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1.
Clin Ther ; 45(5): 468-477, 2023 05.
Article in English | MEDLINE | ID: mdl-37045708

ABSTRACT

PURPOSE: Low-dose naltrexone (LDN) is commonly used to control pain and other symptoms, especially in patients with autoimmune diseases, but with limited evidence. This study tests the efficacy of LDN in reducing chronic pain in patients with osteoarthritis (OA) and inflammatory arthritis (IA), where existing approaches often fail to adequately control pain. METHODS: In this randomized, double-blind, placebo-controlled, crossover clinical trial, each patient received 4.5 mg LDN for 8 weeks and placebo for 8 weeks. Outcome measures were patient reported, using validated questionnaires. The primary outcome was differences in pain interference during the LDN and placebo periods, using the Brief Pain Inventory (scale, 0-70). Secondary outcomes included changes in mean pain severity, fatigue, depression, and multiple domains of health-related quality of life. The painDETECT questionnaire classified pain as nociceptive, neuropathic, or mixed. Data were analyzed using mixed-effects models. FINDINGS: Seventeen patients with OA and 6 with IA completed the pilot study. Most patients described their pain as nociceptive (n = 9) or mixed (n = 8) rather than neuropathic (n = 3). There was no difference in change in pain interference after treatment with LDN (mean [SD], -23 [19.4]) versus placebo (mean [SD], -22 [19.2]; P = 0.90). No significant differences were seen in pain severity, fatigue, depression, or health-related quality of life. IMPLICATIONS: In this small pilot study, findings do not support LDN being efficacious in reducing nociceptive pain due to arthritis. Too few patients were enrolled to rule out modest benefit or to assess inflammatory or neuropathic pain. CLINICALTRIALS: gov identifier: NCT03008590.


Subject(s)
Arthritis , Chronic Pain , Peripheral Nervous System Diseases , Humans , Naltrexone/therapeutic use , Chronic Pain/diagnosis , Chronic Pain/drug therapy , Chronic Pain/etiology , Pilot Projects , Quality of Life , Arthritis/drug therapy , Fatigue/drug therapy , Double-Blind Method , Treatment Outcome
2.
Ann Am Thorac Soc ; 19(10): 1669-1676, 2022 10.
Article in English | MEDLINE | ID: mdl-35536690

ABSTRACT

Rationale: Differences in body composition may contribute to variability in exercise capacity (EC) and physical activity (PA) in individuals with chronic obstructive pulmonary disease (COPD). Most studies have used bioimpedance-based surrogates of muscle (lean) mass; relatively few studies have included consideration of fat mass, and limited studies have been performed using dual X-ray absorptiometry (DXA) to assess body composition. Objectives: To determine whether DXA-assessed muscle (lean) and fat mass exhibit differential correlations with EC and PA in subjects with COPD. Methods: U.S. veterans with COPD (defined as forced expiratory volume in 1 second/forced vital capacity < 0.7 or emphysema on clinical chest computed tomography) had DXA-assessed body composition, EC (6-minute-walk distance), objective PA (average daily step counts), and self-reported PA measured at enrollment. Associations among EC, PA, and body composition were examined using Spearman correlations and multivariable models adjusted a priori for age, sex, race, and lung function. Results: Subjects (n = 98) were predominantly White (90%), obese (mean body mass index, 30.2 ± 6.2 kg/m2), and male (96%), with a mean age of 69.8 ± 7.9 years and moderate airflow obstruction (mean forced expiratory volume in 1 second percentage predicted, 68 ± 20%). Modest inverse correlations of EC and PA with fat mass were observed (Spearman's rho range, -0.20 to -0.34), whereas measures of muscle (lean) mass were not significantly associated with EC or PA. The ratio of appendicular skeletal muscle mass (ASM) to weight, which considers both muscle (lean) and fat mass, was consistently associated with EC (8.4 [95% confidence interval, 2.9-13.8] meter increase in 6-minute walk distance per 1% increase in ASM-to-weight ratio), objective PA (194.8 [95% confidence interval, 15.2-374.4] steps per day per 1% increase in ASM-to-weight ratio), and self-reported PA in multivariable-adjusted models. Conclusions: DXA-assessed body composition measures that include consideration of both lean and fat mass are associated with cross-sectional EC and PA in COPD populations. Clinical trial registered with www.clinicaltrials.gov (NCT02099799).


Subject(s)
Pulmonary Disease, Chronic Obstructive , Veterans , Aged , Body Composition , Cross-Sectional Studies , Exercise , Exercise Tolerance , Female , Humans , Male , Middle Aged
3.
Sci Rep ; 12(1): 1946, 2022 02 04.
Article in English | MEDLINE | ID: mdl-35121763

ABSTRACT

We examined the performance of a commercially-available handheld bioimpedance (BIA) device relative to dual X-ray absorptiometry (DXA) to assess body composition differences among Veterans with chronic obstructive pulmonary disease (COPD). Body composition was measured using DXA and BIA (Omron HBF-306C) at a single time point. Correlations between BIA- and DXA-assessed percent fat, fat mass, and fat-free mass were analyzed using Spearman (ρ) and Lin Concordance Correlation Coefficients (ρc). Mean differences in fat mass were visualized using Bland-Altman plots. Subgroup analyses by obesity status (BMI < 30 versus ≥ 30) were performed. Among 50 participants (96% male; mean age: 69.5 ± 6.0 years), BIA-assessed fat mass was strongly correlated (ρ = 0.94) and demonstrate excellent concordance (ρc = 0.95, [95%CI: 0.93-0.98]) with DXA, with a mean difference of 2.7 ± 3.2 kg between BIA and DXA. Although Spearman correlations between BIA- and DXA-assessed percent fat and fat-free mass were strong (ρ = 0.8 and 0.91, respectively), concordance values were only moderate (ρc = 0.67 and 0.74, respectively). Significantly stronger correlations were observed for obese relative to non-obese subjects for total percent fat (ρobese = 0.85 versus ρnon-obese = 0.5) and fat mass (ρobese = 0.96 versus ρnon-obese = 0.84). A handheld BIA device demonstrated high concordance with DXA for fat mass and moderate concordance for total percent fat and fat-free mass.ClinicalTrials.gov: NCT02099799.


Subject(s)
Absorptiometry, Photon , Adiposity , Point-of-Care Testing , Pulmonary Disease, Chronic Obstructive/diagnostic imaging , Aged , Boston , Clinical Trials as Topic , Cross-Sectional Studies , Electric Impedance , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Pulmonary Disease, Chronic Obstructive/physiopathology , Reproducibility of Results , Veterans
5.
Spinal Cord ; 58(4): 513, 2020 Apr.
Article in English | MEDLINE | ID: mdl-32055043

ABSTRACT

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

6.
Spinal Cord ; 58(4): 504-512, 2020 Apr.
Article in English | MEDLINE | ID: mdl-31949283

ABSTRACT

STUDY DESIGN: Observational study. OBJECTIVE: Assess associations between vitamin D levels and other risk factors on future chest illness in a chronic spinal cord injury (SCI) cohort. SETTING: Veterans Affairs Boston and the Boston, MA community. METHODS: Between August 2009 and August 2017, 253 participants with chronic SCI were followed over a median of 3.2 years (up to 7.4 years) with two to four visits a median of 1.7 years apart. At each visit, plasma 25-hydroxyvitamin D level was obtained, spirometry performed, and a respiratory questionnaire assessing chest illnesses since last visit was completed. Repeated measures negative binomial regression was used to assess chest illness risk longitudinally. RESULTS: At entry, 25% had deficient vitamin D levels (<20 nanograms/milliliter (ng/ml)), 52% were insufficient (20 to <30 ng/ml), and 23% were sufficient (≥30 ng/ml). Over 545 study visits, chest illnesses (n = 106) were reported by 60 participants. In multivariable models (including previous chest illness history), deficient vitamin D levels (compared with those with sufficient levels) were associated with future chest illness though with wide confidence limits (relative risk (RR) = 1.36, 95% confidence intervals (CI) = 0.74, 2.47). The strongest association with chest illness during the follow-up period was in persons who reported pneumonia/bronchitis after injury and a chest illness in the three years before study entry (RR = 7.62; 95% CI = 3.70, 15.71). CONCLUSION: Assessed prospectively in chronic SCI, there was a suggestive association between deficient vitamin D levels and future chest illness. Past chest illness history was also strongly associated with future chest illness.


Subject(s)
Lung Diseases/etiology , Spinal Cord Injuries/blood , Spinal Cord Injuries/complications , Vitamin D/analogs & derivatives , Adult , Aged , Chronic Disease , Female , Humans , Longitudinal Studies , Lung Diseases/diagnosis , Male , Middle Aged , Prognosis , Risk Factors , United States , United States Department of Veterans Affairs , Vitamin D/blood
7.
J Spinal Cord Med ; 42(2): 171-177, 2019 03.
Article in English | MEDLINE | ID: mdl-29424660

ABSTRACT

CONTEXT/OBJECTIVE: Individuals with chronic spinal cord injury (SCI) have an increased risk of morbidity and mortality attributable to respiratory diseases. Previous studies in non-SCI populations suggest that vitamin D may be a determinant of respiratory health. Therefore, we sought to assess if lower vitamin D levels were associated with decreased pulmonary function in persons with chronic SCI. DESIGN: Cross-sectional study. SETTING: Veterans Affairs Medical Center. PARTICIPANTS: 312 participants (260 men and 52 women) with chronic SCI recruited from VA Boston and the community participating in an epidemiologic study to assess factors influencing respiratory health. METHODS: Participants provided a blood sample, completed a respiratory health questionnaire, and underwent spirometry. Linear regression methods were used to assess cross-sectional associations between plasma 25-hydroxyviatmin D and spirometric measures of pulmonary function. OUTCOME MEASURES: Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and FEV1/FVC. RESULTS: Adjusted and unadjusted for a number of confounders, there was no significant association between plasma vitamin D levels and FEV1, FVC, or FEV1/FVC. For example, in fully adjusted models, each 10 ng/ml increase in vitamin D was associated with a 4.4 ml (95%CI -64.4, 73.2, P = 0.90) ml change in FEV1. Conclusion: There was no significant cross-sectional association between plasma vitamin D and FEV1, FVC, or FEV1/FVC in this cohort of individuals with chronic SCI.


Subject(s)
Calcifediol/blood , Forced Expiratory Volume/physiology , Spinal Cord Injuries/blood , Spinal Cord Injuries/physiopathology , Vital Capacity/physiology , Adult , Aged , Chronic Disease , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Spirometry , United States , United States Department of Veterans Affairs
8.
Spinal Cord ; 57(2): 117-127, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30089890

ABSTRACT

STUDY DESIGN: Cross-sectional study. OBJECTIVES: Determine dietary, lifestyle, and clinical factors associated with plasma 25-hydroxyvitamin D [25(OH)D] levels in persons with chronic spinal cord injury (SCI). SETTING: Veterans Affairs Medical Center in Boston, MA. METHODS: 174 participants completed food frequency and health questionnaires, provided a blood sample, and underwent dual x-ray absorptiometry (DXA) to assess %total body fat. Linear regression models were used to assess cross-sectional associations of personal, lifestyle, and nutritional factors with plasma 25(OH)D. RESULTS: Independent factors positively associated with higher plasma 25(OH)D included vitamin D intake, age, hours of planned exercise, female sex, white race, wine consumption, and if a never or former smoker. The most important predictor of 25(OH)D was supplement intake. The majority of subjects (98.9% for vitamin D and 74.1% for calcium) did not meet the recommended daily allowance for adults from their diet alone. Level and completeness of SCI, injury duration, mobility, %total body fat, time outside, and comorbid diseases were not associated with plasma 25(OH)D. CONCLUSIONS: Plasma 25(OH)D level in chronic SCI is not associated with clinical factors specific to SCI such as injury level and completeness, injury duration, and mobility mode, but related to supplement intake and other lifestyle factors.


Subject(s)
Diet , Life Style , Nutritional Status/physiology , Spinal Cord Injuries/blood , Spinal Cord Injuries/psychology , Vitamin D/analogs & derivatives , Absorptiometry, Photon , Adult , Aged , Body Composition , Female , Humans , Linear Models , Longitudinal Studies , Male , Middle Aged , Multivariate Analysis , Neurologic Examination , Retrospective Studies , Surveys and Questionnaires , United States , United States Department of Veterans Affairs , Vitamin D/blood
9.
PM R ; 10(3): 276-285, 2018 03.
Article in English | MEDLINE | ID: mdl-28827209

ABSTRACT

BACKGROUND: Adipose tissue produces leptin, which is pro-inflammatory, and adiponectin, which has anti-inflammatory properties. Participants with chronic spinal cord injury (SCI) have increased body fat and are at increased risk for respiratory illness. OBJECTIVE: To assess the associations between leptin and adiponectin with pulmonary function in a chronic SCI cohort. DESIGN: Cross-sectional study. SETTING: Veterans Affairs Medical Center. PARTICIPANTS: A total of 285 participants (237 men and 48 women) with chronic SCI with mean (standard deviation) injury duration 17.8 (13.2) years from the VA Boston and the community participating in an epidemiologic study assessing factors associated with respiratory health. METHODS: Participants (24.6% cervical American Spinal Injury Association Impairment Scale (AIS) level A, B, and C; 33.6% other AIS A, B, and C; 41.8% AIS D) provided a blood sample, completed a respiratory health questionnaire, and underwent spirometry. Linear regression methods were used to assess cross-sectional associations between plasma leptin and adiponectin with spirometric measures of pulmonary function adjusted for age, race, gender, and height. Level and severity of SCI, mobility mode, body mass index, smoking, chronic obstructive pulmonary disease, asthma, chest injury history, laboratory batch, and other potential confounders were also considered. MAIN OUTCOME MEASUREMENTS: forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and FEV1/FVC. RESULTS: There was a statistically significant inverse relationship between plasma leptin assessed in quartiles or as a continuous covariate with FEV1 and FVC. In fully adjusted models, each interquartile range (16,214 pg/mL) increase in leptin was associated with a significant decrease in FEV1 (-93.1 mL; 95% confidence interval = -166.2, -20.0) and decrease in FVC (-130.7 mL; 95% confidence interval = -219.4, -42.0). There were no significant associations between leptin and FEV1/FVC or between plasma adiponectin with FEV1, FVC, or FEV1/FVC. CONCLUSION: Plasma leptin in individuals with chronic SCI is inversely associated with FEV1 and FVC, independently of SCI level and severity and other covariates. This finding suggests that plasma leptin may contribute to reduced pulmonary function in chronic SCI. LEVEL OF EVIDENCE: II.


Subject(s)
Forced Expiratory Volume/physiology , Leptin/blood , Lung/physiopathology , Spinal Cord Injuries/blood , Vital Capacity/physiology , Biomarkers/blood , Chronic Disease , Cross-Sectional Studies , Female , Follow-Up Studies , Humans , Male , Middle Aged , Respiration , Retrospective Studies , Spinal Cord Injuries/physiopathology , Spirometry
10.
J Spinal Cord Med ; 41(6): 667-675, 2018 11.
Article in English | MEDLINE | ID: mdl-28992807

ABSTRACT

Context/Objective Persons with chronic spinal cord injury (SCI) have an increased risk of respiratory-related morbidity and mortality and chronic respiratory symptoms are clinical markers of future respiratory disease. Therefore, we sought to assess potentially modifiable factors associated with respiratory symptoms, with a focus on circulating vitamin D and measures of body fat. Design Cross-sectional study. Setting Veterans Affairs Medical Center. Participants Three hundred forty-three participants (282 men and 61 women) with chronic SCI participating in an epidemiologic study to assess factors influencing respiratory health recruited from VA Boston and the community. Methods Participants provided a blood sample, completed a respiratory health questionnaire, and underwent dual x-ray absorptiometry (DXA) to assess % body fat. Logistic regression was used to assess cross-sectional associations between respiratory symptoms and plasma vitamin D and measures of body fat with adjustment for a number of potential confounders. Outcome Measures Chronic cough, chronic phlegm, any wheeze, persistent wheeze. Results After adjustment for a number of confounders (including smoking), participants with greater %-android, gynoid, trunk, or total body fat had increased odds ratios for any wheeze and suggestive associations with persistent wheeze, but not with chronic cough or phlegm. Vitamin D levels were not associated with any of the respiratory symptoms. Conclusion Increased body fat, but not vitamin D, was associated with wheeze in chronic SCI independent of a number of covariates.


Subject(s)
Adiposity , Respiration , Spinal Cord Injuries/physiopathology , Vitamin D/blood , Adult , Aged , Female , Humans , Male , Middle Aged , Spinal Cord Injuries/blood
11.
Curr Opin Endocrinol Diabetes Obes ; 24(6): 395-401, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28857845

ABSTRACT

PURPOSE OF REVIEW: It is well-recognized that individuals with epilepsy have an increased risk of vertebral and nonvertebral fractures; this increased risk has been described to be secondary to an increased bone fragility and to an increased risk of falls. Osteoporosis is the most common bone disease which has been characterized by microarchitectural deterioration of trabecula and cortical bone mass with a decrease in bone mineral density and bone strength. Specific side effects of antiepileptic drugs (AEDs) on bone metabolism have been identified; recent research publications further characterized some of the specific side effects of AEDs on bone metabolism. It is the purpose of this review to describe recent advances on the knowledge of the effects of AEDs on bone metabolism and the cause of osteoporosis in the field of epilepsy. RECENT FINDINGS: Recent literature demonstrates that the increased risk of fractures in the epileptic patient population is likely multifactorial and includes seizure activity, injuries from falls, decreased bone strength, adverse effects from AEDs. Reviewed publications suggest that the mechanism of adverse effects on bone metabolism may differ among different AEDs. The impact of vitamin D deficiency or its metabolism in the epileptic population has also been a concern of several reviewed publications. SUMMARY: This is a review is of the recent epilepsy and osteoporosis literature published over the past 18 months, highlighting reports and studies concerning the cause, pathogenesis, and possible preventive measures and effects of AEDs on changes of bone metabolism, bone loss, and development of osteoporosis. In addition, we also reviewed articles focusing on issues of prevention and treatment of osteoporosis in individuals with epilepsy. We utilized the search engines of PubMed and Cochrane Reviews from January 2016 to June 2017.


Subject(s)
Anticonvulsants/therapeutic use , Epilepsy/drug therapy , Osteoporosis/chemically induced , Animals , Anticonvulsants/adverse effects , Bone Density/drug effects , Bone Density/genetics , Bone and Bones/drug effects , Bone and Bones/metabolism , Epilepsy/epidemiology , Epilepsy/genetics , Fractures, Bone/chemically induced , Fractures, Bone/epidemiology , Fractures, Bone/genetics , Humans , Osteoporosis/epidemiology , Osteoporosis/genetics , Risk Factors , Vitamin D Deficiency/chemically induced , Vitamin D Deficiency/epidemiology , Vitamin D Deficiency/genetics
12.
J Clin Densitom ; 17(1): 32-7, 2014.
Article in English | MEDLINE | ID: mdl-23489972

ABSTRACT

The osteoporosis self-assessment tool (OST) is a screening instrument that uses age and weight as parameters to predict the risk of osteoporosis. This study was designed to evaluate OST in predicting osteoporosis in males. Male veterans aged 50yr and older with no prior diagnosis of osteoporosis and no prior bone densitometry (dual-energy X-ray absorptiometry [DXA]) testing were eligible for the study. Sociodemographic information, medical history, and risk factors for osteoporosis were recorded. Anthropometric measurements were taken and DXA testing performed. The OST index for each subject was calculated and predictive values and receiver operating characteristic (ROC) curves were evaluated for OST and osteoporosis. Five hundred eighteen subjects underwent DXA, 92 (17.8%) had osteoporosis, 281 (54.2%) had low bone mass, and 145 (28.0%) had normal bone mineral density. The OST index ranged from -8 to 23 with a mean of 4 (standard deviation ± 4.3). An OST index of 6 or lower predicted osteoporosis with a sensitivity of 82.6%, specificity of 33.6%, and an area under the curve for the ROC curve of 0.67. OST index performed better in non-Hispanic whites and males >65 yr. OST predicts osteoporosis with moderate sensitivity and poor specificity in men.


Subject(s)
Osteoporosis/diagnosis , Self-Assessment , Veterans , Absorptiometry, Photon , Aged , Bone Density , Cohort Studies , Humans , Male , Middle Aged , Predictive Value of Tests , ROC Curve , Risk Assessment , Risk Factors , United States
13.
J Bone Miner Res ; 29(1): 251-9, 2014 Jan.
Article in English | MEDLINE | ID: mdl-23787489

ABSTRACT

Adipose tissue is a major regulator of bone metabolism and in the general population obesity is associated with greater bone mineral density (BMD). However, bone-fat interactions are multifactorial, and may involve pathways that influence both bone formation and resorption with competing effects on the skeleton. One such pathway involves adipocyte production of adipokines that regulate bone metabolism. In this study we determined the association between BMD, walking status, and circulating adipokines (adiponectin and leptin) in 149 men with chronic spinal cord injury (SCI). Although adipokine levels did not vary significantly based on walking status, there was a significant inverse association between adiponectin and BMD in wheelchair users independent of body composition. We found no association between adiponectin and BMD in the walkers and no association between leptin and BMD in either group. These findings suggest that for subjects with chronic SCI, walking may mitigate the effect of adiponectin mediated bone loss. For wheelchair users, adipose-derived adiponectin may contribute to SCI-induced osteoporosis because the osteoprotective benefits of obesity appear to require mechanical loading during ambulation.


Subject(s)
Adiponectin/blood , Biomarkers/blood , Spinal Cord Injuries/physiopathology , Absorptiometry, Photon , Adult , Bone Density/physiology , Bones of Lower Extremity/metabolism , Humans , Leptin/blood , Male , Middle Aged , Osteoporosis/etiology , Osteoporotic Fractures/etiology , Spinal Cord Injuries/complications , Walking/physiology , Wheelchairs
14.
Epilepsia ; 54(11): 1997-2004, 2013 Nov.
Article in English | MEDLINE | ID: mdl-24010637

ABSTRACT

PURPOSE: To evaluate whether use of a bisphosphonate (risedronate) in addition to calcium and vitamin D in male veterans with epilepsy who were taking antiepileptic drugs (AEDs) long term can prevent the loss of bone mass (BMD, bone mineral density) associated with AED use compared to patients who were treated with a placebo plus calcium and vitamin D. As a secondary end point we studied the incidence of new morphometric vertebral and nonvertebral fractures. METHODS: Antiepileptic drug and osteoporosis prevention trial (ADOPT) was designed as a prospective 2-year double-blind, randomized placebo controlled study involving 80 male veterans with epilepsy who were being treated with AEDs such as phenytoin, phenobarbital, sodium valproate, or carbamazepine for a minimum of 2 years. All enrolled participants received calcium and vitamin D supplementation, and were randomized to risedronate or matching placebo. Total body, bilateral proximal femora, and anteroposterior (AP) lumbar spine BMDs in addition to morphometric lateral vertebral assessments (LVAs) were evaluated by a dual energy x-ray absorptiometry (DXA) instrument. Comparisons of BMDs were made between baseline, 1 year, and after 2 years of enrollment in the study. The incidence of new vertebral and nonvertebral fractures was secondary end point. KEY FINDINGS: Of the 80 patients initially enrolled in the study, 53 patients completed the study. Baseline characteristics of the two groups were similar. At the end of the study, in the placebo plus calcium and vitamin D group, we observed a significant improvement in BMD at any of the evaluated sites when compared to their baseline scans in 69% (18/26) of the participants. In the risedronate plus calcium and vitamin D group, we observed significant improvement of BMDs in 70% (19/27) of the participants. At the end of the study, the risedronate group experienced a significant increase of BMD at the lumbar spine L1-4 (1.267-1.332 g/cm(2)), which was significantly larger than that seen in the placebo group) (1.229 g/cm(2) vs. 1.245 g/cm(2) ; p = 0.0066).There were nonsignificant differences between the two groups regarding changes of total body BMD or at the proximal bilateral femora. Five new vertebral fractures and one nonvertebral fracture were observed only in the placebo group. SIGNIFICANCE: Calcium and vitamin D supplementation or calcium and vitamin D supplementation in addition to risedronate improved BMD in more than 69% of male veterans with epilepsy who were taking AEDs. In the group receiving risedronate plus calcium and vitamin D there was a significant improvement of BMD at the lumbar spine as compared to the placebo group, which also received calcium and vitamin D. The use of risedronate plus calcium and vitamin D prevented the incidence of new vertebral fractures and one nonvertebral fracture in this cohort.


Subject(s)
Anticonvulsants/adverse effects , Bone Density Conservation Agents/therapeutic use , Bone Density/drug effects , Diphosphonates/therapeutic use , Osteoporosis/prevention & control , Osteoporotic Fractures/prevention & control , Spinal Fractures/prevention & control , Adult , Aged , Aged, 80 and over , Anticonvulsants/therapeutic use , Calcium, Dietary/pharmacology , Chronic Disease , Double-Blind Method , Epilepsy/drug therapy , Humans , Male , Middle Aged , Osteoporosis/chemically induced , Prospective Studies , Treatment Outcome , Vitamin D/pharmacology
16.
Curr Osteoporos Rep ; 10(4): 278-85, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22983921

ABSTRACT

Spinal cord injury causes rapid, severe osteoporosis with increased fracture risk. Mechanical unloading after paralysis results in increased osteocyte expression of sclerostin, suppressed bone formation, and indirect stimulation of bone resorption. At this time, there are no clinical guidelines to prevent bone loss after SCI, and fractures are common. More research is required to define the pathophysiology and epidemiology of SCI-induced osteoporosis. This review summarizes emerging therapeutics including anti-sclerostin antibodies, mechanical loading of the lower extremity with electrical stimulation, and mechanical stimulation via vibration therapy.


Subject(s)
Osteoporosis/etiology , Osteoporotic Fractures/etiology , Spinal Cord Injuries/complications , Adaptor Proteins, Signal Transducing , Bone Density , Bone Density Conservation Agents/therapeutic use , Bone Morphogenetic Proteins/metabolism , Electric Stimulation Therapy , Exercise Therapy , Genetic Markers , Humans , Osteoporosis/epidemiology , Osteoporosis/physiopathology , Osteoporosis/prevention & control , Osteoporotic Fractures/epidemiology , Osteoporotic Fractures/physiopathology , Osteoporotic Fractures/prevention & control , Parathyroid Hormone/metabolism , Risk Factors , Spinal Cord Injuries/physiopathology , Vibration , Vitamin D Deficiency/etiology
17.
Bone ; 51(3): 600-5, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22575440

ABSTRACT

Spinal cord injury (SCI) causes profound bone loss due to muscle paralysis resulting in the inability to walk. Sclerostin, a Wnt signaling pathway antagonist produced by osteocytes, is a potent inhibitor of bone formation. Short-term studies in rodent models have demonstrated increased sclerostin in response to mechanical unloading that is reversed with reloading. Although sclerostin inhibition has been proposed as a potential therapy for bone loss, it is not known if sclerostin levels vary with duration of SCI in humans. We analyzed circulating sclerostin in 155 men with varying degrees of SCI who were 1 year or more post-injury. We report that sclerostin levels are greatest in subjects with short-term SCI (≤5 years post-injury) and decrease significantly over the first 5 years post-injury. There was no association between sclerostin and injury duration in subjects with long-term SCI (>5 years post-injury). In subjects with long-term SCI, sclerostin levels were positively associated with lower extremity bone density and bone mineral content. These data suggest that sclerostin levels are initially increased after SCI in response to mechanical unloading. This response is time-limited and as bone loss progresses, circulating sclerostin is lowest in subjects with severe osteoporosis. These findings support a dual role for sclerostin after SCI: a therapeutic target in acute SCI, and a biomarker of osteoporosis severity in chronic SCI.


Subject(s)
Bone Morphogenetic Proteins/blood , Spinal Cord Injuries/blood , Adaptor Proteins, Signal Transducing , Adult , Aged , Aged, 80 and over , Aging/blood , Aging/pathology , Bone Density , Bone and Bones/pathology , Bone and Bones/physiopathology , Female , Genetic Markers , Humans , Male , Middle Aged , Osteoporosis/blood , Osteoporosis/diagnosis , Osteoporosis/physiopathology , Spinal Cord Injuries/pathology , Spinal Cord Injuries/physiopathology , Time Factors , Vitamin D/blood
18.
PM R ; 1(3): 240-4, 2009 Mar.
Article in English | MEDLINE | ID: mdl-19627901

ABSTRACT

OBJECTIVE: Although osteoporosis is common following spinal cord injury (SCI), no guidelines exist for its treatment, diagnosis, or prevention. The authors hypothesized that wide variations in diagnosis and treatment practices result from the absence of guidelines. This study sought to characterize the diagnosis and management practices within the VA health care system for osteoporosis following SCI. DESIGN: Online survey regarding osteoporosis management in SCI composed of 27 questions designed to gather information on responder demographics, osteoporosis diagnostics, and treatment options. SETTING: VA health care system. PARTICIPANTS: VHA National SCI Staff Physicians and VHA National SCI Nurses (total n = 450) were sent an email with an invitation to participate. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Practice patterns were assessed, including factors associated with ordering a clinical workup and prescribing osteoporosis treatment. RESULTS: The response rate was 28%. Ninety-two prescribing practitioners (physicians, nurse practitioners, and physician assistants) were included in the analysis. Of these respondents, 50 (54%) prescribe medications for SCI-induced bone loss; 39 (42%) prescribe bisphosphonates and 46 (50%) prescribe vitamin D. There were 54 (59%) respondents who routinely order diagnostic tests, including dual energy x-ray absorptiometry scans in 50 (54%). Variations in practice were not explained by age, gender, or years practicing SCI medicine. Many respondents (23%) reported barriers to osteoporosis testing including lack of scanning protocols, cost, wheelchair inaccessibility of scanning facilities, and lack of effective treatment guidelines once osteoporosis is diagnosed. CONCLUSIONS: Despite an absence of screening and treatment guidelines, more than half of all respondents are actively diagnosing and treating osteoporosis with bisphosphonates within the VA health care setting. These data suggest that evidence-based practice guidelines are necessary to reduce practice variations and improve clinical care for this population.


Subject(s)
Absorptiometry, Photon/statistics & numerical data , Bone Density Conservation Agents/therapeutic use , Hospitals, Veterans , Osteoporosis/diagnosis , Osteoporosis/prevention & control , Practice Patterns, Physicians' , Spinal Cord Injuries/complications , Adult , Data Collection , Female , Humans , Internet , Male , Middle Aged , Nurse Practitioners , Osteoporosis/etiology , Physician Assistants , Physicians , Spinal Cord Injuries/rehabilitation
19.
Arch Phys Med Rehabil ; 90(5): 827-31, 2009 May.
Article in English | MEDLINE | ID: mdl-19406303

ABSTRACT

OBJECTIVE: To evaluate the precision of dual energy x-ray absorptiometry scanning at 2 skeletal sites at the knee (proximal femur and distal tibia) in people with SCI. DESIGN: Cross-sectional. SETTING: Veterans Affairs Medical Center. PARTICIPANTS: Subjects (N=20) with chronic SCI. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Precision as determined by root mean square coefficient of variation (RMS-CV) and root mean square standard deviation (RMS-SD). RESULTS: At the distal femur the root RMS-CV was 3.01% and the RMS-SD was 0.025g/cm2. At the proximal tibia the RMS-CV was 5.91% and the RMS-SD was 0.030g/cm2. CONCLUSIONS: Precision at the distal femur is greater than at the proximal tibia and we recommend it as the preferred site for the longitudinal assessment of bone mineral density at the knee in chronic SCI.


Subject(s)
Absorptiometry, Photon/methods , Bone Density/physiology , Femur/diagnostic imaging , Spinal Cord Injuries/diagnosis , Tibia/diagnostic imaging , Adult , Aged , Cross-Sectional Studies , Femur/pathology , Humans , Injury Severity Score , Male , Middle Aged , Osteoporosis/diagnostic imaging , Osteoporosis/etiology , Paraplegia/complications , Quadriplegia/complications , Sensitivity and Specificity , Spinal Cord Injuries/complications , Spinal Cord Injuries/rehabilitation , Tibia/pathology , Veterans
20.
Am J Phys Med Rehabil ; 88(1): 57-60, 2009 Jan.
Article in English | MEDLINE | ID: mdl-18824888

ABSTRACT

To assess barriers to bone mineral density testing in individuals with chronic spinal cord injury, a cross-sectional study of 20 individuals with spinal cord injury was conducted with assessment of physical and logistical barriers to dual energy x-ray absorptiometry scanning. We identified several barriers, including scanner design and configuration in the scanning room that limited accessibility, increased typical scanning time, and made additional staff necessary. For dual energy x-ray absorptiometry to become a routine component of ongoing care in spinal cord injury medicine, we recommend the following changes: (1) install ceiling-mounted hydraulic lifts and grab bars to facilitate transfers in the scanning room; (2) increase staffing during scans; (3) increase time allotment for scans; (4) install the scanner in an adequately-sized room; and (5) partner with administrators and staff to raise awareness of access issues faced by individuals with spinal cord injury.


Subject(s)
Absorptiometry, Photon/instrumentation , Fractures, Bone/etiology , Health Services Accessibility , Health Services Needs and Demand , Osteoporosis/diagnostic imaging , Spinal Cord Injuries/complications , Bone Density , Cross-Sectional Studies , Female , Humans , Male , Massachusetts/epidemiology , Middle Aged , Osteoporosis/complications , Osteoporosis/etiology , Osteoporosis/physiopathology , Risk Factors , Spinal Cord Injuries/physiopathology , United States/epidemiology
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