Christopher M. Cirnigliaro

Effect of pamidronate administration on bone in patients with acute spinal cord injury.

Eleven subjects participated in a prospective placebo-controlled trial to address the efficacy of pamidronate in reducing bone loss in persons with acute spinal cord injury (SCI). We administered pamidronate (treatment) or normal saline (placebo) intravenously at baseline (22 to 65 days after injury) and sequentially over 12 months, with follow-up at 18 and 24 months. Regional bone mineral density (BMD) was lost over time, regardless of group. In the treatment group compared with the placebo group, we noted a mild early reduction in loss of total leg BMD. Significant bone loss from baseline occurred earlier in the placebo group at the regional sites than in the treatment group. However, by the end of the treatment and follow-up phases, both groups demonstrated a similar percent bone loss from baseline. Despite an early reduction in bone loss, pamidronate failed to prevent major, long-term bone loss in persons with acute neurologically complete SCI.

Neuromotor and Musculoskeletal Responses to Locomotor Training for an Individual With Chronic Motor Complete AIS-B Spinal Cord Injury

Abstract Background/objective: To determine the effects of locomotor training (LT)using body weight support(BWS), treadmill, and manual assistance on muscle activation, bone mineral density (BMD), and body composition changes for an individual with motor complete spinal cord injury (AIS B), 1 year after injury. Methods: A man with chronic C6 AIS B (motor complete and sensory incomplete) spinal cord injury (SCI),1 year after injury, completed 2 blocks of LT over a 9-monthtraining period (35-session block followed by8.6 weeks of no training and then a 62-session block). Results: Before training, muscle activation was minimal for any muscle examined, whereas after the 2 blocksof LT (97 sessions), hip and knee muscle activation patterns for the bilateral rectus femoris, biceps femoris,and gastrocnemius were in phase with the kinematics. Mean EMG amplitude increased for all bilateral muscles and burst duration increased for rectus femoris and gastrocnemius muscles, whereas burst duration decreased for the biceps femoris after 62 LT sessions. Before LT, left biceps femoris had a pattern that reflected muscle stretch, whereas after training, muscle stretch of the left biceps femoris could not totally account for mean EMG amplitude or burst duration. After the62 training sessions, total BMD decreased (1.54%), and regional BMD decreased (legs: 6.72%). Total weight increased, lean mass decreased (6.6%), and fat mass increased (7.4%) in the arms, whereas fat mass decreased (3.5%) and lean mass increased (4%) in the legs. Conclusions: LT can induce positive neural and body composition changes in a nonambulatory personwith chronic SCI, indicating that neuromuscular plasticity can beinduced by repetitive locomotor trainingafter a motor complete SCI.

Comparison of 24-hour cardiovascular and autonomic function in paraplegia, tetraplegia, and control groups: implications for cardiovascular risk.

Abstract Background Fluctuations in 24-hour cardiovascular hemodynamics, specifically heart rate (HR) and blood pressure (BP), are thought to reflect autonomic nervous system (ANS) activity. Persons with spinal cord injury (SCI) represent a model of ANS dysfunction, which may affect 24-hour hemodynamics and predispose these individuals to increased cardiovascular disease risk. Objective To determine 24-hour cardiovascular and ANS function among individuals with tetraplegia (n = 20; TETRA: C4–C8), high paraplegia (n = 10; HP: T2–T5), low paraplegia (n = 9; LP: T7–T12), and non-SCI controls (n = 10). Twenty-four-hour ANS function was assessed by time domain parameters of heart rate variability (HRV); the standard deviation of the 5-minute average R–R intervals (SDANN; milliseconds/ms), and the root-mean square of the standard deviation of the R–R intervals (rMSSD; ms). Subjects wore 24-hour ambulatory monitors to record HR, HRV, and BP. Mixed analysis of variance (ANOVA) revealed significantly lower 24-hour BP in the tetraplegic group; however, BP did not differ between the HP, LP, and control groups. Mixed ANOVA suggested significantly elevated 24-hour HR in the HP and LP groups compared to the TETRA and control groups (P < 0.05); daytime HR was higher in both paraplegic groups compared to the TETRA and control groups (P < 0.01) and nighttime HR was significantly elevated in the LP group compared to the TETRA and control groups (P < 0.01). Twenty-four-hour SDANN was significantly increased in the HP group compared to the LP and TETRA groups (P < 0.05) and rMSSD was significantly lower in the LP compared to the other three groups (P < 0.05). Elevated 24-hour HR in persons with paraplegia, in concert with altered HRV dynamics, may impart significant adverse cardiovascular consequences, which are currently unappreciated.

A Small-Scale Clinical Trial to Determine the Safety and Efficacy of Testosterone Replacement Therapy in Hypogonadal Men with Spinal Cord Injury

Men with spinal cord injury are at an increased risk for secondary medical conditions, including metabolic disorders, accelerated musculoskeletal atrophy, and, for some, hypogonadism, a deficiency, which may further adversely affect metabolism and body composition. A prospective, open label, controlled drug intervention trial was performed to determine whether 12 months of testosterone replacement therapy increases lean tissue mass and resting energy expenditure in hypogonadal males with spinal cord injury. Healthy eugonadal (n = 11) and hypogonadal (n = 11) outpatients with chronic spinal cord injury were enrolled. Hypogonadal subjects received transdermal testosterone (5 or 10 mg) daily for 12 months. Measurements of body composition and resting energy expenditure were obtained at baseline and 12 months. The testosterone replacement therapy group increased lean tissue mass for total body (49.6 ± 7.6 vs. 53.1 ± 6.9 kg; p < 0.0005), trunk (24.1 ± 4.1 vs. 25.8 ± 3.8 kg; p < 0.005), leg (14.5 ± 2.7 vs. 15.8 ±2.6  kg; p = 0.005), and arm (7.6 ± 2.3 vs. 8.0 ± 2.2 kg; p < 0.005) from baseline to month 12. After testosterone replacement therapy, resting energy expenditure (1328 ± 262 vs. 1440 ± 262 kcal/d; p < 0.01) and percent predicted basal energy expenditure (73 ± 9 vs. 79 ± 10%; p < 0.05) were significantly increased. In conclusion, testosterone replacement therapy significantly improved lean tissue mass and energy expenditure in hypogonadal men with spinal cord injury, findings that would be expected to influence the practice of clinical care, if confirmed. Larger, randomized, controlled clinical trials should be performed to confirm and extend our preliminary findings.

Dual-energy X-ray absorptiometry overestimates bone mineral density of the lumbar spine in persons with spinal cord injury

Background:Bone mineral density (BMD) of the lumbar spine (L-spine) has been reported to be normal or increased in persons with chronic spinal cord injury (SCI).Objective:To determine BMD of the L-spine by dual-energy X-ray absorptiometry (DXA) and quantitative computerized tomography (qCT) in men with chronic SCI compared with able-bodied controls.Design:Cross-sectional, comparative study.Setting:Clinical research unit, Veterans Affairs Medical Center, Bronx, NY, USA and Kessler Institute of Rehabilitation, West Orange, NJ, USA.Methods:Measurements of the L-spine were made in 20 men with SCI and compared with 15 able-bodied controls. The DXA images were acquired on a GE Lunar DPX-IQ. The qCT images of the L-spine were acquired on a Picker Q series computerized tomographic scanner.Results:The mean ages for the SCI and control groups were 44±13 vs 42±9 years, and the duration of injury of the group with SCI was 14±11 years. There were no significant differences between the SCI and control groups for L-spine DXA BMD (1.391±0.210 vs 1.315±0.178 g/m2) or for L-spine DXA T-score (1.471±1.794 vs 0.782±1.481). L-spine qCT BMD was significantly lower in the SCI compared with the control group (1.296±0.416 vs 1.572±0.382 g/m2, P=0.05); the T-score approached significance (−1.838±1.366 vs −0.963±1.227, P=0.059). Subjects with moderate degenerative joint disease (DJD) had significantly higher T-scores by DXA than those without or with mild DJD.Conclusion:Individuals with SCI who have moderate to severe DJD may have bone loss of the L-spine that may be underestimated by DXA, reducing awareness of the risk of fracture.

Assessment of Measures for Abdominal Adiposity in Persons with Spinal Cord Injury

Ultrasound may be a useful tool to assess abdominal adiposity, but it has not been validated in the spinal cord injury (SCI) population. This study evaluated associations between abdominal ultrasound and other methods to assess adiposity in 24 men with SCI and 20 able-bodied (AB) men. Waist (WC) and hip circumference (HC) and waist-to-hip ratio (WHR) were measured. Trunk (TRK%), android (A%) and waist fat (W%) were determined by dual energy x-ray absorptiometry (DXA); ultrasonography determined abdominal subcutaneous (SF) and visceral fat (VF). The SCI group had greater TRK% (40.0 ± 9.6 vs. 32.0 ± 10.3), W% (47.0 ± 9.7 vs. 40.6 ± 9.4), A% (43.0 ± 9.8 vs. 35.8 ± 10.6) and WHR (0.99 ± 0.1 vs. 0.92 ± 0.06) than the AB group. WC and WHR correlated with VF in the SCI group. These associations suggest that ultrasound may be a useful tool in clinical practice for the measurement of VF in weight loss programs and for the assessment of cardiometabolic disorders.

The influence of visceral fat on the postprandial lipemic response in men with paraplegia.

Background: Postprandial lipemia (PPL) is associated with vascular dysfunction and may be an etiologic factor in the progression of atherogenic cardiovascular disease. Objective: In 10 men with paraplegia and 10 able-bodied men, the magnitude of the PPL responses and the relationship of abdominal adiposity and the PPL responses were determined. Methods: Anthropometrics, dual energy x-ray absorptiometry, and abdominal ultrasonography were performed to determine visceral fat and total body fat. A fasting lipid profile was performed. A high-fat milkshake (1.3 g fat/kg body mass) was administered with serum collected at baseline and at 2, 4, and 6 hours after the test meal for subsequent measurement of triglyceride. The triglyceride response was determined by the area under the triglyceride curve. Results: No significant differences were noted between the groups in fasting lipid values or in measures of visceral fat. Total body fat tended to be higher in men with paraplegia than in able-bodied men (34.9 ± 10.0 vs. 27.3 ± 6.7%, p  =  0.07). No significant difference between the groups was observed in triglyceride response. In men with paraplegia, visceral fat was strongly associated with the triglyceride (r  =  0.8, p  =  0.005), fasting low-density lipoprotein (r  =  0.66, p  =  0.04), and triglyceride responses (r  =  0.80, p  =  0.005); a significant relationship was not found between fasting high-density lipoprotein and any measure of adiposity. In men with paraplegia, triglyceride response was positively related to all measures of abdominal adiposity. Conclusion: Visceral abdominal fat was related to delayed triglyceride clearance after a fat load, which may contribute to coronary heart disease (CHD) risk and progression of vascular disease in men with paraplegia.

An effective oral vitamin D replacement therapy in persons with spinal cord injury

Abstract Background/objective Vitamin D deficiency is prevalent in chronic spinal cord injury (SCI). A 3-month course of oral vitamin D3 to ‘normalize’ serum vitamin D levels was investigated. Design Prospective drug-intervention study. Setting VA Medical Center; private rehabilitation facility. Methods Seven individuals with chronic SCI and vitamin D deficiency completed 3 months of oral vitamin D3 (i.e. cholecalciferol) supplementation. At screening, baseline, and months 1 and 3, blood was collected for serum calcium, 25 hydroxyvitamin D [25(OH)D], intact parathyroid hormone (iPTH), and N-telopeptide (NTx); 24-hour urine for calcium, creatinine, and NTx was performed. Oral vitamin D3 (2000 IU daily) and elemental calcium (1.3 g daily) were prescribed for 90 days. The results are expressed as mean ± standard deviation (SD). Analysis of variance with a Fishers post-hoc analysis was performed to test for differences between study visits. Subjects were classified as deficient (<20 ng/ml), relatively deficient (20–30 ng/ml), or not deficient (>30 ng/ml) in 25(OH)D. Results Serum 25(OH)D levels were greater at months 1 and 3 than at baseline (26 ± 6 and 48 ± 17 vs. 14 ± 2 ng/ml; P = 0.005). Six of seven subjects were no longer deficient [25(OH)D >30 ng/ml] by month 3. Serum iPTH levels were significantly decreased at month 1 and month 3; serum NTx levels were significantly lower at month 3 than at baseline. Serum and urinary calcium levels remained within the normal range. Conclusion A daily prescription of 2000 IU of oral vitamin D3 for 3 months safely raised serum 25(OH)D levels into the normal range in persons with chronic SCI on calcium supplementation.

Visceral adiposity in persons with chronic spinal cord injury determined by dual energy X-ray absorptiometry.

To determine visceral adipose tissue (VAT) volume (VATvol) by dual energy X‐ray absorptiometry (DXA) in spinal cord injured (SCI) and able‐bodied (AB) participants and to explore the relationships between VATvol and routine anthropometric measures.

Underestimation of bone loss of the spine with posterior-anterior dual-energy X-ray absorptiometry in patients with spinal cord injury.

Abstract Background: Bone mineral density (BMD) of the lumbar spine (L-spine) has been reported to be normal by routine posterior-anterior (PA) bone density imaging in patients with chronic spinal cord injury (SCI). Objective: To determine BMD of the L-spine by PA and lateral (LAT) dual-energy radiographic absorptiometry (DXA) in patients with chronic SCI. Design: Prospective study. Setting: Veterans Affairs Medical Center and a private rehabilitation facility. Methods: Measurements of the PA and LAT L-spine and hip were performed in 15 patients with SCI: 9 with tetraplegia and 6 with paraplegia. The DXA (GE Lunar Advance DXA) images were obtained using standard software. Results are reported as mean ± SD. Results: The mean age was 35 ± 15 years (range = 20–62 years), and the duration of injury was 57 ± 74 months (range = 3–240 months). T-and Z-scores were lower for the LAT L-spine than those for PA L-spine (T-scores L2: -0.7 ± 1.2 vs 0.0 ± 1.4, P< 0.01; L3: -0.9 ± 1.6 vs 0.3 ± 1.3, P< 0.002; L2-L3: -0.8 ± 1.3 vs 0.2 ±1.3, P< 0.001; Z-scores L2: -0.3 ± 1.1 vs 0.2 ± 1.2, P< 0.05; L3: -0.6 ± 1.3 vs 0.5 ± 1.3, P < 0.01; L2-L3: -0.4 ± 1.1 vs 0.4 ± 1.2, P < 0.005). The T-and Z-scores for the total hip (-1.1 ± 1.0 and -1.0 ± 1.0, respectively) and L2-L3 LAT L-spine demonstrated remarkable similarity, whereas the L2-L3 PA L-spine scores were not reduced. Bone mineral density of the LAT L-spine, but not the PA L-spine, was significantly reduced with increasing duration of injury. Conclusions: Individuals with SCI may have bone loss of the L-spine that is evident on LAT DXA that may be misdiagnosed by PA DXA, underestimating the potential risk of fracture.