Takafumi Majima

Decreased bone mineral density at the distal radius, but not at the lumbar spine or the femoral neck, in Japanese type 2 diabetic patients.

The purpose of this study is to assess the association between typexa02 diabetes and bone mineral density. This study included 145 Japanese patients (64 men and 81 women) with typexa02 diabetes and 95 non-diabetic control subjects (41 men and 54 women) of similar age. We measured bone mineral density (BMD) at the sites with different cortical/cancellous bone ratio (lumbar spine, femoral neck, and distal radius) using dual-energy X-ray absorptiometry. BMD and Zxa0score at the distal radius were significantly lower in typexa02 diabetic patients than those in control subjects, and in typexa02 diabetic patients, the Zxa0score at the distal radius was lower than that at their own lumbar spine and femoral neck. In typexa02 diabetic patients, negative correlation between BMD and the mean HbA1c during the previous 2 years was found significantly at the distal radius in both genders and at the femoral neck in women. These results indicate the selective cortical bone loss in typexa02 diabetes and suggest the importance of also determining BMD at the radius and keeping good metabolic control to prevent bone loss in typexa02 diabetic patients.

Highly purified eicosapentaenoic acid reduces cardio-ankle vascular index in association with decreased serum amyloid A-LDL in metabolic syndrome.

A recent clinical trial revealed that highly purified eicosapentaenoic acid (EPA), an n-3 polyunsaturated fatty acid, reduces the incidence of cardiovascular diseases. However, the detailed mechanism underlying the anti-atherogenic effect of EPA is still poorly understood. In this study, we examined the effect of EPA on cardio-ankle vascular index (CAVI), a new index of arterial stiffness that is less influenced by blood pressure (BP), as well as on serum amyloid A-low-density lipoprotein (SAA–LDL), an oxidized LDL (oxLDL), in the metabolic syndrome. Ninety-two obese Japanese subjects with metabolic syndromes were randomly divided into two groups (n=46): the EPA-treated group (1.8u2009g administered daily for 3 months) and the control group. Measurements were taken to assess the changes in glucose-lipid metabolism, SAA–LDL, C-reactive protein (CRP), leptin, adiponectin and pulse wave velocity (PWV), and CAVI. EPA treatment significantly reduced the levels of immunoreactive insulin, triglycerides, SAA–LDL, CRP, PWV and CAVI and increased the levels of adiponectin relative to the control group for 3 months (P<0.05). Stepwise multivariate linear regression analysis revealed that the only significant determinant for a decrease in CAVI by EPA is a reduction in SAA–LDL (P<0.05). Moreover, the EPA-induced reduction of SAA–LDL was only significantly correlated with a decrease in total cholesterol and an increase in adiponectin (P<0.05). This study is the first demonstration that EPA improves arterial stiffness and is less influenced by BP, possibly through the suppression of SAA–LDL, thereby leading to a reduction in the frequency of cardiovascular disease development in metabolic syndrome.

Urinary Cystatin C as a Potential Risk Marker for Cardiovascular Disease and Chronic Kidney Disease in Patients with Obesity and Metabolic Syndrome

BACKGROUND AND OBJECTIVESnObesity and metabolic syndrome (MS) increase the risk of cardiovascular disease (CVD), chronic kidney disease (CKD), and all-cause mortality. Serum cystatin C (S-CysC), a marker of GFR, has been shown to be associated with CVD and CKD. This study was designed to elucidate the association of urinary CysC (U-CysC), a marker of renal tubular dysfunction, with CVD and CKD risk factors in patients with obesity and MS.nnnDESIGN, SETTING, PARTICIPANTS, & MEASUREMENTSnThe U-CysC-creatinine ratio (UCCR) was examined in 343 Japanese obese outpatients enrolled in the multi-centered Japan Obesity and Metabolic Syndrome Study.nnnRESULTSnUCCR was positively correlated with urine albumin-creatinine ratio (UACR) and S-CysC and negatively correlated with estimated GFR (eGFR). Among obese patients, UCCR was significantly higher in MS patients than in non-MS patients. UCCR had significant correlations with the number of components of MS and arterial stiffness, all of which are CVD predictors, similarly to UACR (P<0.05). Interestingly, diet- and exercise-induced weight reduction for 3 months significantly decreased only UCCR among all of the renal markers examined (P<0.01), in parallel with the decrease in BMI, HbA1c, and arterial stiffness, suggesting the beneficial effect of weight reduction on renal tubular dysfunction.nnnCONCLUSIONSnThis study demonstrates that UCCR is significantly associated with renal dysfunction, the severity of MS, arterial stiffness, and weight change in obese patients. The data of this study suggest that U-CysC could serve as a CVD and CKD risk factor in patients with obesity and MS.

Clinical significance of risedronate for osteoporosis in the initial treatment of male patients with Graves' disease

It has been well established that hyperthyroidism leads to diminished bone mineral density (BMD), and that a previous history of hyperthyroidism remains a risk factor for fractures. However, little is known about how to manage the reduction in BMD caused by hyperthyroidism. The purpose of this study was to evaluate the efficacy of risedronate for the treatment of osteoporosis/osteopenia in patients with Graves disease (GD). Of 34 Japanese male patients with newly diagnosed GD, 27 with osteoporosis/osteopenia were included in this study. They were randomly divided into two groups by therapeutic regimen. Group A consisted of 14 patients treated with an antithyroid drug and risedronate. Group B consisted of 13 patients treated with the same antithyroid drug only. We used dual-energy X-ray absorptiometry to measure BMD at the lumber spine, femoral neck, and distal radius at baseline, and at 6 and 12 months after the trial. Bone-specific alkaline phosphatase and urinary N-terminal telopeptide of type I collagen normalized by creatinine were significantly more reduced in group A than in group B after both 6 and 12 months. The percentage increases in BMD at the lumbar spine and distal radius were significantly greater in group A than in group B. These beneficial effects of risedronate for patients with osteoporosis/osteopenia caused by GD may lead to a reduced risk of future fractures. We thus conclude that risedronate should be considered for the treatment of decreased bone mass associated with GD.

Negative correlation between bone mineral density and TSH receptor antibodies in male patients with untreated Graves' disease

IntroductionAlthough it has been established that hyperthyroidism leads to reduced bone mineral density (BMD), with accelerated bone turnover promoting bone resorption in female patients, there is a dearth of data for male patients with hyperthyroidism. This study evaluated BMD and bone metabolism in male patients with Graves’ disease.MethodsThe study included 56 Japanese male patients with newly diagnosed Graves’ disease and 34 normal Japanese male control subjects of similar age and body mass index. We used dual energy x-ray absorptiometry to measure BMD at sites with different cortical/cancellous bone ratios (lumbar spine, femoral neck, and distal radius).ResultsAt the lumbar spine and the distal radius, BMD and T-scores were significantly lower for patients than for controls. At the femoral neck, on the other hand, the same values were relatively, but not significantly, lower in patients than in controls. However, Z-scores at all three sites were significantly lower for patients than for controls. The Z -score at the distal radius of patients was significantly lower than that at their lumbar spine and femoral neck. In addition, Z-score at the distal radius correlated negatively with age, free thyroxine, thyroid stimulating hormone receptor antibodies, thyroid stimulating antibody, and urinary N-terminal telopeptide of type I collagen normalized by creatinine.ConclusionsThese results indicate a high prevalence of cortical bone loss in male patients with Graves’ disease, especially elderly patients. We conclude that BMD measurement is crucial in all Graves’ disease patients regardless of their gender and that the radial BMD as well as BMD at the lumbar spine and femoral neck should be monitored to effectively prevent bone loss and subsequent fracture.

Effects of risedronate or alfacalcidol on bone mineral density, bone turnover, back pain, and fractures in Japanese men with primary osteoporosis: results of a two-year strict observational study

Although osteoporosis in men is already a major public health problem, there is still a dearth of data about the effects of risedronate in male osteoporosis, especially in Japanese with primary osteoporosis. Therefore, the objective of our study was to investigate the effects of risedronate on bone mineral density (BMD), bone turnover, back pain, and fractures in these patients prospectively for two years (at baseline, threexa0months, six months, twelvexa0months, and twenty-fourxa0months) both longitudinally and compared with those of alfacalcidol. The subjects enrolled for this study were 66 Japanese male patients with untreated primary osteoporosis (mean age 63.52xa0±xa08.7xa0years), who were divided into two groups (44 with risedronate and 22 with alfacalcidol). We measured BMD by dual energy X-ray absorptiometry at three sites—the lumbar spine, femoral neck, and distal radius. Risedronate treatment significantly increased BMD at the lumbar spine and at the femoral neck, reduced bone-specific alkaline phosphatase (BAP) and serum N-terminal telopeptide of type I collagen (NTx), and reduced back pain, both longitudinally and compared with alfacalcidol treatment. We observed a lower rate of incident fracture in risedronate users. However, multiple logistic regression analysis revealed that this trend was not statistically significant, possibly because of the small number of patients enrolled. These potentially beneficial effects of risedronate on bone in male patients with primary osteoporosis suggest the possibility that osteoporosis should be treated with risedronate regardless of gender in order to effectively prevent subsequent osteoporotic fractures.

Three-month changes in bone turnover markers and bone mineral density response to raloxifene in Japanese postmenopausal women with osteoporosis

It has been well established that raloxifene (RLX) improves bone turnover, increases bone mineral density (BMD), and reduces the risk of fractures. However, it remains obscure how to monitor the therapeutic effects of RLX, while numerous clinical trials for other antiresorptive agents have suggested that greater short-term reductions of bone turnover markers (BTMs) can predict greater increases in BMD and greater reduction in risk of future fractures. The purpose of this study was to investigate associations between short-term reductions of BTMs and subsequent changes of BMD after 1-year treatment with RLX. Seventy-three Japanese postmenopausal women with untreated osteoporosis were selected for this study. Reductions in BTMs [bone-specific alkaline phosphatase (BAP) or serum N-terminal telopeptide of type I collagen (NTx)] after 3 months did not correlate with increases of BMD at any major sites (lumbar spine, femoral neck, total neck, and distal 1/3 radius) either after 6 months or after 12 months. Our results suggest that short-term reductions or 3-month reductions of BTMs with RLX treatment cannot be used to predict increases of BMD. However, this does not directly mean that short-term reductions or 3-month reductions of BTMs with RLX treatment cannot be used to predict risk reduction of future fractures or the ultimate effects of RLX on bone. Further studies with fracture endpoints in longer observation and larger number of patients are warranted to establish how to monitor the therapeutic effects of RLX or early identification of responders or nonresponders to RLX treatment.