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Nutritional Supplements and Skeletal Health.
Tabatabai, LS, Sellmeyer, DE
Current osteoporosis reports. 2021;(1):23-33
Abstract
PURPOSE OF REVIEW Nutrition influences skeletal health throughout the lifespan, from the impact of maternal intakes during development, through the development of peak bone mass, to the rate of bone loss during aging. However, there are limited data available on the effects of nutritional supplements on bone density, let alone fracture risk. This review will assess the current literature, focusing on human studies, and emphasizing nutrients where bone density or fracture data are available. RECENT FINDINGS Calcium and vitamin D supplements, in combination, reduce fracture risk, particularly in populations with low intakes. Extensive recent analyses have supported the safety of these interventions at recommended intakes. There is growing evidence that specific isoflavones may improve bone density although fracture data are lacking. Multiple other nutrient supplements may benefit skeletal health, but data are limited. The effect size of nutrient interventions are relatively small, requiring large sample sizes for trials with bone outcomes, may be difficult to blind, and the impact of supplementation may depend on baseline intake. However, nutrition is the only intervention that can be implemented life long and on a population wide basis. Further investigation is needed into the potential benefits of nutritional supplements to determine in which settings supplements may add benefit in addition to dietary intakes.
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Fracture Patterns in Type 1 and Type 2 Diabetes Mellitus: A Narrative Review of Recent Literature.
Van Hulten, V, Rasmussen, N, Driessen, JHM, Burden, AM, Kvist, A, van den Bergh, JP
Current osteoporosis reports. 2021;(6):644-655
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Abstract
PURPOSE OF REVIEW In this narrative review, we have summarized the literature on fracture risk in T1DM and T2DM with a special focus on fracture site, time patterns, glucose-lowering drugs, and micro- and macrovascular complications. RECENT FINDINGS T1DM and T2DM were associated with an overall increased fracture risk, with preferent locations at the hip, vertebrae, humerus, and ankle in T1DM and at the hip, vertebrae, and likely humerus, distal forearm, and foot in T2DM. Fracture risk was higher with longer diabetes duration and the presence of micro- and macrovascular complications. In T2DM, fracture risk was higher with use of insulin, sulfonylurea, and thiazolidinediones and lower with metformin use. The increased fracture risk in T1DM and T2DM concerns specific fracture sites, and is higher in subjects with longer diabetes duration, vascular complications, and in T2DM with the use of specific glucose-lowering medication.
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Therapies for Preventing Bone Loss with Glucocorticoid Treatment.
Agarwal, A, Adachi, JD
Current osteoporosis reports. 2021;(1):34-39
Abstract
PURPOSE OF REVIEW We aim to critically review recent recommendations regarding preventative strategies for glucocorticoid-induced osteoporosis and provide a summary of key evidence regarding available interventions. RECENT FINDINGS Lifestyle optimization remains the hallmark of bone health preservation. Early initiation of anti-osteoporotic agents in the setting of glucocorticoid exposure is essential, guided by appropriate risk stratification. Recommendations for calcium and vitamin D intake optimization are well-supported across all risk strata. Bisphosphonates are the mainstay of pharmacological therapy. Newer agents such as denosumab and teriparatide have demonstrated comparative benefit in terms of incident fracture risk reduction and bone mineral density preservation, with comparable adverse events. With due consideration to cost, resource availability, and patient values and preferences, these agents may warrant use as the first-line agents in this setting. Glucocorticoid-induced osteoporosis remains preventable and warrants early and targeted evidence-based therapy.
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Dual-energy CT in musculoskeletal trauma.
Wong, AJN, Wong, M, Kutschera, P, Lau, KK
Clinical radiology. 2021;(1):38-49
Abstract
Dual-energy computed tomography (DECT) combines the advantages of conventional CT with the ability to detect bone marrow oedema (BMO), which was previously limited to magnetic resonance imaging (MRI). By analysing DECT virtual non-calcium (VNCa) maps, radiologists can improve the detection of subtle and occult fractures and approximate the acuity/healing of fractures of indeterminate age. This review highlights the role of DECT in the assessment of musculoskeletal trauma, particularly among elderly, post-menopausal women and those at risk for osteoporosis. DECT is especially useful in investigating trabecular bone predominant regions (e.g., vertebral bodies, pelvis, hip, and long bone metaphyses) for stress (i.e., fatigue or insufficiency) and fragility fractures. CT is often performed first due to its increased availability, especially in the emergency setting, shorter imaging duration, and possible patient contraindications to magnetic resonance imaging (MRI). By enabling BMO detection, DECT may have a role in triaging patients for definitive MRI assessment. Understanding the role of anatomical, pathological, and patient factors in image interpretation can improve radiologist adoption of DECT, increase diagnostic confidence, and improve patient management.
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Bone-Targeting Systems to Systemically Deliver Therapeutics to Bone Fractures for Accelerated Healing.
Nielsen, JJ, Low, SA
Current osteoporosis reports. 2020;(5):449-459
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Abstract
PURPOSE OF REVIEW Compared with the current standard of implanting bone anabolics for fracture repair, bone fracture-targeted anabolics would be more effective, less invasive, and less toxic and would allow for control over what phase of fracture healing is being affected. We therefore sought to identify the optimal bone-targeting molecule to allow for systemic administration of therapeutics to bone fractures. RECENT FINDINGS We found that many bone-targeting molecules exist, but most have been developed for the treatment of bone cancers, osteomyelitis, or osteoporosis. There are a few examples of bone-targeting ligands that have been developed for bone fractures that are selective for the bone fracture over the body and skeleton. Acidic oligopeptides have the ideal half-life, toxicity profile, and selectivity for a bone fracture-targeting ligand and are the most developed and promising of these bone fracture-targeting ligands. However, many other promising ligands have been developed that could be used for bone fractures.
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Diabetes and Bone Fragility: SGLT2 Inhibitor Use in the Context of Renal and Cardiovascular Benefits.
Jackson, K, Moseley, KF
Current osteoporosis reports. 2020;(5):439-448
Abstract
PURPOSE OF REVIEW Type 2 diabetes mellitus (T2DM) has been shown to negatively impact bone quality and increase fracture risk. While the pathophysiology of bone fragility in T2DM is not clear and likely multifactorial, medications used to treat T2DM are increasingly scrutinized for their potential role in aberrant bone metabolism. Sodium-glucose co-transporter 2 (SGLT2) inhibitors are gaining popularity in patients with T2DM. In addition to lowering blood glucose, there is evidence that these drugs offer cardiac and renal benefit to individuals with T2DM, leading to FDA-approved indications for use in at-risk individuals. At the same time, there remain concerns that SGLT2 inhibitors, specifically canagliflozin, have adverse effects on bone metabolism and increase fracture risk in T2DM. This review seeks to further clarify the impact of these agents on the skeleton. RECENT FINDINGS SGLT2 inhibitors may indirectly disrupt calcium and phosphate homeostasis, contribute to weight loss, and cause hypotension, resulting in bone mineral density (BMD) losses and increased falls. The true long-term impact of SGLT2 inhibitors on the diabetic skeleton is still unclear; this review summarizes the results in studies investigating the impact of SGLT2 inhibitors on fracture risk in T2DM. Whereas studies performed with dapagliflozin and empagliflozin have not shown an increased risk of bone fractures compared with placebo, some studies have shown increased markers of bone turnover and reduced bone mineral density with canagliflozin treatment. While an increased fracture risk was observed with canagliflozin in the CANVAS trial (HR 1.26; 95% CI 1.04, 1.52), an increased risk was not seen in the CANVAS-R (HR 0.86) or CREDENCE (HR 0.98) trials. There is substantial evidence of the cardiac and renal protective benefits of SGLT2 inhibitors. There does not appear to be an increased fracture risk with the use of dapagliflozin or empagliflozin. Given the possible association between canagliflozin and adverse bone outcomes described in CANVAS, canagliflozin use should be pursued in individuals with T2DM only after careful consideration of the individual's skeletal risk.
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Diagnosis and management of pediatric metabolic bone diseases associated with skeletal fragility.
Charoenngam, N, Cevik, MB, Holick, MF
Current opinion in pediatrics. 2020;(4):560-573
Abstract
PURPOSE OF REVIEW The goal of this review is to give an overview of diagnosis and up-to-date management of major pediatric metabolic bone diseases that are associated with bone fragility, including nutritional rickets, hypophosphatemic rickets, osteogenesis imperfecta, Ehlers--Danlos syndrome, Marfan's syndrome, hypophosphatasia, osteopetrosis and skeletal fluorosis. RECENT FINDINGS During the past decade, a number of advanced treatment options have been introduced and shown to be an effective treatment in many metabolic bone disorders, such as burosumab for hypophosphatemic rickets and asfotase alfa for hypophosphatasia. On the other hand, other disorders, such as nutritional rickets and skeletal fluorosis continue to be underrecognized in many regions of the world. Genetic disorders of collagen-elastin, such as osteogenesis imperfecta, Ehlers--Danlos syndrome and Marfan's syndrome are also associated with skeletal fragility, which can be misdiagnosed as caused by non-accidental trauma/child abuse. SUMMARY It is essential to provide early and accurate diagnosis and treatment for pediatric patients with metabolic bone disorders in order to maintain growth and development as well as prevent fractures and metabolic complications.
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The Latest Evidence from Vitamin D Intervention Trials for Skeletal and Non-skeletal Outcomes.
Sami, A, Abrahamsen, B
Calcified tissue international. 2020;(1):88-93
Abstract
Vitamin D has long been considered a central part of the treatment paradigm for osteoporosis. Initial studies in high-risk populations with widespread vitamin D deficiency found a reduction of both vertebral and non-vertebral fractures. Subsequent studies in the general population have yielded mixed but mostly disappointing results both for skeletal and especially non-skeletal outcomes. Recent sequential trial meta-analyses suggest that future studies are likely to be futile given the overall disappointing result. However, mega-trials are still in progress, and additional results have been released. This narrative review aims to evaluate new literature to determine if there has been any substantial change in the message. In conclusion, there is no longer a strong case for initiating vitamin D alone trials in the general adult population, irrespective of age and gender, for significant health outcomes such as fractures, cardiovascular disease and cancer. New studies should focus on risk groups and take directions from the Heaney criteria for evaluation of threshold nutrients. Indeed, real benefits may still be reaped by directing vitamin D supplementation to persons with proven or likely vitamin D deficiency. Further, the role of dietary calcium as a critical co-nutrient remains controversial and could contribute to the discrepancy between studies in terms of cancer outcomes and possibly falls and fractures.
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Vitamin D for Improved Bone Health and Prevention of Stress Fractures: A Review of the Literature.
Lawley, R, Syrop, IP, Fredericson, M
Current sports medicine reports. 2020;(6):202-208
Abstract
Vitamin D is a vital nutrient and hormone needed for many essential functions in overall health. There is growing literature examining the role of vitamin D not only in the general population but also in athletes. The most predominantly studied area of vitamin D pertains to bone health. Recently, there has been increased investigation into the relationship of vitamin D and stress fractures, including genetic polymorphisms, levels of 25-hydroxyvitamin D, and bioavailable vitamin D. This review will address the most recent developments of vitamin D research and its important role in bone health in athletes.
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The Impact of Vitamin D Levels in Foot and Ankle Surgery.
Giakoumis, M
Clinics in podiatric medicine and surgery. 2020;(2):305-315
Abstract
Hypovitaminosis D has been established as a global health problem. As an important regulator of skeletal health homeostasis throughout one's life, optimal levels are presumed. Debate, however, still exists surrounding the definition of normal vitamin D levels and what affect hypovitaminosis D has on fracture prevention, fracture healing, and successful arthrodesis. A literature search failed to show any level 1 studies examining hypovitaminosis D and union rates in foot and/or ankle arthrodesis procedures. Several retrospective studies do point to some sort of association between nonunion and hypovitaminosis D. Because of lack of high-level studies, a potential study design is proposed.