Total Deoxypyridinoline Research Articles

Rapid bone microarchitecture decline in older men with high bone turnover-the prospective STRAMBO study.

Older men with high bone turnover have faster bone loss. We assessed the link between the baseline levels of bone turnover markers (BTMs) and the prospectively assessed bone microarchitecture decline in men. In 825 men aged 60-87yr, we measured the serum osteocalcin (OC), bone alkaline phosphatase (BAP), N-terminal propeptide of type I procollagen (PINP), and C-terminal telopeptide of type I collagen (CTX-I), and urinary total deoxypyridinoline (tDPD). Bone microarchitecture and strength (distal radius and distal tibia) were estimated by high-resolution pQCT (XtremeCT, Scanco Medical) at baseline and then after 4 and 8yr. Thirty-seven men took medications affecting bone metabolism. Statistical models were adjusted for age and BMI. At the distal radius, the decrease in the total bone mineral density (Tt.BMD), cortical BMD (Ct.BMD), cortical thickness (Ct.Thd), and cortical area (Ct.Ar) and failure load was faster in the highest vs the lowest CTX-I quartile (failure load: -0.94 vs -0.31% yr-1, P < .001). Patterns were similar for distal tibia. At the distal tibia, bone decline (Tt.BMD, Ct.Thd, Ct.Ar, Ct.BMD, and failure load) was faster in the highest vs the lowest tDPD quartile. At each skeletal site, the rate of decrease in Tb.BMD differed between the extreme OC quartiles (P < .001). Men in the highest BAP quartile had a faster loss of Tt.BMD, Tb.BMD, reaction force, and failure load vs the lowest quartile. The link between PINP and bone decline was poor. The BTM score is the sum of the nos. of the quartiles for each BTM. Men in the highest quartile of the score had a faster loss of cortical bone and bone strength vs the lowest quartile. Thus, in the older men followed prospectively for 8yr, the rate of decline in bone microarchitecture and estimated bone strength was 50%-215% greater in men with high bone turnover (highest quartile, CTX-I above the median) compared to the men with low bone turnover (lowest quartile, CTX-I below the median).

Reference values for bone metabolism in a Japanese cohort survey randomly sampled from a basic elderly resident registry

The aim of this study was to provide definitive reference values for bone mineral density (BMD) and bone turnover markers in the general elderly population. Registered citizens of 50 to 89 years old were targeted for this survey. After random sampling from the resident registry of Obuse town, we established eight groups based on age (50 s, 60 s, 70 s, and 80 s) and gender. A total of 411 people were enrolled. We used a dual-energy x-ray absorptiometry device to measure and evaluate BMD. The bone formation marker bone alkaline phosphatase (BAP) was measured as a bone turnover marker. Bone quality marker pentosidine, and bone resorption markers including urinary total deoxypyridinoline (DPD), tartrate-resistant acid phosphatase 5b (TRACP-5b), 25-hydroxyvitamin D (25[OH]D), and whole parathyroid hormone (PTH) were also measured as bone turnover markers. Sixty-three people (15.3%) were diagnosed as osteoporosis. BMD decreased with age in the femoral neck and total hip. On the other hand, there was no characteristic change with age in the lumber spine. As for bone markers, pentosidine and DPD increased with aging, although 25(OH)D, whole PTH, and BAP showed no characteristic associations with gender and aging. In terms of the relationship between low BMD and bone markers, there was a significant independent association between low BMD and TRACP-5b in females. In conclusions, hip BMD decreased with aging in men and women. However, there was no characteristic decline with aging in the lumbar spine. All bone markers showed no significant independent characteristics associated with age or gender in a multivariate analysis model, except for a significant association between low BMD and TRACP-5b in females. TRACP-5b was a potentially useful marker for the detection of low BMD.

The effects of parity and litter size on bone metabolic activity in pregnant and lactating sows.

During gestation and lactation, female mammals often mobilize endogenous nutrient reserves to meet the resource demands of offspring production. These mobilized stores include calcium, phosphorous and other minerals that are resorbed from maternal bone to facilitate rapid mineralization of offspring bones. The extent to which bone mineral is resorbed is governed by the total amount of mineral taken in from the diet, but also by the competing demands of offspring and the minimum level of bone density that a female must sustain to support self-maintenance. The maximum amount of bone that a female may mobilize is undoubtedly dependent a variety of maternal traits, including age and reproductive experience (i.e., parity). We evaluated changes in serum concentrations of biomarkers of metabolic activity (total deoxypyridinoline [tDPD] and osteocalcin [OC]) of maternal bone and its relationship to reproductive output and parity throughout pregnancy and lactation in Yorkshire sows. Litter size did not affect bone metabolism; however, serum concentrations of both tDPD and OC were significantly higher in sows with little or no reproductive experience when compared to sows that had produced at least 3 litters prior to the current reproductive bout. This suggests a shift in ability or physiological strategy to meet offspring mineral demands that is acquired or associated with reproductive experience.

Evaluation of Bone Resorption in Type I diabetes Mellitus Patients by Measuring Urinary Total Deoxypyridinoline ( U. DPD) as a Biomarker of Bone Resorption

Background: Diabetes mellitus is a common disease in most parts of the world, the metabolic abnormalities of diabetes potentially affect bone metabolism, structure, mineral density, and bone resorption, as part of physiological bone turnover. Aim: This study aimed to estimate urinary total deoxypyridinoline as a biomarker of mature bone collagen degradation and bone resorption in type I diabetes mellitus patients and evaluate its relationship with fasting blood sugar, serum bone minerals profile and the duration of disease and also to investigate the degree of severity of bone resorption and the probability of fracture risk. Patients and methods:165patients with type I diabetes mellitus from Diabetes mellitus and Endocrine Disease Centre at AL -Nasiriyah city in Thi-Qar province, Iraq were studied.100 (60.6%) were female and 65(39.4%) were male, age was between(25-65) year, mean44.27±11.1,their duration with type 1 DM disease ranged from 5 months to 10 years, they were classified into three groups: the first group included 45 (27.3 %) patient their duration with type 1 DM were less than one year, the second group included 65 (39.4%) their duration with type I DM were 1 to 5 year and the third group included 55 (33.3%) patient their duration with disease were from 6 to 10 year. Fasting blood venous and first-morning urine samples were collected for biochemical investigation according to standard methods and Urine DPD was measured by the quantitative competitive enzyme immunoassay. Also, this study included 165 normal people selected as a control group.

Nível de atividade física no lazer após a cirurgia bariátrica afeta parâmetros ósseos?

Bariatric surgery (BS) causes an exacerbated loss of body weight and fat, and can promote changes in other body tissues such as bone tissue. The aim of this study was to compare the profile of serum and urinary bone markers and bone mineral density (BMD) of active and sedentary patients after BS. The sample consisted of 89 patients, of both sexes, who underwent BS through the gastric bypass in Roux-Y, between years 2003 and 2013. Anthropometry, body composition, spine and femur BMD was evaluated by dual energy x-ray absormetry (DEXA), as well as biochemical variables through serum collected for the dosage of calcium, osteocalcin and PTH levels, and also 24-hours urine for deoxypyridinoline and calcium. The level of leisure-time physical activity was assessed by questionnaire. Statistical significance was set at 5%. The average age of active and sedentary groups was [51.76 (9.66)] and [47.06 (12.16)] and body mass index [34.98 (6.90)] and [29,26 (5.92)], respectively. There are statistically significant differences in osteocalcin levels between groups (p = 0.021), as well as small effect size observed in the following variables: BMD of the total femur, osteocalcin, deoxypyridinoline and serum calcium (respectively d = 0:36; d = 0:39; d = 00:41 d = 0.3). The incorporation of an active lifestyle demonstrated a positive impact on circulating levels of osteocalcin and other bone parameters, thereby indicating a possible preservation of BMD during the aging process.

Osteocalcin, but not deoxypyridinoline, increases in response to isoflurane-induced anaesthesia in young female guinea pigs.

The effect of the inhaled anaesthetic isoflurane was investigated on bone biomarkers, both during maturation and on minerals and glucose postpartum. Female guinea pigs (n=10) were anaesthetized during maturation (5 and 9weeks) and postpartum (26weeks of age) with isoflurane during dual-energy X-ray absorptiometry scanning. Blood collection was performed at all ages before and after anaesthesia for measurement of plasma osteocalcin (OC), total deoxypyridinoline (tDPD), and cortisol. Postpartum measurements also included: blood ions, acid-base parameters and glucose, plasma minerals, total alkaline phosphatase (tALP), and albumin. Plasma OC concentration almost doubled after exposure to isoflurane at 5weeks (30.1±5.0-57.9±11.2nmol/L, p<0.001) and at 9weeks (29.1±7.5-62.9±15.9nmol/L, p<0.001), but did not change postpartum (3.7±3.3-4.3±3.9nmol/L, p=0.88). There was no effect of isoflurane exposure on plasma tDPD at any age. Plasma cortisol increased after exposure to isoflurane at 9weeks (1859.6±383.2-2748.0±235.3nmol/L, p<0.01) and postpartum (3376.7±322.2-4091.6±195.6nmol/L, p<0.001) but not at 5weeks (2088.3±326.4-2464.1±538.0nmol/L, p>0.05). Blood ionized Ca(2+), Na(+) and plasma total Ca did not change, whereas plasma albumin decreased, and inorganic phosphate (PO4) and Cl(-) increased upon exposure to isoflurane. Isoflurane decreased tALP (43.2±6.6-40.2±5.9IU/L, p=0.01) and increased glucose (7.5±0.6-10.9±1.7mmol/L, p<0.0001) postpartum. Isoflurane inflates the assessment of a bone-derived biomarker, OC, during rapid growth, but not following pregnancy when formation is very low. Measurements prior to anaesthesia are recommended to reflect normal metabolism.

RETRACTED: Bone mineral density of lumbar spine and femur in patients with gynecologic cancer.

Objective To compare the bone mineral density (BMD) of the lumbar spine and femur in postmenopausal women with cervical and endometrial cancer without bone metastasis with that in normal control postmenopausal women Methods We retrospectively analyzed the BMD of the lumbar spine and femur using dual-energy X-ray absorptiometry in 130 patients with cervical cancer, 68 patients with endometrial cancer, and 225 healthy controls. Results The serum levels of calcium, phosphorus, osteocalcin, total alkaline phosphatase and urine deoxypyridinoline were measured in all participants. Age, body mass index, parity and time since menopause were not significantly different between the three groups. The T-scores of basal BMD at the fourth lumbar vertebra (L4) were significantly lower in patients with cervical cancer (- 0.68 ± 0.10) compared to those in the other two groups. Additionally, the incidence of osteoporosis at L4 according to the basal status of bone mass was significantly higher in patients with cervical cancer (10.0%) compared to that in controls (0.4%). Urine deoxypyridinoline levels were significantly higher in patients with cervical cancer compared to those in controls. No differences in basal BMD of the lumbar spine and femur were observed between patients with endometrial cancer and controls, and no significant differences in biochemical markers were detected between patients with endometrial cancer and controls. Conclusion Our results suggest that postmenopausal women with cervical cancer have a lower BMD and are at increased risk of osteoporosis in the lumbar spine before receiving anticancer treatment compared with postmenopausal women with endometrial cancer.

RETRACTED: Different bone mineral density in cervical and endometrial cancer.

Objectives Patients with cervical cancer have lower bone mass than women without cancer, whereas women with endometrial cancer have higher bone mineral density (BMD) than control subjects, possibly due to the prevalence of high body-fat mass. The aim of this study was to compare BMD in patients with cervical cancer, endometrial cancer and controls. Methods We analyzed and compared spinal and femoral BMD in 130 patients with cervical cancer, 68 with endometrial cancer, and 140 age-matched menopausal female control subjects. We also compared serum calcium, phosphorus, total alkaline phosphatase, osteocalcin, and urinary deoxypyridinoline levels. Results Compared with the control group, T-scores for some lumbar vertebrae (L4), the femoral neck, and Ward's triangle were lower in patients with cervical cancer, whereas only L4 T-scores were significantly lower in patients with endometrial cancer. Deoxypyridinoline levels were significantly lower in women with endometrial cancer (p < 0.002) than in women with cervical cancer, but no other biochemical variables differed among groups. Conclusions Cervical cancer was associated with lower BMD, especially in femoral BMD, and may be a risk factor for secondary osteoporosis. However, endometrial cancer generally seemed to have no damaging effect on bone except at L4. A further larger follow-up study in more populations is required to clarify these findings.

Relationships between age-related biochemical markers of bone turnover and OPG, TGF-β1 and TGF-β2 in native Chinese women

Osteoprotegerin (OPG), transforming growth factor-β1 (TGF-β1) and TGF-β2 are cytokines closely associated with bone metabolism. However, their association with bone turnover markers in native Chinese women remains unknown. The study aims to investigate the relationship between bone metabolism related cytokines including OPG, TGF-β1, TGF-β2 and bone turnover markers in native Chinese women. The cross-sectional study was conducted on 691 healthy Chinese women (20–80 years old). Levels of OPG, TGF-β1, TGF-β2, serum bone-specific alkaline phosphatase (BAP), osteocalcin (OC), cross-linked N-terminal telopeptides of type I collagen (sNTX), cross-linked C-terminal telopeptides of type I collagen (sCTX), urinary NTX (uNTX), urinary CTX (uCTX) and total urinary deoxypyridinoline (uDPD) were determined. The present study showed that OPG and TGF-β2 had positive correlation with BAP, OC, uNTX, uCTX and uDPD, while TGF-β1 showed negative correlation with BAP, OC, sCTX, uNTX and uCTX, and most of the coefficients of partial correlation remained significant after adjustments for age and body mass index (BMI). Multiple linear regression stepwise analysis showed that OPG and TGF-β2 were positive determinative factors for BAP, sCTX, uNTX and uCTX, which could explain 0.6–16.6% of the variation in these markers. TGF-β1 was a negative determinative factor for BAP, OC, sCTX and uCTX, which could explain 0.7–7.3% of the variation in these markers. This study suggested that measuring bone turnover indicators and serum cytokines simultaneously might help evaluating changes in bone turnover rate caused by aging or menopause in women.

Noninvasive assessment of bone health in Indian patients with chronic kidney disease.

Abnormalities in mineral and bone disease are common in chronic kidney disease (CKD). Evaluation of bone health requires measurement of parameters of bone turnover, mineralization, and volume. There are no data on bone health in CKD patients from India. In this cross-sectional study, we evaluated serum biomarkers of bone turnover: Bone-specific alkaline phosphatase (BAP) and total deoxypyridinoline (tDPD) along with parathyroid hormone, 25(OH) vitamin D, and bone mineral density (BMD) using dual absorption X-ray absorptiometry in a cohort of 74 treatment-naive patients with newly diagnosed stage 4 and 5 CKD (age 42 ± 14.5 years, 54 men) and 52 non-CKD volunteers (age 40.2 ± 9.3 years, 40 men). Compared to the controls, CKD subjects showed elevated intact PTH (iPTH), BAP, and tDPD and lower BMD. There was a strong correlation between iPTH and BAP (r = 0.88, P < 0.0001), iPTH and tDPD (r = 0.51, P < 0.0001), and BAP and tDPD (r = 0.46, P = 0.0004). The iPTH elevation was greater than twice the upper range of normal in 73% cases, and BAP was >40 U/L in 66% cases. The combination of these markers suggests high turnover bone disease in over 60% cases. The prevalence of osteopenia and osteoporosis was 37% and 12%, respectively. Osteoporotic subjects had higher iPTH, BAP, and tDPD, suggesting a role of high turnover in genesis of osteoporosis. Vitamin D deficiency was seen in 80%, and another 13% had insufficient levels. Vitamin D correlated inversely with BAP (r = −0.3, P = 0.009), and levels were lower in those with iPTH >300 pg/ml (P = 0.0.04). In conclusion, over 60% of newly diagnosed Indian stage 4–5 CKD patients show biochemical parameters consistent with high turnover bone disease. High turnover could contribute to the development of osteoporosis in CKD subjects. Deficiency of 25 (OH) vitamin D is widespread and seems to have a role in the genesis of renal bone disease. Studies on the effect of supplementation of native vitamin D are needed.

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.

The Effect of Hyperthyroidism on Bone Mineral Density in Premenopausal Women

Background: The effects of subclinical hyperthyroidism and clinical hyperthyroidism on bone metabolism in premenopausal women are contradictory. Methods: Sixteen hyperthyroid (31.3±9.5 yrs), 23 subclinical hyperthyroid (33.7±7.3 yrs) and 20 healthy (31.7±8.1 yrs) premenopausal women were evaluated. Bone mineral density (BMD) was assessed by dual energy X-ray absorptiometry (DXA). Osteocalcin, total alkaline phosphatase (tALP), homocysteine, β-2 microglobulin, hsCRP and deoxypyridinoline (DPD) concentrations were assessed. Demographic and anthropometrical parameters; and osteoporotic risk factors were evaluated. Results: Serum calcium, tALP, osteocalcin, β-2 microglobulin and DPD were significantly different in hyperthyroid group. However there was no difference for any of the study parameters between control and subclinical hyperthyroid group. BMD was similar for all the three groups. Thyroid hormones were correlated with osteocalcin, β-2 microglobulin, tALP, lumbar vertebrae and femur BMD. Osteocalcine and tALP were significantly and negatively correlated with vertebral and femoral total BMD. Homocysteine was not different within groups but significantly correlated with tALP. Conclusions: There is limited and conflicting data about the effects of subclinical hyperthyroidism on bone turnover in premenopausal period. Despite we could not establish any difference for bone turnover markers between control group and subclinical hyperthyroid patients; with tight correlations between thyroid hormones; we can conclude that subclinical hyperthyroid patients are prone to osteoporosis even in premenopausal period.

Telomerase-deficient mice exhibit bone loss owing to defects in osteoblasts and increased osteoclastogenesis by inflammatory microenvironment

Telomere shortening owing to telomerase deficiency leads to accelerated senescence of human skeletal (mesenchymal) stem cells (MSCs) in vitro, whereas overexpression leads to telomere elongation, extended life span, and enhanced bone formation. To study the role of telomere shortening in vivo, we studied the phenotype of telomerase-deficient mice (Terc(-/-)). Terc(-/-) mice exhibited accelerated age-related bone loss starting at 3 months of age and during 12 months of follow-up revealed by dual-energy X-ray absorptiometric (DXA) scanning and by micro-computed tomography (µCT). Bone histomorphometry revealed decreased mineralized surface and bone-formation rate as well as increased osteoclast number and size in Terc(-/-) mice. Also, serum total deoxypyridinoline (tDPD) was increased in Terc(-/-) mice. MSCs and osteoprogenitors isolated from Terc(-/-) mice exhibited intrinsic defects with reduced proliferating cell number and impaired osteogenic differentiation capacity. In addition, the Terc(-/-) -MSC cultures accumulated a larger proportion of senescent β-galactosidase(+) cells and cells exhibiting DNA damage. Microarray analysis of Terc(-/-) bone revealed significant overexpression of a large number of proinflammatory genes involved in osteoclast (OC) differentiation. Consistently, serum obtained from Terc(-/-) mice enhanced OC formation of wild-type bone marrow cultures. Our data demonstrate two mechanisms for age-related bone loss caused by telomerase deficiency: intrinsic osteoblastic defects and creation of a proinflammatory osteoclast-activating microenvironment. Thus telomerization of MSCs may provide a novel approach for abolishing age-related bone loss.

Association between bone turnover rate and bone microarchitecture in men: The STRAMBO study

Few data concern the relationship between bone turnover and microarchitecture in men. We investigated the association between levels of biochemical markers of bone turnover (BTM) and bone microarchitecture in 1149 men aged 19 to 85 years. Bone microarchitecture was assessed by high-resolution peripheral quantitative computed tomography at the distal radius and tibia. Bone formation was assessed by serum osteocalcin, bone alkaline phosphatase, and N-terminal extension propeptide of type I collagen. Bone resorption was assessed by serum C-terminal telopeptide of type I collagen and urinary excretion of total deoxypyridinoline. BTM levels were high in young men and decreased until age 50 years. Urinary deoxypyridinoline (DPD) increased after age 70 years, whereas other BTMs remained stable. Before 50 years of age, only cortical volumetric bone mineral density (D(cort)) correlated negatively with BTM levels. Between 50 and 70 years of age, D(cort) and some microarchitectural parameters correlated significantly with BTM at the radius and tibia. After 70 years of age, higher BTM levels were associated with lower cortical thickness and D(cort) at both the skeletal sites. At the distal radius, men in the highest BTM quartile had lower trabecular density, number (Tb.N), and thickness (Tb.Th) and more heterogeneous trabecular distribution compared with men in the lower quartiles. At the distal tibia, higher BTM levels were associated with lower Tb.N and Tb.Th in the central but not subendocortical area. Thus, in men, bone microarchitecture depends weakly on the current bone turnover rate until age 70. Thereafter, bone turnover seems to be a significant determinant of bone microarchitecture.

Significant increase in plasma osteocalcin in response to isoflurane induced anaesthesia in guinea pigs

The effect of the inhaled anaesthetic, isoflurane was studied on osteocalcin (OC) and total deoxypyridinoline (tDPD) in pigmented guinea pigs. Ten female guinea pigs were anaesthetized at five and nine weeks of age with isoflurane. The duration of anaesthesia was similar (20–25 min) in all guinea pigs across both age. Blood samples were collected at both time points, before and after the induction of the anaesthesia. Osteocalcin and tDPD were measured using ELISA (Quidel Corp.). Osteocalcin concentration increased due to isoflurane from 30.1±4.9 to 57.9±11.2 nmol/L (p&lt;0.001) and from 29.1±7.5 to 62.9±15.9 nmol/L (p&lt;0.001), at five and nine weeks of age, respectively. The effect of isoflurane on tDPD was inconsistent for the fifth and ninth week of age. Isoflurane increased tDPD (8.6±1.9 to 10.3±3.0 nmol/L) at five week of age while it decreased it (12.3±4.0 to 10.5±1.7 nmol/L) at nine week of age. The results demonstrate that administration of isoflurane changes both OC and tDPD. Therefore the interpretation of results obtained from animals anaesthetised by isoflurane on bone biomarkers should be made with caution since they may be highlighted or masked by the effect of the anaesthetic. Measurements prior to anaesthesia are recommended for better consistency and comparability in research. This study was funded by CIHR.

Increased Bone Resorption Is Associated With Higher Mortality in Community-Dwelling Men ≥50 Years of Age: The MINOS Study

Low BMD, high concentration of 17beta-estradiol (17betaE2), and decreased level of 25-hydroxycholecalciferol [25(OH)D] predict mortality. Our hypothesis is that high levels of biochemical bone turnover markers (BTMs) are independent predictors of mortality in home-dwelling men. In 781 men >or=50 yr of age followed up prospectively for 10 yr, we studied the association of BTMs with mortality after adjustment for confounders including BMD, major osteoporotic fractures, and concentrations of 17betaE2 and 25(OH)D. Men who died had lower BMD and higher BTM levels. In multivariate models, mortality was higher in men with low BMD (lowest quartile) at the total hip, whole body, and ultradistal radius (HR = 1.49-1.70, p < 0.05). After exclusion of the first 3 yr, higher levels (fourth quartile) of bone resorption markers (free and total deoxypyridinoline and urinary and serum type I collagen C-telopeptide) predicted mortality in multivariate models adjusted for age, BMI, smoking habits, alcohol intake, physical performance and activity, comorbidities, total hip BMD, major osteoporotic fractures, creatinine clearance, season, and concentrations of 17betaE2 and 25(OH)D (HR = 1.58-2.44, p < 0.05-0.001). In conclusion, in older community-dwelling men, increased bone resorption markers levels predicted mortality regardless of age and other confounders. Thus, in older men, high bone resorption may reflect poor current health status and poor aging.

Murine TNFΔARE Crohnʼs disease model displays diminished expression of intestinal Ca2+ transporters

Patients suffering from Crohn's disease (CD) show increased incidence of low bone mineral density. Investigating this complication is difficult because the exact etiology of CD remains elusive. Mice carrying a deletion in the tumor necrosis factor (TNF) AU-rich elements (ARE) are reported as a model for human CD and are characterized by elevated TNF-alpha levels and inflammations in the terminal ileum. To evaluate whether these mice have a Ca(2+) handling problem, this study analyzed the Ca(2+) homeostasis in heterozygous TNF(DeltaARE) mice (TNF(DeltaARE/+)) in comparison to wildtype littermates. Beside serum Ca(2+) and vitamin D levels, the expression of Ca(2+) transporters was analyzed in intestine, kidney and bone using quantitative real-time PCR, Western blot and immunohistochemistry. Bone scans were performed to measure bone parameters. Ca(2+) transporters in duodenum (TRPV6, calbindin-D(9K), PMCA1b) and kidney (TRPV5, calbindin-D(28K), NCX1) showed significantly reduced mRNA expression levels in TNP(DeltaARE/+) mice, except for renal TRPV5. In bone, only calbindin-D(9K) mRNA displayed a significant down-regulation. These findings were supported by declined duodenal calbindin-D(9K) and renal calbindin-D(28K) protein values. Likely, this down-regulation of Ca(2+) transporters in TNP(DeltaARE/+) mice is mediated by the 58 +/- 9% reduction in serum 1,25(OH)(2)D(3) levels. Diminished expression of Ca(2+) transporters combined with unchanged serum Ca(2+) levels assumes Ca(2+) loss from bone to compensate for the body's overall Ca(2+) shortage. Indeed, microcomputed tomography scanning demonstrated reduced trabecular and corticol bone thickness and volume in TNF(DeltaARE/+) mice. This finding is further supported by increased total deoxypyridinoline in serum. Our results imply that TNF(DeltaARE/+) mice have a disturbed Ca(2+) homeostasis characterized by reduced duodenal and renal Ca(2+) transporters, diminished 1,25(OH)(2)D(3) levels, and increased bone resorption associated with profound bone abnormalities.

Biochemical markers of bone turnover may predict progression to osteoporosis in osteopenic women: the JPOS Cohort Study

We evaluated the value of bone turnover markers, including osteocalcin (OC) and bone-specific alkaline phosphatase in the serum, and type I collagen C-terminal telopeptide and free and total deoxypyridinoline (tDPD) in the urine of fasting patients, in an attempt to predict which osteopenic women [i.e., those with > or = 70% and <80% of the young adult mean (YAM) bone mineral density (BMD)] would progress to the osteoporosis level of BMD (<70% of YAM). Of the 1153 women without defects in bone metabolism who completed the 3-year follow-up, 147, 161, and 144 women were judged by dual X-ray absorptiometry to be osteopenic from baseline measurements of BMD in the spine (LS), hip (TH), and distal radius (DR), respectively. Progression to the osteoporotic level of BMD was noted for 23.8%, 16.1%, and 12.5% of the subjects with osteopenia of the LS, TH, and DR, respectively, while most of them were in the lower half of the osteopenic level of BMD at baseline. Among the subjects in this lower-level osteopenia category, a significantly higher OC level was observed for the subjects with osteoporosis progression at the LS than those without. The subjects with progression at DR showed a significantly higher tDPD level. The association between OC level and disease progression remained unchanged after adjustments for age, body size, and BMD at baseline. The subjects in the upper one-third category of OC levels showed a 6.4 fold greater risk of progression at LS (95% confidence interval, 1.8-23.1) compared with those in the lower one-third category after the adjustments for age, body size, and BMD at baseline. Receiver operating characteristics analysis showed that the area under the curve was 0.716 for the OC level in the prediction of osteoporosis progression at LS. The levels of OC and tDPD may be useful in predicting which osteopenic women will progress to osteoporosis.

Soy isoflavones attenuate bone loss in early postmenopausal Chinese women

Previous studies show that daily doses of 40-99 mg soy isoflavones produce inconsistent effects on preventing estrogen-related bone loss in postmenopausal women. To examined the bone-sparing effect of isoflavones at a higher dose in early Chinese postmenopausal women. A total of 90 eligible women aged 45-60 years were randomly assigned to three treatment groups (30 subjects/group) with daily dosages of 0 (placebo), 84 and 126 mg isoflavones for 6 months. Further inclusion criteria included body mass index <30 kg/m(2) and Kuppermann Climacteric Scale >15. Bone mineral density (BMD) of the spine and hip were measured using dual- energy X-ray absorptiometry at 0 and 6 months. Serum osteocalcin, bone-specific alkaline phosphatase (BAP) and urinary deoxypyridinoline were examined at 0, 3 and 6 months. Mean percent changes in BMD at the lumbar spine (p = 0.114) and femoral neck (p = 0.053) increased with the supplementations of soy isoflavones after adjusting for age, years since menopause, body weight and height, dietary intakes of isoflavones, calcium and protein, physical activities and baseline BMD at the relevant sites. We observed significantly dose-dependent linear relationship between the supplemental isoflavones and percent changes of BMD at the spine (p = 0.042) and femoral neck (p = 0.016) post-treatment, and urinary total deoxypyridinoline (p = 0.014) at 12 weeks but not at 24 weeks after adjusting for the above factors. No significant difference in percent changes in serum osteocalcin (p > 0.05) and BAP (p > 0.05) was found among the three treatment groups at 12-week and 24-week post-treatment. There is a significantly dose-dependent effect of soy isoflavones on attenuating bone loss at the spine and femoral neck possibly via the inhibition of bone resorption in non-obese postmenopausal Chinese women with high Kuppermann Scale.