture risk

Vertebral fractures are the most common osteoporotic fractures. Data on the vertebral fracture risk in Asia remain sparse. This study observed that Hong Kong Chinese and Japanese populations have a less dramatic increase in hip fracture rates associated with age than Caucasians, but the vertebral fracture rates were higher, resulting in a high vertebral-to-hip fracture ratio. As a result, estimation of the absolute fracture risk for Asians may need to be readjusted for the higher clinical vertebral fracture rate. Introduction: Vertebral fractures are the most common osteoporotic fractures. Data on the vertebral fracture risk in Asia remain sparse. The aim of this study was to report the incidence of clinical vertebral fractures among the Chinese and to compare the vertebral-to-hip fracture risk to other ethnic groups. Methods: Four thousand, three hundred eighty-six community-dwelling Southern Chinese subjects (2,302 women and 1,810 men) aged 50 or above were recruited in the Hong Kong Osteoporosis Study since 1995. Baseline demographic characteristics and medical history were obtained. Subjects were followed annually for fracture outcomes with a structured questionnaire and verified by the computerized patient information system of the Hospital Authority of the Hong Kong Government. Only non-traumatic incident hip fractures and clinical vertebral fractures that received medical attention were included in the analysis. The incidence rates of clinical vertebral fractures and hip fractures were determined and compared to the published data of Swedish Caucasian and Japanese populations. Results: The mean age at baseline was 62 ± 8.2 years for women and 68 ± 10.3 years for men. The average duration of follow-up was 4.0 ± 2.8 (range, 1 to 14) years for a total of 14,733 person-years for the whole cohort. The incidence rate for vertebral fracture was 194/100,000 person-years in men and 508/100,000 person-years in women, respectively. For subjects above the age of 65, the clinical vertebral fracture and hip fracture rates were 299/100,000 and 332/100,000 person-years, respectively, in men, and 594/100,000 and 379/100,000 person-years, respectively, in women. Hong Kong Chinese and Japanese populations have a less dramatic increase in hip fracture rates associated with age than Caucasians. At the age of 65 or above, the hip fracture rates for Asian (Hong Kong Chinese and Japanese) men and women were less than half of that in Caucasians, but the vertebral fracture rate was higher in Asians, resulting in a high vertebral-to-hip fracture ratio. Conclusions: The incidences of vertebral and hip fractures, as well as the vertebral-to-hip fracture ratios vary in Asians and Caucasians. Estimation of the absolute fracture risk for Asians may need to be readjusted for the higher clinical vertebral fracture rate. © 2011 The Author(s).published_or_final_versionSpringer Open Choice, 21 Feb 201

Future possibilities in the prevention of breast cancer: Breast cancer prevention trials

The available results from breast cancer chemoprevention trials are reviewed. Four trials using tamoxifen have been performed, of which three have reported efficacy results. A fifth trial using raloxifene has also been reported. The largest tamoxifen trial showed approximately 50% reduction in breast cancer incidence in the short term, but the two smaller trials did not find any reduction. Greater agreement exists for side effects; incidences of thromboembolic disease and endometrial cancers are raised approximately threefold when tamoxifen is used for 5 years. The possible reasons for the discrepancy in breast cancer reduction are explored. A review of trial parameters does not clearly explain this difference, and a meta-analysis indicates that all results are compatible with a 40% reduction in short-term incidence. Several important questions remain regarding the clinical implications of this result, including the effect on mortality, the appropriate risk groups for chemoprevention and the long-term effects on incidence. Continued follow up of these trials is crucial for resolving these issues

Bone turnover is adequately suppressed in osteoporotic patients treated with bisphosphonates in daily practice

<p>Abstract</p> <p>Background</p> <p>Monitoring osteoporosis therapy by measurement of bone turnover markers (BTMs) might detect non-compliance in an earlier stage of anti-osteoporosis treatment and improve persistence.</p> <p>Methods</p> <p>BTMs were measured in two groups. The first group consisted of patients newly diagnosed with osteoporosis and starting treatment. We observed which proportion of patients had a decrease of serum levels of procollagen type 1 N-terminal propeptide (P1NP) and C-terminal crosslinking telopeptide (CTX) greater than the least significant change (LSC) after 3 months of treatment. Secondly, we determined which proportion of patients who were treated with bisphosphonates for ≥ 3 months reached the biological goal of therapy, BTMs in the lower half of the normal premenopausal range. P1NP and CTX were also measured in a reference population of 34 healthy premenopausal women.</p> <p>Results</p> <p>In the first group 31 patients were included, in 25 patients (81%) levels of both markers decreased with ≥ LSC, in the other patients a possible explanation was found.</p> <p>In the second group 95 patients were included, in 95% the serum P1NP levels and CTX levels were in the lower half of the premenopausal range. In 6 of the 7 patients with a level above the premenopausal range a possible explanation was found.</p> <p>Conclusion</p> <p>A decrease in bone turnover ≥ LSC can be observed in the majority of newly treated patients. In chronically treated patients, 95% have a bone turnover in the premenopausal range. In most patients with inadequate suppression of BTMs during bisphosphonate treatment, an explanation was found. Monitoring treatment effect with BTMs in daily practice is feasible, and might be an additive tool in improving therapy compliance.</p

Strontium ranelate and alendronate have differing effects on distal tibia bone microstructure in women with osteoporosis

The structural basis of the antifracture efficacy of strontium ranelate and alendronate is incompletely understood. We compared the effects of strontium ranelate and alendronate on distal tibia microstructure over 2 years using HR-pQCT. In this pre-planned, interim, intention-to-treat analysis at 12 months, 88 osteoporotic postmenopausal women (mean age 63.7 ± 7.4) were randomized to strontium ranelate 2 g/day or alendronate 70 mg/week in a double-placebo design. Primary endpoints were changes in microstructure. Secondary endpoints included lumbar and hip areal bone mineral density (aBMD), and bone turnover markers. This trial is registered with http://www.controlled-trials.com, number ISRCTN82719233. Baseline characteristics of the two groups were similar. Treatment with strontium ranelate was associated with increases in mean cortical thickness (CTh, 5.3%), cortical area (4.9%) and trabecular density (2.1%) (all P < 0.001, except cortical area P = 0.013). No significant changes were observed with alendronate. Between-group differences in favor of strontium ranelate were observed for CTh, cortical area, BV/TV and trabecular density (P = 0.045, 0.041, 0.048 and 0.035, respectively). aBMD increased to a similar extent with strontium ranelate and alendronate at the spine (5.7% versus 5.1%, respectively) and total hip (3.3% versus 2.2%, respectively). No significant changes were observed in remodeling markers with strontium ranelate, while suppression was observed with alendronate. Within the methodological constraints of HR-pQCT through its possible sensitivity to X-ray attenuation of different minerals, strontium ranelate had greater effects than alendronate on distal tibia cortical thickness and trabecular volumetric density

Design and baseline characteristics of a prospective cohort study for determinants of osteoporotic fracture in community-dwelling elderly Japanese men: the Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) Study

<p>Abstract</p> <p>Background</p> <p>Osteoporosis and osteoporotic fracture in men are significant public health problems in an aging society. However, information on male osteoporosis remains impressively lacking, especially for Asians. We designed the Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) study as an ancillary study of a cohort study, the Fujiwara-kyo study, to determine risk factors for osteoporotic fractures in Japanese men.</p> <p>Methods/Design</p> <p><it><b>Design</b></it>: A community-based single-centre prospective cohort study with at least a 5-year follow-up</p> <p><it><b>Subjects</b></it>: All the male participants of the Fujiwara-kyo study who were living in the four cities studied, aged 65 years and older, and able to walk without aid from others.</p> <p><it><b>Primary outcome</b></it>: Incidence of osteoporotic fractures including vertebral and clinical non-vertebral fractures.</p> <p><it><b>Additional outcomes</b></it>: Change in bone mineral density (BMD), change in hip geometry, onset of receiving benefits from Long-term Care Insurance (LCI), health-related quality of life, and mortality.</p> <p><it><b>Baseline measurements</b></it>: BMD at the lumbar spine (LS) and hip (TH), hip geometry, vertebral deformity assessment, bone turnover markers, physical and cognitive performance, various medical and lifestyle factors, and geriatric psychosocial measures confirmed by interviews based on self-administrated questionnaires.</p> <p><it><b>Outcome surveillance</b></it>: Annual mail surveys and a follow-up survey at the fifth year comprising similar items to the baseline study will be used to determine the outcomes. Receipt of benefits from LCI and mortality will be obtained from the city governments.</p> <p><it><b>Current status</b></it>: The baseline study was conducted for 2174 eligible men, and 2012 completed the study and were eligible for follow-up. Prevalence rates of osteoporosis (BMD 2.5 SD or more below the young adult mean (YAM)) and low BMD (BMD 1 SD or more below YAM) in at least one of LS and TH were calculated to be 4.4% and 41.8%, respectively. The proportion of men with low BMD only at TH showed a significant increasing trend with aging (p < 0.0001) while that only at LS showed a decreasing trend (p = 0.0386). The prevalence rate of osteoporosis was underestimated when diagnosed using only BMD at LS. Other baseline measurements were successfully obtained.</p> <p>Discussion</p> <p>FORMEN baseline study was performed as designed and the FORMEN cohort study was successfully launched.</p