ABSTRACT
Bariatric surgery is associated with a postoperative reduction of 25(OH) vitamin D levels (25(OH)D) and with skeletal complications. Currently, guidelines for 25(OH)D assessment and vitamin D supplementation in bariatric patients, pre- and post-surgery, are still lacking. The aim of this work is to analyse systematically the published experience on 25(OH)D status and vitamin D supplementation, pre- and post-surgery, and to propose, on this basis, recommendations for management. Preoperatively, 18 studies including 2,869 patients were evaluated. Prevalence of vitamin D insufficiency as defined by 25(OH)D < 30 ng/mL (75 nmol/L) was 85%, whereas when defined by 25(OH)D < 20 ng/mL (50 nmol/L) was 57%. The median preoperative 25(OH)D level was 19.75 ng/mL. After surgery, 39 studies including 5,296 patients were analysed and among those undergoing either malabsorptive or restrictive procedures, a lower rate of vitamin D insufficiency and higher 25(OH)D levels postoperatively were observed in patients treated with high-dose oral vitamin D supplementation, defined as ≥ 2,000 IU/daily (mostly D3-formulation), compared with low-doses (< 2,000 IU/daily). Our recommendations based on this systematic review and meta-analysis should help clinical practice in the assessment and management of vitamin D status before and after bariatric surgery. Assessment of vitamin D should be performed pre- and postoperatively in all patients undergoing bariatric surgery. Regardless of the type of procedure, high-dose supplementation is recommended in patients after bariatric surgery.
Subject(s)
Bariatric Surgery , Vitamin D Deficiency , Humans , Vitamin D , Vitamin D Deficiency/drug therapy , Vitamin D Deficiency/epidemiology , Vitamin D Deficiency/etiology , Dietary Supplements , Vitamins/therapeutic useABSTRACT
The purpose of the study was to identify potential predictors of muscle hypertrophy responsiveness following neuromuscular electrical stimulation resistance training (NMES-RT) in persons with chronic spinal cord injury (SCI). Data for twenty individuals with motor complete SCI who completed twice weekly NMES-RT lasting 12-16 weeks as part of their participation in one of two separate clinical trials were pooled and retrospectively analyzed. Magnetic resonance imaging (MRI) was used to measure muscle cross-sectional area (CSA) of the whole thigh and knee extensor muscle before and after NMES-RT. Muscle biopsies and fasting biomarkers were also measured. Following the completion of the respective NMES-RT trials, participants were classified into either high-responders (n = 8; muscle CSA > 20%) or low-responders (n = 12; muscle CSA < 20%) based on whole thigh muscle CSA hypertrophy. Whole thigh muscle and knee extensors CSAs were significantly greater (P < 0.0001) in high-responders (29 ± 7% and 47 ± 15%, respectively) compared to low-responders (12 ± 3% and 19 ± 6%, respectively). There were no differences in total caloric intake or macronutrient intake between groups. Extensor spasticity was lower in the high-responders compared to the low-responders as was the dosage of baclofen. Prior to the intervention, the high-responders had greater body mass compared to the low-responders with SCI (87.8 ± 13.7 vs. 70.4 ± 15.8 kg; P = 0.012), body mass index (BMI: 27.6 ± 2.7 vs. 22.9 ± 6.0 kg/m2; P = 0.04), as well as greater percentage in whole body and regional fat mass (P < 0.05). Furthermore, high-responders had a 69% greater increase (P = 0.086) in total Akt protein expression than low-responders. High-responders also exhibited reduced circulating IGF-1 with a concomitant increase in IGFBP-3. Exploratory analyses revealed upregulation of mRNAs for muscle hypertrophy markers [IRS-1, Akt, mTOR] and downregulation of protein degradation markers [myostatin, MurF-1, and PDK4] in the high-responders compared to low-responders. The findings indicate that body composition, spasticity, baclofen usage, and multiple signaling pathways (anabolic and catabolic) are involved in the differential muscle hypertrophy response to NMES-RT in persons with chronic SCI.
Subject(s)
Electric Stimulation Therapy , Resistance Training , Spinal Cord Injuries , Humans , Baclofen/metabolism , Resistance Training/methods , Proto-Oncogene Proteins c-akt/metabolism , Retrospective Studies , Muscle, Skeletal/physiology , Muscle Spasticity , Spinal Cord Injuries/metabolism , Hypertrophy/pathology , Electric Stimulation Therapy/methodsABSTRACT
The 4th International Conference on Controversies in Vitamin D was held as a virtual meeting in September, 2020, gathering together leading international scientific and medical experts in vitamin D. Since vitamin D has a crucial role in skeletal and extra-skeletal systems, the aim of the Conference was to discuss improved management of vitamin D dosing, therapeutic levels and form or route of administration in the general population and in different clinical conditions. A tailored approach, based on the specific mechanisms underlying vitamin D deficiency in different diseases that were discussed, was recommended. Specifically, in comparison to healthy populations, higher levels of vitamin D and greater amounts of vitamin D were deemed necessary in osteoporosis, diabetes mellitus, obesity (particularly after bariatric surgery), and in those treated with glucocorticoids. Emerging and still open issues were related to target vitamin D levels and the role of vitamin D supplementation in COVID-19 since low vitamin D may predispose to SARS-CoV-2 infection and to worse COVID-19 outcomes. Finally, whereas oral daily cholecalciferol appears to be the preferred choice for vitamin D supplementation in the general population, and in most clinical conditions, active vitamin D analogs may be indicated in patients with hypoparathyroidism and severe kidney and liver insufficiency. Parenteral vitamin D administration could be helpful in malabsorption syndromes or in states of vitamin D resistance.Specific guidelines for desired levels of vitamin D should be tailored to the different conditions affecting vitamin D metabolism with the goal to define disease-specific normative values.
Subject(s)
COVID-19 , Vitamin D Deficiency , Cholecalciferol , Humans , SARS-CoV-2 , Vitamin D , Vitamin D Deficiency/drug therapyABSTRACT
STUDY DESIGN: Secondary analysis of a clinical trial. OBJECTIVES: To perform a secondary analysis on the effects of neuromuscular electrical stimulation resistance training (RT) combined with testosterone replacement therapy (TRT) compared with TRT on the untrained muscles after spinal cord injury (SCI). SETTING: Medical research center. METHODS: Twenty-two men with chronic motor complete SCI were randomized into TRT + RT group (n = 11) or TRT group (n = 11). Both groups received 16 weeks of TRT (2-6 mg/day) via testosterone patches. The TRT + RT group received twice weekly progressive RT of the knee extensor muscles using electrical stimulation and ankle weights. Magnetic resonance images were captured to measure cross-sectional areas (CSAs) of trunk, glutei, and leg muscles. RESULTS: Total and absolute gluteus maximus m. (14%, P = 0.003 and 16%, P = 0.001), gluteus medius m. (10%; P = 0.008 and 14%; P = 0.02), and total glutei m. (8%, P = 0.01 and 11%, P = 0.005) CSAs increased overtime for the TRT + RT group. Mean between-group differences of 2.86 (95% CI: 0.30, 5.4), 1.89 (95% CI: 0.23, 3.58) and 5.27 (95% CI: 0.90, 9.69) cm2 were noted for absolute gluteus maximus, total gluteus medius and total glutei CSAs, respectively (P < 0.05). Trunk muscle CSAs showed a trend towards an interaction between groups. CONCLUSIONS: RT combined with low-dose TRT results in significant hypertrophy compared with TRT only on the adjacent untrained glutei muscles. Trunk muscles may require direct stimulation to evoke hypertrophy. These exploratory findings may be of clinical relevance in the reduction of incidence and severity of pelvic pressure injuries.
Subject(s)
Androgens/pharmacology , Electric Stimulation Therapy , Muscle, Skeletal , Outcome Assessment, Health Care , Resistance Training , Spinal Cord Injuries/therapy , Testosterone/pharmacology , Adult , Androgens/administration & dosage , Combined Modality Therapy , Electric Stimulation Therapy/methods , Hormone Replacement Therapy , Humans , Hypertrophy/etiology , Male , Middle Aged , Muscle, Skeletal/drug effects , Pilot Projects , Resistance Training/methods , Spinal Cord Injuries/drug therapy , Spinal Cord Injuries/rehabilitation , Testosterone/administration & dosageABSTRACT
Glucocorticoid-induced osteoporosis remains the most common type of secondary osteoporosis, mostly due to use of oral glucocorticoids rather than due to endogenous overproduction of cortisol. Partly because glucocorticoids are prescribed by a wide variety of clinicians for many different inflammatory disorders, only a minority of older individuals have adequate and timely assessment of their enhanced fracture risk, and fewer are offered treatment. Assessment should include bone density, the FRAX calculation, and, in many cases, images of the spine. Glucocorticoids decrease osteoblast function and increase apoptosis of osteoblasts and osteocytes, leading to increased fracture risk soon after starting glucocorticoids. Guidelines provide evidence-based recommendations for evaluation and treatment, but there are differences in extant guidelines, and methods to improve adherence to the guidelines have mostly failed. A strong case can be made to use anabolic drugs first in high-risk patients based on pathophysiology and head-to-head clinical trials.
Subject(s)
Glucocorticoids/adverse effects , Osteoporosis/chemically induced , Osteoporosis/therapy , Aged , Aged, 80 and over , Anabolic Agents/therapeutic use , Apoptosis/drug effects , Bone Density/drug effects , Glucocorticoids/therapeutic use , Humans , Middle Aged , Osteoblasts/physiology , Osteocytes/physiology , Practice Guidelines as Topic , Risk AssessmentABSTRACT
STUDY DESIGN: Cross-sectional study. OBJECTIVE: To establish the association between serum testosterone (T) levels, biomarkers of cardiometabolic health and regional body composition variables after spinal cord injury (SCI). SETTING: Medical research center. METHODS: Metabolic and body composition measurements were collected from thirty-six men with chronic motor complete SCI. Serum T, carbohydrate, and lipid profiles were measured after an overnight fast. Body composition was measured using anthropometrics, dual-energy X-ray absorptiometry, and magnetic resonance imaging. Participants were evenly classified into tertiles based on their serum T levels into low, mid-normal and normal ranges. RESULTS: Low, mid-normal, and normal range serum T were 288.8 ± 84.9 ng/dL, 461.0 ± 52.5 ng/dL and 648.0 ± 53.5 ng/dL, respectively. Low range serum T group had greater total (9.6%, P = 0.04) percentage fat mass and visceral adipose tissue (VAT) area (72%, P = 0.01) compared to normal range serum T group. Serum T was related to the absolute whole thigh muscle area (r = 0.40, P < 0.05) after controlling for body mass index. Serum T was negatively related to fasting plasma glucose (r = -0.46, P = 0.006) and insulin (r = -0.42, P = 0.01), HbA1c (r = -0.39, P = 0.02) and triglycerides (r = -0.36, P = 0.03). CONCLUSION: Men with low serum T have more unfavorable body composition and cardiometabolic health outcomes after SCI. Testosterone replacement therapy may serve as a potential strategy in preventing cardiometabolic disorders after SCI.
Subject(s)
Body Composition , Lipids/blood , Spinal Cord Injuries/diagnostic imaging , Spinal Cord Injuries/metabolism , Testosterone/blood , Absorptiometry, Photon , Adipose Tissue/diagnostic imaging , Adolescent , Adult , Aged , Biomarkers/blood , Body Composition/physiology , Chronic Disease , Cross-Sectional Studies , Heart Diseases/blood , Heart Diseases/diagnostic imaging , Heart Diseases/etiology , Humans , Magnetic Resonance Imaging , Male , Metabolic Diseases/blood , Metabolic Diseases/diagnostic imaging , Metabolic Diseases/etiology , Middle Aged , Young AdultABSTRACT
STUDY DESIGN: Repeated measures design. OBJECTIVES: To determine the reproducibility of total-body and regional-body composition assessments from a total-body scan using dual-energy x-ray absorptiometry (DXA) in persons with spinal cord injury (SCI). METHODS: Twenty-four individuals with SCI completed within-day short-term precision testing by repositioning study participants between scans. An additional and separate cohort of 22 individuals with SCI were scanned twice on a GE-Lunar DXA scanner separated by a 4-week interval to assess the long-term precision assessment. The root mean square coefficient of variation percent (RMS-CV%) values for the regional and total body composition was calculated. RESULTS: For the same day, short-term precision assessment, the RMS-CV% for each region did not exceed 5.6, 2.7, 3.8, 6.5, 5.8, and 2.3% for arms, legs, trunk, android and gynoid regions, and total body mass, respectively. In the long-term precision assessment, the RMS-CV% for each region did not exceed 6.0, 3.0, 4.4, 8.2, 3.4, and 2.0% for arms, legs, trunk, android, gynoid, and total body mass. Moreover, the interclass-correlation coefficient in the long-term precision group demonstrated excellent linear agreement between repeat scans for all regions (r > 0.97). CONCLUSIONS: The precision error of the total body composition variables in our SCI cohort was similar to those reported in the literature for nondisabled individuals, and the precision errors of the regional body composition compartments were notably higher, but similar to the regional precision errors reported in the general population.
Subject(s)
Absorptiometry, Photon , Body Composition , Spinal Cord Injuries/diagnostic imaging , Whole Body Imaging , Absorptiometry, Photon/instrumentation , Adolescent , Adult , Chronic Disease , Humans , Image Interpretation, Computer-Assisted , Longitudinal Studies , Male , Middle Aged , Phantoms, Imaging , Reproducibility of Results , Whole Body Imaging/instrumentation , Whole Body Imaging/methods , Young AdultABSTRACT
OBJECTIVE: The use of prescription opioids has increased dramatically over the past 20 years. Opioids appear to affect multiple endocrine pathways leading to abnormal levels of different hormones such as testosterone, cortisol, and prolactin (PRL). In this article, we review the current data regarding opioid effects on the hypothalamus, pituitary, and bone metabolism. METHODS: We conducted a PubMed search for articles regarding opioids and each of the following subjects: testosterone, estrogen, cortisol, thyroid, growth hormone (GH), and bone. Most articles were primary source studies conducted between 1980 and 2014. Articles were included if studies were conducted within the time period, published in English, and available as full-length articles. Case reports were reviewed, but controlled studies were given more weight. RESULTS: Opioids appear to affect each of the pituitary hormone pathways in addition to altering bone metabolism. The most commonly reported and substantial effect was hypogonadism in both sexes; however, suppression of the adrenal axis may be more common than initially thought. Although some studies report a change in thyroid and GH levels, overall effects have not been thoroughly studied. There is some evidence for increased fracture risk, possibly mediated by hypogonadism and fall risk. CONCLUSION: More research is needed to determine which opioids are more likely to cause endocrine dysfunction and which patients need to be screened and treated. Also unknown is the length of time to the development of hormonal changes after starting opioid therapy and if cessation of opioid therapy can normalize hormone levels.
Subject(s)
Analgesics, Opioid/adverse effects , Endocrine System Diseases/chemically induced , Bone and Bones/metabolism , Human Growth Hormone/blood , Humans , Hypothalamo-Hypophyseal System/drug effects , Pituitary-Adrenal System/drug effects , Prolactin/bloodABSTRACT
Osteoporosis in men is an underappreciated public health issue, accounting for approximately 30% of the societal burden of osteoporosis. Although the prevalence of osteoporosis in men is lower, fracture-related morbidity and mortality rates exceed those of women. Abaloparatide is a synthetic, 34-amino acid peptide with homology to human parathyroid hormone-related protein (PTHrP), which favors bone formation by selective activation of PTH receptor type 1. In the Abaloparatide for the Treatment of Men With Osteoporosis (ATOM; NCT03512262) trial, 228 men with primary or hypogonadism-associated osteoporosis were randomized to receive subcutaneous injections of abaloparatide 80 µg or placebo. Abaloparatide significantly improved LS, TH, and FN BMD when compared with placebo. In this prespecified analysis, the proportion of men with a percent change from baseline of >0%, >3%, and > 6% in BMD at the LS, TH, and FN at 3, 6, and 12 mo and/or a shift in T-score category (based on LS and TH T-scores) at 12 mo was compared between the abaloparatide and placebo groups in ATOM. There were significantly more men with a BMD gain of >3% at all 3 anatomical sites in the abaloparatide than placebo group at month 6 (18/122 [14.8%] vs 1/70 [1.4%], P = .002) and at month 12 (38/119 [31.9%] vs 1/66 [1.5%], P < .0001). At month 3, more men treated with abaloparatide than placebo had a > 3% BMD increase at the LS (82/134 [61.2%] vs 21/68 [30.9%], P < .0001). A greater proportion of men treated with abaloparatide had an improvement in T-score category from osteoporosis to low BMD or normal when compared with placebo. In conclusion, use of abaloparatide compared with placebo for 12 mo resulted in significant and rapid improvements in BMD in men with osteoporosis from the ATOM study.
ABSTRACT
The 6th International Conference, "Controversies in Vitamin D," was convened to discuss controversial topics, such as vitamin D metabolism, assessment, actions, and supplementation. Novel insights into vitamin D mechanisms of action suggest links with conditions that do not depend only on reduced solar exposure or diet intake and that can be detected with distinctive noncanonical vitamin D metabolites. Optimal 25-hydroxyvitamin D (25(OH)D) levels remain debated. Varying recommendations from different societies arise from evaluating different clinical or public health approaches. The lack of assay standardization also poses challenges in interpreting data from available studies, hindering rational data pooling and meta-analyses. Beyond the well-known skeletal features, interest in vitamin D's extraskeletal effects has led to clinical trials on cancer, cardiovascular risk, respiratory effects, autoimmune diseases, diabetes, and mortality. The initial negative results are likely due to enrollment of vitamin D-replete individuals. Subsequent post hoc analyses have suggested, nevertheless, potential benefits in reducing cancer incidence, autoimmune diseases, cardiovascular events, and diabetes. Oral administration of vitamin D is the preferred route. Parenteral administration is reserved for specific clinical situations. Cholecalciferol is favored due to safety and minimal monitoring requirements. Calcifediol may be used in certain conditions, while calcitriol should be limited to specific disorders in which the active metabolite is not readily produced in vivo. Further studies are needed to investigate vitamin D effects in relation to the different recommended 25(OH)D levels and the efficacy of the different supplementary formulations in achieving biochemical and clinical outcomes within the multifaced skeletal and extraskeletal potential effects of vitamin D.
ABSTRACT
Diabetes mellitus (particularly type 2) and osteoporosis are two very common disorders, and both are increasing in prevalence. Adolescents with type 1 diabetes mellitus may not reach potential peak bone mass, putting them at greater fracture risk. In adults with type 2 diabetes, fracture risk is increased and is not explained by the bone mineral density measured by dual-energy X-ray absorptiometry, still considered the gold standard predictor of fracture. In this review, we explore potential mechanisms behind the increased fracture risk that occurs in patients with diabetes, even those with increased bone mineral density. One potential link between diabetes and bone is the osteoblast-produced factor, osteocalcin. It remains to be established whether osteocalcin reflects or affects the connection between bone and glucose metabolism. Several other potential mediators of the effects of diabetes on bone are discussed.
Subject(s)
Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 2/complications , Osteoporosis/etiology , Animals , Bone Density , Diabetes Mellitus, Type 1/physiopathology , Diabetes Mellitus, Type 2/physiopathology , Fractures, Bone/etiology , Fractures, Bone/physiopathology , Humans , Osteoporosis/physiopathologyABSTRACT
The core of the 2012 Santa Fe Bone Symposium consisted of plenary presentations on new developments in the fields of osteoporosis and metabolic bone disease, with a focus on current and future implications for patient care. These were complemented by oral abstracts, interactive discussions of challenging cases, a debate on benefits and risks of long-term bisphosphonate therapy, and a panel discussion of controversial issues in the management of osteoporosis. Other topics included a review of the most important scientific publications in the past year, new and emerging therapy for osteoporosis, the benefits and limitations of clinical practice guidelines in the care of individual patients, the effects of metallic elements on skeletal health, clinical applications of bone turnover markers, an engineering perspective of skeletal health and disease, and an update on the role of the International Society for Clinical Densitometry in education, certification, accreditation, and advocacy for high-quality bone density testing. The symposium was highlighted by an inaugural presentation of "2 Million 2 Many," a national campaign of the National Bone Health Alliance to increase awareness of osteoporosis.
Subject(s)
Absorptiometry, Photon/methods , Bone Density , Congresses as Topic , Disease Management , Osteoporosis/diagnostic imaging , Osteoporosis/therapy , Practice Guidelines as Topic , Humans , United StatesABSTRACT
Objective: To examine the combined effects of neuromuscular electrical stimulation-resistance training (NMES-RT) and functional electrical stimulation-lower extremity cycling (FES-LEC) compared to passive movement training (PMT) and FES-LEC in adults with SCI on (1) oxygen uptake (VO2), insulin sensitivity and glucose disposal in adults with SCI; (2) Metabolic and inflammatory biomarkers; (3) skeletal muscle, intramuscular fat (IMF) and visceral adipose tissue (VAT) cross-sectional areas (CSAs). Materials and methods: Thirty-three participants with chronic SCI (AIS A-C) were randomized to 24 weeks of NMES-RT + FES or PMT + FES. The NMES-RT + FES group underwent 12 weeks of evoked surface NMES-RT using ankle weights followed by an additional 12 weeks of progressive FES-LEC. The control group, PMT + FES performed 12 weeks of passive leg extension movements followed by an additional 12 weeks of FES-LEC. Measurements were performed at baseline (BL; week 0), post-intervention 1 (P1; week 13) and post-intervention 2 (P2; week 25) and included FES-VO2 measurements, insulin sensitivity and glucose effectiveness using the intravenous glucose tolerance test; anthropometrics and whole and regional body composition assessment using dual energy x-ray absorptiometry (DXA) and magnetic resonance imaging to measure muscle, IMF and VAT CSAs. Results: Twenty-seven participants completed both phases of the study. NMES-RT + FES group showed a trend of a greater VO2 peak in P1 [p = 0.08; but not in P2 (p = 0.25)] compared to PMT + FES. There was a time effect of both groups in leg VO2 peak. Neither intervention elicited significant changes in insulin, glucose, or inflammatory biomarkers. There were modest changes in leg lean mass following PMT + FES group. Robust hypertrophy of whole thigh muscle CSA, absolute thigh muscle CSA and knee extensor CSA were noted in the NMES-RT + FES group compared to PMT + FES at P1. PMT + FES resulted in muscle hypertrophy at P2. NMES-RT + FES resulted in a decrease in total VAT CSA at P1. Conclusion: NMES-RT yielded a greater peak leg VO2 and decrease in total VAT compared to PMT. The addition of 12 weeks of FES-LEC in both groups modestly impacted leg VO2 peak. The addition of FES-LEC to NMES-RT did not yield additional increases in muscle CSA, suggesting a ceiling effect on signaling pathways following NMES-RT. Clinical trial registration: identifier NCT02660073.
ABSTRACT
Osteoporosis causes no symptoms until there is a fracture. Although screening for osteoporosis is recommended for some populations, patients may present with a fragility fracture. Such patients are at high risk for subsequent fractures. Despite this high risk and the presence of generally safe and effective osteoporosis therapy, only a minority of low trauma fracture patients have evaluation and treatment of underlying osteoporosis. A brief summary of the evaluation and medical treatment of the post-fracture patient is provided. Several institutions, integrated health systems, and countries have instituted programs to identify, evaluate, and treat fragility fracture patients. Such programs have had variable success. This article describes some of the programs that work, their cost-effectiveness, and the applicability to the generally non-integrated US health care system. It is clear that better management of the post-fracture patient (and other high-risk patients) will lead to fewer fractures, decreased morbidity and mortality, and long-term cost savings.
Subject(s)
Osteoporotic Fractures/prevention & control , Secondary Prevention , Absorptiometry, Photon , Disease Management , Humans , Osteoporosis/diagnosis , Osteoporosis/etiology , Osteoporotic Fractures/epidemiology , Patient Care Team , Recurrence , Risk AssessmentABSTRACT
Current guidelines recommend primary osteoporosis screening for at-risk men to reduce the morbidity, mortality, and cost associated with osteoporotic fractures. However, analyses in a national Veterans Health Administration cohort of over 4,000,000 men demonstrated that primary osteoporosis screening as it is currently operationalized does not benefit most older Veterans due to inefficient targeting and low subsequent treatment and adherence rates. The overall objective of this study is to determine whether a new model of primary osteoporosis screening reduces fracture risk compared to usual care. We are conducting a pragmatic group randomized trial of 38 primary care teams assigned to usual care or a Bone Health Service (BHS) screening model in which screening and adherence activities are managed by a centralized expert team. The study will: 1) compare the impact of the BHS model on patient-level outcomes strongly associated with fracture rates (eligible proportion screened, proportion meeting treatment criteria who receive osteoporosis medications, medication adherence, and femoral neck bone mineral density); 2) quantify the impact on provider and facility-level outcomes including change in DXA volume, change in metabolic bone disease clinic volume, and PACT provider time and satisfaction; and 3) estimate the impact on health system and policy outcomes using Markov models of screening program cost per quality adjusted life year based from health system and societal perspectives.
Subject(s)
Osteoporosis , Osteoporotic Fractures , Bone Density , Humans , Male , Mass Screening/methods , Morpholines , Osteoporosis/diagnostic imaging , Osteoporosis/epidemiology , Osteoporotic Fractures/epidemiology , Osteoporotic Fractures/prevention & control , Quality-Adjusted Life Years , Randomized Controlled Trials as TopicABSTRACT
INTRODUCTION: Long pulse width stimulation (LPWS; 120-150 ms) has the potential to stimulate denervated muscles and to restore muscle size in denervated people with spinal cord injury (SCI). We will determine if testosterone treatment (TT)+LPWS would increase skeletal muscle size, leg lean mass and improve overall metabolic health in persons with SCI with denervation. We hypothesise that the 1-year TT+LPWS will upregulate protein synthesis pathways, downregulate protein degradation pathways and increase overall mitochondrial health. METHODS AND ANALYSIS: Twenty-four male participants (aged 18-70 years with chronic SCI) with denervation of both knee extensor muscles and tolerance to the LPWS paradigm will be randomised into either TT+neuromuscular electrical stimulation via telehealth or TT+LPWS. The training sessions will be twice weekly for 1 year. Measurements will be conducted 1 week prior training (baseline; week 0), 6 months following training (postintervention 1) and 1 week after the end of 1 year of training (postintervention 2). Measurements will include body composition assessment using anthropometry, dual X-ray absorptiometry and MRI to measure size of different muscle groups. Metabolic profile will include measuring of basal metabolic rate, followed by blood drawn to measure fasting biomarkers similar to hemoglobin A1c, lipid panels, C reactive protein, interleukin-6 and free fatty acids and then intravenous glucose tolerance test to test for insulin sensitivity and glucose effectiveness. Finally, muscle biopsy will be captured to measure protein expression and intracellular signalling; and mitochondrial electron transport chain function. The participants will fill out 3 days dietary record to monitor their energy intake on a weekly basis. ETHICS AND DISSEMINATION: The study was approved by Institutional Review Board of the McGuire Research Institute (ID # 02189). Dissemination plans will include the Veteran Health Administration and its practitioners, the national SCI/D services office, the general healthcare community and the veteran population, as well as the entire SCI community via submitting quarterly letters or peer-review articles. TRIAL REGISTRATION NUMBER: NCT03345576.
Subject(s)
Spinal Cord Injuries , Testosterone , Biomarkers , C-Reactive Protein/metabolism , Fatty Acids, Nonesterified , Glucose/metabolism , Glycated Hemoglobin/metabolism , Humans , Interleukin-6/metabolism , Male , Muscle, Skeletal , Randomized Controlled Trials as Topic , Spinal Cord Injuries/therapyABSTRACT
Not all fractures heal well. One method that has been used to improve fracture healing is low-intensity pulsed ultrasound (LIPUS). LIPUS has been US Food and Drug Administration approved for several years, and some preclinical and clinical evidence indicates that fracture healing can be improved by this technique, which appears to be generally safe. There are several suggested mechanisms of action of LIPUS. Clinical studies generally support its usefulness in accelerating fracture healing. A less-established modality is whole body vibration (WBV), which appears to stimulate bone and muscle growth while suppressing adipogenesis in animal studies. Early studies in humans, including some in children with disabilities, suggest that WBV holds promise as a technique for reducing fracture risk. The exact place of WBV in preventing fracture remains to be established.
Subject(s)
Bone Regeneration/radiation effects , Fracture Healing/radiation effects , Fractures, Bone/therapy , Ultrasonic Therapy/methods , Vibration/therapeutic use , Adolescent , Animals , Bone Density/radiation effects , Bone and Bones , Child , Disabled Children , Disease Models, Animal , Female , Fractures, Bone/prevention & control , HumansABSTRACT
Osteoporosis in men is finally receiving some attention; it has been realized that men are more likely to die after hip fracture. Methods for screening men for osteoporosis include dual energy x-ray absorptiometry and use of fracture risk calculators such as FRAX (World Health Organization) and the Garvan nomogram. Evaluation of men will often identify secondary causes of osteoporosis as well as multiple risk factors. Alendronate, risedronate, zoledronic acid, and teriparatide are US Food and Drug Administration (FDA)--approved therapy for men. Men on androgen deprivation therapy (ADT) are at high risk for bone loss and fracture, and all the bisphosphonates have been shown to increase bone density. The new antiresorptive drug, denosumab, although FDA-approved only for postmenopausal women, has been shown in a study of men on ADT to increase bone density in spine, hip, and forearm and decrease vertebral fractures on x-ray. Thus, there is great progress in osteoporosis in men, and recognition of its importance is increasing.
Subject(s)
Bone Density Conservation Agents/therapeutic use , Bone Density/drug effects , Osteoporosis , Androgen Antagonists/adverse effects , Antibodies, Monoclonal/pharmacology , Antibodies, Monoclonal, Humanized , Denosumab , Diphosphonates/therapeutic use , Fractures, Bone/epidemiology , Fractures, Bone/etiology , Humans , Male , Osteoporosis/complications , Osteoporosis/diagnosis , Osteoporosis/prevention & control , RANK Ligand/pharmacology , Randomized Controlled Trials as TopicABSTRACT
Tools to predict fracture risk are useful for selecting patients for pharmacological therapy in order to reduce fracture risk and redirect limited healthcare resources to those who are most likely to benefit. FRAX® is a World Health Organization fracture risk assessment algorithm for estimating the 10-year probability of hip fracture and major osteoporotic fracture. Effective application of FRAX® in clinical practice requires a thorough understanding of its limitations as well as its utility. For some patients, FRAX® may underestimate or overestimate fracture risk. In order to address some of the common issues encountered with the use of FRAX® for individual patients, the International Society for Clinical Densitometry (ISCD) and International Osteoporosis Foundation (IOF) assigned task forces to review the medical evidence and make recommendations for optimal use of FRAX® in clinical practice. Among the issues addressed were the use of bone mineral density (BMD) measurements at skeletal sites other than the femoral neck, the use of technologies other than dual-energy X-ray absorptiometry, the use of FRAX® without BMD input, the use of FRAX® to monitor treatment, and the addition of the rate of bone loss as a clinical risk factor for FRAX®. The evidence and recommendations were presented to a panel of experts at the Joint ISCD-IOF FRAX® Position Development Conference, resulting in the development of Joint ISCD-IOF Official Positions addressing FRAX®-related issues.