Gaining full benefits from osteoporosis medications requires long-term treatment. Investigating the real-world persistence of women receiving osteoporosis medications in the UK, we found that most patients stop treatment within a year. To prevent osteoporotic fragility fractures, long-term treatment persistence must be improved. Persistence with osteoporosis therapies has historically been poor. To treat this chronic and progressive disease, it is essential that patients receive the full benefit of these medications. We estimated persistence and compliance with osteoporosis therapies in a large sample of postmenopausal women in the UK. Data were obtained from the Clinical Practice Research Datalink for all women aged 50 years and over or women with early menopause, who received at least one prescription in primary care for any licensed osteoporosis therapy between January 1, 2010 and December 31, 2015. Persistence and compliance at 24 months (primary objective) and at 5 years (exploratory objective) were estimated in three patient cohorts: “All Patients,” “Naïve Patients,” and “Drug-Specific.” The All Patients cohort included 72,256 women. Persistence with any therapy was 56.1%, 43.6%, 36.4%, and 31.0% at 6, 12, 18, and 24 months, respectively, and 23.2% and 13.1% at 3 years and 5 years, respectively. Patients were generally more persistent and compliant if evaluated from their first exposure to osteoporosis therapy (Naïve Patients cohort). In the drug-specific analysis, 64% of patients receiving denosumab (administered subcutaneously every 6 months) were persistent at 24 months compared with 28% and 23% of those taking oral bisphosphonates and intravenous bisphosphonates, respectively. Only about one in three patients who received osteoporosis therapy continued to be on treatment after 2 years. There is a need to improve persistence with osteoporosis therapy, especially for high-risk patients

Rationale, aims and objectives Clinical trial data suggest that patients who have received bisphosphonates continue to benefit from them after discontinuation. However, data from real-world clinical practice are inconclusive. We assessed the impact of persistence and discontinuation on health resource utilization (HRU) and fracture rate in women who were prescribed oral bisphosphonates.Method The study used data from the UK Clinical Practice Research Datalink. Women aged 50 years or older with a first prescription of oral bisphosphonate therapy between January 2000 and December 2007 were included. Multivariate modelling compared rate ratios for fracture and HRU between patients who had discontinued medication (shorter persistence group) and patients who took their medication for longer (longer persistence group). The interactions of elapsed time (measured as 6-month intervals) with HRU and with fracture rate for all patients within paired groups were also assessed.Results Overall, 36320 patients were included. Pairwise comparisons showed that HRU and fracture rates were lower in longer persistence groups than in shorter persistence groups. Analysis by 6-month interval showed that, across all patients in persistence group pairs, HRU significantly increased for each additional 6 months elapsed; trends towards increased risk of fracture were also seen.Conclusion In contrast to results from clinical trials, in this patient population the protective effect of oral bisphosphonates after discontinuation was not sufficient to reduce HRU and fracture rates to the levels that would be seen if patients had continued on therapy. Reducing the rate of treatment discontinuation may decrease the burden that osteoporosis places on both patients and health care systems.

Summary Distinguishing oral bisphosphonates from other bone-sparing therapies, this retrospective observational study, first, characterized treated osteoporosis patients in the UK, and secondly, explored factors associated with the risk of discontinuation or switching between therapies. The latter should be considered when evaluating real-world data. Purpose This retrospective observational study evaluated the characteristics of women with postmenopausal osteoporosis, including comorbidities and determinants of treatment patterns with bone-sparing agents. Methods The UK Clinical Practice Research Datalink was used to identify postmenopausal women (aged ≥50 years) treated with a bone-sparing agent or diagnosed with osteoporosis between 1 January 1993 and 31 December 2008. Two non-mutually-exclusive subpopulations were defined: (1) patients active in the database on 31 December 2008; (2) patients treated with a bone-sparing agent since 1 January 1993. Subpopulation 1 was used to describe patient comorbidities and osteoporosis treatment history, and subpopulation 2 was used to explore the characteristics associated with bone-sparing treatment patterns use via multivariable regression for repeated multinomial responses. Results A total of 62,657 individuals met the inclusion criteria; subpopulation 1 comprised 38,469 women (61.4 %), of whom 21,687 received a bone-sparing agent in 2008 (99.7 % oral bisphosphonates and the remainder other agents). Those receiving other agents were more likely to have had previous treatment with bone-sparing agents, to have experienced previous fractures, and to have visited their doctor more frequently. Analyses also identified several comorbidities associated with an increased risk of discontinuation of bone-sparing agents, including heart disease, gastrointestinal disease, and renal failure. Anticonvulsant use was associated with a dramatic increase in the risk of switching. Conclusions Several patient characteristics were associated with discontinuation of, or switching between, bone-sparing treatments. Patients receiving bone-sparing medication other than oral bisphosphonates were more likely to have comorbid conditions and a history of fracture and to have taken an oral bisphosphonate previously.

To assess the impact of persistence and compliance on fracture rates and health care resource use (HRU) in women treated with oral bisphosphonates (oBPs). This analysis of the UK CPRD included women with first oBP prescription (index event) between January 2004–December 2007, ≥50 years of age, with no history of cancer and a minimum of 12 months’ data before and 6 months’ after the index event. Follow-up for any osteoporotic fracture was until December 2008. Persistence was defined as duration of continuous oBP use with no gaps >3 months; compliance was assessed using the medication possession ratio (MPR; proportion of time with treatment available). HRU was evaluated using total primary care contact (including prescriptions), and all specialist referrals and hospitalisations. Analyses were stratified by persistence and compliance. A total of 21,717 patients were included (mean age, 73.5 years). Between 2004–2007, fracture rates per patient–year were: 0.14 (95% CI: 0.12, 0.16; group with MPR <80%) and 0.11 (0.10, 0.12; MPR ≥80%) for patients with 12–24 months’ persistence vs 0.09 (0.08, 0.10) and 0.07 (0.06, 0.08), respectively, for patients with ≥36 months’ persistence. Hospitalisation rates were 0.38 (0.34, 0.42; MPR <80%) and 0.30 (0.29, 0.32; MPR ≥80%) for patients with 12–24 months’ persistence vs 0.55 (0.52, 0.59) and 0.18 (0.17, 0.19), respectively, for patients with ≥36 months’ persistence. Among patients who discontinued oBPs and had <12 months’ persistence and MPR ≥80% before discontinuation, fracture rates were 0.02 (0.01, 0.03) and 0.09 (0.07, 0.12) in the first and second 6 months following discontinuation, respectively, and hospitalisation rates were 0.09 (0.07, 0.11) and 0.48 (0.42, 0.55), respectively. Outcomes associated with oBPs were improved with longer persistence and higher compliance. However, in patients with <12 months’ persistence, protection against fractures and hospitalisation diminished 6 months after discontinuation of oBPs.

Alun Cooper rightly points out the burdens of fragility fractures and the difficulties that arise if we focus on the risk factor (osteoporosis) and not the end organ damage (the fracture).1 The slow evolution of meaningful guidance from the National Institute for Health and Clinical Excellence (NICE) has attracted criticism as has its restrictive health economic model. The suggestion that a solution presents itself in the new FRAX® algorithm3 allied to new rival guidance from the National Osteoporosis Guidelines Group (NOGG) should be critically appraised. Generic alendronate is now £20/year or about one-tenth of its cost when NICE first formulated their relevant technology appraisal, and cost-effectiveness arguments may now make it affordable for many more patients even if NICE may alter the model constantly. The suggestion by the NOGG authors however, that treatment should be considered in 24% of 50-year-old women and 47% of 80 year olds1 may raise alarm bells for a number of reasons. How long should …

Jarvinen et al remind us that falls assessment is too often ignored in people at high risk of fractures.1 However, we believe that falls assessment and prevention must be in addition to, and not at the expense of, osteoporosis treatment. The British Orthopaedic Association advocates a dual approach to fracture prevention,2 and indicators supporting both have been submitted …

BACKGROUND:Recent guidelines recommend that patients receiving treatment for osteoporosis should also receive supplementation with calcium and vitamin D unless they are calcium and vitamin D replete. Given that the majority of elderly patients have inadequate levels of vitamin D and that determining nutritional status is time-consuming and costly, it seems prudent to ensure that the majority of patients aged over 65 and receiving medication for osteoporosis should receive supplementation as a matter of course.OBJECTIVES:To determine the level of co-prescription of calcium and vitamin D in patients receiving treatment for osteoporosis with bisphosphonates, teriparatide, raloxifene or strontium.STUDY DESIGN AND METHODS:A pilot audit of nine general practices covering a population of 61 202.RESULTS:Overall, 1.1% (n = 662) of patients were receiving treatment for osteoporosis; of those, only 34.1% of patients were co-prescribed calcium or calcium and vitamin D. Levels of co-prescription varied considerably across practices from 74.0% to 12.2%.CONCLUSIONS:Despite national guidelines, co-prescription of calcium and vitamin D with treatment for osteoporosis remains sub-optimal with considerable variation between practices. Strategies should be adopted to increase physician awareness of widespread vitamin D inadequacy, the rationale for supplementation and poor compliance.

Infrared spectra of liquid H2O, D2O, and HDO from 0.7 to 10 μm have been obtained. The H2O spectrum is based on that of natural water, the D2O spectrum on that of heavy water containing approximately 99.6 weight per cent D2O. The HDO spectrum has been deduced from spectra of H2O-HDO-D2O mixtures by application of Beer's law. The spectra are presented in terms of logarithms of both an extinction length, L, the sample thickness that has unit optical density, and the molecular extinction coefficient, ϵ, plotted against logarithms of both wavelegnth and wave number. Vibration mode assignments have been made for most of the absorption bands observed. The spectral data obtained have been useful in the development of infrared monitoring instrumentation and methods of analysis for H2O-HDO-D2O mixtures in connection with the heavy water reactor research programs at the Chalk River Nuclear Laboratories.

The isotopic composition of caesium samples which had been subject to intense reactor neutron irradiation was measured with a 6 in. radius, 60° sector field, mass spectrometer fitted with a triple filament thermal ionization source. The cross-section of the reaction 134Cs(nγ)135Cs was calculated from the observed isotopic composition and found to be 134 ± 12 barns. By measuring the change with time of the 134Cs/(133Cs + 135Cs) ratio using the mass spectrometer the half life of 134Cs was found to be 2·15 ± 0.040.08 years. In a subsidiary experiment the cross-section of the reaction 133Cs(nγ)134Cs was found by activation to be 30·4 ± 1·7 barns.