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A 54-year-old woman was referred by her rheumatologist for evaluation of an elevated serum alkaline phosphatase (ALP) in the setting of polyarthritis. The metabolic work-up was significant for an elevated bone fraction of alkaline phosphatase isoenzymes, and high bone turnover markers, including fasting C- telopeptide (CTX). A diagnosis of Paget's disease of bone (PDB) was considered. A whole-body nuclear bone scan showed diffuse increased uptake in the calvarium, suggestive of PDB, with no other localizing areas of increased uptake. Skull X-rays show mild sclerosis and medullary expansion of the posterior parietal bones and occiput, interpreted by the radiologist as unlikely to be PDB with a high level of uncertainty. Bone density testing with dual-energy X-ray absorptiometry showed low bone mass (osteopenia) with fracture probability that was below the treatment threshold. The case was presented and discussed on Bone Health ECHO, a virtual community of practice with the aim of enhancing global capacity to deliver best practice skeletal health care. The results of the discussion are presented here. [ABSTRACT FROM AUTHOR]

Dual-energy X-ray absorptiometry (DXA) has a colorful history of development and evolution over the past 30 years, from early predecessors that were cumbersome and limited in their clinical applications to current elegant instruments with a wide range of uses. DXA is used to diagnose osteoporosis, assess fracture risk, and monitor changes in bone mineral density (BMD). Non-BMD applications include vertebral fracture assessment, measurement of hip geometry, measurement of whole body tissue mass (i.e., bone, fat, and lean mass), abdominal aortic calcification detection and trabecular bone score measurement. This is an introduction to a special issue of this journal devoted to the celebration of the innovators in this field, the progress that has been made, and the challenges that remain. [ABSTRACT FROM AUTHOR]

Abstract: Denosumab is a fully human monoclonal antibody against receptor activator of nuclear factor-κB ligand, an essential mediator of osteoclast activity and survival. In postmenopausal women with low bone mineral density (BMD), subcutaneous denosumab decreases bone resorption and increases BMD. This post hoc analysis reports on subjects treated for up to 24 months with denosumab 60mg 6 monthly (N=39), placebo (N=39), or open-label alendronate 70mg once weekly (N=38) in a phase 2 study. Hip scans were done by dual-energy X-ray absorptiometry at baseline, 12, and 24 months; these were analyzed with hip structural analysis software to evaluate BMD and cross-sectional geometry parameters at the narrowest segment of the femoral neck, the intertrochanter, and the proximal shaft. Geometric parameters and derived strength indices included bone cross-sectional area, section modulus, and buckling ratio. At 12 and 24 months denosumab and alendronate improved these parameters compared with placebo. Denosumab effects were greater than alendronate at the intertrochanteric and shaft sites. The magnitude and direction of the changes in structural geometry parameters observed in this study suggest that denosumab treatment may lead to improved bone mechanical properties. Ongoing phase 3 studies will determine whether denosumab reduces fracture risk. [Copyright &y& Elsevier]

Background: Alendronate, an oral bisphosphonate, is available for the treatment of osteoporosis in a 70-mg once-weekly and a 10-mg once-daily formulation.Objectives: This study aimed to determine patient preference for once-weekly versus once-daily dosing with alendronate, and to determine which treatment regimen the patients believed was more convenient and would be easier to comply with for a long period.Methods: This was a multicenter, randomized, open-label, preference study in which postmenopausal women with osteoporosis were enrolled to receive 9 weeks of treatment in crossover fashion (4 weeks with each study regimen separated by a 1-week washout period). The study regimens included once-weekly alendronate 70 mg and once-daily alendronate 10 mg. The primary and secondary end points were assessed with a questionnaire completed by the patient. Adverse events (AEs) were recorded to assess patient tolerability of the study medications.Results: A total of 324 patients met the eligibility requirements; 288 were randomized to treatment, 287 (mean age, 64.8 years) received treatment, 272 completed the questionnaire, and 266 completed the study. Of the patients who completed the questionnaire, 235 patients preferred the 70-mg once-weekly dosing regimen compared with the 10-mg once-daily regimen (86.4% vs 9.2%; P < 0.001). Most patients also believed that once-weekly dosing was more convenient than once-daily dosing (89.0% vs 7.7%; P < 0.001) and would allow them to achieve better long-term compliance (87.5% vs 8.5%; P < 0.001). Clinical AEs were reported in 30.7% of patients treated with once-weekly alendronate and 30% of patients treated with once-daily alendronate, with no significant differences between treatments.Conclusion: When once-weekly alendronate 70 mg was compared with once-daily alendronate 10 mg in this study, 70-mg once-weekly alendronate was the preferred dosing regimen. [Copyright &y& Elsevier]

Purpose A large proportion of women with osteoporosis do not comply with current osteoporosis therapies, resulting in diminished therapeutic effect. Noncompliance may be due to the occurrence of gastrointestinal (GI) events during the course of therapy. The objective of this study was to estimate the rate of GI events among women taking oral bisphosphonates and to determine the association between GI events and compliance with bisphosphonate therapy. Methods This was a retrospective analysis of data from a US Medicare claims database (HUMANA). The study period was from January 2007 to June 2013. The index date was the date of the first oral bisphosphonate prescription (alendronate, ibandronate, or risedronate) occurring between January 2008 and June 2012. The pre- and postindex periods were the 1-year periods before and after the index date, respectively. The analysis included women 65 years of age and older who were naïve to all osteoporosis treatments before the index date. GI events included nausea/vomiting; dysphagia; esophagitis; esophageal reflux; esophageal, gastric, duodenal, and peptic ulcer; stricture, perforation, or hemorrhage of the esophagus; acute gastritis; and GI hemorrhage. GI events were assessed during the preindex period and at 3, 6, and 12 months in the postindex period. Compliance was defined as a medication possession ratio of ≥80%. The medication possession ratio was calculated as the total days׳ supply of bisphosphonate in the postindex period divided by 365 days. The association of postindex GI events with compliance was assessed using multivariate logistic regression. Findings The analysis included 37,886 women initiating oral bisphosphonate therapy. In the preindex year, 37.5% of the women experienced a GI event, and in the postindex year, 38.9% had a GI event. Patients with preindex GI events had numerically higher rates of postindex GI events than patients without preindex GI events (61.8% vs 25.1% at 12 months postindex). Patients who experienced postindex GI events were less likely to be compliant with bisphosphonate therapy, with odds of compliance of 0.76 (95% CI, 0.72–0.80) after 12 months. Implications Among US women who were prescribed oral bisphosphonates, on-treatment GI events were associated with decreased compliance at 1 year. [ABSTRACT FROM AUTHOR]