Alcohol Consumption Moderated the Association Between Levels of High Blood Lead or Total Urinary Arsenic and Bone Loss.

Metal exposure and lifestyle are important risk factors for osteoporosis. Our study aimed to investigate the association between red blood cell lead and cadmium, total urinary arsenic, and plasma selenium levels and bone mineral density (BMD). In addition, we explored whether alcohol and coffee consumption modified the association between BMD and metals and metalloids. In total, 437 participants who underwent adult or senile physical examinations were recruited. Bone loss was defined as a calcaneus BMD T-score of <-1. Blood cadmium and lead and plasma selenium levels were measured using inductively coupled plasma mass spectrometry. Levels of urinary arsenic species were determined using high-performance liquid chromatography-hydride generator-atomic absorption spectrometry. The total urinary arsenic level was defined as the sum of the levels of urinary arsenic species. The BMD T-scores decreased significantly with increasing blood lead levels. The BMD T-scores also showed a downward trend with increasing total urinary arsenic levels. The odds ratio (OR) and 95% confidence interval (CI) for bone loss in patients with blood lead levels >57.58 versus 35.74 µg/dL were 1.98 and 1.17-3.34. In addition, the greater the lead or arsenic exposure and alcohol intake was the higher the OR for bone loss with multivariate ORs of 2.57 (95% CI 1.45-4.56) and 2.96 (95% CI 1.67-5.22), respectively. To the best of our knowledge, this study is the first to demonstrate that high total urinary arsenic or blood lead levels and frequent or occasional alcohol consumption had a significant multiplicative interaction for increasing the OR for bone loss.

The effects of dietary changes on bone markers in postmenopausal vertebral osteopenia.

BACKGROUND & AIMS: Nutrition is one of the most important environmental factors affecting the formation of osteopenia. The purpose of this study was to investigate the effects of dietary changes on bone formation and bone resorption markers of postmenopausal women with vertebral osteopenia. METHODS: In this study, 108 women with postmenopausal vertebral osteopenia were included. Patients were observed for a month to identify their regular nutritional status. Before intervention, blood and urine samples were taken from all patients. Then, 2-day food consumption records were taken and the patients were divided into 4 groups. Different types of diets (opposite of their regular diets) were prepared for these groups (1: control, 2: reduced-carbohydrate, 3: reduced-protein, 4: reduced-sodium) and followed for 3 months. At the end of follow-ups, blood and urine samples were taken again and changes in osteocalcin (OC) and N-terminal telopeptide (NTX) levels were examined. RESULTS: According to biochemical analysis, there was a significant decrease (p < 0,001) in OC levels in reduced protein group and an increase (p > 0,05) in reduced carbohydrate group. When NTX levels were assessed, a significant decrease (p < 0.001) in the reduced carbohydrate group and a significant increase in the reduced protein group (p < 0.05) were found. CONCLUSION: Our findings show that reduced carbohydrate diet protected whereas, reduced protein diet negatively affected bone health. Osteopenic individuals were thought to be able to improve bone health and their quality of life by early dietary intervention.

Associations of Bone Mineral Density and Bone Metabolism Indices with Urine Albumin to Creatinine Ratio in Chinese Patients with Type 2 Diabetes.

OBJECTIVE: To identify correlations of bone mineral density (BMD) and bone metabolism indices with the urine albumin to creatinine ratio (ACR) as an indicator of nephropathy in Chinese patients with type 2 diabetes (T2D). METHODS: In this retrospective analysis, 297 patients with T2D were divided into 3 groups according to the urine ACR. Patients' data were analyzed to identify associations of general conditions, blood glucose level, lipid levels, and uric acid level with BMD and bone metabolism indices. RESULTS: BMD at every location tested (femoral neck, trochanter, inside hip, Ward's triangle, total hip, and lumbar vertebrae) was negatively correlated with the urine ACR (all p<0.05). Osteocalcin, beta-C-terminal telopeptide (ß-CTX), and procollagen type 1 N- peptide (P1NP) were positively correlated with urine ACR (all p<0.05). Finally, 25-hydroxyvitamin D [25(OH)D] was negatively correlated with urine ACR (p<0.05). Multiple regression analysis with adjustment for age, body mass index, disease duration, and other clinical measurements revealed no significant correlation between urine ACR and BMD measurements or ß-CTX (p>0.05). However, significant correlations remained between urine ACR and osteocalcin, P1NP, and 25(OH)D (p<0.05). The same results were obtained for postmenopausal women specifically, with the exception of a significant correlation between the ACR and ß-CTX (p<0.05). CONCLUSION: In the early stage of diabetic nephropathy, BMD changes and bone transformation acceleration may occur, and the acceleration of bone transformation may occur before the change in BMD. Therefore, it is important to monitor bone metabolism indices in the early stage of diabetic nephropathy in T2D patients.

Use of calcimimetics in children with normal kidney function.

The calcium-sensing receptor (CaSR) plays an important role in the homeostasis of serum ionized calcium by regulating parathyroid hormone (PTH) secretion and tubular calcium handling. Calcimimetics, which act by allosteric modulation of the CaSR, mimic hypercalcemia resulting in suppression of PTH release and increase in calciuria. Mostly used in children to treat secondary hyperparathyroidism associated with advanced renal failure, we have shown that calcimimetics can also be successfully used in children with bone and mineral disorders in which elevated PTH plays a detrimental role in skeletal pathophysiology in the face of normal kidney function. The current review briefly discusses the role of the CaSR and calcimimetics in calcium homeostasis, and then addresses the potential applications of calcimimetics in children with normal kidney function with disorders in which suppression of PTH is beneficial.

Association of Dietary Carotenoids Intake with Skeletal Fluorosis in the Coal-burning Fluorosis Area of Guizhou Province.

OBJECTIVE: To explore whether the intake of dietary carotenoids could protect against skeletal fluorosis in Guizhou province in which coal-burning fluorosis is endemic. METHODS: A case-control study of 196 patients with skeletal fluorosis and 196 age and gender-matched controls was conducted in Zhijin, Guizhou Province. Face-to-face interviews were conducted to assess habitual dietary intake using a 75-item food frequency questionnaire and various covariates with structured questionnaires. Urinary fluoride was measured using an ion-selective electrode method. The genotype of superoxide dismutase 2 (SOD2) rs11968525 was detected by TaqMan method. RESULTS: We observed significant dose-dependent inverse associations of skeletal fluorosis with intake of ß-carotene, lutein/zeaxanthin, lycopene, and total carotenoids (P-trend = 0.002 to 0.018), whereas α-carotene and ß-cryptoxanthin intakes were not found to be related to skeletal fluorosis, after adjustment for potential confounders. The adjusted ORs and 95% CI of skeletal fluorosis for the highest versus lowest quartile were 0.30 (0.10, 0.86) for ß-carotene, 0.23 (0.08, 0.66) for lycopene, 0.26 (0.10, 0.75) for lutein/zeaxanthin and 0.34 (0.14, 0.74) for total carotenoids (all P-trend < 0.05). Stratified analyses showed that the protective effects of lutein/zeaxanthin and total carotenoids on skeletal fluorosis were more evident for individuals with the AG+AA genotypes of SOD2 (rs11968525). CONCLUSION: Increased intakes of ß-carotene, lutein/zeaxanthin, lycopene, and total carotenoids are independently associated with a lower risk of coal-burning skeletal fluorosis. SOD2 (rs11968525) polymorphisms might modify the inverse associations between dietary carotenoids and skeletal fluorosis.

FRZB1 rs2242070 polymorphisms is associated with brick tea type skeletal fluorosis in Kazakhs, but not in Tibetans, China.

Skeletal fluorosis is a metabolic bone and joint disease caused by excessive accumulation of fluoride in the bones. Compared with Kazakhs, Tibetans are more likely to develop moderate and severe brick tea type skeletal fluorosis, although they have similar fluoride exposure. Single nucleotide polymorphisms (SNPs) in frizzled-related protein (FRZB) have been associated with osteoarthritis, but their association with the risk of skeletal fluorosis has not been reported. In this paper, we investigated the association of three SNPs (rs7775, rs2242070 and rs9288087) in FRZB1with brick tea type skeletal fluorosis risk in a cross-sectional case-control study conducted in Sinkiang and Qinghai, China. A total of 598 individuals, including 308 Tibetans and 290 Kazakhs, were enrolled in this study, in which cases and controls were 221 and 377, respectively. The skeletal fluorosis was diagnosed according to the Chinese diagnostic criteria of endemic skeletal fluorosis (WS192-2008). The fluoride content in tea water or urine was detected using the fluoride ion electrode. SNPs were assessed using the Sequenom MassARRAY system. Binary logistic regressions found evidence of association with rs2242070 AA genotype in only Kazakh participants [odds ratio (OR) 0.417, 95% CI 0.216-0.807, p = 0.009], but not in Tibetans. When stratified by age, this protective effect of AA genotype in rs2242070 was pronounced in Kazakh participants aged 46-65 (OR 0.321, 95% CI 0.135-0.764, p = 0.010). This protective association with AA genotype in rs2242070 in Kazakhs also appeared to be stronger with tea fluoride intake > 3.5 mg/day (OR 0.396, 95% CI 0.182-0.864, p = 0.020). Our data suggest there might be differential genetic influence on skeletal fluorosis risk in Kazakh and Tibetan participants and that this difference might be modified by tea fluoride intake.

Clinical utility of bone turnover markers in the management of common metabolic bone diseases in adults.

Bone turnover marker (BTMs) concentrations in blood and urine reflect bone-remodelling activity, and may be useful adjuncts in the diagnosis and management of metabolic bone diseases. Newer biomarkers, mainly bone regulatory proteins, are currently being investigated to elucidate their role in bone metabolism and disease and may in future be useful in clinical diagnosis and management of metabolic bone disease. BTM concentrations increase around menopause in women, and at a population level the degree of increase in BTMs reflect bone loss. However, lack of adequate data precludes their use in individual patients for fracture risk assessment in clinical practice. The rapid and large changes in BTMs following anti-resorptive and anabolic therapies for osteoporosis treatment indicate they may be useful for monitoring therapy in clinical practice. The offset of drug effect on BTMs could be helpful for adjudicating the duration of bisphosphonate drug holidays. BTMs may offer useful additional data in skeletal diseases that are typically characterised by increased bone remodelling: chronic kidney disease (CKD), primary hyperparathyroidism (PHPT) and Paget's disease. In CKD, bone specific alkaline phosphatase (bAP) is currently endorsed for use for the assessment of mineral bone disease. The role of BTMsin predicting the bone mineral density response to successful parathyroidectomy in PHPT shows some utility but the data are not consistent and studies are limited in size and/or duration. In Paget's disease of bone, BTMs are used to confirm diagnosis, evaluate extent of disease or degree of activity and for monitoring the response to bisphosphonate treatment. Whilst BTMs are currently used in specific clinical practice instances when investigating or managing metabolic bone disease, further data are needed to consolidate their clinical use where evidence of utility is limited.

The value of hypercalciuria in patients with osteopenia versus osteoporosis.

The aim of this study was to analyze the presence of lithogenic metabolic factors in the blood and urine of patients with osteopenia versus osteoporosis. This is a cross-sectional study including 67 patients who were divided into two groups according to the presence of either osteopenia or osteoporosis as measured by bone densitometry: group 1-40 patients with osteopenia (22 men and 18 women) and group 2-27 patients with osteoporosis (13 men and 14 women). Metabolic studies were performed on the blood and urine; statistical analysis was performed comparing means and conducting linear correlation and multivariate analyses with SPSS. Statistical significance was considered to be p ≤ 0.05. The mean age of patients in group 1 was 52.9 ± 12.8 years versus 50.3 ± 11.4 in group 2; the difference was not statistically significant. In group 2, higher levels of osteocalcin, ß-crosslaps, urinary calcium, fasting urine calcium/creatinine, 24 h urine calcium/creatinine and 24 h oxaluria were observed compared to group 1. In the multivariate analysis, only the ß-crosslaps and urinary calcium were independently associated with osteoporosis. It would be advisable to determine the urinary calcium levels in patients with osteoporosis since altered levels may necessitate modifying the diagnostic and therapeutic approach to osteoporosis.

Acid retention with reduced glomerular filtration rate increases urine biomarkers of kidney and bone injury.

Diets high in acid of developed societies that do not cause metabolic acidosis in patients with chronic kidney disease nevertheless appear to cause acid retention with associated morbidity, particularly in those with reduced glomerular filtration rate. Here we used a rat 2/3 nephrectomy model of chronic kidney disease to study induction and maintenance of acid retention and its consequences on indicators of kidney and bone injury. Dietary acid was increased in animals eating base-producing soy protein with acid-producing casein and in casein-eating animals with added ammonium chloride. Using microdialysis to measure the kidney cortical acid content, we found that nephrectomized animals had greater acid retention than sham-operated animals when both ate the soy diet. Each increment in dietary acid further increased acid retention more in nephrectomized than in sham rats. Nephrectomized and sham animals achieved similar steady-state daily urine net acid excretion in response to increments in dietary acid but nephrectomized animals took longer to do so, contributing to greater acid retention that was maintained until the increased dietary acid was stopped. Acid retention was associated with increased urine excretion of both N-acetyl-ß-D-glucosaminidase and deoxypyridinoline, greater in nephrectomized than control rats, consistent with kidney tubulointerstitial and bone matrix injury, respectively. Greater acid retention in nephrectomized than control animals was induced by a slower increase in urinary net acid excretion rate in response to the increment in dietary acid and also maintained until the dietary acid increment was stopped. Thus, acid retention increased biomarkers of kidney and bone injury in the urine, supporting untoward consequences to these two tissues.

Association between Urinary Sodium Excretion and Bone Health in Male and Female Adults.

BACKGROUND: High salt intake is a well-known risk factor for osteoporosis, but the association between bone mass and urinary sodium excretion has not been studied as yet. This study investigates the hypothesis that urinary sodium excretion is negatively associated with bone mass and the risk of osteoporosis. METHODS: This cross-sectional study was performed using data from the Korea National Health and Nutrition Examination Survey, 2008-2011. Participants (n = 16,279) were divided into age groups; men were categorized as younger than 50 years of age or 50 years or greater, women were categorized as pre- or post-menopausal. RESULTS: Multivariate linear regression analysis showed that urinary sodium excretion was negatively associated with bone mineral content (BMC) and bone mineral density (BMD) in premenopausal and postmenopausal women. Sodium excretion was negatively associated with BMC and BMD of the lumbar spine in women with normal bone health, osteopenia and osteoporosis, but there was no association in men. Increased sodium excretion was significantly associated with risk for osteoporosis/osteopenia in premenopausal women. CONCLUSIONS: This study demonstrates that urinary sodium excretion is negatively associated with bone health, suggesting that high salt intake could be a possible risk factor for osteoporosis in Korean women, but not in men.

Association between urinary lead and bone health in a general population from Taiwan.

Lead accumulates in adult bones for many decades; previous studies have shown lead's detrimental effects on osteoblast and osteoclast activity in association with bone remodeling. Osteoporosis is a disease of the bones resulting in low bone mass that induces fragile bones and hence susceptibility of fracture. We estimated the association between urinary lead (U-Pb) levels and bone health in adults participating in the third Nutrition and Health Survey in Taiwan (NAHSIT) from 2005 to 2008. A total of 398 participants were divided into normal (T-score>-1), osteopenic (T-score between -1 and -2.5), or osteoporotic (T-score<-2.5) groups according to the results of bone mineral density (BMD) measurements. Heavy metals were measured in urine specimens using inductively coupled plasma-mass spectrometry. In the multivariable logistic regression analysis, age (OR=1.08; 95% CI=1.05-1.10), former smokers (OR=2.95; 95% CI=1.22-7.11) and higher U-Pb levels than upper tertile (OR=2.30; 95% CI=1.19-4.48) were associated with osteopenia/osteoporosis. Furthermore, age (OR=1.06; 95% CI=1.02-1.10) and higher U-Pb levels (OR=2.81; 95% CI=1.13-6.97) were significantly associated with osteopenia and osteoporosis in women. These results suggest that adults, particularly in women, with higher U-Pb levels may have increased odds of osteopenia and osteoporosis.

Retrospective review of serum and urinary lithogenic risk factors in patients with osteoporosis and osteopenia.

OBJECTIVE: To analyze differences in bone remodeling markers, lithogenic factors and bone densitometry among the 3 groups of patients (controls, patients with relapsing calcium renal lithiasis, and patients with loss of bone mineral density without lithiasis). MATERIAL AND METHODS: This is a cross-sectional study including 203 patients who were divided in 3 groups: group 1 (controls), group 2 (patients with relapsing calcium renal lithiasis), and group 3 (patients with osteopenia and/or osteoporosis in the lumbar spine or hip). Bone densitometry, calcium-phosphorous and bone metabolism analysis, and analysis of lithogenic risk factors in fasting urine samples and 24-hour urine samples were performed. Statistical analysis was performed with SPSS 17.0. A P ≤.05 was considered statistically significant. RESULTS: Patients in group 2 presented greater calcium excretion and a lower citrate excretion in 24-hour urine samples as compared with the other 2 groups. The proportion of hypercalciuria and hypocitraturia was higher in group 2. In addition, patients in group 2 presented a lower loss of bone mineral density as well as altered bone remodeling markers as compared with those in group 1. Patients in group 3 also presented alterations in urine calcium and citrate excretion with respect to the control group, with elevated fasting calcium and citrate levels and calcium-to-citrateratio. CONCLUSION: Lithogenic risk factors are altered in patients with osteopenia and/or osteoporosis without renal lithiasis although to a lesser extent than patients with calcium renal lithiasis.

Utilidad de los marcadores de remodelado óseo en la detección de enfermedad mineral ósea en pacientes con fenilcetonuria / Utility of bone turnover markers in metabolic bone disease detection in patients with phenylketonuria

Fundamento y objetivo: La enfermedad mineral ósea (EMO) es más frecuente en pacientes con fenilcetonuria. Los objetivos del estudio son conocer la utilidad de los marcadores de remodelado óseo para identificar a pacientes con fenilcetonuria con EMO y conocer las alteraciones del remodelado óseo subyacentes. Pacientes y método: Estudio observacional transversal de 43 pacientes con fenilcetonuria > 7 años (extremos 7,1-41 años). Se realizó encuesta nutricional, densitometría, determinación de fosfatasa alcalina ósea (FAO), procollagen type 1 N-terminal propeptide (PNP-1, «propéptido aminoterminal del procolágeno tipo 1»), beta-crosslaps y relación calcio/creatinina en orina. Se estratificó a los pacientes por edad y tipo de tratamiento. Resultados: El 20,9% de los pacientes presentaron marcadores de remodelado óseo patológicos; el 90% de ellos eran adultos. La FAO estaba disminuida en el 70% de ellos, y el beta-crosslaps en el 42,8%. Los valores de FAO fueron patológicos con más frecuencia en diagnosticados de fenilcetonuria tardíamente (41,7 frente a 10,7%; p < 0,05) y en pacientes con EMO (60 frente a 14,3%; p < 0,05). Los valores de PNP-1 y calcio/creatinina fueron similares entre todos los pacientes con fenilcetonuria independientemente de presentar EMO, diagnóstico tardío o tratamiento con tetrahidrobiopterina. Los pacientes con disminución de FAO y beta-crosslaps recibieron menor ingesta de proteínas naturales: FAO (media [DE] de 0,21 [0,13] frente a 0,65 [0,65] g/kg; p < 0,05); beta-crosslaps (media de 0,29 [0,23] frente a 0,65 [0,66] g/kg; p < 0,05). Ninguno de los tratados con tetrahidrobiopterina presentó valores alterados de marcadores óseos. Conclusiones: Los pacientes adultos fenilcetonúricos con menor ingesta de proteínas naturales tienden a presentar valores disminuidos de FAO, marcador que puede resultar útil para identificar a los pacientes con riesgo de presentar EMO (AU)

Background and objective: Mineral bone disease is more common in phenylketonuric patients. The objectives of this study were to determine the usefulness of biochemical bone markers to identify phenylketonuric patients with mineral bone disease (MBD) and know the underlying bone remodeling alterations. Patients and method: Cross-sectional study of 43 phenylketonuric patients > 7 years (range: 7.1-41 years). A nutritional survey was performed and bone alkaline phosphatase (BAP), procollagen type 1 N-terminal propeptide (PNP-1), beta-crosslaps and ratio calcium/creatinine in urine were determined. Results: A percentage of 20.9 of patients had pathological biochemical bone markers, 90% of them being adults. BAP was decreased in 70% of them and beta-crosslaps in 42.8%. BAP values were more often pathological in phenylketonuric patients with a late diagnosis (41.7 vs. 10.7%; P < .05) and in patients with MBD (60 vs. 14.3%; P < .05). PNP-1 values and calcium/creatinine were similar among all phenylketonuric patients regardless of presenting MBD, late diagnosis or tetrahydrobipterin treatment (enzyme cofactor). Patients with decreased BAP and beta-crosslaps had lower natural protein intake: BAP (0.21 ± 0.13 vs. 0.65 ± 0.65 g/kg; P < .05); beta-crosslaps (0.29 ± 0.23 vs. 0.65 ± 0.66 g/kg; P < .05). None of the tetrahydrobiopterin treated patients showed altered values of BAP, PNP-1 or calcium/creatinine. Conclusions: Adult phenylketonuric patients with lower natural protein intake tend to have lower values of BAP, which is a marker that may be useful to identify patients at risk for MBD (AU)

The importance of calciuria as lithogenic factors in patients with osteopenia/osteoporosis.

PURPOSE: Recurrent kidney stones are associated with bone mineral density loss, altered bone remodeling markers, hypercalciuria and increased in fasting calcium/creatinine ratio. The objective was to determine biochemical alterations in urine in patients with osteopenia/osteoporosis without calcium kidney stones compared with patients with calcium kidney stones. METHODS: This is a cross-sectional study including 142 patients who were divided in two groups: Group 1 (patients with recurrent calcium kidney stones) and Group 2 (patients with osteopenia/osteoporosis in the lumbar spine or hip). Analyses of bone mineral density, calcium-phosphorous and bone metabolism and lithogenic risk factors in fasting urine samples and 24-h urine samples were performed. Statistical analysis was carried out with SPSS 17.0. A p ≤ 0.05 was considered statistically significant. RESULTS: Patients in Group 2 presented greater loss of bone mineral density and more elevated alkaline phosphatase, iPTH, phosphorous and ß-crosslaps levels, as compared to patients in Group 1. However, Group 1 presented greater urine calcium, oxalate and uric acid and a higher proportion of hypocitraturia, hypercalciuria and hyperoxaluria, as compared to Group 2. Multivariate analysis revealed that advanced age and ß-crosslaps levels are risk factors for bone mineral density loss, while low urinary calcium excretion was protective against bone demineralization. CONCLUSION: Patients with osteopenia/osteoporosis without lithiasis present some urinary biochemical alterations. This would explain the lack of lithogenic activity, although low calcium excretion in 24-h urine samples is a protective factor against the loss of bone mineral density.

The protective effect of lycopene intake on bone loss in ovariectomized rats.

Antioxidant lycopene supplementation has been shown to decrease oxidative stress and have beneficial effects on bone health. However, it remains unclear whether lycopene exerts its beneficial effect on bone metabolism through mitigation of oxidative stress in vivo. The aim of this study was to investigate whether lycopene intake protects against bone loss by reducing oxidative stress in ovariectomized rats. Female Sprague-Dawley 6-week-old rats were ovariectomized and randomly divided into four groups according to the lycopene content of their diet: 0, 50, 100, and 200 ppm. The tibial bone mineral density (BMD) in the 50, 100, and 200 ppm groups was significantly higher than that in the 0 ppm group. Serum and urinary bone resorption marker levels were significantly lower in the 50, 100, and 200 ppm groups than in the 0 ppm group. There was no significant difference in systemic oxidative stress markers among all groups. However, systemic oxidative stress levels were inversely correlated with the tibial BMD. Our findings suggest that lycopene intake significantly inhibits bone loss by suppressing bone resorption in ovariectomized rats. Further studies are necessary to clarify the effect of lycopene on oxidative stress in local tissues such as bone tissue.

[Utility of bone turnover markers in metabolic bone disease detection in patients with phenylketonuria]. / Utilidad de los marcadores de remodelado óseo en la detección de enfermedad mineral ósea en pacientes con fenilcetonuria.

BACKGROUND AND OBJECTIVE: Mineral bone disease is more common in phenylketonuric patients. The objectives of this study were to determine the usefulness of biochemical bone markers to identify phenylketonuric patients with mineral bone disease (MBD) and know the underlying bone remodeling alterations. PATIENTS AND METHOD: Cross-sectional study of 43 phenylketonuric patients>7 years (range: 7.1-41 years). A nutritional survey was performed and bone alkaline phosphatase (BAP), procollagen type 1 N-terminal propeptide (PNP-1), beta-crosslaps and ratio calcium/creatinine in urine were determined. RESULTS: A percentage of 20.9 of patients had pathological biochemical bone markers, 90% of them being adults. BAP was decreased in 70% of them and beta-crosslaps in 42.8%. BAP values were more often pathological in phenylketonuric patients with a late diagnosis (41.7 vs. 10.7%; P<.05) and in patients with MBD (60 vs. 14.3%; P<.05). PNP-1 values and calcium/creatinine were similar among all phenylketonuric patients regardless of presenting MBD, late diagnosis or tetrahydrobipterin treatment (enzyme cofactor). Patients with decreased BAP and beta-crosslaps had lower natural protein intake: BAP (0.21 ± 0.13 vs. 0.65 ± 0.65 g/kg; P<.05); beta-crosslaps (0.29 ± 0.23 vs. 0.65 ± 0.66 g/kg; P<.05). None of the tetrahydrobiopterin treated patients showed altered values of BAP, PNP-1 or calcium/creatinine. CONCLUSIONS: Adult phenylketonuric patients with lower natural protein intake tend to have lower values of BAP, which is a marker that may be useful to identify patients at risk for MBD.

Evaluation of the anti-osteoporotic effects of metformin and sitagliptin in postmenopausal diabetic women.

Osteoporosis is the most important metabolic bone disease in patients with diabetes mellitus. Several studies have documented that metformin is osteogenic in vitro. In contrast, others showed no effect of metformin on the osteogenic differentiation of bone marrow-derived mesenchymal stem cells. Incretin hormones have received much attention because of their beneficial effects beyond glycemia, including on bone health. The study evaluated the anti-osteoporotic effect of metformin and sitagliptin in postmenopausal diabetic women. Forty postmenopausal diabetic women were randomly divided into two equal groups. Group 1 received metformin (Glucophage(®) 500 mg) 1 tablet twice daily, and group 2 received sitagliptin (Januvia(®) 100 mg) 1 tablet/day, for 12 weeks. Fasting blood and urine samples were collected for measurement of serum total alkaline phosphatase (ALP), osteocalcin, and urinary deoxypyridinoline (DPD). Laboratory tests were measured at baseline, after 4 and 8 weeks, and at the end of the study. Bone mineral density of the anterior posterior lumbar spine was measured by dual energy X-ray absorptiometry at baseline and after 12 weeks of the intervention. In the metformin-treated group, the mean values for all markers of bone turnover at 12 weeks of treatment were not significantly different from baseline. In group 2, the mean serum total ALP was significantly decreased, serum osteocalcin levels were non-significantly decreased gradually by 10% at 12 weeks, while urinary DPD decreased significantly and was then maintained at 28% decrease at 12 weeks. In conclusion, metformin is neither osteogenic nor has anti-osteoporotic effect, while sitagliptin could positively regulate bone metabolism.

The relationship between fibroblast growth factor 23 and osteoporosis in postmenopausal women.

AIM: A lack of estrogen in postmenopausal women is an important factor causing the development of osteoporosis. Our purpose is to investigate the effects of Fibroblast Growth Factor 23 (FGF-23) on bone mineral metabolism and bone turnover. METHODS: Twenty-eight patients with postmenopausal osteoporosis (PMO), 32 patients with postmenopausal osteopenia and 30 healthy control subjects (postmenopausal non-osteoporosis) were included in this study. In order to assess the bone mineral metabolism; FGF 23, parathyroid hormone, vitamin D, calcium, phosphate, osteocalcin, alkaline phosphatase and hydroxyproline levels were measured. RESULTS: FGF 23 levels were found significantly higher in PMO group compared with postmenopausal osteopenia and control groups (P<0.01 and P<0.05 respectively). Urine hydroxyproline level was detected to be significantly lower in PMO patients compared with control group (P<0.01). Lomber and femur BMD levels were found to be significantly lower in PMO patients compared with postmenopausal osteopenia and control groups (P<0.001, P<0.001; P<0.001, P<0.001 respectively). On the other hand, when we categorized the PMO group subjects according to the age of menopause, the FGF 23 levels were found to be significantly higher in the group of menopausal age <5 years compared to the group of menopausal age >10 and to the group of menopausal age 5-10 years (P<0.05, P<0.05). CONCLUSION: We think our findings indicate that serum FGF 23 level is a significant determinant of increased bone turnover at early periods in PMO patients.

Mitigation of oxidative damage by green tea polyphenols and Tai Chi exercise in postmenopausal women with osteopenia.

BACKGROUND: Osteoporosis is a degenerative bone disease predominantly in postmenopausal women. Green tea polyphenols (GTP) and Tai Chi (TC) have been shown to be beneficial on human bone health. This study examined the efficacy of GTP and TC on mitigation of oxidative damage in postmenopausal women with osteopenia. METHODS: A 6-month randomized and placebo-controlled clinical trial was conducted in 171 postmenopausal women with osteopenia, who were recruited from Lubbock County, Texas. These participants were treated with placebo, GTP (500 mg daily), placebo + TC (60-minute group exercise, 3 times/week), or GTP (500 mg daily) + TC (60-minute group exercise, 3 times/week), respectively. Their blood and urine samples were collected at the baseline, 1-, 3- and 6-months during intervention for assessing levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), an oxidative DNA damage biomarker, and concentrations of serum and urine GTP components. RESULTS: The elevated concentrations of serum and urinary GTP components demonstrated a good adherence for the trial. A significant reduction of urinary 8-OHdG concentrations was found in all three treated groups during 3-month (P<0.001) and 6-month (P<0.001) intervention, as compared to the placebo group. The significant time- and dose-effects on mitigation of the oxidative damage biomarker were also found for GTP, TC, and GTP+TC intervened groups. CONCLUSION: Our study demonstrated that GTP and TC interventions were effective strategies of reducing the levels of oxidative stress, a putative mechanism for osteoporosis in postmenopausal women, and more importantly, working in an additive manner, which holds the potential as alternative tools to improve bone health in this population. TRIAL REGISTRATION: ClinicalTrials.gov NCT00625391.

[Prevention of bone mineral deficiency in premature infants: review of the literature with focus on monitoring of urinary calcium and phosphate]. / Knochenmineralmangel bei Frühgeborenen: Prävention mittels Urinmonitoring von Kalzium und Phosphat.

BACKGROUND: Bone mineral deficiency of prematurity (BMDoP) is caused by the lack of simultaneous availability of calcium (Ca) and anorganic phosphate (P) during rapid skeletal growth. METHODS: Review of the literature on the prevention of BMDoP, with specific attention to the limitations of the monitoring of urinary calcium and phosphate concentrations. RESULTS: Intrauterine bone mineral accretion (BMA) can be achieved in preterm infants if urinary concentrations of Ca and P continuously show that the supplementation with these ions slightly exceeds the actual need. An individually adjusted supplementation with Ca and P appears rational because both growth velocity and enteral Ca absorption are highly variable and determine the need for enteral Ca and P administration. If, however, urinary concentrations of Ca and P are used to determine whether Ca and P supplementation is adequate, mechanisms affecting the urinary excretion of these ions other than nutrition have to be taken into account. Specifically, methylxanthines and diuretics increase the renal Ca losses, and the renal P threshold may be lowered in premature infants. A positive effect of physical activity on BMA has been shown in several studies. CONCLUSIONS: An individualized Ca and P supplementation in preterm infants aiming for supplementation in a slight excess of the actual need and guided by urinary Ca and P concentrations appears able to prevent BMDoP. Monitoring of urinary Ca and P concentrations needs to take into account non-nutritional factors affecting these concentrations. BMA may further be improved by physical activity.