Osteoporosis is the most common metabolic bone disease in the USA and the world. It is a subclinical condition until complicated by fracture(s). These fractures place an enormous medical and personal burden on individuals who suffer from them and take a significant economic toll. Any new fracture in an adult aged 50 years or older signifies imminent elevated risk for subsequent fractures, particularly in the year following the initial fracture. What a patient perceives as an unfortunate accident may be seen as a sentinel event indicative of bone fragility and increased future fracture risk even when the result of considerable trauma. Clinical or subclinical vertebral fractures, the most common type of osteoporotic fractures, are associated with a 5-fold increased risk for additional vertebral fractures and a 2- to 3-fold increased risk for fractures at other sites. Untreated osteoporosis can lead to a vicious cycle of recurrent fracture(s), often resulting in disability and premature death. In appropriate patients, treatment with effective antifracture medication prevents fractures and improves outcomes. Primary care providers and medical specialists are critical gatekeepers who can identify fractures and initiate proven osteoporosis interventions. Osteoporosis detection, diagnosis, and treatment should be routine practice in all adult healthcare settings. The Bone Health and Osteoporosis Foundation (BHOF) – formerly the National Osteoporosis Foundation – first published the Clinician’s Guide in 1999 to provide accurate information on osteoporosis prevention and treatment. Since that time, significant improvements have been made in diagnostic technologies and treatments for osteoporosis. Despite these advances, a disturbing gap persists in patient care. At-risk patients are often not screened to establish fracture probability and not educated about fracture prevention. Most concerning, the majority of highest risk women and men who have a fracture(s) are not diagnosed and do not receive effective, FDA-approved therapies. Even those prescribed appropriate therapy are unlikely to take the medication as prescribed. The Clinician’s Guide offers concise recommendations regarding prevention, risk assessment, diagnosis, and treatment of osteoporosis in postmenopausal women and men aged 50 years and older. It includes indications for bone densitometry as well as fracture risk thresholds for pharmacologic intervention. Current medications build bone and/or decrease bone breakdown and dramatically reduce incident fractures. All antifracture therapeutics treat but do not cure the disease. Skeletal deterioration resumes sooner or later when a medication is discontinued—sooner for nonbisphosphonates and later for bisphosphonates. Even if normal BMD is achieved, osteoporosis and elevated risk for fracture are still present. The diagnosis of osteoporosis persists even if subsequent DXA T-scores are above − 2.5. Ongoing monitoring and strategic interventions will be necessary if fractures are to be avoided. In addition to pharmacotherapy, adequate intake of calcium and vitamin D, avoidance of smoking and excessive alcohol intake, weight-bearing and resistance-training exercise, and fall prevention are included in the fracture prevention armamentarium. Where possible, recommendations in this guide are based on evidence from RCTs; however, relevant published data and guidance from expert clinical experience provides the basis for recommendations in those areas where RCT evidence is currently deficient or not applicable to the many osteoporosis patients not considered for RCT participation due to age and morbidity.

Antiresorptive therapies reduce fracture risk; however, long-term bone turnover inhibition may raise concerns about rare, but serious, skeletal adverse events-atypical femoral fracture (AFF) and osteonecrosis of the jaw (ONJ). Denosumab, a fully human monoclonal antibody against RANKL, has demonstrated sustained low vertebral and nonvertebral fracture rates with low skeletal adverse event rates in the 3-year FREEDOM trial and its 7-year Extension (in which all subjects received open-label denosumab). In this analysis, we aimed to estimate fractures prevented relative to skeletal adverse events observed with 10 years of denosumab therapy. We modeled a hypothetical placebo group using the virtual-twin method, thereby allowing calculation of fractures prevented with denosumab treatment (relative to the virtual-placebo group) in the context of AFF or ONJ events observed in the long-term denosumab group. Estimated virtual-placebo and observed long-term denosumab exposure-adjusted fracture rates per 100,000 subject-years were calculated for fractures classified as clinical (3180 and 1777, respectively), major osteoporotic (2699 and 1525), vertebral (1879 and 901), and nonvertebral (2924 and 1528), and compared with observed AFF and ONJ in the long-term denosumab group (5 and 35 per 100,000 subject-years, respectively). The skeletal benefit/risk ratio (fractures prevented per adverse event observed) for clinical fractures was 281 (AFF) and 40 (ONJ). Based on this model, denosumab treatment for up to 10 years has a favorable skeletal benefit/risk profile when comparing fractures prevented per skeletal adverse event observed.

The surgeon general of the USA defines osteoporosis as "a skeletal disorder characterized by compromised bone strength, predisposing to an increased risk of fracture." Measuring bone strength, Biomechanical Computed Tomography analysis (BCT), namely, finite element analysis of a patient's clinical-resolution computed tomography (CT) scan, is now available in the USA as a Medicare screening benefit for osteoporosis diagnostic testing. Helping to address under-diagnosis of osteoporosis, BCT can be applied "opportunistically" to most existing CT scans that include the spine or hip regions and were previously obtained for an unrelated medical indication. For the BCT test, no modifications are required to standard clinical CT imaging protocols. The analysis provides measurements of bone strength as well as a dual-energy X-ray absorptiometry (DXA)-equivalent bone mineral density (BMD) T-score at the hip and a volumetric BMD of trabecular bone at the spine. Based on both the bone strength and BMD measurements, a physician can identify osteoporosis and assess fracture risk (high, increased, not increased), without needing confirmation by DXA. To help introduce BCT to clinicians and health care professionals, we describe in this review the currently available clinical implementation of the test (VirtuOst), its application for managing patients, and the underlying supporting evidence; we also discuss its main limitations and how its results can be interpreted clinically. Together, this body of evidence supports BCT as an accurate and convenient diagnostic test for osteoporosis in both sexes, particularly when used opportunistically for patients already with CT. Biomechanical Computed Tomography analysis (BCT) uses a patient's CT scan to measure both bone strength and bone mineral density at the hip or spine. Performing at least as well as DXA for both diagnosing osteoporosis and assessing fracture risk, BCT is particularly well-suited to "opportunistic" use for the patient without a recent DXA who is undergoing or has previously undergone CT testing (including hip or spine regions) for an unrelated medical condition.

We investigated the factors associated with readiness for initiating osteoporosis treatment in women at high risk of fracture. We found that women in the contemplative stage were more likely to report previously being told having osteoporosis or osteopenia, acknowledge concern about osteoporosis, and disclose prior osteoporosis treatment. Understanding factors associated with reaching the contemplative stage of readiness to initiate osteoporosis treatment may inform the design of behavioral interventions to improve osteoporosis treatment uptake in women at high risk for fracture. We measured readiness to initiate osteoporosis treatment using a modified form of the Weinstein Precaution Adoption Process Model (PAPM) among 2684 women at high risk of fracture from the Activating Patients at Risk for OsteoPOroSis (APROPOS) clinical trial. Pre-contemplative participants were those who self-classified in the unaware and unengaged stages of PAPM (stages 1 and 2). Contemplative participants were those in the undecided, decided not to act, or decided to act stages of PAPM (stages 3, 4, and 5). Using multivariable logistic regression, we evaluated participant characteristics associated with levels of readiness to initiate osteoporosis treatment. Overall, 24% (N = 412) self-classified in the contemplative stage of readiness to initiate osteoporosis treatment. After adjusting for age, race, education, health literacy, and major osteoporotic fracture in the past 12 months, contemplative women were more likely to report previously being told they had osteoporosis or osteopenia (adjusted odds ratio [aOR] (95% CI) 11.8 (7.8–17.9) and 3.8 (2.5–5.6), respectively), acknowledge concern about osteoporosis (aOR 3.5 (2.5–4.9)), and disclose prior osteoporosis treatment (aOR 4.5 (3.3–6.3)) than women who self-classified as pre-contemplative. For women at high risk for future fractures, ensuring women’s recognition of their diagnosis of osteoporosis/osteopenia and addressing their concerns about osteoporosis are critical components to consider when attempting to influence stage of behavior transitions in osteoporosis treatment.

Persistence with prescribed medications for chronic diseases is important; however, persistence with osteoporosis treatments is historically poor. In this prospective cohort study of postmenopausal women treated for osteoporosis in real-world clinical practice settings in the USA and Canada, 24-month persistence with denosumab was 58%.

Background High-consequence, albeit rare, adverse side effects of osteoporosis medication raise patients’ risk perceptions and contribute to non-adherence. In the past decade, fears of osteonecrosis of the jaw (ONJ) and atypical femoral fractures (AFF) have been increasingly reported as barriers to both the initiation of and adherence to osteoporosis medications. Objectives To examine the temporal prevalence of self-reported concern about ONJ and AFF as reason for discontinuation of osteoporosis medication. Methods Activating Patients at Risk for OsteoPOroSis (APROPOS) enrolled US women from the Global Longitudinal Study of Osteoporosis (GLOW) with previous self-reported fractures and no current use of osteoporosis medication. Using mailed surveys in 2010 (T1), 2012 (T2) and 2013 (T3), women were asked whether they discontinued osteoporosis medication in the prior year because of concerns about ONJ at three time points (T1, T2, T3) and AFF at two time points (T2, T3). We calculated the proportion of women reporting fears of ONJ and AFF among those who discontinued osteoporosis medication, and compared the proportions using chi-square tests. Results A total of 833 women discontinued osteoporosis treatment at three time points,T1 (n=255), T2 (n=471), and T3 (n=107), respectively. There were no differences in the demographic characteristics between groups. The proportion of women reporting concerns of ONJ was 18.4% (T1), 26.7% (T2) and 64.5% (T3), while 23.5% (T2) and 60.7% (T3) reported fear of AFF as reason to discontinue osteoporosis treatment. These differences were statistically significant (p<0.0001) for all comparisons. Conclusions The proportion of women reporting concerns of ONJ and AFF increased over time among those women who discontinue osteoporosis medications. Strategies are needed to help patients balance risks and benefits given a significant and temporally growing concern of rare bisphosphonate side effects. Disclosure of Interest M. I. Danila: None declared, E. Rahn: None declared, A. Mudano: None declared, R. Outman: None declared, P. Li: None declared, D. Redden: None declared, F. Anderson Grant/research support from: Portola, Consultant for: Millennium Pharmaceuticals, S. Greenspan Grant/research support from: Amgen, Lilly, Consultant for: Merck, A. LaCroix Consultant for: Amgen, Pfizer, Sermonix, J. Nieves: None declared, S. Silverman Grant/research support from: Amgen, Lilly, Consultant for: Amgen, Speakers bureau: Amgen, Lilly, E. Siris Consultant for: Amgen, Radius, N. Watts Shareholder of: OsteoDynamics, Grant/research support from: Shire, Consultant for: AbbVie, Amgen, Janssen, Merck, Radius, Sanofi, Paid instructor for: Amgen, Shire, S. Ladores: None declared, K. Meneses: None declared, J. Curtis Grant/research support from: Amgen, Consultant for: Amgen, K. Saag Grant/research support from: Amgen, Lilly, Merck, Consultant for: Amgen, Lilly, Merck

Osteoporotic hip fractures in 4344 patients were more common during winter. Lower temperatures were associated with higher rates of fracture only in those not vaccinated for influenza. Influenza outbreaks increased the risk of hip fractures. Further studies are needed to assess whether influenza vaccination can prevent hip fractures.

The name of the first author, E.M. Lewiecki, was rendered incorrectly in the original publication. The publisher regrets any inconvenience and is pleased to correct the error here.

We evaluated the prevalence of osteoporosis using the osteoporosis diagnostic criteria developed by the National Bone Health Alliance (NBHA), which includes qualified fractures, FRAX score in addition to BMD. The expanded definition increases the prevalence compared to BMD alone definitions; however, it may better identify those at elevated fracture risk. Recently an NBHA working Group published a paper in OI with recommendations for expanding the criteria that would constitute an osteoporosis diagnosis in postmenopausal women and in men over age 50 for use in the US – Siris et al., Osteoporosis International 25(%): 1439–1443, 2014. The recommendations have now been endorsed by NOF, ASBMR and a number of professional medical groups and appear in the NOF Clinician’s Guide. The new diagnostic criteria continue to include a T-score by DXA of spine or hip that is less than or equal to −2.5, but alternatively also include a hip fracture with or without BMD testing or a vertebral, pelvis, proximal humerus and in some cases a distal forearm fracture in a person with low bone mass, or a FRAX score that meets or exceeds the NOF Guide osteoporosis treatment cut point.

In this study, we report that self-perception of fracture risk captures some aspect of fracture risk not currently measured using conventional fracture prediction tools and is associated with improved medication uptake. It suggests that adequate appreciation of fracture risk may be beneficial and lead to greater healthcare engagement and treatment.

BACKGROUND:A large proportion of patients do not persist with osteoporosis (OP) therapy. Gastrointestinal (GI) events (e.g., gastroesophageal reflux disease and nausea/vomiting) are common among OP patients receiving OP therapy and may impact persistence with treatment.OBJECTIVE:To examine the association of GI events and persistence with OP therapy.METHODS:Using a large U.S. administrative claims database, we studied women aged ≥ 55 years who received oral bisphosphonate (BIS) as their first OP therapy from 2002-2009. The index date was the first pharmacy claim date recorded for oral BIS therapy; the baseline period was 12 months pre-index, and follow-up was 12 months post-index. Patients were considered persistent with therapy if they had continuous refills of the index drug class without additional drug therapy from a different drug class from the index date until the end of the follow-up period with no gaps in supply greater than 45 days. Discontinuation was defined as the first gap greater than 45 days during which there was no evidence of refills of OP medication. The association between post-treatment GI events and the risk of discontinuation or switching was modeled with Cox regression stratified by presence of baseline GI events and adjusted for baseline clinical and demographic characteristics.RESULTS:Of the 75,593 women who met eligibility criteria, 59.9% discontinued BIS; 39.3% were persistent; and 0.5% switched to non-BIS. GI events were diagnosed in 20,073 patients (26.6%) during baseline and in 21,142 (28.0%) in the post-treatment period (12-month follow-up post-index). Patients with post-treatment GI diagnosis were 35.6% more likely to discontinue or switch treatment (HR = 1.356, 95% CI = 1.318-1.396) during the 12-month follow-up compared with those without post-treatment GI diagnosis. GI events that occurred closer to treatment discontinuation or switching were associated with a greater risk of discontinuation or switching: 37.9% (HR = 1.379, 95% CI = 1.338-1.421) for GI events within 6 months of discontinuation or switching and 45.6% (HR = 1.456, 95% CI = 1.408-1.505) for GI events within 3 months of discontinuation or switching.CONCLUSIONS:Among women aged 55 years or older in a U.S. managed care population, post-treatment GI events were associated with a higher risk of discontinuation of oral BIS or switching to non-BIS.

We used the GLOW database to study the bone health management postmenopausal women with glucocorticoid exposure. GLOW is a 5-year observational study of 60,000 postmenopausal women enrolled in 17 sites in 10 countries in Europe, North America, and Australia. We studied the use of BMD testing within the past 3 years of the study and medical management in glucocorticoid-exposed individuals during the third year of survey in GLOW. Of the 40,058 women with complete data over the 5 years, 893 (2 %) reported continuous use of glucocorticoids over the past 2 or more years at the 3-year survey and 29,080 (73 %) were nonusers. Our study demonstrated considerable differences in BMD management in glucocorticoid users by site and region (see Table 1). Glucocorticoid-exposed individuals had greater use of BMD testing and medical management than nonusers, although the number of individuals remained low (?51 %) worldwide in current continuous users. The proportion of individuals with current continuou ...

Osteoporosis causes an elevated fracture risk. We propose the continued use of T-scores as one means for diagnosis but recommend that, alternatively, hip fracture; osteopenia-associated vertebral, proximal humerus, pelvis, or some wrist fractures; or FRAX scores with ≥3 % (hip) or 20 % (major) 10-year fracture risk also confer an osteoporosis diagnosis.

To determine persistence with subcutaneous denosumab every 6 months in women being treated for osteoporosis, we conducted a single-arm prospective, observational study in the United States and Canada. Among 935 patients enrolled, 12-month persistence was 82 %, with 66 patients (7 %) reporting serious adverse events and 19 patients (2 %) reporting fractures.

Accurate patient risk perception of adverse health events promotes greater autonomy over, and motivation towards, health-related lifestyles.