Tomohiro Kanoko

Low-dose vitamin D prevents muscular atrophy and reduces falls and hip fractures in women after stroke: a randomized controlled trial.

OBJECTIVE Vitamin D supplementation is suggested to reduce the risk of falls among ambulatory or institutionalized elderly subjects. The present study was undertaken to address the reduced risk of falls and hip fractures in patients with long-standing stroke by vitamin D supplementation. METHODS Ninety-six elderly women with poststroke hemiplegia were followed for two years. Patients were randomly assigned to one of the two groups, and 48 patients received 1,000 IU ergocalciferol daily, and the remaining 48 received placebo. The number of falls per person and incidence of hip fractures were compared between the two groups. Strength and tissue ATPase of skeletal muscles on the nonparetic side were assessed before and after the study. RESULTS At baseline, serum 25-hydroxyvitamin D levels were in the deficient range (<10 ng/ml) in all patients; and vitamin D treatment enhanced serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels. Vitamin D treatment accounted for a 59% reduction in falls (95% CI, 28-81%; p = 0.003). There were increases in the relative number and size of type II muscle fibers and improved muscle strength in the vitamin D-treated group. Hip fractures occurred in 4 of 48 placebo group and 0 in 48 vitamin D2 group during the 2-year study period (log-rank, p = 0.049). CONCLUSION Vitamin D may increase muscle strength by improving atrophy of type II muscle fibers, which may lead to decreased falls and hip fractures.

Risedronate therapy for prevention of hip fracture after stroke in elderly women

BACKGROUND There is a high incidence of hip fractures in patients with hemiplegic stroke. Bone mineral density (BMD) is decreased in the hemiplegic side in patients after stroke, correlating with the degree of paralysis and of hypovitaminosis D. OBJECTIVE To evaluate the efficacy of risedronate in reducing the severity of osteoporosis and in decreasing the risk of hip fractures in elderly women following an acute stroke. METHODS This was a 12-month, randomized, double blind, placebo-controlled trial. In a prospective study of stroke patients, 187 patients received a daily dose of 2.5 mg risedronate for 12 months, and the remaining 187 received placebo. Incidence of hip fracture was compared between the two groups at the endpoint of the study. RESULTS Seven patients sustained hip fractures on the hemiplegic side in the placebo group, and one hip fracture occurred in the risedronate group (p = 0.0360; OR = 7.0). BMD increased by 1.5% and decreased by 4.9% in the risedronate group and placebo group (p < 0.0001). Urinary deoxypyridinoline, a bone resorption marker, decreased by 53.4% in the risedronate group and increased by 35.8% in the placebo group. CONCLUSION Treatment with risedronate increases bone mineral density in elderly women following an acute stroke and prevents hip fractures.

Amelioration of osteoporosis and hypovitaminosis D by sunlight exposure in hospitalized, elderly women with Alzheimer's disease: a randomized controlled trial

The JBMR editors express a note of concern that a substantial amount of the text of Sato et al., Amelioration of Osteoporosis and Hypovitaminosis D by Sunlight Exposure in Hospitalized Elderly Women With Alzheimers Disease: A Randomized Controlled Trial. J Bone Miner Res. 2005;20(8): 1327–1333 (DOI: 10.1359/JBMR.050402) is duplicated in Sato et al., Amelioration of osteoporosis and hypovitaminosis D by sunlight exposure in Parkinsons disease (Parkinsonism Relat Disord. 2011;17(1):22‐26 (DOI:10.1016/j.parkreldis.2010.10.008).

Risk factors for hip fracture among elderly patients with Alzheimer's disease

Incidence of hip fracture among patients with Alzheimers disease (AD), especially in elderly patients, is high. To analyze risk factors of hip fracture, we prospectively studied a cohort of elderly female patients with AD. Subjects studied were 225 female patients with AD, and the average age was 76 years old. At baseline, we recorded body mass index (BMI), a score of Mini-Mental State Examination (MMSE) and bone mineral density (BMD), and measured serum concentrations of ionized calcium, intact parathyroid hormone (PTH), pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP), intact bone Gla protein (BGP), 25-hydroxyvitamin (25-OHD) and 1, 25-dihydroxyvitamin D (1, 25-[OH]2D). The patients were followed for 2 years. During the 2-year study, hip fractures occurred in 29 patients. We compared baseline variables between the 29 patients with and 176 patients without hip fracture. AD patients with lower BMD, low concentrations of serum ionized calcium and 25-OHD (mean 3.0 ng/ml) with compensatory hyperparathyroidism were found to have an increased risk of hip fracture. Also, concentrations of serum ICTP and BGP were higher in the fracture group than in the nonfracture group. Elderly female AD patients with low BMD and serum 25-OHD concentrations <5 ng/ml with secondary hyperparathyroidism have a high risk of hip fracture, and the risk may be reduced by vitamin D supplementation.

Abnormal bone and calcium metabolism in immobilized Parkinson's disease patients

The above article, published online on 19 August 2005 in Wiley Online Library (http://wileyonlinelibrary.com) has been retracted by agreement between the authors, the Journal Editor‐in‐Chief, Jose A. Obeso, MD, PhD and John Wiley & Sons Inc. The Retraction has been agreed due to extensive duplication of work previously published by the same authors and concerns with authorship and data integrity. Reference Sato, Y. , Honda, Y. , Iwamoto, J. , Kanoko, T. and Satoh, K. (2005), Abnormal bone and calcium metabolism in immobilized Parkinsons disease patients. Mov. Disord., 20: 1598‐1603. doi:10.1002/mds.20658

Alendronate and vitamin D2 for prevention of hip fracture in Parkinson's disease: a randomized controlled trial.

The above article, published online on 14 March 2006 in Wiley Online Library (wileyonlinelibrary.com), and in Volume 21, Issue 7, Pages 924–929, has been retracted by agreement between the authors, the Editor‐in‐Chief, Jose A. Obeso, and Wiley Periodicals, Inc. The retraction has been agreed due to an acknowledgement from the authors that the co‐authors did not participate in study design, data collection, data analysis, interpretation of data and drafting the manuscript. Thus all co‐authors are honorary.

Beneficial effect of etidronate therapy in immobilized hip fracture patients.

OBJECTIVES Hip fracture is among the most common causes of acute immobilization in elderly patients leading to increased bone resorption, and elderly patients with hip fracture are at high risk for a subsequent hip fracture. DESIGN In this double-blind, randomized, prospective study, 80 female patients who were immobilized because of a hip fracture were divided into two groups. The etidronate group received oral administration of 200 mg/day etidronate for 2 wks starting 1 day after the surgery. Then, after a 9-wk intermission, etidronate administration was resumed for 2 wks. The placebo group received placebo in a similar manner. RESULTS At baseline, both groups had high serum concentrations of ionized calcium, high urinary deoxypyridinoline (D-Pyr) concentrations, and decreased calcitriol concentrations, suggesting immobilization-induced hypercalcemia and inhibition of renal synthesis of calcitriol. After treatment, serum calcitriol concentrations increased in the etidronate and placebo groups. The etidronate group had significant decreases in serum ionized calcium and urinary D-Pyr, and the placebo group had higher serum calcium and urinary D-Pyr concentrations. CONCLUSIONS Etidronate therapy inhibits bone resorption and improves calcium balance, and such therapy may prevent bone loss and reduce the risk of subsequent hip fracture.

Amelioration by mecobalamin of subclinical carpal tunnel syndrome involving unaffected limbs in stroke patients

Our previous study showed that overuse of the nonparetic hand and wrist of the nonparetic side following stroke result in significantly more abnormal on the nonparetic side than on the hemiparetic side in terms of electrophysiologic indices of median nerve function. The purpose of this study was to evaluate the effects of the orally administered mecobalamin, an analogue of vitamin B12, for carpal tunnel syndrome (CTS) in the nonparetic side in patients following stroke. In a randomized open label and prospective study of stroke patients, 67 received of 1500 mug mecobalamin daily for 2 years, and the remaining 68 (untreated group) did not. At baseline, sensory nerve conduction velocity, motor nerve conduction velocity, sensory nerve action potentials (SNAP) at the wrist, palm-to-wrist distal sensory latency, palm-to-wrist SNAP, motor nerve conduction velocity compound motor action potentials, and distal motor latency of median nerve were significantly more abnormal on the nonparetic side than on the hemiparetic side or in controls. Before the treatment 21 patients (31%) of untreated and 20 patients (30%) of treated group met electrophysiologic criteria for CTS. Sensory impairment of the nonparetic side had lessened in the treated group. After 2 years, all electrophysiologic indices of nonparetic side were significantly improved in the treated group compared with those in the untreated group. The improvement from baseline of electrophysiologic parameters in sensory nerve in the treated group was greater than the improvement measured in motor nerve. There were no side effects. Oral mecobalamin treatment is a safe and potentially beneficial therapy for CTS in stroke patients.

Cardiac Involvement in Malignant Syndrome in Parkinson’s Disease

Little is known about cardiac abnormalities in neuroleptic malignant syndrome (NMS) in Parkinsons disease (PD), although high levels of serum creatine kinase (CK) suggest the presence of cardiac involvement. We have also been aware of elevated serum myosin light chain I (MLCI) in these patients with no clear evidence of an acute coronary syndrome. To evaluate cardiac involvement in NMS in PD, we recorded the electrocardiogram (ECG) and measured serum MLCI and CK-MB levels. Plasma levels of noradrenaline and adrenaline were also determined. The patients were classified based on the in-hospital outcome into 55 survivors and 5 nonsurvivors. Age- and gender-matched PD patients without NMS served as controls (n = 51). All patients had high serum concentrations of CK-MB and MLCI. The mean values of CK, CK-MB, MLCI, adrenaline and noradrenaline were higher in both patient groups as compared to control subjects, and the values in nonsurvivors were significantly higher than those in survivors. A positive correlation was observed between serum MLCI and CK levels (p < 0.01), and between serum MLCI levels and plasma noradrenaline concentrations (p < 0.01). ECG abnormalities such as prolonged QTc interval, abnormal Q wave, ST elevation and T wave inversion were observed in all nonsurvivors and 32 (58.2%) survivors. We conclude that myocardial involvement is common in patients with NMS even when they have no symptoms suggestive of myocardial injury, and MLCI and CK-MB as well as ECG are useful indicators of mortality.

Negative myoglobin staining in hemiplegic muscle of acute stroke patients predicts functional recovery.

OBJECTIVE There is little information on skeletal muscle changes in patients with acute stroke, despite the repeated observation that levels of serum creatine kinase (CK) and myoglobin (Mb) increase in the initial phase of strokes. It is also not clearly known whether the CK and Mb are derived from skeletal muscle or myocardium. DESIGN Biceps muscle biopsies of the hemiplegic side were obtained from 157 ischemic stroke patients on the second day of stroke onset and were examined for immunoreactivity to Mb, and measurements of Mb, total CK, troponin T, epinephrine, and norepinephrine were made on the same day. The degree of disability of patients was assessed at 7 days and at 12 mos after stroke using the Barthel index and the Scandinavian Stroke Scale. The control group consisted of 159 healthy volunteers matched in age and sex. RESULTS Lack of Mb immunoreactivity was observed in 109 patients. The prevalence of negatively stained muscle fibers ranged from 0.0% to 22.0%, with a mean of 5.9% +/- 6.0%. The mean values of serum Mb, CK, troponin T, and norepinephrine were higher in patients than those in the control group (P < 0.0001 for all indices; percentage differences were 658% for Mb, 529% for CK, and 258% for norepinephrine). A positive correlation was observed between the prevalence of negative Mb immunostaining in fibers and the Mb (r2 = 0.968, P < 0.0001), CK (r 2= 0.910, P < 0.0001), and norepinephrine levels (r2 = 0.835, P < 0.0001). During the 12-mo study period, Barthel index and Scandinavian Stroke Scale values improved. The percentage change of the Barthel index and Scandinavian Stroke Scale correlated positively with the prevalence of negative Mb immunostaining in fibers. CONCLUSIONS It was speculated that ischemia, resulting from vasoconstriction induced by an increase in norepinephrine, may be responsible for the occurrence of fibers with negative immunoreactivity for Mb. Patients with higher negative immunostaining for Mb fibers had poor functional recovery of hemiplegia 12 mos after stroke onset. This implies that these muscular alterations may hamper functional recovery.