Drug Therapy For Osteoporosis Research Articles

Assessing the awareness of doctors of various specialties in the treatment of osteoporosis

Objective: to assess the degree of doctors’ awareness on the prevention, diagnosis and treatment of patients with osteoporosis.Material and methods. The study was conducted using the Yandex Forms service through an original anonymous questionnaire comprising 16 questions concerning personal characteristics (specialty, work experience, category, and academic degree), as well as the degree of awareness in the prevention, diagnosis and treatment of osteoporosis. The questions about the treatment of the disease were compiled based on Russian and foreign clinical guidelines.Results. Knowledge of the causes and symptoms of osteoporosis was relatively high, but further findings from the survey on prevention, diagnosis and treatment revealed a lack of awareness among physicians in this area. Only 13.7% of respondents identified the potential use of the promising FRAX tool in osteoporosis diagnosing, and only 25% correctly selected first-line medications for treating the disease.Conclusion. The study revealed that doctors lack sufficient knowledge regarding the prevention, diagnosis, and drug therapy for osteoporosis. In our view, this finding underscores the need for a more comprehensive approach to this issue within the context of continuing medical education. The therapy effectiveness and patients’ complience directly depend on the communication between physicians and pharmacists. Therefore, it becomes essential to consider enhancing their collaboration in osteoporosis prevention and management.

Ångstrom-scale gold particles loaded with alendronate via alpha-lipoic acid alleviate bone loss in osteoporotic mice

Osteoporosis is a highly prevalent metabolic disease characterized by low systemic bone mass and deterioration of bone microarchitecture, resulting in reduced bone strength and increased fracture risk. Current treatment options for osteoporosis are limited by factors such as efficacy, cost, availability, side effects, and acceptability to patients. Gold nanoparticles show promise as an emerging osteoporosis therapy due to their osteogenic effects and ability to allow therapeutic delivery but have inherent constraints, such as low specificity and the potential for heavy metal accumulation in the body. This study reports the synthesis of ultrasmall gold particles almost reaching the Ångstrom (Ång) dimension. The antioxidant alpha-lipoic acid (LA) is used as a dispersant and stabilizer to coat Ångstrom-scale gold particles (AuÅPs). Alendronate (AL), an amino-bisphosphonate commonly used in drug therapy for osteoporosis, is conjugated through LA to the surface of AuÅPs, allowing targeted delivery to bone and enhancing antiresorptive therapeutic effects. In this study, alendronate-loaded Ångstrom-scale gold particles (AuÅPs-AL) were used for the first time to promote osteogenesis and alleviate bone loss through regulation of the WNT signaling pathway, as shown through in vitro tests. The in vivo therapeutic effects of AuÅPs-AL were demonstrated in an established osteoporosis mouse model. The results of Micro-computed Tomography, histology, and tartrate-resistant acid phosphatase staining indicated that AuÅPs-AL significantly improved bone density and prevented bone loss, with no evidence of nanoparticle-associated toxicity. These findings suggest the possible future application of AuÅPs-AL in osteoporosis therapy and point to the potential of developing new approaches for treating metabolic bone diseases using Ångstrom-scale gold particles.

Deprescribing bisphosphonates in the osteoporosis treatment in older people

The term deprescribing (de-prescribe) means the abolition of appointments. In the modern researches, deprescribing is presented as a planned and controlled process of dose reduction or drug cessation, which can potentially harm the patient and/or does not benefit the patient. The target population for deprescribing is the older people, as old age and limited life expectancy are themselves reasons to try to reduce and optimize the drug load. Frailty syndrome or dementia, decreased kidney function and comorbidity are expected to coexist with polypragmasy and inconsistent appointments of different specialists. In foreign and domestic scientific studies there are manuals and recommendations on deprescribing of various groups of drugs for the elderly and seniors: proton pump inhibitors, sugary drugs, psychotropic drugs and others. However, with regard to osteoporosis drug therapy, the concept of deprescribing is debated rather sparingly, despite the possible serious side effects of osteoporosis treatment in the older age group.The review presents data from small clinical studies and systematic reviews describing deprescribing antiosteoporotic drugs from the bisphosphonate group, the reasons for their withdrawal and its consequences for the elderly and seniors with osteoporosis, as well as the analysis of tools for optimizing pharmacotherapy in elderly and seniors with respect to deprescribing of bisphosphonates.

Balancing fracture risk versus risk of mortality before fracture among women aged 80 years or older.

Most fractures occur in women aged ≥80 years but competing mortality unrelated to fracture may limit the benefit of osteoporosis drug therapy for some women in late life. Our primary aim was to develop separate prediction models for non-spine fracture (NSF) and mortality before fracture to identify subsets of women with varying fracture versus mortality risks. Separate prediction models were developed for NSF and mortality before NSF for 4895 women aged ≥80 years enrolled in the Study of Osteoporotic Fractures (SOF) or the Health Aging and Body Composition (HABC) study. Proportional hazards models modified to account for competing mortality were used to identify candidate risk factors for each outcome. Predictors associated with NSF or mortality (p < 0.2) were included in separate competing risk models to estimate the cumulative incidence of NSF and mortality before NSF during 5 years of follow-up. This process was repeated to develop separate prediction models for hip fracture and mortality before hip fracture. Significant predictors of NSF (race, total hip BMD, grip strength, prior fracture, falls, and use of selective serotonin reuptake inhibitors, benzodiazepines, or oral/transdermal estrogen) differed from predictors of mortality before NSF (age, walking speed, multimorbidity, weight change, shrinking, smoking, self-rated health, dementia, and use of warfarin). Within nine subsets of women defined by tertiles of risk, 5-year outcomes varied from 28% NSF and 8% mortality in the high-risk NSF/low-risk mortality subset, to 9% NSF and 22% mortality in the low-risk NSF/high-risk mortality subset. Similar results were seen for predictors of hip fracture and mortality before hip fracture. Considerable variation in 5-year competing mortality risk is present among women in late life with similar 5-year NSF risk. Both fracture risk and life expectancy should inform shared clinical decision-making regarding initiation or continuation of osteoporosis drug therapy for women aged ≥80 years.

Pharmacolgic osteoporosis treatment of nursing home residents

Fragility fractures in older people are common and are often associated with nursing home admission in frail people. Only few institutionalized residents with documented osteoporosis receive pharmacologic osteoporosis treatment. Studies demonstrating the benefit of osteoporosis drug therapy in this multimorbid and vulnerable population are lacking.

Morphological and biochemical characteristics of osteogenesis during drug therapy of experimental osteoporosis

Relevance. Osteoporosis is a clinical and economic problem on a global scale. A significant contribution to solving the problem of effective treatment of osteoporosis can be the creation of drugs based on unique biologically active compounds.The aim of the study was the morphological substantiation of the experimental model of osteoporosis and a comprehensive (multifactorial) assessment of the effectiveness of its drug therapy.Materials and methods. The study was carried out on 40 mature female Wistar rats, which comprised 6 groups. A model of osteoporosis was formed in animals of four experimental groups (6 animals in each): the first and second groups (respectively) consisted of young rats, the third and fourth — old ones. Animals of the second and fourth groups were injected with a drug tested for its ability to activate the process of osteosynthesis. Rats of the fifth and sixth groups (young and old, 8 animals each), subjected to sham surgery, served as controls. As a result of the use of the histo-morphometric method and atomic absorption spectroscopy in the diaphysis of the femur, the thickness of the layers of the compact substance, the number of bone plates and osteocytes, as well as the amount of collagen, calcium and phosphorus were determined. Using enzyme immunoassay, bone remodeling markers — osteocalcin, sclerostin, osteoprotegerin, fibroblast growth factor-23 and nuclear factor kappa-β activator ligand (RANKL) — were determined in the blood serum. Statistical processing of the data was carried out using the GraphPad PRISM (USA) program to determine the median, upper and lower quartiles. Differences were considered significant at p &lt; 0.01.Results. Modeling of osteoporosis induces atrophic thinning of the compact substance, a decrease in the number of osteocytes and bone plates in the diaphysis of the femur, a decrease in the content of collagen, calcium and phosphorus in them, a decrease in the concentration of osteocalcin, sclerostin, fibroblast growth factor, osteoprotegerin and an increase in the concentration of RANKL in the blood plasma, more pronounced in old animals. As a result of the use of the drug X3 for the treatment of osteoporosis, the following were revealed: a significant increase in the thickness of the compact substance, the number of osteocytes and bone plates in the diaphysis, the content of collagen, calcium and phosphorus in them, an increase in the concentration of biochemical markers of osteosynthesis, and a mild imbalance of RANKL. The increase in plasma levels of markers of bone remodeling was most pronounced when the drug X3 was combined with vitamin D3.Conclusion. 1. The used surgical-endocrine method of modeling osteoporosis leads to pronounced degenerative changes in osteocytes and their derivatives in all parts of the compact bone substance, and also causes significant disturbances in the mineral composition and an imbalance of bone remodeling markers, more pronounced in senile rats. 2. The tested drug X3, used for the treatment of osteoporosis, has a high degree of effectiveness, since it stimulates regenerative osteogenesis, restores the damaged structure of bone tissue elements, its organic and mineral components. 3. The restorative effect of the drug is more pronounced in senile rats.

Regulation of cholesterol homeostasis in osteoporosis mechanisms and therapeutics.

Osteoporosis is a metabolic bone disease that affects hundreds of millions of people worldwide and is characterized by excessive loss of bone protein and mineral content. The incidence and mortality of osteoporosis increase with age, creating a significant medical and economic burden globally. The importance of cholesterol levels has been reported in the development of diseases including osteoporosis. It is important to note that key enzymes and molecules involved in cholesterol homeostasis are closely related to bone formation. Excessive cholesterol may cause osteoporosis, cholesterol and its metabolites affect bone homeostasis by regulating the proliferation and stimulation of osteoblasts and osteoclasts. Therefore, antagonism of elevated cholesterol levels may be a potential strategy to prevent osteoporosis. There is sufficient evidence to support the use of bisphosphonates and statin drugs for osteoporosis in the clinic. Therefore, in view of the aggravation of the aging problem, we summarize the intracellular mechanism of cholesterol homeostasis and its relationship with osteoporosis (including cholesterol and cholesterol oxidation products (COPs) in osteoporosis). Furthermore, the current clinical cholesterol-lowering drugs for osteoporosis were also summarized, as are new and promising therapies (cell-based therapies (e.g., stem cells) and biomaterial-delivered target drug therapies for osteoporosis as well).

Cuproptosis-a potential target for the treatment of osteoporosis.

Osteoporosis is an age-related disease of bone metabolism marked by reduced bone mineral density and impaired bone strength. The disease causes the bones to weaken and break more easily. Osteoclasts participate in bone resorption more than osteoblasts participate in bone formation, disrupting bone homeostasis and leading to osteoporosis. Currently, drug therapy for osteoporosis includes calcium supplements, vitamin D, parathyroid hormone, estrogen, calcitonin, bisphosphates, and other medications. These medications are effective in treating osteoporosis but have side effects. Copper is a necessary trace element in the human body, and studies have shown that it links to the development of osteoporosis. Cuproptosis is a recently proposed new type of cell death. Copper-induced cell death regulates by lipoylated components mediated via mitochondrial ferredoxin 1; that is, copper binds directly to the lipoylated components of the tricarboxylic acid cycle, resulting in lipoylated protein accumulation and subsequent loss of iron-sulfur cluster proteins, leading to proteotoxic stress and eventually cell death. Therapeutic options for tumor disorders include targeting the intracellular toxicity of copper and cuproptosis. The hypoxic environment in bone and the metabolic pathway of glycolysis to provide energy in cells can inhibit cuproptosis, which may promote the survival and proliferation of various cells, including osteoblasts, osteoclasts, effector T cells, and macrophages, thereby mediating the osteoporosis process. As a result, our group tried to explain the relationship between the role of cuproptosis and its essential regulatory genes, as well as the pathological mechanism of osteoporosis and its effects on various cells. This study intends to investigate a new treatment approach for the clinical treatment of osteoporosis that is beneficial to the treatment of osteoporosis.

Establishment of Standardized Diagnostic System for Brucella Spondylitis in the Elderly and Clinical Application of Precise Treatment Strategy

Objectives Establish a clinical standardized diagnosis and treatment strategy system for senile brucellosis spondylitis, and evaluate the clinical effect of applying this diagnosis and treatment system in order to improve the diagnosis rate and cure rate of the disease. Methods A diagnostic system was established based on the medical history, clinical, imaging, laboratory, bacteriological and pathological examinations of 70 elderly patients with brucellosis spondylitis admitted from January 2002 to December 2017. All patients received standardized drug therapy, anti-osteoporosis therapy and adjuvant hyperbaric oxygen therapy. Forty-two patients with spinal nerve injury received surgical treatment. Follow-up and evaluation were conducted at 2 weeks, 1 month, 3 months, 6 months, and 12 months after treatment. Results All patients were diagnosed after admission according to the diagnostic system standard examination. In this group, 28 patients (40%) received standardized drug therapy for non-surgical indications (group A), and 42 patients (60%) received surgical treatment for surgical indications (group B). VAS scores were significantly different between the two groups (P<0.05), group B was better than group a. Imaging scores showed that in group B, the myelopathy segments were stable without abscess and inflammatory granuloma, except for slow bone repair in the debridement area of the original myelopathy. Group A had no obvious vertebral lesion infiltration and interstitial infection absorption after 3 months of treatment, and gradually absorbed vertebral inflammatory infiltration and interstitial infection after 6 months. Clinical efficacy evaluation showed that both groups achieved good cure rates over time, and group B was better than group A (P<0.05). Conclusion Elderly brucellosis spondylitis has characteristic manifestations, and the establishment of a standardized diagnosis system will help improve the diagnosis rate; Synchronous drug therapy for BS and osteoporosis according to the treatment strategy has a good effect, and for patients who meet the indications for surgery, timely surgery can relieve or relieve pain, maintain spinal stability, and promote rapid recovery of nerve and spinal functions. It has obvious advantages and can better improve the clinical cure rate.

The problem is the prescription of drug therapy to reduce the risk of fractures and its solution

The older people with osteoporosis, especially those with low-energy fractures, are the most vulnerable group of geriatric patients. They are shown the appointment of anti-osteoporotic therapy, which should be effective and safe. Unfortunately, the real prescription of medical treatment of osteoporosis in the world barely reaches 20%. This is due not only to low adherence to therapy by elderly patients, but also to financial and economic difficulties in obtaining drugs. For most patients, drug therapy for osteoporosis is quite expensive, especially given its long-term, often lifelong, course of action. However, new opportunities have now emerged to provide certain anti-osteoporotic drugs not only to patients in the preferential category, but also without disabilities. This will not only increase the number of patients receiving treatment for osteoporosis, but also reduce the risk of fractures, both primary and recurrent, the risk of falls, injuries and premature death among the elderly population. The article presents modern possibilities of providing medicines to patients with osteoporosis and its complications in the form of pathological fractures using clinical and statistical groups (CSG) as new methods of payment for inpatient and hospital-replacing care in the Russian Federation.

A Review Article of Polyherbal Tablet for the Management of Osteoporosis

Osteoporosis is an aging problem. The declining bone mineral density (BMD) enhances the chances of fractures during minor falls. Effective pharmaceuticals are available for a rapid improvement of BMD Osteoporosis is an enormous and growing public health problem. Once considered an inevitable consequence of ageing, it is now eminently preventable and treatable. Ironically, despite tremendous therapeutic advances, there is an increasing treatment gap for patients at high fracture risk. In this Series paper, we trace the evolution of drug therapy for osteoporosis, which began in the 1940s with the demonstration by Fuller Albright that treatment with oestrogen could reverse the negative calcium balance that developed in women after menopause or oophorectomy. We note a watershed in osteoporosis drug discovery around the year 2000, when the approach to developing novel therapeutics shifted from one driven by discoveries in animal studies and clinical observations (eg, oestrogen, calcitonin, and teriparatide) or opportunistic repurposing of existing compounds (eg, bisphosphonates) to one driven by advances in fundamental bone biology (eg, denosumab) coupled with clues from patients with rare bone diseases (eg, romosozumab, odanacatib). Despite these remarkable advances, concerns about rare side-effects of anti-resorptive drugs, particularly bisphosphonates, and the absence of clear evidence in support of their long-term efficacy is leading many patients who could benefit from drug therapy to not take these drugs. As such, there remains an important clinical need to develop ways to enhance patient acceptance and compliance with these effective drugs, and to continue to develop new drugs that do not cause these side-effects and have prolonged anabolic effects on bone. Such changes could lead to a true reversal of this potentially devastating disease of ageing.&#x0D;

Therapeutic Drug Review on Romosozumab: The First Sclerostin Inhibitor

Osteoporosis is a progressive skeletal disorder which is characterised by low bone mass, normal mineralisation and abnormal bone microarchitecture. This disruption of bone microarchitecture causes subsequent increase in bone fragility and raises risk of fractures. Osteoporosis is a growing public health problem and affects approximately over 200 million people worldwide. In the United Kingdom, it is estimated that around 3 million people have osteoporosis. Since the evolution of drug therapy for osteoporosis in the 1940's with oestrogen therapy several approaches to developing novel therapeutics for osteoporosis in animal studies and clinical observations (e.g., oestrogen, calcitonin, and teriparatide) or opportunistic repurposing of existing compounds (e.g., bisphosphonates) to one driven by advances in fundamental bone biology (e.g., denosumab). The advent of biologic agents has provided a more specific and targeted approach to the treatment of osteoporosis. Sclerostin is a glycoprotein secreted by osteocytes and regulates bone metabolism by inhibiting activation of osteoblast function and bone formation. By inhibiting sclerostin, targeted therapeutic pharmacological agents are being developed to address severe osteoporosis and patients who do not respond well to primary line of medical management of osteoporosis. Romosozumab is humanised as a monoclonal antibody designed to target sclerostin. This review assesses the mechanism and current role of romosozumab in osteoporosis treatment.

Health Disparities Scientific Research in the Division of Geriatrics and Clinical Gerontology

The Division of Geriatrics and Clinical Gerontology (DGCG) supports clinical and translational research on health and disease in the aged, and research on aging over the human lifespan, including its relationships to health outcomes. Key areas include development of new interventions for age-related conditions and pathologies, prevention and treatment of multiple chronic conditions, geriatric palliative care, factors influencing the progression of chronic diseases over the life span, and predictive markers of aging that may inform potential interventions for extension of health span. Population diversity and health disparities are critical aspects of science that cut across DGCG research areas. This presentation will highlight several examples of DGCG-supported studies related to health disparities and discuss potential future research directions. One potential upcoming research area of interest involves leveraging large data sets to examine disparities in risks and benefits of long-term osteoporosis drug therapy and drug holidays according to racial and ethnic groupings

Network Pharmacology-Based Strategy for the Investigation of the Anti-Osteoporosis Effects and Underlying Mechanism of Zhuangguguanjie Formulation.

As the society is aging, the increasing prevalence of osteoporosis has generated huge social and economic impact, while the drug therapy for osteoporosis is limited due to multiple targets involved in this disease. Zhuangguguanjie formulation (ZG) is extensively used in the clinical treatment of bone and joint diseases, but the underlying mechanism has not been fully described. This study aimed to examine the therapeutic effect and potential mechanism of ZG on postmenopausal osteoporosis. The ovariectomized (OVX) mice were treated with normal saline or ZG for 4 weeks after ovariectomy following a series of analyses. The bone mass density (BMD) and trabecular parameters were examined by micro-CT. Bone remodeling was evaluated by the bone histomorphometry analysis and ELISA assay of bone turnover biomarkers in serum. The possible drug–disease common targets were analyzed by network pharmacology. To predict the potential biological processes and related pathways, GO/KEGG enrichment analysis was performed. The effects of ZG on the differentiation phenotype of osteoclasts and osteoblasts and the predicted pathway were verified in vitro. The results showed that ZG significantly improved the bone mass and micro-trabecular architecture in OVX mice compared with untreated OVX mice. ZG could promote bone formation and inhibit bone resorption to ameliorate ovariectomy-induced osteoporosis as evidenced by increased number of osteoblast (N.Ob/Tb.Pm) and decreased number of osteoclast (N.Oc/Tb.Pm) in treated group compared with untreated OVX mice. After identifying potential drug–disease common targets by network pharmacology, GO enrichment analysis predicted that ZG might affect various biological processes including osteoblastic differentiation and osteoclast differentiation. The KEGG enrichment analysis suggested that PI3K/Akt and mTOR signaling pathways could be the possible pathways. Furthermore, the experiments in vitro validated our findings. ZG significantly down-regulated the expression of osteoclast differentiation markers, reduced osteoclastic resorption, and inhibited the phosphorylation of PI3K/Akt, while ZG obviously up-regulated the expression of osteogenic biomarkers, promoted the formation of calcium nodules, and hampered the phosphorylation of 70S6K1/mTOR, which can be reversed by the corresponding pathway activator. Thus, our study suggested that ZG could inhibit the PI3K/Akt signaling pathway to reduce osteoclastic bone resorption as well as hamper the mTORC1/S6K1 signaling pathway to promote osteoblastic bone formation.

Awareness of postmenopausal women about the risk of osteoporosis (literature review)

Osteoporosis is a systemic disease of the skeleton, characteri­zed by a decrease in bone mass and qualitative changes in bone structure, which lead to increased fragility and increased risk of fractures. Objective. To analyze the published information on the awareness of women in the United States, Europe and Ukraine about the risk of osteoporosis in the postmenopausal period. It is estimated that in general, about 50 % of postmenopausal women in most countries do not receive osteoporosis drug therapy and are unaware of the different treatment options for disease, 25 % associate it only with femur and spine fractures. Surveys have found that most respondents without a diagnosis of osteoporosis have had one or more risk factors for developing it, but osteoporosis is often not diagnosed until one or more fractures have occurred. That is why orthopedists-traumatologists, who most often face pathological fractures on the background of osteoporosis, have proposed special protocols for the timely diagnosis and treatment of fragile fractures. Treatment standards require women aged 65–85 who have suffered a fracture to be screened and receive osteotropic therapy for 6 months. However, the diagnosis and treatment of osteoporosis for 6 and 12 months after femoral neck fractures received only 17–23 % of respondents. Misconceptions about the causes and consequences of postmenopausal women fractures, combined with insufficient information from health professionals, point to the low level of attention of the population and the health care system in general to osteoporosis in all countries. The incidence of fractures in women was 3.1 higher than in men and progressively increased the age 50+. For high risk fractures women due to osteoporosis ensuring their osteoporosis awareness is a critical preventive point. This is essentialy can influence positive changes in the fight against osteoporosis around the world. Osteoporosis is a systemic disease of the skeleton, characteri­zed by a decrease in bone mass and qualitative changes in bone structure, which lead to increased fragility and increased risk of fractures. Objective. To analyze the published information on the awareness of women in the United States, Europe and Ukraine about the risk of osteoporosis in the postmenopausal period. It is estimated that in general, about 50 % of postmenopausal women in most countries do not receive osteoporosis drug therapy and are unaware of the different treatment options for disease, 25 % associate it only with femur and spine fractures. Surveys have found that most respondents without a diagnosis of osteoporosis have had one or more risk factors for developing it, but osteoporosis is often not diagnosed until one or more fractures have occurred. That is why orthopedists-traumatologists, who most often face pathological fractures on the background of osteoporosis, have proposed special protocols for the timely diagnosis and treatment of fragile fractures. Treatment standards require women aged 65–85 who have suffered a fracture to be screened and receive osteotropic therapy for 6 months. However, the diagnosis and treatment of osteoporosis for 6 and 12 months after femoral neck fractures received only 17–23 % of respondents. Misconceptions about the causes and consequences of postmenopausal women fractures, combined with insufficient information from health professionals, point to the low level of attention of the population and the health care system in general to osteoporosis in all countries. The incidence of fractures in women was 3.1 higher than in men and progressively increased the age 50+. For high risk fractures women due to osteoporosis ensuring their osteoporosis awareness is a critical preventive point. This is essentialy can influence positive changes in the fight against osteoporosis around the world.

OR13-06 Implementation of a High-Risk Fracture Program in an Integrated Healthcare Delivery System

BACKGROUND: Fracture events in older adults are important opportunities for secondary prevention. In response to national (HEDIS) quality metrics in 2008, our medical group implemented a fracture prevention program, identifying women age ≥65y who experienced a fracture and targeting them for osteoporosis screening or treatment within six months. In 2015, we added an outreach program for “high-risk secondary fracture prevention” targeting women age 60-85y and men age 70-85y for osteoporosis therapy within 6 months after a hip, pelvic, humerus, wrist or vertebral fracture. This study examines whether targeting “high-risk fracture” in women and men results in higher treatment rates following a non-vertebral major osteoporotic fracture.METHODS: This retrospective study was conducted using data from women age 60-85y and men age 70-85y who experienced a fracture of the hip, humerus, and wrist in 2013-2014 (Cohort 1, the era of our HEDIS-only program) or 2015-2016 (Cohort 2, the era of our added “high-risk secondary fracture prevention” program). We excluded patients with primary bone disorders or metastatic cancer and those with osteoporosis treatment in the year prior to fracture. Osteoporosis drug therapy (oral/IV bisphosphonates, denosumab, raloxifene or teriparatide) initiated within six months after the fracture date was assessed. Differences between groups were compared using the chi-squared test, and multivariable logistic regression was used to examine predictors of treatment.RESULTS: There were 5727 (Cohort 1) and 6469 (Cohort 2) adults identified with hip, humerus, or wrist fracture (high risk fracture). Wrist fracture was the most prevalent fracture in women and hip fracture the most prevalent in men. Osteoporosis treatment initiation within 6 months of the fracture date was achieved for 38% of women and 13% of men in Cohort 1 and 37% of women and 25% of men in Cohort 2. Among women age 60-64, treatment increased from 14% (Cohort 1) to 25% (Cohort 2). Overall, fracture in the later era (2015-2016) was associated with a slightly lower odds of post fracture treatment initiation (adjusted odds ratio OR 0.8, 95% confidence interval (CI) 0.7-0.9) in women 65-85y; however, a much higher odds of treatment was seen (OR 2.3, 95% CI 1.9-2.9) for men 70-85y. Older age, hip fracture, and past osteoporosis therapy were also associated with greater odds of treatment within 6 months.CONCLUSION: Targeted high-risk fracture intervention resulted in a 2-fold increase in osteoporosis treatment after major non-vertebral osteoporotic fracture in men 70-85y and women 60-64y, the demographic subgroups not previously targeted by HEDIS-based intervention. However, treatment of fractures in women already targeted by HEDIS-based intervention did not increase. Future studies should address potential barriers to treatment and assess the impact of added high-risk fracture outreach on adherence to therapy.

Underevaluation of fractures by self-report: an analysis from the FRISBEE cohort.

Most fracture cohort studies rely on participant self-report of fracture event. This approach may lead to fracture underreporting. The purpose of the study was to assess the rate of non-reported fractures in a well-characterized population-based cohort of 3560 postmenopausal women, aged 60-85years, included in the Fracture Risk Brussels Epidemiological Enquiry (FRISBEE) study. Incident low-traumatic or non-traumatic fractures were registered annually during phone calls. In 2018, we reviewed the medical files of 67.9% of our study participants and identified non-reported fractures ("false negatives fractures (FN)"). We also evaluated whether the rate of FN was influenced by baseline patients' characteristics and fracture risk factors. Generalized estimating equation (GEE) was used to calculate odds ratio (OR) and 95% CI. Over a median follow-up period of 9.2years, we registered 992 fractures (781 by self-report, confirmed by a radiological report and 211 unreported). The global false negative rate for all fractures was 21.3%, including 22% for MOFs (major osteoporotic fractures), 13.1% for other major fractures, and 25.8% for minor fractures. The rate of non-reported fractures varied by fracture site: for MOFs, it was 2.7% (n = 2/73) at the hip, 5.3% at the proximal humerus (n = 5/94), 7.1% at the wrist (n = 11/154), and 46.5% at the spine (n = 100/215). For "other major" fractures, the highest rate of false negatives fractures was found at the pelvic bone (21%, n = 13/62), followed by the elbow (17.9%, n = 5/28), long bones (10.5%, n = 2/19), ankle (6.2%, n = 4/65), and knee (5.9%, n = 1/17). Older subjects (OR 1.7; 95% CI, 1.2-2.4; P = 0.003), subjects with early non-substituted menopause (OR 1.8; 95% CI, 1.0-3.3; P = 0.04), with a lower education level (OR 1.5; 95%CI, 1.1-2.2; P = 0.01), and those under drug therapy for osteoporosis (OR 1.5; 95% CI, 1.0-2.2; P = 0.05) were associated with a higher rate of FN. In conclusion, underreporting of a substantial proportion of fracture events will influence any model of fracture risk prediction and induce bias when estimating the associations between candidate risk factors and incident fractures.

What is a reasonable rate for specific osteoporosis drug therapy in older fragility fracture patients?

Osteoporosis is the most common condition contributing to 95% of fractures in older patients hospitalized for fracture treatment. Despite the significant impact of fragility fractures on patient morbidity and mortality, efforts in optimizing osteoporotic treatment and prevention remain inadequate. In contrast, in patients with limited life expectancy, withholding specific osteoporosis drug treatment appears reasonable. The threshold between under- and overtreatment is still unclear. In 2016, we implemented a fracture liaison service (FLS) for 18months to improve the quality of osteoporosis care. We collected prospectively the patient's history, current treatment for osteoporosis, and risk factors for fragility fractures using a standardized protocol. Recommendations for drug therapy are discussed during the interdisciplinary ward round. The primary outcome parameter was a recommendation for specific osteoporosis drug treatment. We included 681 patients (mean age 82.5years, 502 (73.7%) females). The inclusion criteria were the following: age of 70years or older, admission to geriatric fracture center between April 2016 and December 2018. Based on our data, specific osteoporosis drug therapy was recommended in 467 (68.6%) patients. Six hundred fifty-one (95.6%) patients received vitamin D3, and 546 (80.2%) calcium. After adjustment, only age (every 5years, OR 0.57; 95% CI 0.45-0.72; p < 0.0001), cognitive impairment (OR 0.41; 95% CI 0.23-0.74; p = 0.003), pre-fracture mobility (OR 1.54; 95% CI 1.34-1.75; p < 0.0001), and living in a nursing home (OR 0.52; 95% CI 0.27-0.99; p = 0.049) remained as independent predictors for an indication of specific osteoporosis drug therapy. We found a higher rate of recommendations for specific osteoporosis drug therapy compared with usual treatment rates in literature. Though in some cases withholding of specific osteoporosis drug therapy seems reasonable, the main proportion of fragility fracture patients is undertreated. Our results could be a benchmark for the quality of osteoporosis care in older fragility fracture patients treated in a geriatric fracture center.

The latest findings about the drug therapy of osteoporosis

The latest findings about the drug therapy of osteoporosis

NIH PATHWAYS TO PREVENTION WORKSHOP: RESEARCH GAPS FOR LONG-TERM DRUG THERAPIES FOR FRACTURE PREVENTION

The NIH Pathways to Prevention Workshop was held on October 30-31, 2018 to present scientific evidence, as well as physician and patient perspectives to better understand the benefits and harms of drug therapies for osteoporosis fracture prevention. Osteoporotic fractures lead to substantial morbidity, mortality, and economic costs. The underlying medical condition, is a skeletal disorder characterized by compromised bone strength predisposing to increased fracture risk. Several medications approved by the U.S. Food and Drug Administration to prevent osteoporotic fractures have been effective when taken by people who are at high risk of fracture. These include bisphosphonates , denosumab, teriparatide, estrogens, and selective estrogen-receptor modulators. However, rare but serious adverse events, such as atypical femoral fractures and osteonecrosis of the jaw associated with bisphosphonates have raised questions regarding the safety of their use. There is limited evidence on the benefits and harms of long-term osteoporosis drug therapy, including the timing and duration of drug discontinuation or drug holidays. It is not clearly known which patients will benefit or may be harmed from continued drug intervention, who should and should not be put on drug holiday, how to identify such patients and properly treat them, and how to predict their outcomes. Key scientific areas covered by the workshop included: the benefits and risks of osteoporotic drugs with short-term and long-term use and factors that influence outcomes; the impact of drug discontinuation and drug holidays on outcomes; and patient and clinician factors that impact the use of and adherence to osteoporotic drugs.