Patient preferences for lifestyle behaviours in osteoporotic fracture prevention: a cross-European discrete choice experiment.

Using a discrete choice experiment, we aimed to assess patients' preferences with regard to adopting lifestyle behaviours to prevent osteoporotic fractures. Overall, the 1042 patients recruited from seven European countries were favourable to some lifestyle behaviours (i.e., engaging in moderate physical activity, taking calcium and vitamin D supplements, reducing their alcohol consumption and ensuring a normal body weight). INTRODUCTION: Alongside medical therapy, healthy lifestyle habits are recommended for preventing osteoporotic fractures. In this study, we aimed to assess patients' preferences with regard to adopting lifestyle changes to prevent osteoporotic fractures. METHODS: A discrete choice experiment was conducted in seven European countries. Patients with or at risk of osteoporosis were asked to indicate to what extent they would be motivated to adhere to 16 lifestyle packages that differed in various levels of 6 attributes. The attributes and levels proposed were physical activity (levels: not included, moderate or high), calcium and vitamin D status (levels: not included, taking supplements, improving nutrition and assuring a minimal exposure to sunlight daily), smoking (levels: not included, quit smoking), alcohol (levels: not included, moderate consumption), weight reduction (levels: not included, ensure a healthy body weight) and fall prevention (levels: not included, receiving general advice or following a 1-day fall prevention program). A conditional logit model was used to estimate a patient's relative preferences for the various attributes across all participants and per country. RESULTS: In total, 1042 patients completed the questionnaire. Overall, patients were favourable to lifestyle behaviours for preventing osteoporotic fractures. However, among the lifestyle behaviours proposed, patients were consensually not prone to engage in a high level of physical activity. In addition, in Ireland, Belgium, the Netherlands and Switzerland, patients were also not inclined to participate in a 1-day fall prevention program and Belgian, Swiss and Dutch patients were not prone to adhere to a well-balanced nutritional program. Nevertheless, we observed globally that patients felt positively about reducing their alcohol consumption, engaging in moderate physical activity, taking calcium and vitamin D supplements and ensuring a normal body weight, all measures aimed at preventing fractures. CONCLUSIONS: In a patient-centred approach, fracture prevention should take these considerations and preferences into account.

Assessment of Cardiovascular Safety of Anti-Osteoporosis Drugs.

The incidence of osteoporosis and cardiovascular disease increases with age, and there are potentially shared mechanistic associations between the two conditions. It is therefore highly relevant to understand the cardiovascular implications of osteoporosis medications. These are presented in this narrative review. Calcium supplementation could theoretically cause atheroma formation via calcium deposition, and in one study was found to be associated with myocardial infarction, but this has not been replicated. Vitamin D supplementation has been extensively investigated for cardiac benefit, but no consistent effect has been found. Despite findings in the early 21st century that menopausal hormone therapy was associated with coronary artery disease and venous thromboembolism (VTE), this therapy is now thought to be potentially safe (from a cardiac perspective) if started within the first 10 years of the menopause. Selective estrogen receptor modulators (SERMs) are associated with increased risk of VTE and may be related to fatal strokes (a subset of total strokes). Bisphosphonates could theoretically provide protection against atheroma. However, data from randomised trials and observational studies have neither robustly supported this nor consistently demonstrated the potential association with atrial fibrillation. Denosumab does not appear to be associated with cardiovascular disease and, although parathyroid hormone analogues are associated with palpitations and dizziness, no association with a defined cardiovascular pathology has been demonstrated. Finally, romosozumab has been shown to have a possible cardiovascular signal, and therefore post-market surveillance of this therapy will be vital.

Uso de fármacos para la osteoporosis en pacientes con diabetes mellitus tipo 2: estudio de cohortes de base poblacional / Use of drugs for osteoporosis treatment in patients with type 2 diabetes mellitus: population-based cohort study

Objetivo: Determinar si existen diferencias en la prevalencia del uso de fármacos para la osteoporosis entre pacientes diabéticos tipo 2 (DM2) y no diabéticos. Material y método: Estudio de cohortes retrospectivas con datos del Sistema de Información para el Desarrollo de la Investigación en Atención Primaria (SIDIAP), que contiene información clínica anonimizada de más de 5 millones de pacientes de Cataluña. Se seleccionaron todos los pacientes de ≥50 años de edad con diagnóstico de DM2, que fueron apareados con dos sujetos sin diabetes. Se recogió información sobre variables descriptivas, fracturas prevalentes y el uso de fármacos para la osteoporosis agrupados en bifosfonatos (BF), suplementos calcio y vitamina D (CaD), y cualquier fármaco para la osteoporosis (FPO). Mediante regresión logística se calculó la asociación entre la presencia de DM2 y el uso de FPO, ajustando por variables confusoras. Resultados: Se identificaron 166.106 pacientes con DM2 y 332.212 no diabéticos. Los DM2 tenían mayor prevalencia de fractura que los no diabéticos (1,3% vs. 0,3%). El uso de BF en los pacientes con DM2 era del 6,6%, frente al 9,3% en los no diabéticos (p<0,001); de CaD, 9,7% vs. 12,3% (p<0,001); y de FPO, 7,6% vs. 10,7% (p<0,001). Tras ajustar por variables confusoras, los pacientes con DM2 presentaban menor probabilidad de ser tratados con BF (OR=0,67; IC95%: 0,64-0,68), con CaD (OR=0,71; IC95%: 0,70-0,73) o con FPO (OR=0,66; IC95%: 0,64-0,67) que los no diabéticos. Conclusiones: A pesar de presentar una mayor prevalencia de fracturas previas, los pacientes con DM2 tienen más del 30% de probabilidad de no recibir un FPO que los no diabéticos. Esto podría ser debido a una infravaloración del riesgo en estos pacientes (AU)

Objective: Ascertain whether there are differences in the prevalence of osteoporosis drugs in patients with type 2 diabetes (DM2) and non-diabetic patients. Material and methods: Retrospective cohort study with data from the Information System for the Development of Primary Care Research (SIDIAP), which contains anonymous clinical information from more than 5 million patients in Catalonia. All 50-year-old patients diagnosed with DM2, who were matched with two subjects without diabetes, were selected. Information on descriptive variables, prevalent fractures and the use of osteoporosis drugs grouped in bisphosphonates (BF), calcium and vitamin D supplements (CaD), and any osteoporosis drug (OD) were collected. Through logistic regression, the association between the presence of DM2 and the use of OD was calculated, adjusting for confounding variables. Results: A total of 166,106 patients with DM2 and 332,212 non-diabetics. The DM2 group presented a higher prevalence of fracture than did diabetics (1.3% vs 0.3%). The use of BF in patients with DM2 was 6.6%, compared to 9.3% in non-diabetics (p<0.001). Of CaD, 9.7% vs 12.3% (p<0.001) and OD, 7.6% vs 10.7% (p<0.001). After adjusting for variable confounders, the patients with DM2 presented a lower probability of being treated with BF (OR=0.67, 95% CI: 0.64-0.68), with CaD (OR=0.71, 95% CI: 0.70-0.73) or with OD (OR=0.66, 95% CI: 0.64-0.67) than non-diabetics. Conclusions: Despite having a higher prevalence of fractures in patients with DM2, they have more than 30% chance of not having received an OD than non-diabetic patients. This may be attributed to an underestimation of risk in these patients (AU)

International Osteoporosis Foundation and European Calcified Tissue Society Working Group. Recommendations for the screening of adherence to oral bisphosphonates.

Adherence to oral bisphosphonates is low. A screening strategy is proposed based on the response of biochemical markers of bone turnover after 3 months of therapy. If no change is observed, the clinician should reassess the adherence to the treatment and also other potential issues with the drug. INTRODUCTION: Low adherence to oral bisphosphonates is a common problem that jeopardizes the efficacy of treatment of osteoporosis. No clear screening strategy for the assessment of compliance is widely accepted in these patients. METHODS: The International Osteoporosis Foundation and the European Calcified Tissue Society have convened a working group to propose a screening strategy to detect a lack of adherence to these drugs. The question to answer was whether the bone turnover markers (BTMs) PINP and CTX can be used to identify low adherence in patients with postmenopausal osteoporosis initiating oral bisphosphonates for osteoporosis. The findings of the TRIO study specifically address this question and were used as the basis for testing the hypothesis. RESULTS: Based on the findings of the TRIO study, specifically addressing this question, the working group recommends measuring PINP and CTX at baseline and 3 months after starting therapy to check for a decrease above the least significant change (decrease of more than 38% for PINP and 56% for CTX). Detection rate for the measurement of PINP is 84%, for CTX 87% and, if variation in at least one is considered when measuring both, the level of detection is 94.5%. CONCLUSIONS: If a significant decrease is observed, the treatment can continue, but if no decrease occurs, the clinician should reassess to identify problems with the treatment, mainly low adherence.

CYP11A1 expression in bone is associated with aromatase inhibitor-related bone loss.

Aromatase inhibitors (AIs) used as adjuvant therapy in postmenopausal women with hormone receptor-positive breast cancer cause diverse musculoskeletal side effects that include bone loss and its associated fracture. About half of the 391 patients treated with AIs in the Barcelona-Aromatase induced bone loss in early breast cancer cohort suffered a significant bone loss at lumbar spine (LS) and/or femoral neck (FN) after 2 years on AI-treatment. In contrast, up to one-third (19.6% LS, 38.6% FN) showed no decline or even increased bone density. The present study aimed to determine the genetic basis for this variability. SNPs in candidate genes involved in vitamin D and estrogen hormone-response pathways (CYP11A1, CYP17A1, HSD3B2, HSD17B3, CYP19A1, CYP2C19, CYP2C9, ESR1, DHCR7, GC, CYP2R1, CYP27B1, VDR and CYP24A1) were genotyped for association analysis with AI-related bone loss (AIBL). After multiple testing correction, 3 tag-SNPs (rs4077581, s11632698 and rs900798) located in the CYP11A1 gene were significantly associated (P<0.005) with FN AIBL at 2 years of treatment. Next, CYP11A1 expression in human fresh bone tissue and primary osteoblasts was demonstrated by RT-PCR. Both common isoforms of human cholesterol side-chain cleavage enzyme (encoded by CYP11A1 gene) were detected in osteoblasts by western blot. In conclusion, the genetic association of CYP11A1 gene with AIBL and its expression in bone tissue reveals a potential local function of this enzyme in bone metabolism regulation, offering a new vision of the steroidogenic ability of this tissue and new understanding of AI-induced bone loss.

Management of osteoporosis of the oldest old.

UNLABELLED: This consensus article reviews the diagnosis and treatment of osteoporosis in geriatric populations. Specifically, it reviews the risk assessment and intervention thresholds, the impact of nutritional deficiencies, fall prevention strategies, pharmacological treatments and their safety considerations, the risks of sub-optimal treatment adherence and strategies for its improvement. INTRODUCTION: This consensus article reviews the therapeutic strategies and management options for the treatment of osteoporosis of the oldest old. This vulnerable segment (persons over 80 years of age) stands to gain substantially from effective anti-osteoporosis treatment, but the under-prescription of these treatments is frequent. METHODS: This report is the result of an ESCEO (European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis) expert working group, which explores some of the reasons for this and presents the arguments to counter these beliefs. The risk assessment of older individuals is briefly reviewed along with the differences between some intervention guidelines. The current evidence on the impact of nutritional deficiencies (i.e. calcium, protein and vitamin D) is presented, as are strategies to prevent falls. One possible reason for the under-prescription of pharmacological treatments for osteoporosis in the oldest old is the perception that anti-fracture efficacy requires long-term treatment. However, a review of the data shows convincing anti-fracture efficacy already by 12 months. RESULTS: The safety profiles of these pharmacological agents are generally satisfactory in this patient segment provided a few precautions are followed. CONCLUSION: These patients should be considered for particular consultation/follow-up procedures in the effort to convince on the benefits of treatment and to allay fears of adverse drug reactions, since poor adherence is a major problem for the success of a strategy for osteoporosis and limits cost-effectiveness.

Management of glucocorticoid-induced osteoporosis.

This review summarizes the available evidence-based data that form the basis for therapeutic intervention and covers the current status of glucocorticoid-induced osteoporosis (GIOP) management, regulatory requirements, and risk-assessment options. Glucocorticoids are known to cause bone loss and fractures, yet many patients receiving or initiating glucocorticoid therapy are not appropriately evaluated and treated. An European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis workshop was convened to discuss GIOP management and to provide a report by a panel of experts. An expert panel reviewed the available studies that discussed approved therapeutic agents, focusing on randomized and controlled clinical trials reporting on bone mineral density and/or fracture risk of at least 48 weeks' duration. There is no evidence that GIOP and postmenopausal osteoporosis respond differently to treatments. The FRAX algorithm can be adjusted according to glucocorticoid dose. Available antiosteoporotic therapies such as bisphosphonates and teriparatide are efficacious in GIOP management. Several other agents approved for the treatment of postmenopausal osteoporosis may become available for GIOP. It is advised to stop antiosteoporotic treatment after glucocorticoid cessation, unless the patient remains at increased risk of fracture. Calcium and vitamin D supplementation as an osteoporosis-prevention measure is less effective than specific antiosteoporotic treatment. Fracture end-point studies and additional studies investigating specific subpopulations (pediatric, premenopausal, or elderly patients) would strengthen the evidence base and facilitate the development of intervention thresholds and treatment guidelines.

Inadequate responders to osteoporosis treatment: proposal for an operational definition.

UNLABELLED: The concept of inadequate response to osteoporosis treatment is not clear. In the literature several criteria have been used. We propose an operational definition of an inadequate responder based on the changes observed in bone mineral density and incident fractures while on therapy. INTRODUCTION: Fractures may occur in compliant patients even while on active treatment. These cases have been defined as inadequate responders (IR). METHODS: We reviewed the basis for this concept and propose an operational definition for IR. RESULTS: Good compliance and adequate calcium and vitamin D supplementation are the first requirement. The second requirement is a treatment period of at least 1 year, since before that time treatment may not have been fully effective. Fractures are the gold standard for measuring efficacy and changes in bone density and turnover markers may be surrogates. We propose classifying patient response as: Inadequate--incident fracture and a decrease in BMD greater than a significant change (Trend Assessment Margin or TAM); Possibly inadequate--incident fracture or a decrease in BMD greater than a significant change (TAM); and Appropriate--no fracture and no decrease in BMD greater than a significant change (TAM). Additional criteria (biochemical markers, bone quality parameters) may be taken into account. CONCLUSION: A wide consensus on the IR concept is required given its clinical, regulatory, and reimbursement implications.

[Guide for the prevention and treatment of glucocorticoid-induced osteoporosis of the Spanish Society of Internal Medicine]. / Guía de prevención y tratamiento de la osteoporosis inducida por glucocorticoides de la Sociedad Española de Medicina Interna.

Our objective has been to elaborate an updated Clinical Guide of the Spanish Society of Internal Medicine (SEMI) for the prevention and treatment of glucocorticoids-induced osteoporosis (GIO), identifying and measuring the grade of evidence that supports the given recommendations. For this, we reviewed studies performed on pathophysiology, diagnosis, prevention and treatment of GIO and after analyzing them we elaborated the present recommendations. This was done after a pre-specified and reproducible process that included an accepted model for the evaluation, and the reference of the evidence that supported it. Once the Scientific Committee elaborated the draft of the Clinical Guide, it was reviewed by all the members of the Working Group on Osteoporosis of the SEMI, and by an External Committee who included experts of many different specialities. Pathophysiology of GIO is complex and yet unknown. Bone effects of glucocorticoids are determined by multiple factors although accumulated doses seems to be the most important one. The best method to diagnose GIO is Dual X-Ray Absorptiometry (DXA), although WHO criteria defined for the diagnosis of postmenopausal osteoporosis are not applicable in GIO. The presence of a T-score lower than -1.5 Tscore indicates the necessity of treatment in any patient who receives or is going to receive more than 3 months treatment with glucocorticoids at a dose higher than 2.5 mg/day (in postmenopausal women) and 5 mg/day (in premenopausal women and men). DXA is also useful to follow up the patients, who can be done annually. Treatment must be prescribed to any patient who is receiving glucocorticoids or is going to receive them at doses higher than 7.5 mg/day for more than 3 months and 5 mg/day if the patient is a postmenopausal woman or has suffered from previous fragility fractures. Risedronate and alendronate are the drugs of election, always together with calcium and vitamin D supplements and general measurements usually prescribed in the treatment of osteoporosis. In very ill patients, parathyroid hormone can be used. The treatment for GIO should be maintained while glucocorticoid therapy is used.

Bone mineral density referral for dual-energy X-ray absorptiometry using quantitative ultrasound as a prescreening tool in postmenopausal women from the general population: a cost-effectiveness analysis.

The aim of our study was to assess, from the perspective of the National Health Services in Spain, the cost-effectiveness of quantitative ultrasound (QUS) as a prescreen referral method for bone mineral density (BMD) assessment by dual-energy X-ray absorptiometry (DXA) in postmenopausal women of the general population. Using femoral neck DXA and heel QUS. We evaluated 267 consecutive postmenopausal women 65 years and older and attending primary care physician offices for any medical reason. Subjects were classified as osteoporotic or nonosteoporotic (normal or osteopenic) using the WHO definition for DXA. Effectiveness was assessed in terms of the sensitivity and specificity of the referral decisions based on the QUS measurement. Local costs were estimated from health services and actual resource used. Cost-effectiveness was evaluated in terms of the expected cost per true positive osteoporotic case detected. Baseline prevalence of osteoporosis evaluated by DXA was 55.8%. The sensitivity and specificity for the diagnosis of osteoporosis by QUS using the optimal cutoff thresholds for the estimated heel BMD T-score were 97% and 94%, respectively. The average cost per osteoporotic case detected based on DXA measurement alone was 23.85 euros. The average cost per osteoporotic case detected using QUS as a prescreen was 22.00 euros. The incremental cost-effectiveness of DXA versus QUS was 114.00 euros per true positive case detected. Our results suggest that screening for osteoporosis with QUS while applying strict cufoff values in postmenopausal women of the general population is not substantially more cost-effective than DXA alone for the diagnosis of osteoporosis. However, the screening strategy with QUS may be an option in those circumstances where the diagnosis of osteoporosis is deficient because of the difficulty in accessing DXA equipment.

The effect of teriparatide [human parathyroid hormone (1-34)] therapy on bone density in men with osteoporosis.

Teriparatide [rhPTH(1-34)] increases bone mineral density and reduces the risk of vertebral fracture in women. We randomized 437 men with spine or hip bone mineral density more than 2 SD below the young adult male mean to daily injections of placebo, teriparatide 20 microg, or teriparatide 40 microg. All subjects also received supplemental calcium and vitamin D. The study was stopped after a median duration of 11 months because of a finding of osteosarcomas in rats in routine toxicology studies. Biochemical markers of bone formation increased early in the course of therapy and were followed by increases in indices of osteoclastic activity. Spine bone mineral density was greater than in placebo subjects after 3 months of teriparatide therapy, and by the end of therapy it was increased by 5.9% (20 microg) and 9.0% (40 microg) above baseline (p < 0.001 vs. placebo for both comparisons). Femoral neck bone mineral density increased 1.5% (20 microg; p = 0.029) and 2.9% (40 microg; p < 0.001), and whole body bone mineral content increased 0.6% (20 microg; p = 0.021) and 0.9% (40 microg;p = 0.005) above baseline in the teriparatide subjects. There was no change in radial bone mineral density in the teriparatide groups. Bone mineral density responses to teriparatide were similar regardless of gonadal status, age, baseline bone mineral density, body mass index, smoking, or alcohol intake. Subjects experienced expected changes in mineral metabolism. Adverse events were similar in the placebo and 20-microg groups, but more frequent in the 40-microg group. This study shows that teriparatide treatment results in an increase in bone mineral density and is a potentially useful therapy for osteoporosis in men.