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Journal of Bone and Mineral Research :... Aug 2023In this international study, we examined the incidence of hip fractures, postfracture treatment, and all-cause mortality following hip fractures, based on demographics,...
In this international study, we examined the incidence of hip fractures, postfracture treatment, and all-cause mortality following hip fractures, based on demographics, geography, and calendar year. We used patient-level healthcare data from 19 countries and regions to identify patients aged 50 years and older hospitalized with a hip fracture from 2005 to 2018. The age- and sex-standardized incidence rates of hip fractures, post-hip fracture treatment (defined as the proportion of patients receiving anti-osteoporosis medication with various mechanisms of action [bisphosphonates, denosumab, raloxifene, strontium ranelate, or teriparatide] following a hip fracture), and the all-cause mortality rates after hip fractures were estimated using a standardized protocol and common data model. The number of hip fractures in 2050 was projected based on trends in the incidence and estimated future population demographics. In total, 4,115,046 hip fractures were identified from 20 databases. The reported age- and sex-standardized incidence rates of hip fractures ranged from 95.1 (95% confidence interval [CI] 94.8-95.4) in Brazil to 315.9 (95% CI 314.0-317.7) in Denmark per 100,000 population. Incidence rates decreased over the study period in most countries; however, the estimated total annual number of hip fractures nearly doubled from 2018 to 2050. Within 1 year following a hip fracture, post-hip fracture treatment ranged from 11.5% (95% CI 11.1% to 11.9%) in Germany to 50.3% (95% CI 50.0% to 50.7%) in the United Kingdom, and all-cause mortality rates ranged from 14.4% (95% CI 14.0% to 14.8%) in Singapore to 28.3% (95% CI 28.0% to 28.6%) in the United Kingdom. Males had lower use of anti-osteoporosis medication than females, higher rates of all-cause mortality, and a larger increase in the projected number of hip fractures by 2050. Substantial variations exist in the global epidemiology of hip fractures and postfracture outcomes. Our findings inform possible actions to reduce the projected public health burden of osteoporotic fractures among the aging population. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Topics: Male; Female; Humans; Middle Aged; Aged; Incidence; Hip Fractures; Osteoporosis; Osteoporotic Fractures; Diphosphonates
PubMed: 37118993
DOI: 10.1002/jbmr.4821 -
The Journal of Clinical Endocrinology... Jun 2023Osteogenesis imperfecta (OI) is a genetic disorder characterized by increased bone fragility largely caused by defects in structure, synthesis, or post-translational... (Review)
Review
CONTEXT
Osteogenesis imperfecta (OI) is a genetic disorder characterized by increased bone fragility largely caused by defects in structure, synthesis, or post-translational processing of type I collagen. The effectiveness of medications used for fracture reduction in adults with OI is understudied and practice recommendations are not well established. Drugs currently used to improve skeletal health in OI were initially developed to treat osteoporosis. Oral and intravenous bisphosphonates have been shown to improve bone mineral density (BMD) in adults with OI and are commonly used; however, conclusive data confirming fracture protection are lacking. Similarly, teriparatide appears to increase BMD, an effect that seems to be limited to individuals with type I OI. The role of denosumab, abaloparatide, romosozumab, and estradiol/testosterone in adult OI have not been systematically studied. Anti-sclerostin agents and transforming growth factor-beta antagonists are under investigation in clinical trials.
OBJECTIVE
This review summarizes current knowledge on pharmacologic treatment options for reducing fracture risk in adults with OI.
METHODS
A PubMed online database search of all study types published in the English language using the terms "osteogenesis imperfecta," "OI," and "brittle bone disease" was performed in June 2022. Articles screened were restricted to adults. Additional sources were identified through manual searches of reference lists.
CONCLUSION
Fracture rates are elevated in adults with OI. Although clinical trial data are limited, bisphosphonates and teriparatide may be useful in improving BMD. Further research is needed to develop medications for adults with OI that will lead to definite fracture rate reduction.
Topics: Adult; Humans; Bone Density Conservation Agents; Osteogenesis Imperfecta; Teriparatide; Fractures, Bone; Diphosphonates; Bone Density; Fracture Fixation
PubMed: 36658750
DOI: 10.1210/clinem/dgad035 -
Aging Clinical and Experimental Research Sep 2023The objective of this systematic review and meta-analysis is to systematically identify and review the efficacy of pharmacological treatments in men with osteoporosis. (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
The objective of this systematic review and meta-analysis is to systematically identify and review the efficacy of pharmacological treatments in men with osteoporosis.
METHODS
Medline (via Ovid) and Cochrane CENTRAL were searched up to May 2023 for any randomized controlled trial (RCT) evaluating the efficacy of osteoporotic treatment on the evolution of Bone Mineral Density (BMD) and incidence of fractures of men suffering from primary osteoporosis. If at least two studies used the same pharmacological treatment and evaluated the same outcome, a random effect model meta-analysis was applied to reported pooled mean difference (MD) and 95% confidence interval (CI).
RESULTS
From the 1,061 studies identified through bibliographic search, 21 RCTs fitted the inclusion criteria. Bisphosphonates (k = 10, n = 2992 men with osteoporosis) improved all three BMD sites compared to placebo; lumbar spine: MD + 4.75% (95% CI 3.45, 6.05); total hip: MD + 2.72% (95% CI 2.06; 3.37); femoral neck: MD + 2.26% (95% CI 1.67; 2.85). Denososumab (k = 2, n = 242), Teriparatide (k = 2, n = 309) and Abaloparatide (k = 2, n = 248) also produced significant improvement of all sites BMD compared to placebo. Romosozumab was only identified in one study and was therefore not meta-analysed. In this study, Romosozumab increased significantly BMD compared to placebo. Incident fractures were reported in 16 RCTs but only four reported fractures as the primary outcome. Treatments were associated with a lower incidence of fractures.
CONCLUSIONS
Medications used in the management of osteoporosis in women appear to provide similar benefits in men with osteoporosis. Therefore, the algorithm for the management of osteoporosis in men could be similar to the one previously recommended for the management of osteoporosis in women.
Topics: Male; Female; Humans; Bone Density Conservation Agents; Osteoporosis; Bone Density; Diphosphonates; Fractures, Bone
PubMed: 37400668
DOI: 10.1007/s40520-023-02478-9 -
Circulation Research Nov 2023Pulmonary hypertension (PH) in heart failure with preserved ejection fraction (HFpEF) is a common and highly morbid syndrome, but mechanisms driving PH-HFpEF are poorly...
BACKGROUND
Pulmonary hypertension (PH) in heart failure with preserved ejection fraction (HFpEF) is a common and highly morbid syndrome, but mechanisms driving PH-HFpEF are poorly understood. We sought to determine whether a well-accepted murine model of HFpEF also displays features of PH, and we sought to identify pathways that might drive early remodeling of the pulmonary vasculature in HFpEF.
METHODS
Eight-week-old male and female C57BL/6J mice received either N-nitro-L-arginine methyl ester and high-fat diet or control water and diet for 2, 5, and 12 weeks. The db/db mice were studied as a second model of HFpEF. Early pathways regulating PH were identified by bulk and single-cell RNA sequencing. Findings were confirmed by immunostain in lungs of mice or lung slides from clinically performed autopsies of patients with PH-HFpEF. ELISA was used to verify IL-1β (interleukin-1 beta) in mouse lung, mouse plasma, and also human plasma from patients with PH-HFpEF obtained at the time of right heart catheterization. Clodronate liposomes and an anti-IL-1β antibody were utilized to deplete macrophages and IL-1β, respectively, to assess their impact on pulmonary vascular remodeling in HFpEF in mouse models.
RESULTS
N-nitro-L-arginine methyl ester/high-fat diet-treated mice developed PH, small vessel muscularization, and right heart dysfunction. Inflammation-related gene ontologies were overrepresented in bulk RNA sequencing analysis of whole lungs, with an increase in CD68 cells in both murine and human PH-HFpEF lungs. Cytokine profiling showed an increase in IL-1β in mouse and human plasma. Finally, clodronate liposome treatment in mice prevented PH in N-nitro-L-arginine methyl ester/high-fat diet-treated mice, and IL-1β depletion also attenuated PH in N-nitro-L-arginine methyl ester/high-fat diet-treated mice.
CONCLUSIONS
We report a novel model for the study of PH and right heart remodeling in HFpEF, and we identify myeloid cell-derived IL-1β as an important contributor to PH in HFpEF.
Topics: Animals; Female; Humans; Male; Mice; Clodronic Acid; Heart Failure; Hypertension, Pulmonary; Interleukin-1beta; Mice, Inbred C57BL; Myeloid Cells; Stroke Volume
PubMed: 37929582
DOI: 10.1161/CIRCRESAHA.123.323119 -
JPMA. the Journal of the Pakistan... May 2024Fever is usually thought to be of an infectious or inflammatory etiology. In this brief communication, we explore the multifaceted connections between fever and... (Review)
Review
Fever is usually thought to be of an infectious or inflammatory etiology. In this brief communication, we explore the multifaceted connections between fever and endocrine dysfunction. Impaired resistance to infection often leads to fever in conditions like diabetes and Cushing's syndrome. Additionally, several endocrine disorders, including hyperthyroidism, subacute thyroiditis, carcinoid syndrome, and pheochromocytoma, can manifest as fever. Furthermore, fever can be an adverse effect of various endocrine treatments, such as bisphosphonates and antithyroid drugs. We refer to these scenarios as 'endocrine fever.' Increased awareness of these clinical associations can aid in prompt diagnosis and management of these conditions.
Topics: Humans; Fever; Endocrine System Diseases; Hyperthyroidism; Cushing Syndrome; Pheochromocytoma; Adrenal Gland Neoplasms; Antithyroid Agents; Diphosphonates
PubMed: 38783456
DOI: 10.47391/JPMA.24-36 -
The Journal of Experimental Medicine Jun 2023Clodronate liposomes (Clo-Lip) have been widely used to deplete mononuclear phagocytes (MoPh) to study the function of these cells in vivo. Here, we revisited the...
Clodronate liposomes (Clo-Lip) have been widely used to deplete mononuclear phagocytes (MoPh) to study the function of these cells in vivo. Here, we revisited the effects of Clo-Lip together with genetic models of MoPh deficiency, revealing that Clo-Lip exert their anti-inflammatory effects independent of MoPh. Notably, not only MoPh but also polymorphonuclear neutrophils (PMN) ingested Clo-Lip in vivo, which resulted in their functional arrest. Adoptive transfer of PMN, but not of MoPh, reversed the anti-inflammatory effects of Clo-Lip treatment, indicating that stunning of PMN rather than depletion of MoPh accounts for the anti-inflammatory effects of Clo-Lip in vivo. Our data highlight the need for a critical revision of the current literature on the role of MoPh in inflammation.
Topics: Humans; Liposomes; Clodronic Acid; Neutrophils; Inflammation; Anti-Inflammatory Agents
PubMed: 36976180
DOI: 10.1084/jem.20220525 -
Archives of Endocrinology and Metabolism Nov 2023Bisphosphonates (BPs) are medications widely used in clinical practice to treat osteoporosis and reduce fragility fractures. Its beneficial effects on bone tissue have... (Review)
Review
Bisphosphonates (BPs) are medications widely used in clinical practice to treat osteoporosis and reduce fragility fractures. Its beneficial effects on bone tissue have been consolidated in the literature for the last decades. They have a high affinity for bone hydroxyapatite crystals, and most bisphosphonates remain on the bone surface for a long period of time. Benefits of long-term use of BPs: Large and important trials (Fracture Intervention Trial Long-term Extension and Health Outcomes and Reduced Incidence with Zoledronic acid Once Yearly-Pivotal Fracture Trial) with extended use of alendronate (up to 10 years) and zoledronate (up to 6 years) evidenced significant gain of bone mineral density (BMD) and vertebral fracture risk reduction. Risks of long-term use of BPs: The extended use of antiresorptive therapy has drawn attention to two extremely rare, although severe, adverse events. That is, atypical femoral fracture and medication-related osteonecrosis of the jaw are more common in patients with high cumulative doses and longer duration of therapy. BPs have demonstrated safety and effectiveness throughout the years and evidenced increased BMD and reduced fracture risks, resulting in reduced morbimortality, and improved quality of life. These benefits overweight the risks of rare adverse events.
Topics: Humans; Female; Diphosphonates; Bone Density Conservation Agents; Quality of Life; Osteoporosis; Alendronate; Zoledronic Acid; Fractures, Bone; Osteoporosis, Postmenopausal
PubMed: 37948565
DOI: 10.20945/2359-4292-2022-0334 -
CMAJ : Canadian Medical Association... Mar 2024
Topics: Humans; Scleritis; Pamidronate; Uveitis, Anterior; Acute Disease
PubMed: 38527748
DOI: 10.1503/cmaj.230859-f