Effect of alendronate on bone mineral density and bone turnover markers in post-gastrectomy osteoporotic patients

Alendronate decreases the urinary levels of cross-linked N-terminal telopeptides of type I collagen (NTX; about 45% at 3 months) and serum levels of alkaline phosphatase (ALP; about 27% at 24 months), leading to an increase in lumbar spine bone mineral density (BMD; about 9% at 24 months) in postmenopausal Japanese women with osteoporosis. However, the effectiveness of oral bisphosphonates on osteoporosis remains to be established in patients who have undergone a gastrectomy. The objective of the present case series study was to examine the effect of alendronate on BMD and bone turnover markers in post-gastrectomy osteoporotic patients. Sixteen patients (3 men and 13 postmenopausal women) with osteoporosis, who had undergone a gastrectomy (mean age: 69.1 years), were recruited in our outpatient clinic. All the patients were treated with alendronate (5 mg daily or 35 mg weekly) for 24 months. The effects of alendronate on lumbar spine (women) or total hip (men) BMD and urinary NTX and serum ALP levels were examined. A total or partial gastrectomy had been performed for eight patients each. The mean duration after surgery was 16.0 years. With alendronate therapy, urinary NTX levels significantly decreased at 3 months (−27.0%). Serum ALP levels decreased (−12.1%) and lumbar spine BMD increased (+5.2%), but total hip BMD did not significantly change (+0.6%) at 24 months. No severe adverse events were observed, and alendronate therapy was well tolerated. These results suggest that alendronate mildly increases lumbar spine BMD by mildly reducing bone turnover in osteoporotic patients after a gastrectomy.     

Intramuscular Granular Cell Tumor in the Lower Extremities

Granular cell tumors are uncommon but typically histologically benign neoplasms that occasionally behave as malignant tumors. Differentiation of benign granular cell tumors from malignant counterparts with radiographic and/or histologic analysis is crucial for physicians. We retrospectively studied five cases of intramuscular granular cell tumors arising in the lower extremities. All tumors had been histologically diagnosed as benign and were resected with a wide surgical margin. The minimum followup was 1 year (mean, 45 months; range, 12–119 months) after surgery. Four patients had no local recurrence or distant metastasis (at a minimum of 18 months followup), whereas one patient with lymph node metastasis had a recurrence and distant metastasis 3 months after surgery resulting in death. Intramuscular granular cell tumors can be diagnosed based on their characteristic MRI features, such as peripheral high intensity on T2-weighed images, and histologic evaluation. The histologic criteria described by Fanburg-Smith et al. can differentiate malignant granular cell tumors from benign tumors. A wide resection seems suitable for most granular cell tumors in the extremities.     

Superdrainage of the ileocolic vein to the internal jugular vein interposed by an inferior mesenteric vein graft in replacing the esophagus with the right hemicolon

The fear of serious complications, such as a necrotic conduit caused by an impaired blood circulation can arise when replacing the esophagus with an intestinal conduit. The aim of this paper is to present effective superdrainage of an intestinal conduit using an inferior mesenteric vein (IMV) interposition graft. In 2008, we performed superdrainage of the ileocolic vein to the internal jugular vein interposed by an IMV graft in replacing the esophagus with the right hemicolon for advanced thoracic esophageal cancer in three patients with a synchronous gastric cancer or a previous gastrectomy. No leakage at the enteric anastomoses occurred. Neither ischemic lesions in these intestinal conduits nor complications caused by harvesting an IMV graft were observed. Superdrainage of the ileocolic vein to the internal jugular vein interposed by an IMV graft effectively improves the blood circulation in intestinal conduits brought up to the neck as an esophageal replacement.     

One-stage posterior instrumentation surgery for the treatment of osteoporotic vertebral collapse with neurological deficits

The number of reports describing osteoporotic vertebral fracture has increased as the number of elderly people has grown. Anterior decompression and fusion alone for the treatment of vertebral collapse is not easy for patients with comorbid medical problems and severe bone fragility. The purpose of the present study was to evaluate the efficacy of one-stage posterior instrumentation surgery for the treatment of osteoporotic vertebral collapse with neurological deficits. A consecutive series of 21 patients who sustained osteoporotic vertebral collapse with neurological deficits were managed with posterior decompression and short-segmental pedicle screw instrumentation augmented with ultra-high molecular weight polyethylene (UHMWP) cables with or without vertebroplasty using calcium phosphate cement. The mean follow-up was 42 months. All patients showed neurologic recovery. Segmental kyphotic angle at the instrumented level was significantly improved from an average preoperative kyphosis of 22.8–14.7 at a final follow-up. Spinal canal occupation was significantly reduced from an average before surgery of 40.4–19.1% at the final follow-up. Two patients experienced loosening of pedicle screws and three patients developed subsequent vertebral compression fractures within adjacent segments. However, these patients were effectively treated in a conservative fashion without any additional surgery. Our results indicated that one-stage posterior instrumentation surgery augmented with UHMWP cables could provide significant neurological improvement in the treatment of osteoporotic vertebral collapse.     

Antiobesity Effect of Eicosapentaenoic Acid in High-Fat/High-Sucrose Diet�CInduced Obesity: Importance of Hepatic Lipogenesis

OBJECTIVE

Given the pleiotropic effect of eicosapentaenoic acid (EPA), it is interesting to know whether EPA is capable of improving obesity. Here we examined the anti-obesity effect of EPA in mice with two distinct models of obesity.

RESEARCH DESIGN AND METHODS

Male C57BL/6J mice were fed a high-fat/high-sucrose diet (25.0% [w/w] fat, 32.5% [w/w] sucrose) (HF/HS group) or a high-fat diet (38.1% [w/w] fat, 8.5% [w/w] sucrose) (HF group) for 4–20 weeks. A total of 5% EPA was administered by partially substituting EPA for fat in the HF/HS + EPA and HF + EPA groups.

RESULTS

Both the HF/HS and HF groups similarly developed obesity. EPA treatment strongly suppresses body weight gain and obesity-related hyperglycemia and hyperinsulinemia in HF/HS-fed mice (HF/HS + EPA group), where hepatic triglyceride content and lipogenic enzymes are increased. There is no appreciable effect of EPA on body weight in HF-fed mice (HF + EPA group) without enhanced expression of hepatic lipogenic enzymes. Moreover, EPA is capable of reducing hepatic triglyceride secretion and changing VLDL fatty acid composition in the HF/HS group. By indirect calorimetry analysis, we also found that EPA is capable of increasing energy consumption in the HF/HS + EPA group.

CONCLUSIONS

This study is the first demonstration that the anti-obesity effect of EPA in HF/HS-induced obesity is associated with the suppression of hepatic lipogenesis and steatosis. Because the metabolic syndrome is often associated with hepatic lipogenesis and steatosis, the data suggest that EPA is suited for treatment of the metabolic syndrome.The metabolic syndrome has been defined as a cluster of visceral fat obesity, impaired glucose metabolism, atherogenic dyslipidemia (high plasma triglyceride and low HDL cholesterol), and hypertension (1). There is considerable evidence that visceral fat obesity is a key etiological factor in the metabolic syndrome (2). Enhanced hepatic lipogenesis and hepatic steatosis also appear to play an important role in the pathogenesis of the metabolic syndrome (3). Indeed, nonalcoholic fatty liver disease may constitute the common features of the metabolic syndrome.Numerous epidemiological studies and clinical trials have revealed that fish oil and n-3 polyunsaturated fatty acids (PUFAs) reduce the risk of coronary heart disease (4). Eicosapentaenoic acid (EPA), one of the major n-3 PUFAs contained in fish oil, has a variety of pharmacological effects such as lipid-lowering (5), anti-platelet (6), anti-inflammatory (7), and anti-atherogenic effects (8,9). Recently, the Japan EPA Lipid Intervention Study (JELIS), a large-scale prospective randomized clinical trial, demonstrated that EPA delays the onset of cardiovascular events via cholesterol-independent mechanisms (10,11), but the molecular mechanisms remain to be elucidated. In a recent sub-analysis of the JELIS, EPA had a great risk reduction of coronary artery events of 53% in patients with high triglycerides and low HDL cholesterol (11), suggesting that EPA may be effective to reduce the incidence of atherosclerosis in the metabolic syndrome. These findings are supported by our recent observations that EPA administration results in decreases in remnant-like particle-triglyceride, small dense LDL, and C-reactive protein and an increase in adiponectin in patients with the metabolic syndrome (12,13).Given the pleiotropic effect of EPA, it is interesting to know whether highly purified EPA is capable of improving obesity. There is currently a controversy as to the anti-obesity effect of EPA; it has been effective (13,14), has been ineffective (15), or has even increased visceral fat accumulation (16). On the other hand, it is noteworthy that EPA suppresses hepatic lipogenesis and steatosis by reducing mRNA and active protein of sterol regulatory element binding protein-1c (SREBP-1c) (17–19). We, therefore, examined the impact of hepatic lipogenesis on the anti-obesity effect of highly purified EPA.Here, we demonstrate that EPA strongly suppresses body weight gain and obesity-related hyperglycemia and hyperinsulinemia in high-fat (HF)/high-sucrose (HS)-induced obese mice with enhanced hepatic lipogenesis but not in HF-induced obese mice without enhanced hepatic lipogenesis. This study is the first demonstration that the anti-obesity effect of EPA is related to the suppression of hepatic lipogenesis. Given that the metabolic syndrome is often associated with hepatic lipogenesis and steatosis, the data of this study suggest that EPA is suited for the treatment of the metabolic syndrome.     

Effect of vitamin K<Subscript>2</Subscript> and growth hormone on the long bones in hypophysectomized young rats: a bone histomorphometry study

The purpose of the present study was to determine whether vitamin K₂ and growth hormone (GH) had an additive effect on the long bones in hypophysectomized young rats. Forty-eight female Sprague–Dawley rats (6 weeks old) were assigned to the following five groups by the stratified weight randomization method: intact controls, hypophysectomy (HX) alone, HX + vitamin K₂ (30 mg/kg, p.o., daily), HX + GH (0.625 mg/kg, s.c., 5 days a week), and HX + vitamin K₂ + GH. The duration of the experiment was 4 weeks. HX resulted in a reduction of the cancellous bone volume/total tissue volume (BV/TV) at the proximal tibial metaphysis, as well as decreasing the total tissue area and cortical area of the tibial diaphysis. These changes resulted from a decrease of the longitudinal growth rate and the bone formation rate (BFR)/TV of cancellous bone, as well as a decrease of the periosteal BFR/bone surface (BS) and an increase of endocortical bone turnover (indicated by the BFR/BS) in cortical bone. Administration of vitamin K₂ to HX rats did not affect the cancellous BV/TV or the cortical area. On the other hand, GH completely prevented the decrease of total tissue area and cortical area in cortical bone, as well as the decrease of marrow area and endocortical circumference, by increasing the periosteal BFR/BS compared with that in intact controls and reversing the increase of endocortical bone turnover (BFR/BS). However, GH only partly improved the reduction of the cancellous BV/TV, despite an increase of the longitudinal growth rate and BFR/TV compared with those of intact controls. When administered with GH, vitamin K₂ counteracted the reduction of endocortical bone turnover (BFR/BS) and circumference caused by GH treatment, resulting in no significant difference of marrow area from that in untreated HX rats. These results suggest that, despite the lack of an obvious effect on bone parameters, vitamin K₂ normalizes the size of the marrow cavity during development of the bone marrow in young HX rats treated with GH.     

Genetic evidence points to an osteocalcin‐independent influence of osteoblasts on energy metabolism

The skeleton has been shown recently to regulate glucose metabolism through an osteoblast‐specific hormone, osteocalcin, which favors β‐cell proliferation, insulin secretion, insulin sensitivity, and energy expenditure. An implication of this finding is that a decrease in osteoblast numbers would compromise glucose metabolism in an osteocalcin‐dependent manner. To test this hypothesis, osteoblasts were inducibly ablated by cross‐breeding transgenic mice expressing a tamoxifen‐regulated Cre under the control of the osteocalcin promoter with mice in which an inactive form of the diphtheria toxin A chain was introduced into a ubiquitously expressed locus. Ablation of osteoblasts in adult mice profoundly affected glucose metabolism. In a manner similar to what is seen in the case of osteocalcin deficiency, a partial ablation of this cell population resulted in hypoinsulinemia, hyperglycemia, glucose intolerance, and decreased insulin sensitivity. However, and unlike what is seen in osteocalcin‐deficient mice, osteoblast ablation also decreased gonadal fat and increased energy expenditure and the expression of resistin, an adipokine proposed to mediate insulin resistance. While administration of osteocalcin reversed (fully) the glucose intolerance and reinstated normal blood glucose and insulin levels, it only partially restored insulin sensitivity and did not affect the improved gonadal fat weight and energy expenditure in osteoblast‐depleted mice. These observations not only strengthen the notion that osteoblasts are necessary for glucose homeostasis and energy expenditure but also suggest that in addition to osteocalcin, other osteoblast‐derived hormones may contribute to the emerging function of the skeleton as a regulator of energy metabolism. © 2011 American Society for Bone and Mineral Research     

Case report of endotracheal intubation using AirWay Scope (Pentax-AWS) in a Forestier's disease patient

A Forestier's disease patient was scheduled for endoscopic mucosal resection under general anesthesia, because of his hypoxic episode during gastric endoscopy. Endotracheal intubation was planned while awake, because he was suspected as a case of difficult airway. By using AWS, we could easily confirm his larynx and aditus of trachea in spite of his narrow pharynx caused by Forestier's disease. The procedure was successful with no complications. AWS seems to be a useful device for endotracheal intubation in Forestier's disease.     

Disseminated carcinomatosis of the bone marrow in two patients with prostate cancer

Disseminated carcinomatosis of the bone marrow is caused by metastasis to the bone marrow and can cause disseminated intravascular coagulation (DIC), leucoerythroblastosis, and microangiopathic hemolytic anemia (MHA). The prognosis of this syndrome is poor. We report herein two rare cases of disseminated carcinomatosis of the bone marrow in association with prostate cancer. Case 1 involved a 61-year-old man admitted to our department with elevated prostate-specific antigen (PSA) levels. Prostate biopsy revealed prostate cancer, and imaging studies were performed. Under a diagnosis of prostate cancer (T3N1Mx), the patient was treated using hormonotherapy, but died 2 months after admission due to gastrointestinal bleeding of unknown cause, refractory DIC, and cachexia. Bone marrow biopsy after his death revealed metastasis of the prostate cancer to the bone marrow. Case 2 involved a 68-year-old man admitted to our department with gross hematuria. Cystoscopy revealed non-papillary tumor in the prostatic urethra. Transurethral biopsy was performed and histology identified prostate cancer. Treatment was initiated with hormonotherapy and zoledronate. After 8 months, he complained of general fatigue and blood testing identified anemia and thrombocytopenia. Bone marrow biopsy revealed adenocarcinoma in the bone marrow. Alternative androgen therapy and chemotherapy with docetaxel was started, and the patient recovered from pancytopenia and general fatigue.