The cost-effectiveness of osteoporosis medications for preventing periprosthetic fractures following femoral neck fracture indicated hip arthroplasty: a break-even analysis.

Osteoporosis treatment following arthroplasty for femoral neck fracture (FNF) is associated with lower rates of periprosthetic fracture (PPF). Our study evaluated the economic viability of treatment in patients following arthroplasty and demonstrates that treatment with oral bisphosphonates can be cost-effective in preventing PPF. INTRODUCTION: Osteoporosis treatment following arthroplasty for femoral neck fracture (FNF) is associated with lower rates of periprosthetic fracture (PPF). Although cost-effective in reducing the rate of secondary fragility fracture, the economic viability of osteoporosis treatment in preventing PPF has not been evaluated. Therefore, the purpose of this study is to use a break-even analysis to determine whether and which current osteoporosis medications are cost-effective in preventing PPF following arthroplasty for FNFs. METHODS: Three-year average cost of osteoporosis medication (oral bisphosphonates, estrogen hormonal therapy, intravenous (IV) bisphosphonates, denosumab, teriparatide, and abaloparatide), costs of PPF care, and PPF rates in patients who underwent hip arthroplasty for FNFs without osteoporosis treatment were used to perform a break-even analysis. The absolute risk reduction (ARR) related to osteoporosis treatment and sensitivity analyses were used to evaluate the cost-effectiveness of this intervention and break-even PPF rates. RESULTS: Oral bisphosphonate therapy following arthroplasty for hip fractures would be economically justified if it prevents one out of 56 PPFs (ARR, 1.8%). Given the current cost and incidence of PPF, overall treatment can only be economically viable for PPF prophylaxis if the 3-year costs of these agents are less than $1500. CONCLUSION: The utilization of lower cost osteoporosis medications such as oral bisphosphonates and estrogen hormonal therapy as PPF prophylaxis in this patient population would be economically viable if they reduce the PPF rate by 1.8% and 1.5%, respectively. For IV bisphosphonates and newer agents to be economically viable as PPF prophylaxis in the USA, their costs need to be significantly reduced.

Exercise and the prevention of major osteoporotic fractures in adults: a systematic review and meta-analysis with special emphasis on intensity progression and study duration.

The role of exercise in preventing osteoporotic fractures is vague, and further recommendations for optimized exercise protocols are very rare. In the present work, we provided positive evidence for exercise effects on the number of osteoporotic fractures in adults, albeit without observing any significant relevance of intensity progression or study duration. INTRODUCTION: Osteoporotic fractures are a major challenge confronting our aging society. Exercise might be an efficient agent for reducing osteoporotic fractures in older adults, but the most promising exercise protocol for that purpose has yet to be identified. The present meta-analysis thus aimed to identify important predictors of the exercise effect on osteoporotic fractures in adults. METHODS: We conducted a systematic search of six literature databases according to the PRISMA guideline that included controlled exercise studies and reported the number of low-trauma major osteoporotic fractures separately for exercise (EG) and control (CG) groups. Primary study outcome was incidence ratio (IR) for major osteoporotic fractures. Sub-analyses were conducted for progression of intensity (yes vs. no) during the trial and the study duration (≤ 12 months vs. > 12 months). RESULTS: In summary, 11 studies with a pooled number of 9715 participant-years in the EG and 9592 in the CG were included. The mixed-effects conditional Poisson regression revealed positive exercise effects on major osteoporotic fractures (RR: 0.75, 95% CI: 0.54-0.94, p = .006). Although studies with intensity progression were more favorable, our subgroup analysis did not determine significant differences for diverging intensity progression (p = .133) or study duration (p = .883). Heterogeneity among the trials of the subgroups (I2 ≤ 0-7.1%) was negligible. CONCLUSION: The present systematic review and meta-analysis provided significant evidence for the favorable effect of exercise on major osteoporotic fractures. However, diverging study and exercise characteristics along with the close interaction of exercise parameters prevented the derivation of reliable recommendations for exercise protocols for fracture reductions. PROSPERO ID: CRD42021250467.

The Capture the Fracture® Partnership: an overview of a global initiative to increase the secondary fracture prevention care for patient benefit.

The Capture the Fracture® Partnership (CTF-P) is a unique collaboration between the International Osteoporosis Foundation, academic units and industry partners to enhance the implementation of effective, efficient fracture liaison services (FLSs) with a good patient experience. CTF-P has generated valuable resources for the specific countries as well as the broader FLS community to improve the initiation, effectiveness and sustainability of FLS in a wide range of healthcare settings.

Fracture liaison service model: project design and accreditation.

Frailty fractures place a significant socioeconomic burden on the health care system. The Italian Society of Orthopaedics and Traumatology (SIOT) is proceeding to fracture liaison service (FLS) model accreditation in several Italian Fracture Units (FUs), which provides a multidisciplinary approach for the management of the fragility fracture patient. INTRODUCTION: Osteoporosis and the resulting fragility fractures, particularly femoral fractures, place significant socioeconomic burdens on the health care system globally. In addition, there is a general lack of awareness of osteoporosis, resulting in underestimation of the associated risks and suboptimal treatment of the disease. The fracture liaison service (FLS) represents an exemplary model of post-fracture care that involves a multidisciplinary approach to the frail patient through the collaboration of multiple specialists. The purpose of this article is to highlight the path undertaken by the Italian Society of Orthopaedics and Traumatology (SIOT) for the purpose of certification of numerous FLS centers throughout Italy. METHODS: SIOT is proceeding with international FLS accreditation in several Italian Fracture Units (FUs), following the creation of a model that provides specific operational and procedural steps for the management of fragility fractures throughout the country. FUs that decide to join the project and implement this model within their facility are then audited by an ACCREDIA-accredited medical certification body. RESULTS: The drafted FLS model, thanks to the active involvement of a panel of experts appointed by SIOT, outlines a reference operational model that describes a fluid and articulated process that identifies the procedure of identification, description of diagnostic framing, and subsequent initiation of appropriate secondary prevention programs for fractures of individuals who have presented with a recent fragility fracture of the femur. CONCLUSION: Accreditation of this prevention model will enable many facilities to take advantage of this dedicated diagnostic-therapeutic pathway for the purpose of fracture prevention and reduction of associated health and social costs.

Romosozumab Efficacy in Postmenopausal Women With No Prior Fracture Who Fulfill Criteria for Very High Fracture Risk.

OBJECTIVE: We evaluated the efficacy of romosozumab in women from FRAME who had no prior fracture but met other criteria for very high fracture risk (VHFR). METHODS: In FRAME, postmenopausal women received romosozumab or placebo for 12 months (year 1) followed by denosumab for 12 months (year 2). In this post hoc analysis, we applied the following criteria from the American Association of Clinical Endocrinology to define VHFR: lumbar spine or total hip T-score <-3.0 and/or Fracture Risk Assessment Tool probability of major osteoporotic fracture >30% or hip fracture >4.5% to women with no fracture history at baseline (no fracture-VHFR [NF-VHFR]). Incidence of new vertebral, clinical, and nonvertebral fractures and mean bone mineral density (BMD) percentage change from baseline were assessed at years 1 and 2. RESULTS: Of the 7180 women in FRAME, 2825 were included in the NF-VHFR subgroup analysis. At year 1, romosozumab versus placebo reduced the incidence of new vertebral fracture (relative risk reduction [RRR]: 76%), clinical fracture (RRR: 60%), and nonvertebral fracture (RRR: 54%) (all P <.05). This fracture reduction was maintained through year 2 in women receiving the romosozumab-to-denosumab sequence versus the placebo-to-denosumab sequence for new vertebral, clinical, and nonvertebral fractures (RRR: 77%, 54%, and 46%, respectively; all P <.05). The mean BMD changes in both treatment groups were similar to those in the overall FRAME population at years 1 and 2. CONCLUSION: Romosozumab significantly reduced vertebral, clinical, and nonvertebral fracture risk and increased the BMD more than placebo in women at VHFR.

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.

Comparative effectiveness and cardiovascular safety of abaloparatide and teriparatide in postmenopausal women new to anabolic therapy: A US administrative claims database study.

Real-world evidence on the comparative effectiveness and safety of abaloparatide versus teriparatide in women with osteoporosis may help inform treatment decisions. Following 18 months of treatment, abaloparatide was comparable to teriparatide for prevention of nonvertebral fractures, resulted in a 22% risk reduction for hip fractures, and demonstrated similar cardiovascular safety. Osteoporotic fracture risk can be reduced with anabolic or antiresorptive medications. In addition to efficacy and safety data from controlled clinical trials, real-world evidence on comparative effectiveness and safety may help inform treatment decisions. INTRODUCTION: The real-world effectiveness of abaloparatide versus teriparatide on nonvertebral fracture (NVF) incidence and cardiovascular safety during the 19-month period after treatment initiation were evaluated (NCT04974723). METHODS: Anonymized US patient claims data from Symphony Health, Integrated Dataverse (IDV)®, May 1, 2017 to July 31, 2019, included women aged ≥ 50 years with ≥ 1 prescription of abaloparatide or teriparatide and no prior anabolic therapy. Most were enrolled in commercial and Medicare health plans. Index was the date of the initial prescription dispensed during the identification period. In 1:1 propensity score matched cohorts, time to first NVF following index date, major adverse cardiovascular events (MACE), and MACE + heart failure (HF) were compared between cohorts using a Cox proportional hazards model. RESULTS: Propensity score matching yielded 11,616 patients per cohort. Overall median age (interquartile range) was 67 (61, 75) years, and 25.6% had a fracture history. Over 19 months, 335 patients on abaloparatide and 375 on teriparatide had a NVF (hazard ratio [95% confidence interval]: 0.89 [0.77, 1.03]), and 121 and 154 patients, respectively, had a hip fracture [HR (95% CI): 0.78 (0.62, 1.00)]. The MACE and MACE + HF rates were similar between cohorts. CONCLUSIONS: Following 18 months of treatment, abaloparatide was comparable to teriparatide for prevention of NVF and similar cardiovascular safety was demonstrated between cohorts.

Advanced Prostate Cancer: AUA/ASTRO/SUO Guideline PART II.

PURPOSE: The summary presented herein represents Part II of the two-part series dedicated to Advanced Prostate Cancer: AUA/ASTRO/SUO Guideline discussing prognostic and treatment recommendations for patients with castration-resistant disease. Please refer to Part I for discussion of the management of patients with biochemical recurrence without metastatic disease after exhaustion of local treatment options as well as those with metastatic hormone-sensitive prostate cancer. RESULTS: The Advanced Prostate Cancer Panel created evidence- and consensus-based guideline statements to aid clinicians in the management of patients with advanced prostate cancer. Such statements are summarized in figure 1[Figure: see text] and detailed herein. MATERIALS AND METHODS: The systematic review utilized to inform this guideline was conducted by an independent methodological consultant. A research librarian conducted searches in Ovid MEDLINE (1998 to January Week 5 2019), Cochrane Central Register of Controlled Trials (through December 2018), and Cochrane Database of Systematic Reviews (2005 through February 6, 2019). An updated search was conducted prior to publication through January 20, 2020. The methodology team supplemented searches of electronic databases with the studies included in the prior AUA review and by reviewing reference lists of relevant articles. CONCLUSIONS: This guideline attempts to improve a clinician's ability to treat patients diagnosed with advanced prostate cancer. Continued research and publication of high-quality evidence from future trials will be essential to improve the level of care for these patients.

Cancer patients with fractures are rarely assessed or treated for osteoporosis: a population-based study.

Among 4238 cancer and 16,418 cancer-free individuals with incident major non-traumatic fractures (hip, clinical vertebral, forearm, humerus), post-fracture osteoporosis care was equally poor for both groups, whether assessed from bone mineral density (BMD) testing, initiation of osteoporosis therapy or either intervention (BMD testing and/or osteoporosis therapy). INTRODUCTION: Most individuals sustaining a fracture do not undergo evaluation and/or treatment for osteoporosis. Cancer survivors are at increased risk for osteoporosis and fracture. Whether cancer survivors experience a similar post-fracture "care gap" is unclear. Using population-based databases, we assessed whether cancer patients are evaluated and/or treated for osteoporosis after a major fracture. METHODS: From the Manitoba Cancer Registry, we identified cancer cases (first cancer diagnosis between 1987 and 2013) and cancer-free controls with incident major non-traumatic fractures (from provincial physician billing claims and hospitalization databases). The outcomes were performance of BMD testing (from the BMD Registry), initiation of osteoporosis therapy (from drug dispensation database) or either intervention (BMD testing and/or osteoporosis therapy) in the 12 months post-fracture. RESULTS: There were 4238 cancer and 16,418 cancer-free individuals who sustained a fracture after the index date (cancer diagnosis) and were followed for at least 1 year post-fracture. Subsequent BMD testing was performed in 11.0% of cancer cases versus 11.5% non-cancer controls (P = 0.43), osteoporosis treatment in 22.9% cancer cases versus 21.8% non-cancer controls (P = 0.15), and either testing or treatment in 28.9% cancer cases versus 28.4% non-cancer controls (P = 0.53). Predictors of BMD testing and/or initiation of therapy were similar for non-cancer and cancer patients. Post-fracture interventions were consistently used more frequently among women, older patients (age 50 years or older), those who sustained fractures in a later calendar period, and (for treatment) after vertebral fracture. Cancer-specific variables (cancer type, years from cancer diagnosis to fracture, specialty of care provider) showed only weak and inconsistent effects. CONCLUSIONS: A large care gap exists among cancer patients who sustain a fracture, similar to the general population, whereby the evaluation or treatment for osteoporosis is seldom conducted. Care maps may need to be developed for cancer populations to improve post-fracture care.

Osteoporosis in men: underappreciated and undertreated.

Osteoporotic fractures of the vertebrae and the proximal end of the femur dramatically impair quality of life and increase morbidity and mortality. Although up to 40% of all osteoporotic fractures occur in men, physicians tend to underestimate the osteoporosis in men, and it remains underdiagnosed and undertreated. Though, there is no evidence that current approved osteoporosis medications work any less well in men than in women, insufficient awareness of the risk of fractures, fear of side effects of drugs and other barriers have made management challenging in men at risk for fracture. Our review provides updates on pathophysiology and current options for diagnosis and treatment of male osteoporosis.

Adherence to fracture liaison service programs in patients over 70: the hidden part of the iceberg.

Significant dropout rates have been observed throughout Fracture Liaison Service (FLS) programs, especially for elderly patients. In an FLS program set up specifically for patients over 70, the non-initiation of osteoporosis treatment was the only factor associated with poor adherence to the program. Neither age nor frailty factors affected adherence. INTRODUCTION: FLS programs are considered the most effective interventions for secondary prevention of osteoporotic fractures. Our objective was to identify risk factors for non-adherence to an FLS program set up specifically for patients over 70. METHODS: Our multifaceted, intensive program included five appointments over a 2-year period. One hundred sixty-seven patients (mean age 83.5 years) who presented with a recent fragility fracture were enrolled. Multivariable analysis was conducted to determine whether the demographic, clinical, frailty, and osteoporotic risk factors of the patients influenced their adherence to the program. RESULTS: About half of the patients did not attend the follow-up visits. According to the regression analysis, non-initiation of osteoporosis treatment was associated with poor adherence to the program (aHR 3.66). Demographic, clinical, dwelling, frailty factors, osteoporotic risk factors, fracture type, or densitometric scores were not associated with adherence. The first self-reported reason for withdrawal was the difficulty of attending several follow-up visits, and the second was the feeling of not being concerned. CONCLUSION: We observed that non-initiation of osteoporosis treatment was the only factor correlated with non-adherence to an FLS program. Thus, neither age nor frailty factors should result in patients not being included in FLS. Beyond the necessity of the osteoporosis treatment, good patient understanding of the relevance of all the interventions included in the program is the key.

Few fragility fracture patients perceive that their bone health is affected by their comorbidities and medications.

We examined fragility fracture patients' perceptions of associations between bone health and other chronic conditions and medications. Awareness of the associations between bone health and these conditions and medications was low. Providers should increase patients' awareness of these associations in order to minimize the risk of future fracture. INTRODUCTION: Among patients with a fragility fracture presenting with at least one other chronic health condition, we examined (1) perceptions of the association between bone health and their other health conditions, and (2) perceptions of the association between bone health and prescribed medications taken for other health conditions. METHODS: We identified fragility fracture patients presenting to a Canadian urban fracture clinic with at least one self-reported chronic health condition (in addition to bone fragility). In-depth interviews, 60-90 min in duration, were conducted. Our qualitative methodology was informed by saliency analysis. RESULTS: We interviewed 26 patients (21 females, 5 males) aged 45 to 84 years old. Participants were taking 1-13 medications each and presented with a variety of comorbidities (range 1-7). All participants described at least one condition or medication they were currently taking for which there existed evidence of a negative effect on bone health (increased risk of fracture, bone loss, falling). Two participants perceived a correct association between their other health conditions and compromised bone health, and four participants perceived a correct association between their medications and compromised bone health. CONCLUSION: All patients reported a chronic health condition and/or were taking at least one medication that potentially compromised their bone health. Patient awareness of the association between bone health and other health conditions and prescribed medications was low. Health care providers should increase patients' awareness of the bone health significance of their chronic conditions and medications in order to minimize the risk of future fracture.

Bone Health in Men with Prostate Cancer: Review Article.

PURPOSE OF REVIEW: The improvement in prostate cancer survival over time, even in those with advanced disease, has led to an increasing recognition of the impact of prostate cancer and its treatment on bone health. Cancer treatment-induced bone loss (CTIBL) is a well-recognized entity but greater awareness of the risks associated with CTIBL and its treatment is required. RECENT FINDINGS: The principal culprit in causing CTIBL is hormonal ablation induced by prostate cancer treatment, including several new agents which have been developed in recent years which significantly improve survival, but may cause CTIBL. This review discusses the impact of prostate cancer and its treatment on bone health, including published evidence on the underlying pathophysiology, assessment of bone health, and strategies for prevention and treatment. It is important to recognize the potential cumulative impact of systemic prostate cancer treatments on bone health.

[Diagnostics and treatment of osteoporosis in patients over 65 years old : Current status and future perspectives]. / Osteoporosediagnostik und -therapie bei über 65-Jährigen : Aktueller Stand und Zukunftsaussichten.

Only one third of all women with osteoporosis over the age of 65 years are adequately treated; therefore, many experience fractures. For men the data are insufficient. Using a newly developed algorithm and based on the current guidelines, the diagnosis and specific treatment of osteoporosis can be easily set up. The differential treatment should be selected in an individualized approach based on the side effect profile of the specific medication. No statistically significant differences were found between most specific osteoporotic drugs in head-to-head comparisons. This article presents an overview of the currently available pharmaceutical and non-pharmaceutical forms of treatment as well as approaches with novel medications and interventions for a better control of osteoporosis.

Factors related to intentional non-initiation of bisphosphonate treatment in patients with a high fracture risk in primary care: a qualitative study.

BACKGROUND: Adherence to osteoporosis treatment is crucial for good treatment effects. However, adherence has been shown to be poor and a substantial part of the patients don't even initiate treatment. This study aimed to gain insight into the considerations of both osteoporosis patients and general practitioners (GP) concerning intentional non-initiation of bisphosphonate treatment. METHODS: Osteoporosis patients and GPs were recruited from the SALT Osteoporosis Study and a transmural fracture liaison service, both carried out in the Netherlands. Using questionnaires, we identified non-starters and starters of bisphosphonate treatment. Semi-structured interviews were conducted to gain a detailed overview of all considerations until saturation of the data was reached. Starters were asked to reflect on the considerations that were brought forward by the non-starters. Interviews were open coded and the codes were classified into main themes and subthemes using an inductive approach. RESULTS: 16 non-starters, 10 starters, and 13 GPs were interviewed. We identified three main themes: insufficient medical advice, attitudes towards medication use including concerns about side effects, and disease awareness. From patients' as well as GPs' perspective, insufficient or ambiguous information from the GP influenced the decision of the non-starters to not start bisphosphonates. In contrast, starters were either properly informed, or they collected information themselves. Patients' aversion towards medication, fear of side effects, and a low risk perception also contributed to not starting the medication, whereas starters were aware of their fracture risk and were confident of the outcome of the treatment. Concerns about osteoporosis treatment and its side effects were also expressed by several GPs. Some GPs appeared to have a limited understanding of the current osteoporosis guidelines and the indications for treatment. CONCLUSIONS: Many reasons we found for not starting bisphosphonate treatment were related to the patients or the GPs themselves being insufficiently informed. Attitudes of the GPs were shown to play a role in the decision of patients not to start treatment. Interventions need to be developed that are aimed at GPs, and at education of patients.

[Osteoporosis and quality of bone]. / Osteoporóza a kvalita kostní hmoty.

The risk of osteoporotic fracture is determined collectively by bone mineral density, bone mass, architecture and properties of the mineral and organic matrix composite. Changes in these distinct aspects of quality of bone with age, estrogen deficiency, diseases leading to increased risk of fracture and differential mode of action of antiresorptive and bone anabolic treatments have to be considered in clinical therapeutic strategies. In patients at high risk of low impact fracture, sequential therapy switching to antiresorptives after patients have an adequate response to 2 years teriparatide may be the optimal strategy of long term therapy.Key words: aging - bone quality - osteoporosis - prevention - therapy.