Association Between Papillary Thyroid Carcinoma and Vertebral Fracture.

Suppression of TSH levels associated with levothyroxine treatment is a known risk factor for fracture. However, it is unclear whether patients with papillary thyroid carcinoma (PTC) have a higher risk of vertebral fracture (VF) before TSH suppression. The aim of the study was to examine whether the risk of VF is higher in PTC than in healthy subjects. A hospital-based, matched case-control study was conducted comparing PTC and healthy individuals. We enrolled 43 postoperative patients with PTC scheduled for radioiodine therapy and 43 age- and sex-matched healthy controls. Serum and urinary biological parameters, bone mineral density (BMD), and presence of VFs were evaluated in both groups. We compared these indices using χ2 and Mann-Whitney U-test and analyzed the association between PTC and VF by logistic regression analysis. The PTC group had higher BMI, HbA1c and phosphorus, and lower intact PTH than the control group. Lumbar and femoral neck BMD did not differ between the two groups. Prevalence of VFs was significantly higher in the PTC group (44.1%) than in the control group (16.3%). Multivariate logistic regression analyses adjusted for age, sex, and BMI identified PTC as being associated with the presence of VFs (odds ratio, 5.63; 95% confidence interval: 1.82 to 17.5). This relationship remained significant after additional adjustment for HbA1c and BMD. There is an association between PTC and a risk of VF independent of sex, BMI, glucose metabolism, and BMD, suggesting the importance of fracture risk assessment before TSH suppression.

Graves' disease and vertebral fracture: Possible pathogenic link in postmenopausal women.

BACKGROUND AND OBJECTIVE: Thyrotoxicosis is associated with accelerated bone turnover and increases the risk of fractures and osteoporosis. Graves' disease is the most common cause of hyperthyroidism. However, studies that examined risk factors associated with fragility fractures only in patients with Graves' disease are limited. Here, we investigated whether the risk of vertebral fracture (VF) of postmenopausal Graves' disease patients is high and tried to identify the risk factors for VF in that population. DESIGN AND METHODS: Forty-three postmenopausal women with Graves' disease were enrolled. Physical and biochemical indices, thyroid indices and bone mineral density (BMD) were measured, and lateral X-rays were obtained to evaluate VFs. Age- and sex-matched healthy individuals were enrolled as the control group (n = 86). RESULTS: The prevalence of VFs (35% vs 17%, P < .05), osteoporosis (63% vs 33%, P < .01) and severe osteoporosis (40% vs 17%, P < .01) was significantly higher in the Graves' disease group. Although there was no significant difference in either thyroid hormone levels or the positive ratio of thyroid antibodies, the prevalence of thyroid-stimulating antibody (TSAb) was significantly higher in Graves' disease patients with VF compared to without (100% vs 68%, P < .05). Multivariate logistic regression analyses adjusted for age identified Graves' disease as being associated with the presence of VFs (OR 2.72, 95% CI: 1.13-6.54, P < .05) in postmenopausal women. CONCLUSIONS: Postmenopausal Graves' disease patients had high risks of VF and severe osteoporosis. TSAb could be involved as a risk factor for VF in postmenopausal Graves' disease.

Papillary thyroid carcinoma is a risk factor for severe osteoporosis.

INTRODUCTION: Thyroid-stimulating hormone (TSH)-suppressive therapy is recommended after surgical treatment in high-risk papillary thyroid carcinoma (PTC) patients. TSH-suppressive therapy is a known risk factor for osteoporosis and fractures. However, whether patients with PTC themselves are at a higher risk of osteoporosis than healthy individuals remains unclear. This study aimed to clarify whether PTC is a risk factor for osteoporosis. MATERIALS AND METHODS: Serum and urinary biochemical parameters, bone mineral density (BMD), and presence of vertebral fractures (VFs) and non-VFs were evaluated in 35 PTC patients and 35 age- and sex-matched healthy individuals. We compared the parameters between PTC and control subjects and performed multiple logistic regression analyses after adjustments for variables. RESULTS: Patients with PTC had higher body mass index (BMI) and hemoglobin (Hb)A1c, as well as lower eGFR and intact PTH than controls (p < 0.05, each). There were no significant differences in the prevalence of osteoporosis and VFs and non-VFs between patients with PTC and controls. However, the prevalence of severe osteoporosis diagnosed according to WHO criteria was significantly higher in PTC subjects (34.3%) than in controls (11.4%, p < 0.05). Multivariate logistic regression analyses adjusted for age, BMI, eGFR and HbA1c identified PTC as being associated with the presence of severe osteoporosis (odds ratio, 4.20; 95% confidence interval, 1.05-16.8; p < 0.05). CONCLUSIONS: We identified PTC as a risk factor for severe osteoporosis, independent of BMI, renal function and glucose profile.

Primary Aldosteronism as a Risk Factor for Vertebral Fracture.

Context: Some observational studies have revealed an association between excessive aldosterone levels and reduced bone mineral density (BMD). However, whether patients with primary aldosteronism (PA) are at higher risk of fracture than healthy individuals remains unclear. Objective: This study aimed to clarify whether PA represents a risk factor for vertebral fracture (VF). Design and Patients: We enrolled 56 patients with PA and 56 age- and sex-matched healthy individuals. Serum and urinary biological parameters, BMD, and presence of VFs were evaluated in both groups. We compared parameters between PA and control participants and performed multiple logistic regression analyses after adjustments for variables. Results: Patients with PA showed higher systolic and diastolic blood pressure, higher hemoglobin A1c (HbA1c) and triglycerides, higher urinary calcium-to-creatinine ratio, and lower high-density lipoprotein cholesterol than controls (P < 0.05, each). Prevalence of VFs was significantly higher in patients with PA (44.6%) than in controls (23.2%, P < 0.05). Patients with PA showed severe fracture more frequently than controls. Multivariate logistic regression analyses adjusted for age, sex, and body mass index identified PA as being associated with the presence of VFs (odds ratio, 3.13; 95% confidence interval, 1.30 to 7.51; P < 0.05). This association remained statistically significant after further adjustment for systolic and diastolic blood pressure, HbA1c, triglycerides, and high-density lipoprotein cholesterol but not after adjustment for calcium-to-creatinine ratio and BMD. Conclusions: We identified PA as a risk factor for VF, independent of blood pressure, HbA1c, and lipid profile. Fracture severity was significantly higher in patients with PA than in age- and sex-matched controls.

Increased low-density lipoprotein cholesterol level is associated with non-vertebral fractures in postmenopausal women.

Although a high serum low-density lipoprotein cholesterol (LDL-C) level is an established risk factor for atherosclerosis, it is unclear whether it is associated with osteoporosis. In this study, the associations between the serum LDL-C level and bone mineral density (BMD), bone metabolic markers, and the presence of prevalent vertebral or non-vertebral fractures were examined. A total of 211 healthy postmenopausal women (age range, 46-80 years) who visited a community health center were recruited consecutively. Their radiographic and biochemical characteristics were collected. Prevalent vertebral and non-vertebral fractures were found in 49 (23.2%) and 36 (17.1%) subjects, respectively. Simple regression analyses showed that the serum LDL-C level was not significantly correlated with lumbar or femoral BMD or serum levels of total amino-terminal propeptide of type I collagen (PINP) or carboxy-terminal telopeptide of type I collagen (CTX). Logistic regression analyses adjusted for age and BMI showed that the increased serum LDL-C level was selected as an index affecting the presence of prevalent non-vertebral fractures, but not vertebral fractures. This result was still significant after additional adjustments for years since menopause, physical activity, previous cardiovascular events, bone markers, BMD, serum Ca, P, Cr, 25(OH)D, grip strength, tandem gait test, and use of drugs for hyperlipidemia [odds ratio 1.76 (1.13-2.73), p=0.012]. These findings suggest that a high serum LDL-C level may be a risk factor for prevalent non-vertebral fragility fractures independent of bone turnover, bone mass, vitamin D insufficiency, or frail status in postmenopausal women, and that it may be detrimental to bone, as well as blood vessels.

Association of n-3 polyunsaturated fatty acid intake with bone mineral density in postmenopausal women.

n-3 Polyunsaturated fatty acids (n-3 fatty acids) have been shown to have a beneficial effect on bone in animal studies, although little is known about their role in bone metabolism in humans. We investigated the association between bone mineral density (BMD) and daily n-3 fatty acid intake. This cross-sectional, community-based, epidemiologic study was conducted among 205 healthy postmenopausal women (mean age 63.5 years, range 46-79). We examined BMD, serum N-terminal propeptide of type I collagen (PINP), urinary type-I collagen cross-linked-N-telopeptide (uNTX), total cholesterol, triglycerides, and high-density lipoprotein cholesterol. Nutrient intake was calculated using a food-frequency questionnaire. BMD was measured at the lumbar spine and femoral neck by dual-energy X-ray absorptiometry. Simple regression analysis showed that intake of neither n-3 fatty acid nor n-6 fatty acid was associated with age or lipid metabolism indices. However, simple regression analysis showed that n-3 fatty acid intake was positively associated with both lumbar spine BMD and femoral neck BMD. n-6 fatty acid intake was positively associated with femoral neck BMD but not lumbar spine BMD. Multiple regression analysis showed that n-3 fatty acid intake was positively associated with lumbar spine BMD after adjustment for age, BMI, duration of menopausal state, grip strength, PINP, uNTX, and intakes of calcium, vitamin D, vitamin K, and n-6 fatty acid. In conclusion, n-3 fatty acid intake was positively associated with lumbar spine BMD independent of bone resorption and serum levels of cholesterol and triglycerides in postmenopausal women.

Decreased PTH levels accompanied by low bone formation are associated with vertebral fractures in postmenopausal women with type 2 diabetes.

OBJECTIVE: Patients with type 2 diabetes (T2DM) have an increased risk of vertebral fractures (VF) compared with non-T2DM controls due to poor bone quality. The aim of this study was to investigate the association between VF and bone turnover. RESEARCH DESIGN AND METHODS: We compared clinical parameters, such as serum PTH and osteocalcin (OC), between hospital-based Japanese T2DM patients (123 postmenopausal women and 132 men over 50 yr old) and medical checkup-based non-T2DM controls (189 women and 51 men). The association between PTH and OC levels was investigated, and the VF risks were compared for four subgroups classified by PTH and OC values. RESULTS: T2DM patients had lower PTH and OC levels than the controls for both sexes (P < 0.01). Multivariate regression analysis showed that PTH levels of T2DM patients were significantly and positively correlated with OC levels (women, r = 0.324, P < 0.01; men, r = 0.343, P < 0.01). When participants were divided into two subgroups based on mean PTH and OC levels, the group of T2DM women with lower PTH and lower OC levels had a significantly higher risk of VF than those with higher PTH and higher OC levels after adjusting for age, body mass index, hemoglobin A(1c), creatinine, 25-hydroxyvitamin D, and lumbar bone mineral density (odds ratio, 4.73; 95% confidence interval, 1.20-18.6; P = 0.026). CONCLUSIONS: Patients with T2DM had decreased PTH levels. In T2DM postmenopausal women, lower PTH levels accompanied by low bone formation may elevate VF risk independently of bone mineral density compared with higher bone formation, possibly as a result of reduced bone quality.

Role of parathyroid hormone in bone fragility of postmenopausal women with vitamin D insufficiency.

Vitamin D insufficiency is related to an increase in PTH, which might be critical for an increase in bone fragility. However, the role of endogenous PTH in vitamin D insufficiency-induced fracture risk remains unclear. The present study was performed to examine the relationships among vitamin D insufficiency, bone fragility, and PTH in 202 Japanese postmenopausal women. Serum 25-hydroxyvitamin D (25[OH]D) levels were measured. The percentages of subjects with 25(OH)D levels below 10, 15, and 20 ng/ml were 5.0, 41.0, and 80.7%, respectively. Serum 25(OH)D levels were negatively related to age and serum levels of Cr and PTH; they were positively related to bone mineral density (BMD). In multiple regression analysis, BMD was significantly related to 25(OH)D levels when adjusted for age, body mass index (BMI), and serum levels of Cr and PTH. Multiple logistic regression analysis showed that lower 25(OH)D levels were significantly related to prevalent fracture risk when adjusted for age, BMI, serum levels of Cr and PTH, as well as femoral neck BMD. The proportion of subjects with prevalent fractures was significantly higher in the group with lower PTH and lower 25(OH)D than in the group with lower PTH and higher 25(OH)D or higher PTH and higher 25(OH)D. In conclusion, vitamin D insufficiency was found to be related to prevalent fracture risk independently of PTH. Functional hypoparathyroidism, rather than functional hyperparathyroidism, might be a risk factor for bone fragility in vitamin D insufficiency.

Relationships between undercarboxylated osteocalcin and vitamin K intakes, bone turnover, and bone mineral density in healthy women.

BACKGROUND & AIMS: Low vitamin K intakes and high levels of undercarboxylated osteocalcin (ucOC) are risk factors for hip fractures. However, the relationship between ucOC and vitamin K intakes, bone mineral density (BMD) and bone biochemical markers is not clarified. METHODS: We enrolled 221 healthy women, and examined BMD, urinary type-I collagen cross-linked-N-telopeptide (uNTX), and nutrient intakes. BMD was measured at the lumbar spine and femoral neck. RESULTS: Vitamin K intakes were significantly and negatively correlated with ucOC after adjustment for age, height, and body weight (r=-0.305, p<0.0001). ucOC was negatively associated with lumbar BMD (r=-0.147, p<0.05), but not femoral neck BMD (r=-0.099, p=0.095) after adjustment for age, height, and body weight. In multiple regression analysis, even after adjustment for age, height, body weight, and vitamin K intake, a significant and positive correlation remained between ucOC and urinary NTX (r=0.493, p<0.0001). Moreover, in postmenopausal women, ucOC levels were positively correlated with urinary NTX, but not BMD. CONCLUSION: Dietary vitamin K intakes influence serum levels of ucOC in healthy women. Furthermore, ucOC may be linked to bone biochemical markers.

Increased resting metabolic rate in patients with type 2 diabetes mellitus accompanied by advanced diabetic nephropathy.

Thirty-three patients with type 2 diabetes mellitus (16 men, 17 women) were divided into 3 groups based on urinary excretion of albumin (U-Alb)--group A: U-Alb < 30 mg/d; group B: 30 mg/d < or = U-Alb < or = 300 mg/d; and group C: 300 mg/d < U-Alb. Serum creatinine levels were lower than 2.0 mg/dL in all the subjects. There was no difference in age, sex, therapy, body weight, body mass index (BMI), lean body mass (LBM), or hemoglobin A(1c) (HbA(1c)) levels among the 3 groups. Resting metabolic rate (RMR) (kJ/h/m(2)) and adjusted RMR for lean body mass (kJ/h/m(2)) were significantly increased in group C compared with groups A and B. Hb concentrations, serum albumin levels, and creatinine clearance were much lower in group C than in groups A and B (P < .001). There were no difference in serum urea nitrogen, total cholesterol, cholinesterase and free thyroxine, or plasma insulin-like growth factor I (IGF-I) levels among the 3 groups. Linear regression analysis revealed an inverse correlation between RMR and serum albumin levels, correlation between RMR and U-Alb, and inverse correlation between RMR and Hb concentrations, respectively, in these patients. In conclusion, RMR in diabetic patients correlated directly with U-Alb and inversely with serum albumin and Hb concentration. These findings suggest that RMR is related with urinary albumin loss and anemia in patients with type 2 diabetes mellitus accompanied by diabetic nephropathy.