Denosumab Improves Glomerular Filtration Rate in Osteoporotic Patients With Normal Kidney Function by Lowering Serum Phosphorus.

Higher serum phosphorus (Pi) increases the risk for chronic kidney disease (CKD). It was reported that a single administration of denosumab or zoledronate significantly suppressed serum Pi levels as well as those of bone resorption markers in serum. Also, previous evidences suggest a link between bone anti-resorptive therapy and vasoprotective/renoprotective effects through mechanisms that remain unexplored. The aim of this study is to assess the renoprotective effect of denosumab and involvement of denosumab-induced reduction in serum Pi in osteoporotic patients. Osteoporotic patients (n = 73) without overt proteinuria in dipstick test results were treated with denosumab (60 mg) every 6 months during the study period (24 months). Estimated glomerular filtration rate based on serum cystatin C (eGFRcys) was used as a filtration marker and tartrate-resistant acid phosphatase-5b (TRACP-5b) as a bone resorption marker. For analysis of non-CKD patients (n = 56), those with eGFRcys <60 mL/min/1.73 m2 were excluded. A single injection of denosumab suppressed serum Pi as well as TRACP-5b during the first 6 months, whereas age-related decline in eGFRcys was significantly reversed, with an increase of 2.75 ± 1.2 mL/min/1.73 m2 after 24 months noted. Multivariate analysis showed that serum Pi reduction following the initial denosumab injection was positively associated with serum TRACP-5b suppression during that same period (ß = 0.241, p = 0.049). In addition, a positive association of serum Pi suppression, but not of corrected calcium or TRACP-5b, with eGFRcys increase after 24 months (ß = 0.321, p = 0.014) was found after adjustments for gender, age, BMI, antihypertensive drug use, albumin, and eGFRcys. The same was observed in osteoporotic cases restricted to non-CKD patients. In conclusion, serum Pi reduction resulting from phosphorus load decrement from bone induced by denosumab is a determinant for eGFRcys increase. Early introduction of bone antiresorptive therapy can retain glomerular filtration in osteoporosis cases, including non-CKD patients. © 2019 American Society for Bone and Mineral Research.

Association of Urinary Citrate With Acid-Base Status, Bone Resorption, and Calcium Excretion in Older Men and Women.

Context: Elevated urine net acid excretion (NAE), indicative of subclinical metabolic acidosis, has been associated with higher bone turnover. Urine citrate, which is a common clinical measure, changes in response to acid-base status but its association with bone turnover is uncertain. Objective: We evaluated the association between change in urine citrate and change in bone turnover and calcium excretion. Design, Intervention, and Participants: A total of 233 healthy men and women ≥60 years old were randomly assigned to 1.0 mmol/kg/d potassium bicarbonate (KHCO3), 1.5 mmol/kg/d KHCO3, or placebo for 84 days. Outcome Measures: Urine citrate, NAE, N-telopeptide of collagen type-I (NTX), calcium excretion, and serum amino-terminal propeptide of type 1 procollagen (P1NP) were measured before and after intervention. Results: Urine citrate increased dose dependently after KHCO3 supplementation (P trend < 0.001). The urine citrate change was significantly inversely associated with P1NP change (P = 0.021) but not with change in NTX (P = 0.051) or calcium excretion (P = 0.652). The NAE change was positively associated with change in NTX and calcium excretion (P ≤ 0.003) but not with change in P1NP (P = 0.051). When the urine citrate change and NAE change were included in the same model, the urine citrate change was not associated with change in NTX, calcium excretion, or serum P1NP (P ≥ 0.086), whereas change in NAE remained associated with change in NTX and calcium excretion (P ≤ 0.003). Conclusion: Urine citrate may not be a suitable alternative to NAE when assessing acid-base status in relation to bone turnover in older adults.

Effect of low level laser therapy on local bone resorption during orthodontic treatment: a randomized controlled trial / Efecto del laser terapéutico en la reabsorción osea local durante tratamientos de ortodoncia: un ensayo clínico aleatoriamente controlado

The aim of this study was to assess whether the application of low-level laser therapy (LLLT) during the first stage of orthodontic treatment has an effect on local bone resorption and is detectable at the systemic level by measuring deoxypyridinoline levels (Pyrilinks) in urine. This was a randomized (1:1), double-blind, active-controlled, parallel-group trial. 28 adult patients who were going to start orthodontic treatment were randomly divided into the control group (n: 13) and the experimental group (n: 15), the latter of which received LLLT. All of the subjects underwent testing of urine samples: the first one on the day before the beginning of orthodontic treatment (T0), and the second one 5 days after bracket placement to measure Pyrilinks values (Dpd/Cr) in urine. Group differences were evaluated with Student's paired t-test. At the beginning of the study, the Pyrilinks were in the normal range for 53.57 % of the patients, and 46.43 % had elevated values according to the normal ranges. Only taking into account the normal values at (T0), the average Pyrilinks for control group (T0) were 5.75± 1.20 nM/mM, (T1): 6.02±3.00 nM/mM. For experimental group, (T0) was 5.71± 0.72, and it was 6.63± 0.73 in (T1).There were no significant differences in the Pyrilinks changes. (p= 0.75). In the experimental group levels raised statistically significant (p = 0.009). LLLT on patients starting orthodontic treatment with normal Pyrilinks levels have a statistically significant increment on their levels 5 days post irradiation.

El objetivo de este trabajo fue evaluar si la aplicación de la terapia láser de bajo nivel (TLBN) durante la primera etapa del tratamiento ortodóncico tiene un efecto sobre la resorción ósea local y es detectable a nivel sistémico midiendo los niveles de desoxipiridinolina en la orina. Se trató de un ensayo aleatorizado (1:1), doble ciego, controlado de forma activa y paralelo. 28 pacientes adultos que iban a iniciar el tratamiento de ortodoncia se dividieron al azar en el grupo control (n: 13) y el grupo experimental (n: 15), el último de los cuales recibió TLBN. Todos los sujetos fueron sometidos a pruebas de muestras de orina: la primera en el día anterior al inicio del tratamiento ortodóncico (T0) y la segunda 5 días después de la colocación del bracket para medir los valores de Pyrilinks (Dpd / Cr) en la orina. Las diferencias grupales se evaluaron con la prueba t de Student pareada. Al inicio del estudio, los Pyrilinks estaban en el rango normal para 53,57 % de los pacientes, y 46,43 % tenían valores elevados según los rangos normales. Sólo teniendo en cuenta los valores normales en (T0), los Pyrilinks medios para el grupo de control (T0) fueron 5,75 ± 1,20 nM / mM, (T1): 6,02 ± 3,00 nM / mM. Para el grupo experimental, (T0) fue de 5,71 ± 0,72, y fue de 6,63 ± 0,73 en (T1). No hubo diferencias significativas en los cambios de Pyrilinks. (P = 0,75). En el grupo experimental los niveles aumentaron estadísticamente (p = 0,009). LLLT en los pacientes que comienzan el tratamiento ortodóncico con niveles normales de Pyrilinks tienen un incremento estadísticamente significativo en sus niveles 5 días después de la irradiación.

Reduced bone resorption by intake of dietary vitamin D and K from tailor-made Atlantic salmon: A randomized intervention trial.

Suboptimal vitamin D status is common among humans, and might increase bone resorption with subsequent negative effects on bone health. Fatty fish, including Atlantic salmon, is an important dietary vitamin D source. However, due to a considerable change in fish feed composition, the contribution of vitamin D from salmon fillet has been reduced. The main objective was to investigate if intake of vitamin D3 enriched salmon or vitamin D3 tablets decreased bone biomarkers (urinary N-telopeptides, deoxypyridinoline, serum bone-specific alkaline phosphatase, and osteocalcin) compared to a low vitamin D3 intake. The 122 healthy postmenopausal women included in this 12 weeks intervention trial were randomized into four groups: three salmon groups (150 grams/two times/week) and one tablet group (800 IU vitamin D and 1000 mg calcium/day). The salmon groups also received calcium supplements. The salmon had three different vitamin D3/vitamin K1 combinations: high D3+high K1, low D3+high K1, or high D3+low K1. Increased intake of salmon containing high levels of vitamin D3 (0.35-0.38 mg/kg/fillet) and supplements with the same weekly contribution had a positive influence on bone health as measured by bone biomarkers in postmenopausal women. Consequently, an increased level of vitamin D3 at least to original level in feed for salmonids will contribute to an improved vitamin D3 status and may improve human bone health.

Serum sclerostin increases in healthy adult men during bed rest.

CONTEXT: Animal models and human studies suggest that osteocytes regulate the skeleton's response to mechanical unloading in part by an increase in sclerostin. However, few studies have reported changes in serum sclerostin in humans exposed to reduced mechanical loading. OBJECTIVE: We determined changes in serum sclerostin and bone turnover markers in healthy adult men undergoing controlled bed rest. DESIGN, SETTING, AND PARTICIPANTS: Seven healthy adult men (31 ± 3 yr old) underwent 90 d of 6° head down tilt bed rest at the University of Texas Medical Branch Institute for Translational Sciences-Clinical Research Center. OUTCOMES: Serum sclerostin, PTH, vitamin D, bone resorption and formation markers, urinary calcium and phosphorus excretion, and 24-h pooled urinary markers of bone resorption were evaluated before bed rest [baseline (BL)] and at bed rest d 28 (BR-28), d 60 (BR-60), and d 90 (BR-90). Bone mineral density was measured at BL, BR-60, and 5 d after the end of the study (BR+5). Data are reported as mean ± SD. RESULTS: Consistent with prior reports, bone mineral density declined significantly (1-2% per month) at weight-bearing skeletal sites. Serum sclerostin was elevated above BL at BR-28 (+29 ± 20%; P = 0.003) and BR-60 (+42 ± 31%; P < 0.001), with a lesser increase at BR-90 (+22 ± 21%; P = 0.07). Serum PTH levels were reduced at BR-28 (-17 ± 16%; P = 0.02) and BR-60 (-24 ± 14%; P = 0.03) and remained lower than BL at BR-90 (-21 ± 21%; P = 0.14), but did not reach statistical significance. Serum bone turnover markers were unchanged; however, urinary bone resorption markers and calcium were significantly elevated at all time points after bed rest (P < 0.01). CONCLUSIONS: In healthy men subjected to controlled bed rest for 90 d, serum sclerostin increased, with a peak at 60, whereas serum PTH declined, and urinary calcium and bone resorption markers increased.

Consumption of legumes improves certain bone markers in ovariectomized rats.

Soybeans are known to protect against osteoporosis, but other legumes frequently consumed in Asia have not been studied to learn if they have a similar protective effect. This study investigated the hypothesis that consumption of soybean, mung bean, cowpea, and adzuki bean has beneficial effects on bone biomarkers in ovariectomized rats. Female Sprague-Dawley rats were either sham operated (sham; n = 7) or surgically ovariectomized and then fed a regular AIN-93M diet (OVX; n = 7) or AIN-93M containing soybean (n = 7), mung bean (n = 7), cowpea (n = 7), or adzuki beans (n = 7) for 10 weeks. No bean consumption significantly altered the body, subcutaneous fat, or uterus weight; however, consumption significantly increased the serum calcium/phosphorous ratio and decreased urinary calcium excretion compared with those of the OVX group. Serum concentration of 17ß-estradiol was significantly lower in the OVX group compared with that of the sham group and was lowest in the group fed OVX diet containing soybean. Serum osteocalcin concentration was significantly higher in all OVX rats given a diet with beans compared with the same diet without, but urinary deoxypyridinoline excretion was lowest in the group fed OVX diet containing cowpea. There were no significant differences in bone mineral density or bone mineral content of the right femur, tibia, or lumbar spine or in the trabecular bone volume of the tibia among the diet groups. In conclusion, the consumption of soybean, mung bean, cowpea, and adzuki bean in OVX rats improved osteocalcin, but only those fed cowpea showed decreased bone resorption biomarker, suggesting that cowpea may have the most protective effect on bone in OVX rats.

Silicon supplementation improves the bone mineral density of calcium-deficient ovariectomized rats by reducing bone resorption.

The purpose of this study was to investigate the effect of silicon (Si) supplementation on bone mineral density (BMD) and bone metabolism parameters relative to calcium (Ca) intake levels in ovariectomized rats. A total of 72 female Wistar rats (6 weeks) were ovariectomized (OVX) and divided into six groups, and Si (500 mg of Si per kilogram of feed) was or was not administered with diets containing various levels of Ca (0.1%, 0.5%, and 1.5%) for 10 weeks. The groups were as follows: (1) Ca-deficient group (0.1% Ca), (2) Ca-deficient with Si supplementation group, (3) adequate Ca group (0.5% Ca), (4) adequate Ca with Si supplementation group, (5) high Ca group (1.5% Ca), and (6) high Ca with Si supplementation group. Si supplementation significantly increased the BMD of the femur and tibia in Ca-deficient OVX rats, while no change was observed with Si supplementation in the BMD of the spine, femur, and tibia in the adequate and high Ca groups. Serum alkaline phosphatase and osteocalcin levels were not affected by Si supplementation or Ca intake levels. C-telopeptide type I collagen levels were significantly decreased as a result of Si supplementation in Ca-deficient OVX rats. In summary, Si supplementation produced positive effects on bone mineral density in Ca-deficient OVX rats by reducing bone resorption. Therefore, Si supplementation may also prove to be helpful in preventing osteoporosis in postmenopausal women whose calcium intake is insufficient.

Surveillance results of depleted uranium-exposed Gulf War I veterans: sixteen years of follow-up.

As part of a longitudinal surveillance program, 35 members of a larger cohort of 77 Gulf War I veterans who were victims of depleted uranium (DU) "friendly fire" during combat underwent a 3-day clinical assessment at the Baltimore Veterans Administration Medical Center (VAMC). The assessment included a detailed medical history, exposure history, physical examination, and laboratory studies. Spot and 24-h urine collections were obtained for renal function parameters and for urine uranium (U) measures. Blood U measures were also performed. Urine U excretion was significantly associated with DU retained shrapnel burden (8.821 mug U/g creatinine [creat.] vs. 0.005 mug U/g creat., p = .04). Blood as a U sampling matrix revealed satisfactory results for measures of total U with a high correlation with urine U results (r = .84) when urine U concentrations were >/=0.1 mug/g creatinine. However, isotopic results in blood detected DU in only half of the subcohort who had isotopic signatures for DU detectable in urine. After stratifying the cohort based on urine U concentration, the high-U group showed a trend toward higher concentrations of urine beta(2) microglobulin compared to the low-U group (81.7 v. 69.0 mug/g creat.; p = .11 respectively) and retinol binding protein (48.1 vs. 31.0 mug/g creat.; p = .07 respectively). Bone metabolism parameters showed only subtle differences between groups. Sixteen years after first exposure, this cohort continues to excrete elevated concentrations of urine U as a function of DU shrapnel burden. Although subtle trends emerge in renal proximal tubular function and bone formation, the cohort exhibits few clinically significant U-related health effects.

Prolyl-hydroxyproline dipeptide in non-hydrolyzed morning urine and its value in postmenopausal osteoporosis.

BACKGROUND: Owing to the high correlation between the level of prolyl-4-hydroxyproline dipeptide in non-hydrolyzed urine and that of 4-hydroxyproline in hydrolyzed urine, we examined whether the dipeptide might function as a valuable marker of bone turnover. METHODS: Based on densitometric measurements, 68 postmenopausal women were divided into groups of non-osteopathic, osteopenic and osteoporotic subjects. The dipeptide and current urinary resorption markers were assayed in morning urine, the former using liquid chromatography, the others plus serum formation markers by means of immunoassay procedures. Together with the assay of basal levels, diet-related changes and healing effect of yearly alendronate therapy were assessed. RESULTS: Concentration levels in controls and osteoporotic subjects differed significantly; receiver operating characteristics yielded sensitivity of 0.743, specificity of 0.908, area under curve of 0.903, and cut-off of 10.2 micromol/mmol of creatinine. Spearman rank correlation showed the highest pair coefficient between the dipeptide and osteocalcin. Diet-related changes were not found. Following therapy, a significant decline occurred already within a trimester, whilst with the other resorption markers not until 6 months. CONCLUSIONS: The ease of the dipeptide assay in non-hydrolyzed urine surpasses that of hydroxyproline, and the results present the compound as a real competition to other commonly assessed markers in osteopathies.

Sodium and bone health: impact of moderately high and low salt intakes on calcium metabolism in postmenopausal women.

High salt intake is a well-recognized risk factor for osteoporosis because it induces calciuria, but the effects of salt on calcium metabolism and the potential impact on bone health in postmenopausal women have not been fully characterized. This study investigated adaptive mechanisms in response to changes in salt and calcium intake in postmenopausal women. Eleven women completed a randomized cross-over trial consisting of four successive 5-wk periods of controlled dietary intervention, each separated by a minimum 4-wk washout. Moderately low and high calcium (518 versus 1284 mg) and salt (3.9 versus 11.2 g) diets, reflecting lower and upper intakes in postmenopausal women consuming a Western-style diet, were provided. Stable isotope labeling techniques were used to measure calcium absorption and excretion, compartmental modeling was undertaken to estimate bone calcium balance, and biomarkers of bone formation and resorption were measured in blood and urine. Moderately high salt intake (11.2 g/d) elicited a significant increase in urinary calcium excretion (p = 0.0008) and significantly affected bone calcium balance with the high calcium diet (p = 0.024). Efficiency of calcium absorption was higher after a period of moderately low calcium intake (p < 0.05) but was unaffected by salt intake. Salt was responsible for a significant change in bone calcium balance, from positive to negative, when consumed as part of a high calcium diet, but with a low calcium intake, the bone calcium balance was negative on both high and low salt diets.

[Effects of Dioscorea septemloba on bone metabolism in ovariectomized rats].

OBJECTIVE: To investigate the effects of the decoction of Rhizoma Dioscorea septemlobae (RD) on the bone metabolism in ovariectomized rats. METHOD: Thirty female, 3-month-old Wistar rats without pregnancy and deliver were randomly divided into 6 groups: sham (sham-operation), ovariectomy (OVX), OVX + diethylstilbestrol, OVX + high dose RD (4 g x kg(-1) x d(-1)), OVX + middle dose RD (2 g x kg(-1) x d(-1)) and OVX + low dose RD (1 g x kg(-1) x d(-1)) (n = 5 in every group). After 12-week period of continuous treatment, the urinary samples and blood samples were collected for the determination of serum estrodiol (E2), calcium (Ca), phosphorus (P), bone glaprotein (BGP), alkaline phosphatase (ALP), urinary calcium/creatinine (Ca/Cr), phosphorus/ creatinine (P/Cr) and deoxypyridioline/creatinine (DPD/Cr). The uteri were removed and weighed. The bone mineral density (BMD) and the biomechanical parameters of the femur of the rats in every group were determined, respectively. RESULT: The coefficient of uteri in every dose group of OVX + RD was significantly higher than that in the OVX group (P < 0.01). The concentration of serum ALP, BGP and urinary DPD/Cr, Ca/Cr in the OVX group was significantly higher than that in the sham group (P < 0.05), respectively, However, that in the every dose of OVX + RD was lower than that in the OVX group, respectively. There was no significan difference in the concentration of serum Ca, P and urinary P/Cr in every group, respectively. The bone mineral density (BMD) in the OVX group was (0.032 +/- 0.007) g x cm(-2) and was significantly lower than that in the sham group (P < 0.01). However, the value in the group of every dose OVX + RD was significantly higher than that in the OVX group (P < 0.05, P < 0.01), respectively. The maximum loading, deflection and the maximum strain of the femur in the OVX group were (125.78 +/- 15.48) N, (1.87 +/- 0.22) mm, (9.34 +/- 1.10) % and were significantly lower than those in the sham group (P < 0.05, P < 0.01), respectively. The maximum loading and maximum stress were increased in different extent in the every dose group of OVX + RD, respectively. CONCLUSION: The decoction of RD can inhibit bone absorption, decline bone turnover and improve the loss of bone in ovariectomized rats.

Short- to mid-term effects of ovariectomy on bone turnover, bone mass and bone strength in rats.

To determine the short- to mid-term effects of ovariectomy on bone turnover, bone mass and bone strength in rats. SD rats aged 12 weeks were randomly divided into No-treatment, Sham and OVX groups. The rats were sacrificed for sample collection at week 0, week 4 and week 18 after surgical operation. Chemistries in serum and urine were measured by standard colorimetric methods and bone turnover markers were measured by ELISA kits. Bone mass and bone strength were determined using pQCT system and three-point bending tests, respectively. At week 4, OVX rats showed drastic increase in the level of urine Ca, P and DPD. At week 18, in OVX rats the levels of serum ALP, urine DPD and Ca were much higher and the level of serum Ca was much lower when comparing with Sham rats. Ovariectomy produced significant reduction in cancellous BMD, total BMD and SSI of proximal tibial metaphysis rapidly at week 4 and continuously at week 18 after surgical operation. However, no marked changes of bone mass and bone strength were found in the diaphysis of tibia and femur, respectively. The current study concluded that ovariectomy induced the uncoupling of bone turnover, and the proximal metaphysis of long bone was the sensitive site for the short- to mid-term effect of ovariectomy, demonstrated as the markers of bone mass and stress strain index.

In long-term bedridden elderly patients with dietary copper deficiency, biochemical markers of bone resorption are increased with copper supplementation during 12 weeks.

BACKGROUND: Although the effect of copper on bone has been tested in animals and healthy subjects, no studies concerning the effect of copper supplementation on bone metabolism in patients with copper deficiency have been reported because of the rarity of these patients. This study was conducted to investigate the effect of copper supplementation on bone metabolism in copper-deficient patients. METHOD: This study included 10 patients (83.7 +/- 8.3 years) with dietary copper deficiency under long-term bed rest for more than 12 months. They had their diets supplemented with copper sulfate (3 mg/day) over 12 weeks in addition to their diet of only one kind of enteral food with a low concentration of copper. Serum copper and ceruloplasmin, urinary deoxypyridinoline (DPD) and collagen-type 1 N-telopeptide (NTX) (biomarkers of bone resorption), serum osteocalcin (OC) and bone-specific alkaline phosphatase (Bone ALP) (biomarkers of bone formation) were analyzed at baseline, 4 and 12 weeks after copper supplementation. RESULTS: DPD and NTX excretion were significantly increased 4 weeks after copper supplementation (p = 0.009 and p = 0.013, respectively). Serum bone ALP and OC were not significantly changed 12 weeks after copper supplementation (p = 0.051 and p = 0.594). CONCLUSIONS: In patients with nutritional copper deficiency, bone resorption markers are increased with copper supplementation.

Dietary acid-base balance, bone resorption, and calcium excretion.

OBJECTIVE: Metabolic studies reveal that acidogenic diets increase bone resorption acutely. This study was conducted to examine associations between diet-induced changes in net acid excretion (NAE) and changes in serum parathyroid hormone (PTH), bone resorption, and calcium excretion over a longer period of 60 days. METHODS: Forty healthy older men and women were given 0.75 g/kg of protein as meat, 600 mg of calcium, and 400 IU of vitamin D3 daily and either cereal (acidogenic) or fruit and vegetable (alkalinogenic) foods as substitutes for some of the cereal in their usual diets. Blood and 24-hr urine measurements were made on days 14 (baseline), 44, and 74. RESULTS: In all subjects, change in renal NAE was correlated with changes in serum PTH (r = 0.358, P = 0.023), urinary N-telopeptide (NTX) (r = 0.367, P = 0.020), and urinary calcium excretion (rp = 0.381, P = 0.020, after adjustment for diet group, change in PTH, and change in sodium excretion). CONCLUSIONS: Diet changes that increase renal NAE are associated with increases in serum PTH, bone resorption, and calcium excretion over a 60-day period.

Altered levels of biochemical indices of bone turnover and bone-related vitamins in patients with Crohn's disease and ulcerative colitis.

BACKGROUND: The pathogenesis of inflammatory bowel disease-associated osteopenia may be related to pathological rates of bone turnover; however, the literature shows mixed results. AIM: To compare bone biomarkers in inflammatory bowel disease patients (Crohn's disease: n = 68, and ulcerative colitis: n = 32, separately) with age- and sex-matched healthy controls. SUBJECTS: Patients and controls were recruited from Cork University Hospital and Cork City area, respectively. RESULTS: Relative to that in their respective controls, Crohn's disease (n = 47) and ulcerative colitis (n = 26) patients (i.e. excluding supplement users) had significantly (P < 0.05-0.001) higher serum undercarboxylated osteocalcin (by 27% and 63%, respectively) and bone-specific alkaline phosphatase (by 15% and 21%, respectively) and urinary Type I collagen cross-linked N-telopeptides concentrations (by 87% and 112%, respectively). Relative to that in their respective controls, Crohn's disease and ulcerative colitis patients had significantly (P < 0.01) lower serum total osteocalcin (by 20% and 42%, respectively) and 25-hydroxyvitamin D (by 37% and 42%, respectively), while serum parathyroid hormone levels were similar. In the combined patient group (n = 100), undercarboxylated osteocalcin was positively associated with bone markers. CONCLUSIONS: Both Crohn's disease and ulcerative colitis patients have altered bone turnover relative to that in healthy controls.

Absence of marked seasonal change in bone turnover: a longitudinal and multicenter cross-sectional study.

UNLABELLED: The effect of season on bone turnover is controversial. No information is available on seasonality of new serum markers of bone resorption. In this study, we have been unable to confirm findings of a marked wintertime increase in bone formation and resorption within the general population. Seasonality was assessed by cosinor analysis. INTRODUCTION: We investigated the effect of season on seven markers of bone turnover in a longitudinal study (six men and six premenopausal women; age, 24-44 years) and a separate large population-based multicenter European study (n = 2780 women, Osteoporosis and Ultrasound Study [OPUS]). MATERIALS AND METHODS: Measurements included serum Crosslaps, procollagen type I N-terminal propeptide (PINP), osteocalcin (OC), and the N-telopeptide fragment of type I collagen in urine (NTX). Seasonality was assessed by cosinor analysis with Hotelling's T2 test. RESULTS: Serum 25(OH) vitamin D showed a marked seasonal rhythm. There was no significant seasonal component for any marker of bone turnover in the longitudinal analysis (cosinor analysis, p > 0.05). The percentage of within subject variance accounted for by any seasonal trend was very small for all markers (less than 2.5%). Less than 1% of the between-person variance was accounted for by seasonality in the cross-sectional analysis for all markers (n = 2780). There was a small but statistically significant summertime increase in OC and PINP in the healthy postmenopausal population after exclusions based on disease or medication use (remaining n = 1226, amplitudes 5.6% and 5.4%, respectively, p < 0.001). CONCLUSIONS: We have been unable to confirm findings of a marked wintertime increase in bone formation and resorption within the general population. The absence of marked seasonality was irrespective of age, menopausal status, reported supplemental Vitamin D intake, age or geographical location. The small but statistically significant summertime increase in bone formation in this and other studies is unlikely to confound clinical interpretation of these measurements.

The effects of soy protein containing isoflavones on lipids and indices of bone resorption in postmenopausal women.

OBJECTIVE: To assess the effect of a dietary soy protein supplement containing isoflavones on lipids and indices of bone resorption in postmenopausal women. DESIGN: Placebo-controlled, double-blind, randomized study. PATIENTS: One hundred and six postmenopausal women were randomized to dietary soy supplementation (n = 51) or placebo (n = 55) for 3 months, of which 78 were included in the final analysis. MEASUREMENTS: Lipid profiles including total, low-density lipoprotein (LDL) and HDL cholesterol as well as triacylglycerol were measured. Pyridinoline and deoxypyridinoline were used as markers of bone resorption. Urinary isoflavone excretion was measured to assess compliance. RESULTS: There was a significantly greater increase in urinary isoflavone excretion detected in the soy group compared to placebo. Lipid profiles improved with significant decreases in LDL cholesterol (-0.60 +/- 0.10 vs.-0.29 +/- 0.09 mmol/l, P < 0.05), triacylglycerol (-0.22 +/- 0.07 vs. +0.01 +/- 0.05 mmol/l, P < 0.005) and the LDL : HDL ratio (-0.32 +/- 0.10 vs. +0.20 +/- 0.10, P < 0.005) in the soy group compared to placebo. There were no significant differences between the soy and placebo groups for urinary excretion of pyridinoline (-3.8 +/- 3.1 vs.-0.8 +/- 3.1 nmol/mmolCr, P = 0.4) or deoxypyridinoline (-0.8 +/- 0.9 vs.-0.3 +/- 0.7 nmol/mmolCr, P = 0.4). CONCLUSIONS: In postmenopausal women, dietary supplementation with soy protein containing isoflavones does not appear to have oestrogenic effects on markers of bone resorption. Soy protein favourably affected lipids; however, these effects (fall in triacylglycerol and no change in HDL) differ from those observed with oral oestrogen. These findings suggest that soy may not have biologically significant oestrogenic effects on bone resorption and we hypothesize that the lipid effects may be mediated, at least in part, through nonoestrogenic mechanisms.

Sistema "Point of Care" de medición de la resorción ósea en orina y comparación con otros métodos / System "Point of Care" of mensuration of the bony resorption in urine and comparison with other methods

Introducción. Con la depleción estrogénica se produce un aumento del remodelado óseo, cuyo grado podemos determinar mediante el análisis de los marcadores bioquímicos. Objetivos. Comparar los resultados de los marcadores de resorción CrossLaps (CTx) en orina determinados por el Sistema Osteosal-Instaquant, con otros marcadores de resorción ósea en orina. Material y método. Se seleccionaron aleatoriamente 45 mujeres posmenopáusicas (edades entre 48-52 años) a las cuales se recogió la segunda micción de orina, y se determinó, hidroxiprolina/creatinina, NTx/creatinina, D-piridinolina/creatinina, calcio/creatinina, y fósforo/creatinina y Test Osteosal-Instaquant (CTx).Resultados. Encontramos correlación significativa entre el sistema "point of care" (POC) del Osteosal-Instaquant/C y la determinación de NTx/C (p = 0,008) aunque con asociación débil (r=0,392). Había una correlación significativa entre el Sistema Osteosal-Instaquant/C y la determinación de DPD/C (dexosipiridinolina/C) (p = 0,002) aunque nuevamente con asociación débil (r = 0,455). Existe una correlación significativa (p = 0,0015) con asociación (r = 0,463), entre el Sistema Osteosal-Instaquant/C y la determinación de hidroxiprolina/C (hidroxiprolina/C). Gran asociación entre los DPD/C y el NTx/C (r = 0,953 y p = 000), también existe una gran asociación entre la hidroxiprolina/C y los NTx/C (r = 0,992 y p = 000). Gran asociación entre DPD/C e hidroxiprolina/C (r = 0,940 y p = 000). No existe asociación entre el NTx/C y el calcio/C. Conclusiones. El Test Osteosal-InstaquantTM mide CTx en orina del paciente, mediante el denominado método POC, es fácil de usar, y a la vista de las conclusiones obtenidas, podría tener utilidad en la monitorización de los tratamientos antirresortivos (AU)

Soy protein supplementation increases serum insulin-like growth factor-I in young and old men but does not affect markers of bone metabolism.

Recent studies suggest that soy protein (SP) protects bone in women; however, its effects on bone metabolism in men have not been investigated. Healthy men (59.2 +/- 17.6 y) were assigned to consume 40 g of either SP or milk-based protein (MP) daily for 3 mo in a double-blind, randomized, controlled, parallel design. Serum insulin-like growth factor-I (IGF-I), which is associated with higher rates of bone formation, was greater (P < 0.01) in men supplemented with SP than in those consuming MP. Serum alkaline phosphatase and bone-specific alkaline phosphatase activities, markers of bone formation, and urinary deoxypyridinoline excretion, a specific marker of bone resorption, were not different between the SP and MP groups. Furthermore, because substantial reductions in bone density occur in men at approximately 65 y of age, data were analyzed separately for men >/=65 y and those <65 y of age. The response to protein supplementation was consistent in the two age groups. The effects of SP on serum IGF-I levels suggest that SP may positively influence bone in men. Longer-duration studies examining the effects of SP or its isoflavones on bone turnover and bone mineral density and content in men are warranted.

Effects of dose and timing of calcium supplementation on bone resorption in early menopausal women.

Bone resorption follows a circadian rhythm that peaks at night, reflecting the circadian rhythm of serum parathyroid hormone. Our previous studies in early postmenopausal women have established that 1000 mg of calcium given at 9 p. m. reduced bone resorption markers overnight, but not during the day. In contrast, 1000 mg given as a divided dose (500 mg doses at 9 a. m. and 9 p. m. each) reduced bone resorption markers during the day, but not during the night. We have now evaluated the effect of 1500 mg of calcium given as a divided dose of 500 mg in the morning and 1000 mg in the evening on bone resorption. We studied 26 healthy women (median age 56 years) whose menopause was less than five years before. On two days, urine was collected from 9 a. m. to 9 p. m. (day collection), and from 9 p. m. to 9 a. m. (night collection); a further fasting (spot) urine sample was obtained at 9 a. m. at the end of the night collection. On the second day, 500 mg of calcium in the carbonate form was taken at 9 a. m. (at the start of the collection) and a further 1000 mg at 9 p. m. (at the start of the second night collection). Calcium supplementation decreased urinary deoxypyridinoline (DPyr/Cr) during the day (p = 0.08) and night (p < 0.05), as well as urinary pyridinoline (Pyr/Cr) both by day (p < 0.05) and night (p < 0.001). There were also decreases in urine hydroxyproline. We conclude that the acute administration of 500 mg of calcium in the morning and 1000 mg in the evening to early postmenopausal women suppresses bone resorption markers during both the day and night.