Free Deoxypyridinoline Research Articles

A Mediterranean-like dietary pattern with vitamin D3 (10 µg/d) supplements reduced the rate of bone loss in older Europeans with osteoporosis at baseline: results of a 1-y randomized controlled trial

ABSTRACTBackgroundThe Mediterranean diet (MD) is widely recommended for the prevention of chronic disease, but evidence for a beneficial effect on bone health is lacking.ObjectiveThe aim of this study was to examine the effect of a Mediterranean-like dietary pattern [NU-AGE (New Dietary Strategies Addressing the Specific Needs of the Elderly Population for Healthy Aging in Europe)] on indexes of inflammation with a number of secondary endpoints, including bone mineral density (BMD) and biomarkers of bone and collagen degradation in a 1-y multicenter randomized controlled trial (RCT; NU-AGE) in elderly Europeans.DesignAn RCT was undertaken across 5 European centers. Subjects in the intervention group consumed the NU-AGE diet for 1 y by receiving individually tailored dietary advice, coupled with supplies of foods including whole-grain pasta, olive oil, and a vitamin D3 supplement (10 µg/d). Participants in the control group were provided with leaflets on healthy eating available in their country.ResultsA total of 1294 participants (mean ± SD age: 70.9 ±4.0 y; 44% male) were recruited to the study and 1142 completed the 1-y trial. The Mediterranean-like dietary pattern had no effect on BMD (site-specific or whole-body); the inclusion of compliance to the intervention in the statistical model did not change the findings. There was also no effect of the intervention on the urinary biomarkers free pyridinoline or free deoxypyridinoline. Serum 25-hydroxyvitamin D significantly increased and parathyroid hormone decreased (P < 0.001) in the MD compared with the control group. Subgroup analysis of individuals with osteoporosis at baseline (site-specific BMD T-score ≤ −2.5 SDs) showed that the MD attenuated the expected decline in femoral neck BMD (n = 24 and 30 in MD and control groups, respectively; P = 0.04) but had no effect on lumbar spine or whole-body BMD.ConclusionsA 1-y intervention of the Mediterranean-like diet together with vitamin D3 supplements (10 µg/d) had no effect on BMD in the normal age-related range, but it significantly reduced the rate of loss of bone at the femoral neck in individuals with osteoporosis. The NU-AGE trial is registered at clinicaltrials.gov as NCT01754012.

Serum osteocalcin and urinary free deoxypyridinoline as potential risk factors in predicting the prevalence of bone trauma among the post-menopausal Chinese women

&lt;p&gt;This study was designed to understand whether the post-menopausal Chinese women (n=175) receiving tablet containing vitamin D (500 IU) and calcium (500 mg) had lower incidence of bone fracture compared to the post-menopausal Chinese women ((n=175) receiving a diet rich in calcium, vitamin D, and protein (milk, cheese, and yogurt, soybeans, spinach, fish including fatty fish, cheese, egg). This study assessed whether the levels of serum osteocalcin and urinary free deoxypyridinoline could be used as predictors of early bone trauma during post-menopausal period. After randomization, subjects were followed-up for up to 3 years to capture required data. The results suggested that therapeutic intervention (vitamin D and calcium) does not predict bone fracture among the post-menopausal Chinese women. However, correlation analysis revealed that the decreased level of serum osteocalcin and urinary free deoxypyridinoline were associated with higher incidence of fracture. The results suggest that the low level of serum osteocalcin and urinary free deoxypyridinoline cause increase susceptibility of fracture among the post-menopausal Chinese women.&lt;/p&gt;

Discovery of biomarkers to identify peri-implant osteolysis before radiographic diagnosis.

Peri-implant osteolysis is commonly diagnosed after substantial bone loss has occurred, making revision surgery more challenging. The goal of the current study was to identify urinary biomarkers that differentiate total hip replacement patients who eventually develop osteolysis from patients who do not. We used a repository of 24-h urine samples collected prior to surgery and annually thereafter in 26 patients, 16 who developed osteolysis, and 10 who did not. We examined the markers at radiographic diagnosis, annually for 6 years preceding diagnosis, at the first post-operative sampling point, and pre-operatively. Patients in the osteolysis and non-osteolysis groups were matched according to time post-surgery and did not differ in the male:female ratio or age at surgery. Seven candidate biomarkers were measured, including free deoxypyridinoline (DPD), cross-linked N-telopeptides (NTX), interleukin-6 (IL-6), interleukin-8 (IL-8), osteoprotegerin (OPG), α-crosslaps (α-CTX), and β-crosslaps (β-CTX). As an individual biomarker, DPD demonstrated the highest ability to predict osteolysis, with an area under the curve (AUC) in Receiver Operating Characteristic (ROC) analyses of 0.844 at 6 years prior to diagnosis. A panel of α-CTX and IL-6 was able to identify at-risk patients with an AUC of 0.941 or greater at all post-operative time points and an AUC of 1.000 pre-operatively. The results demonstrate the potential of using non-invasive biomarkers to identify patients at risk for peri-implant osteolysis long before the emergence of radiographic signs. Further, the high accuracy of the pre-operative biomarker levels demonstrates the potential importance of pre-existing, patient-specific factors driving subsequent osteolysis. Study Design © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2754-2761, 2018.

The effects of short-term use of granulocyte colony-stimulating factor on bone metabolism in child cancer patients.

OBJECTIVE:The granulocyte colony-stimulating factor (G-CSF) is the most commonly used hematopoietic growth factor recombinant DNA technology. It affects bone metabolism by modulating both osteoclast and osteoblast functions. The aim of the present study was to investigate the effects of short-term use of G-CSF on bone metabolism in children with leukemia and solid tumors.METHODS:Thirty-six patients with a malignancy who received G-CSF therapy according to chemotherapy protocols and another 20 growth factor-free cancer patients who were enrolled as controls were included in the study. The serum osteocalcin and urinary free deoxypyridinoline levels were measured before the start of G-CSF therapy, on day 3 after treatment, and 7 days after G-CSF therapy was discontinued. In the control group, the measurements were made during corticosteroid and methotrexate-free chemotherapy.RESULTS:The mean osteocalcin level (8.6±2.3 ng/mL) from before the onset of treatment decreased significantly (7.7±2.3 ng/mL) on day 3 of G-CSF therapy and significantly increased after 7 days of G-CSF therapy (7.9±2.2 ng/mL) (p<0.001 and p<0.001, respectively), which was still significantly lower than the pre-G-CSF values (p<0.001). The urinary free deoxypyridinoline level significantly increased on day 3 of G-CSF treatment (25.6±6.5 nmol/mmol Cr) and significantly decreased after 7 days of G-CSF therapy (22.6±6.4 nmol/mmol Cr) (p<0.001 and p<0.001, respectively), which was still significantly higher than the values recorded before G-CSF therapy (p<0.001).CONCLUSION:The findings show that the short-term use of G-CSF in children with cancer can affect bone metabolism and can play a role in metabolic changes. Decreased osteoblastic activity and increased osteoclastic activity suggest that osteoporosis may be associated with bone pain in these patients.

Biochemical markers of bone turnover in benign paroxysmal positional vertigo.

ObjectiveSeveral studies have suggested a possible relationship between recurrent benign paroxysmal positional vertigo (BPPV) and altered calcium homeostasis in the endolymph of the inner ear. The present study aimed to evaluate the association between Ca2+ and vitamin D status and BPPV occurrence as well as the status of bone biochemical markers in osteoporotic patients who were diagnosed with idiopathic BPPV.MethodsThe study included total 132 patients who were referred to our clinic between August 2008 and October 2013. Based on the bone mineral density (BMD) results, the subjects were divided into three groups: normal BMD (n = 34), osteopenia (n = 40) and osteoporosis (n = 58). The biochemical markers of bone turnover including serum Carboxy-terminal telopeptide of type I collagen (s-CTX), osteocalcin, alkaline phosphatase (ALP) and urinary free deoxypyridinoline (u-DPD), were analyzed, along with the serum Ca2+ and vitamin D levels.ResultsThe mean serum calcium, phosphate and creatinine clearance levels were within the standard laboratory reference range. The incidence of vitamin D deficiency was 11.8% (4/34) in the normal BMD group, 15% (6/40) in the osteopenia group and 43.1% (25/58) in the osteoporosis group. There was a positive correlation between the 25(OH)D and BMD results in the patients with BPPV. Among the bone turnover markers, the osteocalcin and u-DPD levels were significantly elevated in the osteoporotic patients with BPPV. Multiple logistic regression analyses showed that osteoporosis and vitamin D deficiency were associated with BPPV.ConclusionOur findings suggest that the prevalence of BPPV in osteoporotic patients is associated with vitamin D deficiency and high bone turnover rates at systemic level, which could disturb local Ca2+ homeostasis in the inner ear.

LC–MS/MS application for urine free pyridinoline and free deoxypyridinoline: Urine markers of collagen and bone degradation

BackgroundPyridinium cross-links pyridinoline (PYD) and deoxypyridinoline (DPD) are established markers of collagen degradation. Measurement of PYD and DPD can be used to evaluate changes in bone turnover in patients with metabolic bone disease and to monitor response to anti-resorptive treatment. ObjectiveTo develop a method to extract and measure urine free PYD (fPYD) and free DPD (fDPD) by liquid chromatography tandem mass spectrometry (LC–MS/MS). The method was used to quantify urine samples from 172 healthy individuals and 63 patients diagnosed with metabolic bone disease. MethodAcidified urine samples were extracted using solid phase extraction with cellulose slurry. PYD and DPD were separated by reversed-phase, ion-paired chromatography prior to MS/MS detection. ResultsThe fully validated method showed good agreement with other laboratories in the UK National External Proficiency Scheme (UK NEQAS). The method was compared against two commercial immunoassays for fDPD and pyridinium cross-links, r2 were 0.906 and 0.816 respectively. Urine concentrations of fDPD/Cr and fPYD/Cr were significantly higher in the patients than healthy individuals (p<0.001). An average (±SD) fDPD:fPYD ratio of 0.29 (±0.08) was consistently observed across all subgroups. A markedly increased fDPD:fPYD ratio of 8.9 was observed in a patient with type VI Ehlers–Danlos Syndrome (EDS). ConclusionSimultaneous measurement of two free pyridinium cross-links provides a valuable, cost effective assessment tool for use in the diagnostic work-up of patients with metabolic bone disease. Improvements in sample extraction efficiency have increased assay specificity and analysis throughput. The use of the fDPD:fPYD ratio can assist in the diagnosis of type VI EDS.

Limited utility of tartrate-resistant acid phosphatase isoform 5b in assessing response to therapy in osteoporosis

Tartrate-resistant acid phosphatase isoform 5b (TRACP5b) is a serum bone resorption marker. Our aim was to investigate its utility in monitoring metabolic bone disease. Serum TRACP5b, C-terminal cross-linking telopeptide of type I collagen, urine N-terminal cross-linking telopeptide of type I collagen and free deoxypyridinoline were measured pre- and post-treatment with a parathyroid hormone analogue [PTH (1-34)] (n = 14) or a bisphosphonate (N-BP) (n = 8). TRACP5b, bone alkaline phosphatase (bone ALP), 25-hydroxyvitamin D (25OHD) and parathyroid hormone (PTH) were measured in 100 osteoporosis patients on prolonged bisphosphonate therapy. Changes in TRACP5b were smaller in magnitude but mimicked those of other bone resorption markers. Absolute changes in TRACP5b and the other resorption markers correlated significantly (p < 0.001). In patients on long-term bisphosphonates, TRACP5b and bone ALP levels were not suppressed. Vitamin D status was consistent with the level of supplementation. TRACP5b has limited utility as a single marker of metabolic bone disease treatment.

Periarticular Bone Gain at Proximal Interphalangeal Joints and Changes in Bone Turnover Markers in Response to Tumor Necrosis Factor Inhibitors in Rheumatoid and Psoriatic Arthritis

Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are characterized by periarticular bone erosion; periarticular bone formation is a feature in PsA. The effect of anti-tumor necrosis factor-α (TNF-α) on periarticular bone remodeling is unclear in both diseases. Our aim was to assess the response of bone turnover markers (BTM) and hand bone mineral density (BMD) to anti-TNF over 3 years in RA and PsA. We measured serum bone-specific alkaline phosphatase (bone ALP), procollagen type-I N-propeptide (PINP), intact osteocalcin, C-terminal cross-linking telopeptides (CTX-I), urinary N-terminal cross-linking telopeptide of type-I collagen (NTX-I), and free deoxypyridinoline crosslinks (fDPD) at baseline, 1, 12, and 36 months. BMD measurements (hands/spine/hip) were obtained at 3 timepoints. We recruited 62 patients (RA 35; PsA 27). BTM correlated significantly with hand BMD but not with central BMD. Low hand BMD was associated with RA and increased BTM. Following anti-TNF therapy, hip BMD declined while spine and hand BMD were unchanged. Periarticular BMD at proximal interphalangeal (PIP) joints increased while it decreased at metacarpophalangeal joints. Bone ALP increased steadily and was always higher in PsA. PINP and intact osteocalcin increased to a lesser extent, but resorption markers did not change. At baseline, hand BMD was inversely associated with BTM. Bone formation rather than resorption markers better showed the bone response to anti-TNF. Despite a lack of effect on central BMD, the modest effect of anti-TNF on PIP BMD may provide evidence that BTM reflect specifically bone remodeling activity at periarticular sites of inflammation in RA and PsA.

The effect of thiazide and loop diuretics on urinary levels of free deoxypyridinoline: an osteoclastic bone-resorption marker

Diuretics can cause changes in calcium levels due to renal effects. Moreover, calcium levels can also vary as a result of changes in intestinal absorption and in the activity of osteoclastic cells. A marker of osteoclastic bone-resorption activity is the level of urinary free deoxypyridinoline (FDP). Deoxypyridinoline (DP) acts as a cross-link between adjacent collagen chains to provide structural rigidity. Our aim was to investigate the association between use of thiazides and loop diuretics and urinary levels FDP. In this follow-up study, data were obtained from the Rotterdam Study, a large population-based prospective cohort study. For a subset of 658 participants, urinary levels of FDP were measured at baseline. Linear regression analysis was performed to assess the association between the use of thiazides and loop diuretics and the urinary levels of FDP. In women, current use of loop diuretics for less than 42days was associated with an increased level of urinary FDP (+3·43nmol deoxypyridinoline per mmol urinary creatinine; 95% CI 1·85; 5·02) compared with no use. However, use for a period of more than 42days was not associated with an increased level of FDP, nor was past use of loop diuretics. For thiazide diuretics, no statistically significant associations were found. In women, short-term use of loop diuretics is associated with an increased level of FDP, reflecting increased bone resorption by osteoclasts. As the difference disappears with longer term use, the clinical significance is unclear and the value of FDP as a biomarker in this setting is not established. The molecular mechanism for the observed differences in bone fracture rates with use of diuretics remains unclear.

A review of minodronic acid hydrate for the treatment of osteoporosis

Minodronic acid hydrate was the first bisphosphonate developed and approved for osteoporosis treatment in Japan. With regard to inhibition of bone resorption, minodronic acid hydrate is 1000 times more effective than etidronic acid and 10–100 times more effective than alendronic acid. Clinical trials conducted to date have focused on postmenopausal female patients suffering from primary osteoporosis. In these trials, 1 mg of oral minodronic acid hydrate was administrated once daily, and a significant increase was observed in lumbar-spine and hip-joint bone density 1–2 years after administration. All markers of bone metabolism urinary collagen type 1 cross-linked N-telopeptide, urinary free deoxypyridinoline, serum bone alkaline phosphatase, and serum osteocalcin were decreased. The incidence rate of new vertebral and nonvertebral fractures was also decreased. Therefore, effectiveness in fracture prevention was confirmed. A form of minodronic acid (50 mg) requiring once-monthly administration has been developed and is currently being used clinically. A comparative study between this new formulation and once-daily minodronic acid (1 mg) showed no significant differences between the two formulations in terms of improvement rates in lumbar-spine and hip-joint bone density, changes in bone metabolism markers, or incidence of side effects. This indicates the noninferiority of the monthly formulation. Side effects such as osteonecrosis of the jaw or atypical femoral fractures were not reported with other bisphosphonates, although it is believed that these side effects may emerge as future studies continue to be conducted. On the basis of studies conducted to date, minodronic acid hydrate is considered effective for improving bone density and preventing fractures. We anticipate further investigations in the future.

Familial resemblance of bone turnover rate in men aged 40 and over—the MINOS study

Familial resemblance of bone mineral density (BMD) is well known in both sexes. Fewer data concern the familial resemblance of bone turnover markers (BTMs) and bone size in men. Our aim was to assess the correlation of BMD, bone size, BTM levels and hormones regulating bone turnover in 50 pairs of brothers aged≥40 and 50 pairs of unrelated men matched for age, weight and height. BMD was measured at the lumbar spine, hip, forearm and whole body. We measured serum osteocalcin (OC), bone-specific alkaline phosphatase (bone ALP), N-terminal propeptide of type I procollagen (PINP) and C-terminal telopeptide of type I collagen (CTX-I) as well as urinary free and total deoxypyridinoline (DPD) and CTX-I. After adjustment for age, weight, bioavailable 17β-estradiol, and parathyroid hormone, all the BTMs (except bone ALP) were significantly correlated in the brothers (ICC=0.36-0.64). Most of these correlations were significantly stronger than in the unrelated men. Bone size correlated significantly between the brothers (ICC=0.55-0.65). These correlations were significantly stronger than in the unrelated men. BMD correlated between the brothers at most of the skeletal sites and, for some of them, more strongly than in the unrelated men. Serum levels of LDL-cholesterol and triglycerides were significantly correlated in the brothers, but not more strongly than in the unrelated men. BTM levels correlated independently in the brothers aged≥40, when their shared environment was limited. These data suggest a substantial hereditary determinism of the BTM levels in men.

Biochemical markers for bone turnover predict risk of vertebral fractures in postmenopausal women over 10 years: the Japanese Population-based Osteoporosis (JPOS) Cohort Study

We evaluated how bone turnover might predict vertebral fracture risk in postmenopausal women over 10 years. After adjusting for age and femoral neck bone mineral density, high bone-specific alkaline phosphatase and total and free deoxypyridinoline at baseline predicted increased vertebral fracture risk in women with ≥ 5 years since menopause. The aim was to evaluate the ability of bone turnover markers (BTMs) in predicting vertebral fractures. Participants in the 1996 baseline survey of the JPOS Cohort Study included 522 postmenopausal women, with no diseases or medications affecting bone metabolism. Vertebral fractures were ascertained in three follow-up surveys (1999, 2002, and 2006). Initial fracture events were diagnosed morphometrically. The Poisson regression model was applied to estimate the rate ratio (RR) of the following log-transformed BTM values at baseline: osteocalcin and bone-specific alkaline phosphatase (BAP) in serum and C-terminal cross-linked telopeptide of type I collagen, total deoxypyridinoline (tDPD), and free deoxypyridinoline (fDPD) in urine. Eighty-three fracture events were diagnosed over a median follow-up period of 10.0 years. RR per standard deviation (SD) (95 % confidence interval) for BAP was 4.38 (1.45, 13.21) among 65 subjects with years since menopause (YSM) < 5 years. RRs per SD (95 % confidence interval) for BAP, tDPD, and fDPD were 1.39 (1.12, 1.74), 1.32 (1.05, 1.67), and 1.40 (1.12, 1.76), respectively, after adjusting for age and femoral neck bone mineral density (FN BMD) among 457 subjects with YSM ≥ 5 years. Of the 451 women followed at least once until 2002, RRs per SD for BAP, tDPD, and fDPD adjusted for age and FN BMD over 6 years were not significantly different from those over 10 years. BAP was associated with vertebral fracture risk among early postmenopausal women. BTMs can predict vertebral fractures independently of BMD among late postmenopausal women over a 10-year follow-up period.

Women with insufficient 25-hydroxyvitamin D without secondary hyperparathyroidism have altered bone turnover and greater incidence of vertebral fractures

BackgroundThe connection of 25-hydroxyvitamin D [25(OH)D] with bone metabolism is reported to occur indirectly through parathyroid hormone (PTH) activity. However, we hypothesized that 25(OH)D insufficiency raises the risk of bone fracture independent of PTH, since 25(OH)D insufficiency is not always accompanied by hyperparathyroidism. The aim of this study was to show a direct association between 25(OH)D, bone turnover markers, and fractures that was independent of PTH. MethodsWe measured serum 25(OH)D in a group of 330 postmenopausal osteoporotic women who did not have secondary hyperparathyroidism. We analyzed the effects of 25(OH)D insufficiency [25(OH)D < 20 ng/mL] on the expression of several bone markers, including serum bone alkaline phosphatase (BAP), osteocalcin (OC), urinary N-terminal telopeptide of type-I collagen and free deoxypyridinoline (DPD), and inorganic phosphorus (IP), as well as on the prevalence of vertebral fractures. ResultsOC/BAP ratios and IP levels were significantly lower and DPD was significantly higher in 25(OH)D insufficient patients. These effects were independent of age, PTH, and estimated glomerular filtration rate (eGFR). 25(OH)D insufficiency, a low OC/BAP ratio, and low IP were related to the presence of prior vertebral fractures independent of PTH, bone mineral density (BMD), and eGFR. ConclusionsWe propose that 25(OH)D insufficiency is associated with a low OC/BAP ratio and high DPD in postmenopausal osteoporosis patients without hyperparathyroidism. This pathological condition is associated with an increased incidence of prior vertebral fractures independent of PTH, BMD, and eGFR.

Relationship between environmental exposure to cadmium and bone metabolism in a non-polluted area of Japan.

The purpose of this study was to investigate the effects of environmental low-grade cadmium exposure on bone in the population of a non-polluted area. We investigated the relationship between environmental cadmium exposure (via rice intake) and bone metabolism in middle-aged and elderly women living in a non-polluted area in Japan. Four hundred and twenty-nine women over the age of 39years (54.6±9.1years; arithmetic mean±SD) participated in this study in 2003. We investigated blood and urine, and rice intake, and performed ultrasonic bone evaluation, and obtained individual information about the subjects' health. Multiple regression analysis was performed in the statistical analysis. The arithmetic mean of cadmium content in rice was 70.8±44.7μg/kg (AM±SD). The geometric mean of daily cadmium intake (Cd intake) from rice calculated based on food consumption data was 9.12μg/day (GSD 2.33). The geometric means of serum and urine cadmium concentrations were 1.57μg/l (GSD 2.11) and 1.93μg/g creatinine (cr.) (GSD 2.05), respectively. Multiple regression analysis showed positive correlations between (1) urinary free deoxypyridinoline (FDPD-U) and Cd intake (p<0.05), (2) urinary cross-linked N-telopeptides of type I collagen (NTx-U) and Cd intake (p<0.05), and (3) FDPD-U or NTx-U and cadmium concentration in urine (p<0.01). No significant correlation between the parameters of ultrasonic bone evaluation and cadmium associated biomarkers was observed. The results of the present study suggest the possibility of bone metabolic disorder induced by environmental low-grade cadmium exposure. With respect to osteoporosis, a long-term follow-up survey is required to assess the tolerable intake of cadmium in environmental exposure.

VARIATIONS IN THE DEFICIENCY LEVELS OF ENDOGENOUS ESTRADIOL ON THE RATE OF POSTMENOPAUSAL BONE RESORPTION

Over a period of three years, 257 healthy postmenopausal women (mean age of 51.7 years) and 47 premenopausal women (control group, mean age of 34.23 years) were selected into the study. The postmenopausal women were divided into three estradiol‐deficient (study) groups based on the endogenous estradiol levels such as Group – I (10–25 pg/ml), Group ‐ II (&gt;25–50 pg/ml) and Group ‐ III (&gt;50 pg/ml). Bone formation marker (total alkaline phosphatase), bone resorption markers (tartrate‐resistant acid phosphatase, calcium, free hydroxyproline, free deoxypyridinoline and calcium/creatinine) and intact paratharmone levels were estimated in every subject. The bone formation marker and bone resorption markers were found to be elevated in all the three study groups over controls (P&lt;0.0010) When the study groups compared among one another, the bone resorption markers were found elevated in Group‐I over Group ‐ II and III and in Group ‐ II over Group ‐ III. But, the intact paratharmone levels were found to be normal in all the groups.This study concludes that the degree of bone resorption was high in Group ‐ III (&gt;50 pg/ml, higher in Group – II (&gt; 25–50 pg/ml) and highest in Group ‐ I (10–25 pg m/l) over controls. This view portends that the endogenous estradiol levels are the important determinants of bone resorption risk and also the variations in deficient endogenous estradiol levels in postmenopausal women might contribute to differences in the rate of postmenopausal bone resorption.

Free deoxypyridinoline in urine and serum--results in children and adolescents.

The urinary excretion of the collagen crosslinking compound dexoypyridinoline (DPD) is considered a specific index of bone resorption. Here we report on the levels of free (i.e., non peptide-bound) DPD in the urine and serum of subjects from 5 to 19 years of age, as determined by a new radioimmunoassay. Reference values for free DPD were established using 24-h urine collections from 118 healthy children and serum samples from 133 children with acute febrile illnesses. Serum and urine levels of free DPD were compared in samples from 23 short, normal children. Additionally, total (the sum of peptide-bound and free) DPD was measured by high-performance liquid chromatography in the 24-h urine collections. Urinary-free DPD was significantly correlated with total DPD (r = 0.90; P < 0.001) and declined steadily with age. Serum levels of free DPD ranged from 0.9 to 5.7 nmol/l and varied with age in boys only. No significant association was found between serum and urine levels of free DPD (r = 0.08; P = 0.37). In conclusion, urinary-free DPD did not reflect enhanced bone turnover during the time of puberty. Free DPD serum levels are very low, which may be due to rapid clearance via the kidneys.

Effect of potassium citrate supplementation or increased fruit and vegetable intake on bone metabolism in healthy postmenopausal women: a randomized controlled trial

BackgroundAlkali provision may explain why fruit and vegetables benefit bone health. ObjectiveWe aimed to determine the effects of alkali-providing potassium citrate (double-blind) and fruit and vegetable intake (single-blind) on bone turnover over 2 y. DesignWe conducted a randomized placebo-controlled trial in 276 postmenopausal women (aged 55–65 y). Women were randomly assigned to 4 groups: high-dose potassium citrate (55.5 mEq/d), low-dose potassium citrate (18.5 mEq/d), placebo, and 300 g additional fruit and vegetables/d (equivalent of 18.5 mEq alkali). Serum and fasted urine for bone markers were collected at baseline and at 3, 6, 12, 18, and 24 mo. An additional urine sample was collected at 4–6 wk. Bone mineral density (BMD) was measured at baseline and 2 y. ResultsRepeated-measures ANOVA showed no difference between groups for urinary free deoxypyridinoline cross-links relative to creatinine (fDPD/Cr), serum N-terminal propeptide of type 1 collagen, or beta C-terminal telopeptide, although, at 4–6 wk, fDPD/Cr was lower in the high-dose potassium citrate group (P = 0.04). Mean ± SD spine BMD loss in the placebo group (1.8 ± 3.9%) did not differ significantly from that in the treatment groups (2.1 ± 3.2%; P = 0.88). Hip BMD loss in the placebo and low-dose potassium citrate groups was 1.3 ± 2.3% and 2.2 ± 2.3%, respectively (P = 0.14). ConclusionsTwo-year potassium citrate supplementation does not reduce bone turnover or increase BMD in healthy postmenopausal women, which suggests that alkali provision does not explain any long-term benefit of fruit and vegetable intake on bone.

Bone mineral density and bone turnover markers in patients receiving a single course of isotretinoin for nodulocystic acne

High-dose isotretinoin has been reported to have adverse effects on bone mineral density (BMD); however, studies evaluating changes in BMD with isotretinoin therapy at different dosages and with varying treatment durations have produced conflicting results. To investigate the effect of a standard, single course of isotretinoin therapy on BMD and bone turnover markers in patients with nodulocystic acne. Thirty-six patients (15 male, 21 female) with severe, recalcitrant, nodulocystic acne and 36 healthy controls (16 male, 20 female) were enrolled in the study. Patients received isotretinoin treatment for 4-6 months until a cumulative dose of 120 mg/kg had been achieved. BMD in the lumbar spine and femur was measured at baseline and at the end of therapy by dual-energy X-ray absorptiometry. Serum calcium, phosphate, parathormone, total alkaline phosphatase, osteocalcin, free deoxypyridinoline, and urinary calcium were also measured before and at the end of treatment. No significant differences were found in lumbar spine and femoral BMD between the patient and control groups at the beginning of the study (P > 0.05), and no statistically significant difference was observed between the BMD values in patients at the beginning vs. the end of treatment (P > 0.05). No statistically significant difference in bone turnover markers was found between patients and controls at the beginning of the study (P > 0.05), and no statistically significant changes in bone turnover markers were observed in patients at the beginning vs. the end of treatment (P > 0.05). A single course of isotretinoin therapy has no clinically significant effect on bone metabolism.

Large-Scale Population-Based Study Shows No Association Between Common Polymorphisms of the TGFB1 Gene and BMD in Women

The TGFB1 gene is a strong functional candidate for regulating genetic susceptibility to osteoporosis. We studied five common polymorphisms of TGFB1 in relation to osteoporosis-related phenotypes in a population-based cohort of 2975 British women, but found no significant association with bone mass, bone loss, bone markers, or fracture. The gene encoding TGFB1 is a strong functional candidate for genetic susceptibility to osteoporosis. Several polymorphisms have been identified in TGFB1, and previous work has suggested that allelic variants of TGFB1 may regulate BMD and susceptibility to osteoporotic fracture. We studied the relationship between common polymorphisms of TGFB1 and several osteoporosis-related phenotypes including BMD at the lumbar spine and femoral neck, measured by DXA; bone loss over a 6-year period; biochemical markers of bone turnover (urinary free deoxypyridinoline and free pyridinoline/creatinine ratio and serum N-terminal propeptide of type 1 collagen), and fractures in a population-based study of 2975 women from the United Kingdom. Participants were genotyped for single nucleotide polymorphisms (SNPs) in the TGFB1 promoter (G-800A; rs1800468; C-509T; rs1800469), exon 1 (T29C; rs1982073 and G74C; rs1982073); and exon 5 (C788T; rs1800471) on PCR-generated fragments of genomic DNA. Haplotypes were constructed from genotype data using the PHASE software program, and genotypes and haplotypes were related to the phenotypes of interest using general linear model ANOVA, with correction for confounding factors including age, height, weight, menopausal status, hormone replacement therapy (HRT) use, physical activity score, and dietary calcium intake. The polymorphisms were in strong linkage disequilibrium, and four common haplotypes accounted for >95% of alleles at the locus. There was no association between individual SNPs and BMD, bone loss, or biochemical markers of bone turnover. Haplotype analysis showed a nominally significant association with femoral neck BMD (p = 0.042) and with incident osteoporotic fracture (p = 0.013), but these were not significant after correcting for multiple testing. Common polymorphic variants of the TGFB1 gene did not influence BMD or bone loss in this population.

Quantitative ultrasound is better correlated with bone mineral density and biochemical bone markers in elderly women

The association between quantitative ultrasound (QUS) and bone turnover in postmenopausal women of different ages is an area of continuous investigation. The aim of this study was to investigate the relationship of ultrasound parameters [broadband ultrasound attenuation (BUA) and speed of sound (SOS)] to bone mineral density (BMD) and biochemical markers of bone turnover in three age groups of postmenopausal women. One hundred and twenty-three postmenopausal Caucasian women were divided into three groups according to their age: group A, range 44-54 years, mean age (+/-SD) 48.3 +/- 2.3; group B, range 55-65 years, mean age 59.4 +/- 2.1; and group C, range 66-77 years, mean age 68.2 +/- 3.1. Ultrasound parameters were measured by the DTU-one imaging ultrasonometer in the calcaneus. BMD was assessed by dual-energy X-ray absorptiometry (DEXA) at the lumbar spine, femoral neck, and trochanter. Bone turnover was assessed by serum bone-specific alkaline phosphatase (BAP), urinary excretion of free deoxypyridinoline, N-telopeptides (NTX), and C-telopeptide breakdown products of type I collagen (CTX). QUS and BMD were significantly correlated in all sites, except hip BMD in group A. The most significant correlation was observed between BUA and femoral neck BMD in group C (r = 0.626, p < 0.01). BUA correlated significantly with BAP, NTX, and CTX (r = -0.434, -0.511, -0.478, respectively; p < 0.01), and SOS with BAP and NTX (r = -0.351 and -0.356, respectively; p < 0.05) only in group C. In groups A and B, ultrasound parameters did not correlate significantly to biochemical markers. Ultrasound parameters were better correlated to hip BMD and to biochemical markers of bone turnover in elderly postmenopausal women. These ultrasound measurements could be used as a screening test for bone status, either in nonambulatory third aged women or in those living in rural areas where attending medical centers with DEXA equipment and biochemical laboratories is difficult.