Individuals with a fragility fracture and a prescription for bone active medication have a positive perception of the medication but do not associate it with fracture risk reduction.

Most participants reported a positive perception of bone active medication despite sustaining a fracture while taking the medication, reporting medication side effects, or having a healthcare provider stop the prescription. Participants did not appear to connect the medication to fracture risk, suggesting this connection should be emphasized by healthcare providers. OBJECTIVE: Our purpose was to examine perceptions about bone active medication from individuals with a fragility fracture and a prescription for bone active medication. METHODS: In this qualitative description study, eligible participants were those who attended an Osteoporosis Canada education session, and reported sustaining a previous fragility fracture and receiving a prescription for bone active medication. We conducted one-on-one interviews and analyzed the data using the analytic hierarchy approach. RESULTS: We interviewed 32 female participants (age range 58-89 years). Based on our analysis, two themes were developed: (1) most participants spoke positively about bone active medication, indicating they were willing to start, or continue to take, their medication. Positive perceptions were held by participants who sustained a fracture while taking bone active medication, participants whose healthcare provider had stopped the prescription, and participants who reported side effects from the medication; (2) most participants did not discuss bone active medication in relation to their fracture and did not appear to connect the medication to the concept of fracture risk. Instead, participants talked about the medication in relation to bone health in general, or to bone density. CONCLUSION: Participants appeared to have positive perceptions of bone active medication, despite sustaining a fracture while taking the medication, reporting medication side effects, or having a healthcare provider stop the prescription. Participants did not connect bone active medication to the concept of fracture risk, illustrating the need for healthcare providers to emphasize the connection between fracture risk and bone active medication.

[Geriatric traumatological management of osteoporosis : "Let the first fracture be the last"]. / Alterstraumatologisches Management der Osteoporose : "Lass die erste Fraktur die Letzte sein".

In Germany more than 800,000 osteoporotic fractures occur every year, with severe medical, social and health economic consequences. Nevertheless, as in many other countries there is a large gap in care. Fractures frequently occur in older geriatric patients, who are increasingly being (or should be) treated in geriatric trauma centers. This multidisciplinary approach offers the opportunity not only to restore the patient's mobility and independence but also to set the course for preventing further fractures. Diagnosing osteoporosis and initiating treatment early after a fracture is particularly important as there is an imminently high risk of further fractures in the months and years following a fracture. This review article describes a pragmatic, guideline-based approach to osteoporosis management for geriatric trauma patients. It discusses fracture risk assessment, current treatment thresholds and treatment strategies as well as the individual osteoporosis drugs, the indications and contraindications. This review aims to show that the treatment of osteoporosis within the framework of a geriatric traumatology team is feasible in the majority of cases. It is suggested that a treatment decision can be systematically made based on a few questions or a flow chart.

A Novel CT-Based Fracture Risk Prediction Model for COPD Patients.

RATIONALE AND OBJECTIVES: The aim of this study was to develop and validate a novel computed tomography (CT)-based fracture risk assessment model (FRCT) specifically tailored for patients suffering from chronic obstructive pulmonary disease (COPD). METHODS: We conducted a retrospective analysis encompassing a cohort of 284 COPD patients, extracting data on demographics, clinical profiles, pulmonary function tests, and CT-based bone quantification metrics. The Boruta feature selection algorithm was employed to identify key variables for model construction, resulting in a user-friendly nomogram. RESULTS: Our analysis revealed that 37.32% of the patients suffered fragility fractures post-follow-up. The FRCT model, integrating age, cancellous bone volume, average cancellous bone density, high-density lipoprotein levels, and prior fracture incidence, demonstrated superior predictive accuracy over the conventional fracture risk assessment tool (FRAX), with a C-index of 0.773 in the training group and 0.797 in the validation group. Calibration assessments via the Hosmer-Lemeshow test confirmed the model's excellent fit, and decision curve analysis underscored the FRCT model's substantial positive net benefit. CONCLUSION: The FRCT model, leveraging opportunistic CT screening, offers a highly accurate and personalized approach to fracture risk prediction in COPD patients, surpassing the capabilities of existing tools. This model is poised to become an indispensable asset for clinicians in managing osteoporotic fracture risks within the COPD population.

Adiposity and Mineral Balance in Chronic Kidney Disease.

PURPOSE OF REVIEW: Bone homeostasis is balanced between formation and resorption activities and remain in relative equilibrium. Under disease states this process is disrupted, favoring more resorption over formation, leading to significant bone loss and fracture incidence. This aspect is a hallmark for patients with chronic kidney disease mineral and bone disorder (CKD-MBD) affecting a significant portion of the population, both in the United States and worldwide. Further study into the underlying effects of the uremic microenvironment within bone during CKD-MBD are critical as fracture incidence in this patient population not only leads to increased morbidity, but also increased mortality. Lack of bone homeostasis also leads to mineral imbalance contributing to cardiovascular calcifications. One area understudied is the possible involvement of bone marrow adipose tissue (BMAT) during the progression of CKD-MBD. RECENT FINDINGS: BMAT accumulation is found during aging and in several disease states, some of which overlap as CKD etiologies. Importantly, research has found presence of BMAT inversely correlates with bone density and volume. Understanding the underlying molecular mechanisms for BMAT formation and accumulation during CKD-MBD may offer a potential therapeutic avenue to improve bone homeostasis and ultimately mineral metabolism.

Higher FSH Level Is Associated With Increased Risk Of Incident Hip Fracture In Older Adults, Independent Of Sex Hormones.

CONTEXT: Higher levels of FSH are associated with bone loss among women during the perimenopausal transition and among older men, independent of estradiol and testosterone levels, but whether higher FSH is an independent fracture risk factor is unknown. OBJECTIVE: Determine whether baseline FSH level predicts subsequent hip fracture in older adults. SETTING, DESIGN, PARTICIPANTS: Using a case-cohort design, we randomly sampled 295 participants stratified by sex from the Age, Gene/Environment Susceptibility (AGES)-Reykjavik cohort, including 25 participants with incident hip fracture within 10 years after baseline. We sampled an additional 230 sex-stratified participants with incident hip fracture. Serum FSH and sex hormone levels were measured at baseline. Robust weighted Cox proportional hazards models were used to determine the relationship between FSH and hip fracture risk. MAIN OUTCOME: Incident hip fracture. RESULTS: As no interaction was identified between FSH and sex for the relationship with fracture, men and women were pooled for analysis. Higher levels of FSH were associated with a significantly increased risk of incident hip fracture in models adjusted for age and sex [hazard ratio (HR) 1.24 (95% CI 1.04-1.48, p=0.02)] and after further adjustment for estradiol, testosterone, and sex hormone binding globulin levels [HR 1.20 (95% CI 1.01-1.44, p=0.04) per sex-specific SD increase in FSH level]. CONCLUSIONS: Higher FSH is associated with increased risk of subsequent hip fracture. Our findings support a growing body of evidence for direct pleiotropic effects of FSH on bone, and for a role for FSH in aging and disability independent of sex hormone levels.

Real-world fracture risk, osteoporosis treatment status, and mortality of Japanese non-dialysis patients with chronic kidney disease stages G3-5.

BACKGROUND: Few studies have investigated fracture risk and mortality in a Japanese chronic kidney disease (CKD) stages G3-5 population using a large-scale clinical database. METHODS: This retrospective cohort study extracted data from 1 April 2008 to 30 April 2023. A single age-sex-matched control without CKD was matched with each non-dialysis CKD (estimated glomerular filtration rate < 60 mL/min/1.73 m2) patient. The incidences of all and hip fractures and all-cause mortality after the index date were calculated. RESULTS: Among 76,598 (38,299 per group) individuals matched, the incidence of all fractures did not differ between the CKD and control groups (5.7% vs 5.8%; hazard ratio [HR] 1.022 [95% confidence interval CI 0.952-1.098], P = 0.542). The CKD group had higher risk of hip fracture than the control group (incidence of hip fracture, 1.7% vs 1.3%; HR 1.415 [95% CI 1.234-1.622], P < 0.001). Multivariable regression analysis showed an increased risk for hip fracture in the CKD vs control groups, and a greater difference in this risk was observed with younger age. Osteoporosis treatment and bone mineral density (BMD) measurements were 10.0% and 5.3% in the CKD group and 4.4% and 4.4% in the control group, respectively. Mortality was also higher in the CKD group (HR 1.413 [95% CI 1.330-1.501], P < 0.001). CONCLUSIONS: Japanese patients with CKD had higher risk of hip fracture than those without. Treatment and BMD measurement for fracture are insufficient in Japanese patients with CKD, and more adequate management of fracture risk is needed.

Long-Term Bone Density Changes and Fracture Risk in Myasthenia Gravis: Implications for FRAX® Tool Application.

Myasthenia gravis (MG) patients often require long-term glucocorticoid therapy, which may affect bone health. This study aimed to assess long-term changes in bone mineral density (BMD), evaluate osteoporotic fracture incidence, and examine the relationship between MG-specific factors and bone health outcomes over a 10-year period. This single-center, prospective cohort study included 28 MG patients. BMD, T-scores, Z-scores, and bone turnover markers were measured at baseline. FRAX® scores were calculated and adjusted for glucocorticoid dose. Fracture occurrence was monitored for over 10 years. Five (17.9%) patients experienced major osteoporotic fractures during follow-up. The fracture group had significantly lower baseline BMD and T-scores than the no-fracture group. Baseline FRAX® scores for major osteoporotic fracture risk were significantly higher in the fracture group (median 19.0% vs. 5.7%, p = 0.001). The fracture group progressed from osteopenia at baseline to osteoporosis by the end of this study. This study highlights the importance of early and regular bone health assessments in MG patients, particularly those receiving long-term glucocorticoid therapy. The FRAX® tool may be valuable for fracture risk stratification in this population. These findings can inform clinical practice and improve long-term management strategies for MG patients who are at risk of osteoporotic fractures.

Short-term risk of fracture is increased by deficits in cortical and trabecular bone microarchitecture independent of DXA BMD and FRAX: bone microarchitecture international consortium (BoMIC) prospective cohorts.

Identifying individuals at risk for short-term fracture is essential to offer prompt beneficial treatment, especially since many fractures occur in those without osteoporosis by DXA-aBMD. We evaluated whether deficits in bone microarchitecture and density predict short-term fracture risk independent of the clinical predictors, DXA-BMD and FRAX. We combined data from eight cohorts to conduct a prospective study of bone microarchitecture at the distal radius and tibia (by HR-pQCT) and 2-year incidence of fracture (non-traumatic and traumatic) in 7327 individuals (4824 women, 2503 men, mean 69 ± 9 years). We estimated sex-specific hazard ratios (HR) for associations between bone measures and 2-year fracture incidence, adjusted for age, cohort, height and weight, and then additionally adjusted for femoral neck (FN) aBMD or FRAX for major osteoporotic fracture. Only 7% of study participants had FN T-score ≤ -2.5, whereas 53% had T-scores between -1.0 to -2.5 and 37% had T-scores ≥-1.0. Two-year cumulative fracture incidence was 4% (296/7327). Each SD decrease in radius cortical bone measures increased fracture risk by 38%-76% for women and men. After additional adjustment for FN-aBMD, risks remained increased by 28%-61%. Radius trabecular measures were also associated with 2-year fracture risk independently of FN-aBMD in women (HRs range: 1.21 per SD for trabecular separation to 1.55 for total vBMD). Decreased failure load was associated with increased fracture risk in both women and men (FN-aBMD ranges of adjusted HR = 1.47-2.42). Tibia measurement results were similar to radius results. Findings were also similar when models were adjusted for FRAX. In older adults, failure load and HR-pQCT measures of cortical and trabecular bone microarchitecture and density with strong associations to short-term fractures improved fracture prediction beyond aBMD and FRAX. Thus, HR-pQCT may be a useful adjunct to traditional assessment of short-term fracture risk in older adults, including those with T-scores above the osteoporosis range.

Identifying individuals at risk for short-term fracture (within 2-years) is essential to offer prompt treatment. We examined bone microarchitecture at arm and lower leg for prediction of short-term fractures in 7327 older adults, independent of the common clinical practice measures ­ DXA-BMD and FRAX. After adjusting for other factors, we found that measures of failure load, cortical and trabecular bone microarchitecture and density predicted short-term risk of fracture beyond the usual clinical measures of DXA and FRAX. These measures of bone that indicate deficits in microarchitecture may be a useful adjunct to traditional assessment of fracture risk in older adults.

Skeletal fragility in pituitary disease: how can we predict fracture risk?

Pituitary hormones play a crucial role in regulating skeletal physiology, and skeletal fragility is a frequent complication of pituitary diseases. The ability to predict the risk of fracture events is crucial for guiding therapeutic decisions; however, in patients with pituitary diseases, fracture risk estimation is particularly challenging. Compared to primary osteoporosis, the evaluation of bone mineral density by dual X-ray absorptiometry is much less informative about fracture risk. Moreover, the reliability of standard fracture risk calculators does not have strong validations in this setting. Morphometric vertebral assessment is currently the cornerstone in the assessment of skeletal fragility in patients with pituitary diseases, as prevalent fractures remain the strongest predictor of future fracture events. In recent years, new tools for evaluating bone quality have shown promising results in assessing bone impairment in patients with pituitary diseases, but most available data are cross-sectional, and evidence regarding the prediction of incident fractures is still scarce. Of note, apart from measures of bone density and bone quality, the estimation of fracture risk in the context of pituitary hyperfunction or hypofunction cannot ignore the evaluation of factors related to the underlying disease, such as its severity and duration, as well as the specific therapies implemented for its treatment. Aim of this review is to provide an up-to-date overview of all major evidence regarding fracture risk prediction in patients with pituitary disease, highlighting the need for a tailored approach that critically integrates all clinical, biochemical, and instrumental data according to the specificities of each disease.

Fracture risk prediction in diabetes patients based on Lasso feature selection and Machine Learning.

Fracture risk among individuals with diabetes poses significant clinical challenges due to the multifaceted relationship between diabetes and bone health. Diabetes not only affects bone density but also alters bone quality and structure, thereby increases the susceptibility to fractures. Given the rising prevalence of diabetes worldwide and its associated complications, accurate prediction of fracture risk in diabetic individuals has emerged as a pressing clinical need. This study aims to investigate the factors influencing fracture risk among diabetic patients. We propose a framework that combines Lasso feature selection with eight classification algorithms. Initially, Lasso regression is employed to select 24 significant features. Subsequently, we utilize grid search and 5-fold cross-validation to train and tune the selected classification algorithms, including KNN, Naive Bayes, Decision Tree, Random Forest, AdaBoost, XGBoost, Multi-layer Perceptron (MLP), and Support Vector Machine (SVM). Among models trained using these important features, Random Forest exhibits the highest performance with a predictive accuracy of 93.87%. Comparative analysis across all features, important features, and remaining features demonstrate the crucial role of features selected by Lasso regression in predicting fracture risk among diabetic patients. Besides, by using a feature importance ranking algorithm, we find several features that hold significant reference values for predicting early bone fracture risk in diabetic individuals.

Similarities and differences between European guidelines for the management of postmenopausal osteoporosis.

We conducted a review of 10 national guidelines from five EU countries to identify similarities or differences in recommendations for the management of patients with osteoporosis. We found general alignment of key recommendations; however, there are notable differences, largely attributed to country-specific approaches to risk assessment and reimbursement conditions. INTRODUCTION: The classification of fracture risk is critical for informing treatment decisions for post-menopausal osteoporosis. The aim of this review was to summarise 10 national guidelines from five European countries, with a focus on identifying similarities or differences in recommendations for the management of patients with osteoporosis. METHODS: We summarised the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Disease-International Osteoporosis Foundation guidelines and reviewed guidelines from France, Germany, Italy, Spain and the UK. RESULTS: The approach to risk assessment differed across the guidelines. In France, and Spain, risk assessment was based on DXA scans and presence of prior fractures, whereas UK, German and Italian guidelines recommended use of a validated risk tool. These differences led to distinct definitions of very high and high-risk patients. Guidelines aligned in recommending antiresorptive and anabolic agents as pharmacologic options for the management of osteoporosis, with sequential treatment recommended. There was agreement that patients at high or very high risk of fracture or with severe osteoporosis should receive anabolic agents first, followed by antiresorptive drugs. Variations were identified in recommendations for follow up of patients on anti-osteoporosis therapies. Reimbursement conditions in each country were a key difference identified. CONCLUSIONS: Criteria for risk assessment of fractures differ across European guidelines which may impact treatment and access to anabolic agents. Harmonisation across EU guidelines may help identify patients eligible for treatment and impact treatment uptake. However, country-specific reimbursement and prescribing processes may present a challenge to achieving a consistent approach across Europe.

The association of type 2 diabetes-related characteristics with fracture risk at different sites.

AIM: To determine the association of diabetes-related characteristics with fractures at different sites in individuals with type 2 diabetes (T2D). MATERIALS AND METHODS: We conducted a cohort study using the Clinical Practice Research Datalink (CPRD) GOLD. Patients aged over 30 years with T2D were identified within the CPRD. Patients were followed from the start of diabetes treatment until the end of data collection, death, or the occurrence of a fracture. Cox proportional hazards models were used to estimate the hazard ratios for the association of the individual characteristics (diabetes duration, glycated haemoglobin [HbA1c] level, and microvascular complications) with fracture risk, adjusted for demographics, comorbidities and comedication. RESULTS: A diabetes duration of >10 years was associated with an increased risk of any fracture and major osteoporotic fractures (MOFs), while a diabetes duration of >8 years was associated with an increased hip fracture risk, compared to a duration <2 years. An HbA1c level <6% was associated with an increased fracture risk compared to HbA1c values of 6% to <7%. The presence of one or two microvascular complications was associated with an increased risk of any fracture and MOFs and the presence of two microvascular complications was associated with an increased hip fracture risk, compared to no microvascular complications. CONCLUSION: In conclusion, our study shows that a diabetes duration of 10 years or more, strict glycaemic control resulting in HbA1c levels below 6%, and/or the presence of at least one microvascular complication increased the risk of any fracture, hip fractures, MOFs, and humerus fractures, but not ankle, scapula or skull fractures.

Periprosthetic bone mineral density, assessed using dual energy x-ray absorptiometry, following arthroplasty in patients with femoral neck fracture: 5-year outcomes of a randomized controlled trial.

OBJECTIVE: The relationship between the surgical approach used for hemiarthroplasty and periprosthetic bone mineral density (BMD) is not well understood. We have previously described a decrease in BMD 1 year postoperatively. Here, we assessed the medium-term changes in periprosthetic BMD. METHODS: We performed a follow-up study of patients with femoral neck fracture (FNF) who underwent uncemented hemiarthoplasty using a direct lateral or anterolateral approach. Dual-energy X-ray absorptiometry (DXA) was used to evaluate the changes in BMD in 23 patients over 5 years. RESULTS: A mean 6% loss of total BMD occurred over 1 year, but between 1 and 5 years, BMD was restored to the baseline value. The mean total BMD in the anterolateral group had decreased by 2% after 3 months and 3% after 12 months, and increased by 2% after 5 years, vs. decreases of 7%, 8%, and 3% for the direct lateral group. Between 1 and 5 years, BMD increased in Gruen zones 2, 3, 4, 5, and 6 in both groups. There was a significantly larger increase in zone 4 in the lateral group (4%) than the anterolateral group. CONCLUSION: The surgical approach affects periprosthetic BMD in patients with FNF. Furthermore, BMD is restored to the baseline value 5 years postoperatively.ClinicalTrials.gov registration number: NCT03753100.

The Fracture Phenotypes in Women and Men of 50 Years and Older with a Recent Clinical Fracture.

PURPOSE OF REVIEW: We review the literature about patients 50 years and older with a recent clinical fracture for the presence of skeletal and extra-skeletal risks, their perspectives of imminent subsequent fracture, falls, mortality, and other risks, and on the role of the fracture liaison service (FLS) for timely secondary fracture prevention. RECENT FINDINGS: Patients with a recent clinical fracture present with heterogeneous patterns of bone-, fall-, and comorbidity-related risks. Short-term perspectives include bone loss, increased risk of fractures, falls, and mortality, and a decrease in physical performance and quality of life. Combined evaluation of bone, fall risk, and the presence of associated comorbidities contributes to treatment strategies. Since fractures are related to interactions of bone-, fall-, and comorbidity-related risks, there is no one-single-discipline-fits-all approach but a need for a multidisciplinary approach at the FLS to consider all phenotypes for evaluation and treatment in an individual patient.

Insulin resistance, bone health, and fracture risk.

Insulin resistance, defined as an impaired biological response to insulin stimulation in target tissues, arises most frequently in the presence of central obesity. Although obesity is generally associated with increased bone mass, recent data challenge this view and, if complicated by T2DM, obese patients are at high risk for fragility fractures. IR may play a key role in this increased fracture risk through effects on bone quality rather than bone quantity. Further understanding of the mechanisms and approaches to prevent osteoporotic fractures in IR-related diseases is needed. CLINICAL RELEVANCE: The dramatic increase in obesity and metabolic syndrome (MetS) over the last half-century has led to a worldwide epidemic of type 2 diabetes mellitus (T2DM) as well as in the incidence of insulin resistance (IR). IR is defined as an impaired biological response to insulin stimulation in target tissues and is primarily related to the liver, muscle, and adipose tissue. The most frequent underlying cause is central obesity, and it is known that excess abdominal adipose tissue secretes increased amounts of free fatty acids, which directly affects insulin signalling, reduces glucose uptake in muscle, and triggers excessive triglyceride synthesis and gluconeogenesis in the liver. When pancreatic ß cells are unable to secrete the higher levels of insulin needed, T2DM, the main complication of IR, occurs. OBSERVATIONS: Although obesity is generally associated with increased bone mass, recent data challenge this view and highlight the multifaceted nature of the obesity-bone relationship. Patients with T2DM are at significant risk for well-known complications of diabetes, including retinopathy, nephropathy, macrovascular disease, and neuropathy, but it is clear that they are also at high risk for fragility fractures. Moreover, recent data provide strong evidence that IR may key role in the increased fracture risk observed in both obesity and T2DM. CONCLUSIONS: In this concise review article, the role of IR in increased risk of osteoporotic fractures in MetS, obesity, and T2DM is discussed and summarised, including consideration of the need for fracture risk assessment as a 'preventive measure', especially in patients with T2DM and chronic MetS with abdominal obesity. Personalised and targeted diagnostic and therapeutic approaches to prevent osteoporotic fractures in IR-related diseases are needed and could make significant contributions to health outcomes.

Involvement of cognitive abilities in the occurrence of fractures in fallers aged 55 years or older: a cross-sectional study.

BACKGROUND: Both bone fragility and poor cognitive functions are known to contribute to fracture occurrence, but it remains unclear whether their contribution is independent of each other and which cognitive dysfunctions are most involved. This study aimed to clarify the involvement of various cognitive abilities in fall-related fractures among community-dwelling fallers aged 55 and over, and to determine whether poor cognitive abilities is a risk factor independent of bone fragility. METHODS: In a cross-sectional study, we collected sociodemographic and medical data, including bone mineral density (BMD), and performed cognitive and mobility assessments in 189 individuals with a history of fall in the previous year. RESULTS: Fallers with a fracture had poorer cognitive and mobility performance than non-injured fallers. Multivariate regressions revealed that cognition, BMD and other risk factors were independently associated with fracture among all participants (OR = 1.04, 95% CI = 1.01-1.08, p = 0.034 for completion time on part A of the Trail Making Test [TMT-A], and OR = 0.53, 95% CI = 0.33-0.84, p < 0.001 for BMD), particularly in women (OR = 0.77, 95% CI = 0.60-0.98, p = 0.039 for backward digit span score, and OR = 0.43, 95% CI = 0.25-0.75, p = 0.001 for BMD). CONCLUSION: Thus, poor cognition, especially poor processing speed and working memory, is associated with an increased risk of fracture in fallers, particularly in women, regardless of BMD or other fracture risk factors. Hence, an in-depth cognitive evaluation should enhance the detection of fallers at risk of fracture, particularly in the absence of signs of osteoporosis, and thus ensure the best possible prevention.

The relationship between treatment-related changes in total hip BMD measured after 12, 18, and 24 mo and fracture risk reduction in osteoporosis clinical trials: the FNIH-ASBMR-SABRE project.

There is a strong association between total hip bone mineral density (THBMD) changes after 24 mo of treatment and reduced fracture risk. We examined whether changes in THBMD after 12 and 18 mo of treatment are also associated with fracture risk reduction. We used individual patient data (n = 122 235 participants) from 22 randomized, placebo-controlled, double-blind trials of osteoporosis medications. We calculated the difference in mean percent change in THBMD (active-placebo) at 12, 18, and 24 mo using data available for each trial. We determined the treatment-related fracture reductions for the entire follow-up period, using logistic regression for radiologic vertebral fractures and Cox regression for hip, non-vertebral, "all" (combination of non-vertebral, clinical vertebral, and radiologic vertebral) fractures and all clinical fractures (combination of non-vertebral and clinical vertebral). We performed meta-regression to estimate the study-level association (r2 and 95% confidence interval) between treatment-related differences in THBMD changes for each BMD measurement interval and fracture risk reduction. The meta-regression revealed that for vertebral fractures, the r2 (95% confidence interval) was 0.59 (0.19, 0.75), 0.69 (0.32, 0.82), and 0.73 (0.33, 0.84) for 12, 18, and 24 mo, respectively. Similar patterns were observed for hip: r2 = 0.27 (0.00, 0.54), 0.39 (0.02, 0.63), and 0.41 (0.02, 0.65); non-vertebral: r2 = 0.27 (0.01, 0.52), 0.49 (0.10, 0.69), and 0.53 (0.11, 0.72); all fractures: r2 = 0.44 (0.10, 0.64), 0.63 (0.24, 0.77), and 0.66 (0.25, 0.80); and all clinical fractures: r2 = 0.46 (0.11, 0.65), 0.64 (0.26, 0.78), and 0.71 (0.32, 0.83), for 12-, 18-, and 24-mo changes in THBMD, respectively. These findings demonstrate that treatment-related THBMD changes at 12, 18, and 24 mo are associated with fracture risk reductions across trials. We conclude that BMD measurement intervals as short as 12 mo could be used to assess fracture efficacy, but the association is stronger with longer BMD measurement intervals.

In this study, we looked at how changes in hip bone density over time relate to the risk of fractures in people taking osteoporosis medications. We analysed data from over 122 000 participants across 22 different clinical trials. We found that the increase in bone density measured after 12, 18, and 24 mo of treatment was linked to the risk of fractures. Specifically, greater improvements in bone density were associated with fewer fractures in the spine, hips, and other bones. Using statistical methods, we calculated the strength of this association. We discovered that the later, we measured BMD in people taking the medication, the stronger the link between improved bone density and reduced fracture risk became. Our findings suggest that bone density measurements after 12 mo of treatment could help predict how well a medication will prevent fractures. However, the best predictions came from bone density changes measured over longer periods.

Recommendations for the optimal use of bone forming agents in osteoporosis.

Bone forming agents, also known as anabolic therapies, are essential in managing osteoporosis, particularly for patients at very high-risk of fractures. Identifying candidates who will benefit the most from these treatments is crucial. For example, this group might include individuals with severe osteoporosis, multiple vertebral fractures, a recent fragility fracture or those unresponsive to antiresorptive treatments. Definitions of patients with a very high fracture risk vary across nations, are often based on fracture history, bone mineral density (BMD), and/or fracture risk calculated by FRAX® or other algorithms. However, for very high-risk patients, anabolic agents such as teriparatide, abaloparatide, or romosozumab are commonly recommended as first-line therapies due to their ability to stimulate new bone formation and improve bone microarchitecture, offering significant benefits in rapid fracture reduction over antiresorptive therapies. The cost-effectiveness of these agents is a critical consideration for decision-makers. Despite their higher costs, their effectiveness in significantly reducing fracture risk and improving quality of life can justify the investment, especially when long-term savings from reduced fracture rates and associated healthcare costs are considered. Additionally, after completing a course of anabolic therapy, transitioning to antiresorptive agents like bisphosphonates or denosumab is crucial to maintain the gains in bone density and minimize subsequent fracture risks. This sequential treatment approach ensures sustained protection and optimal resource utilization. In summary, the effective use of bone forming agents in osteoporosis requires a comprehensive strategy that includes accurate patient identification, consideration of cost-effectiveness, and implementation of appropriate sequential treatments, ultimately maximizing patient outcomes and healthcare efficiency.

Development of a Multidisciplinary Care Pathway for Fracture Prevention in Men with Prostate Cancer at Initiation of Androgen Deprivation Therapy.

Fracture risk is increased in men with prostate cancer (PCa) receiving Androgen Deprivation Therapy (ADT). However, routine assessment of fracture risk is often not systematically applied. We aimed to establish a comprehensive care pathway for fracture prevention in men with PCa starting ADT. Therefore, a multidisciplinary working group designed and implemented a care pathway using the 'Knowledge to Action' framework, based on current Dutch guidelines for PCa, osteoporosis and fracture prevention, and an extensive literature review of other guidelines. The pathway was developed according to a five-step clinical approach including case finding, fracture risk assessment based on risk factors, bone mineral density test, vertebral fracture assessment, differential diagnosis, treatment, and annual follow-up. Our fracture prevention care pathway for patients with PCa at the time of ADT initiation was designed to promote a patient-centered, multidisciplinary approach to facilitate the implementation of early fracture prevention measures.