Persistence to medical treatment of osteoporosis in women at three different clinical settings--a historical cohort study.

PURPOSE: This study was undertaken to assess persistence with bisphosphonates and raloxifene and to identify determinants of adherence (patient age, level of information, educational status, etc.) among women with osteoporosis in three different clinical settings in Denmark. METHODS: We compared persistence to therapy in three historical cohorts of women diagnosed with osteoporosis starting therapy between January 1999 and January 2004. The study comprised 878 patients treated and followed at Odense University Hospital, 285 patients diagnosed and followed at the Hellerup Osteoporosis Clinic (private practice), and 343 patients diagnosed at Aarhus University Hospital and followed by the referring general practitioner. Data on persistence and possible confounders were collected using a mailed questionnaire. Reminders were issued after 1-2 months to non-respondents. RESULTS: Persistence at 2 years as estimated from Kaplan-Meyer analysis was 0.87, 0.84 and 0.88 in the three cohorts, respectively. There were no significant differences between the clinics. Level of persistence was not related to patient assessment of the adequacy of the clinical information provided by the prescribing doctor, presence of prior fractures or a family history of osteoporosis. However, patients who read the information leaflet on their osteoporosis medication tended to be more persistent with treatment (p < 0.09). CONCLUSIONS: Women's persistence with bisphosphonates and raloxifene was surprisingly high and similar between treating centres. This may be due to a high level of public information available on osteoporosis in Denmark.

The Danish national return-to-work program--aims, content, and design of the process and effect evaluation.

The Danish national return-to-work (RTW) program aims to improve the management of municipal sickness benefit in Denmark. A study is currently ongoing to evaluate the RTW program. The purpose of this article is to describe the study protocol. The program includes 21 municipalities encompassing approximately 19 500 working-age adults on long-term sickness absence, regardless of reason for sickness absence or employment status. It consists of three core elements: (i) establishment of multidisciplinary RTW teams, (ii) introduction of standardized workability assessments and sickness absence management procedures, and (iii) a comprehensive training course for the RTW teams. The effect evaluation is based on a parallel group randomized trial and a stratified cluster controlled trial and focuses on register-based primary outcomes - duration of sickness absence and RTW - and questionnaire-based secondary outcomes such as health and workability. The process evaluation utilizes questionnaires, interviews, and municipal data. The effect evaluation tests whether participants in the intervention have a (i) shorter duration of full-time sickness absence, (ii) longer time until recurrent long-term sickness absence, (iii) faster full RTW, (iv) more positive development in health, workability, pain, and sleep; it also tests whether the program is cost-effective. The process evaluation investigates: (i) whether the expected target population is reached; (ii) if the program is implemented as intended; (iii) how the beneficiaries, the RTW teams, and the external stakeholders experience the program; and (iv) whether contextual factors influenced the implementation. The program has the potential to contribute markedly to lowering human and economic costs and increasing labor force supply. First results will be available in 2013. The trial registrations are ISRCTN43004323, and ISRCTN51445682.

Intercellular calcium signaling occurs between human osteoblasts and osteoclasts and requires activation of osteoclast P2X7 receptors.

Signaling between osteoblasts and osteoclasts is important in bone homeostasis. We previously showed that human osteoblasts propagate intercellular calcium signals via two mechanisms: autocrine activation of P2Y receptors, and gap junctional communication. In the current work we identified mechanically induced intercellular calcium signaling between osteoblasts and osteoclasts and among osteoclasts. Intercellular calcium responses in osteoclasts required P2 receptor activation but not gap junctional communication. Pharmacological studies and reverse transcriptase-PCR amplification demonstrated that human osteoclasts expressed functional P2Y1 receptors, but, unexpectedly, desensitization of P2Y1 did not block calcium signaling to osteoclasts. We also found that osteoclasts expressed functional P2X7 receptors and showed that pharmacological inhibition of these receptors blocked calcium signaling to osteoclasts. Thus these studies show that calcium signaling between osteoblasts and osteoclasts occurs via activation of P2 receptors, but that different families of P2 receptors are required for calcium signaling in these two cell types. Intercellular calcium signaling among bone cells is therefore amenable to pharmacological manipulation that will specifically affect only bone-forming or bone-resorbing cells. P2 receptors may be important drug targets for the modulation of bone turnover.