Bone Turnover Markers In Men Research Articles

Bone Turnover Markers Predict Changes in Bone Mineral Density in Men Treated with Abaloparatide: Results from ATOM.

Early increases in bone turnover markers (BTMs) in response to anabolic therapy correlate with 18-month bone mineral density (BMD) increases in postmenopausal women with osteoporosis; however, this relationship has not been assessed in men. In this analysis, the correlation between changes from baseline in fasting intact serum procollagen type I N propeptide (PINP) and serum carboxy-terminal cross-linking telopeptide of type I collagen (CTX) at 1, 3, 6, and 12months and percent increase from baseline in BMD at 12months in men from the randomized phase 3 ATOM study (NCT03512262) were evaluated using Pearson's correlation coefficients. The uncoupling index (UI), a measure of the balance between markers of bone formation (PINP) and bone resorption (CTX), with positive UI favoring bone formation, was calculated. Results in men were compared to 12-month results for women from the ACTIVE study using the z score test after Fisher's Z transformation. In abaloparatide-treated men, PINP increases at 1month (r = 0.485), 3months (r = 0.614), 6months (r = 0.632), and 12months (r = 0.521) were highly correlated (P<.0001) with 12-month lumbar spine BMD increases. The mean UI for abaloparatide-treated men was greater than placebo as early as 1month (2.26 versus -0.25). At month 3, the mean UI for men was greater (1.32) than for women (0.88) (P<.001). There was a significant correlation between 3-month UI and lumbar spine BMD at 12months in both men (r = 0.453; P<.001) and women (r = 0.252; P<.01); UI at months 6 and 12 were also significantly correlated with 12-month lumbar spine BMD in men and women, but the correlation was stronger in men than women. These data support that early changes in BTMs in men treated with abaloparatide are associated with subsequent changes in BMD similar to what has been reported in women. Trial registration: clinicaltrials.gov Identifier NCT03512262.

Changes in the concentration of bone turnover markers in men after maximum intensity exercise.

Physical activity is an important factor in modelling the remodelling and metabolism of bone tissue. The aim of the study was to evaluate the changes in indices demonstrating bone turnover in men under the influence of maximum-intensity exercise. The study involved 33 men aged 20-25, divided into two groups: experimental (n=15) and control (n=18). People training medium- and long-distance running were assigned to the experimental group, and non-training individuals to the control. Selected somatic, physiological and biochemical indices were measured. The level of aerobic fitness was determined using a progressively increasing graded test (treadmill test for subjective fatigue). Blood samples for determinations were taken before the test and 60 minutes after its completion. The concentration of selected bone turnover markers was assessed: bone fraction of alkaline phosphatase (b-ALP), osteoclacin (OC), N-terminal cross-linked telopeptide of the alpha chain of type I collagen (NTx1), N-terminal propeptide of type I progolagen (PINP), osteoprotegerin (OPG). In addition, the concentration of 25(OH)D3 prior to the stress test was determined. Additionally, pre and post exercise, the concentration of lactates in the capillary blood was determined. When comparing the two groups, significant statistical differences were found for the mean level of: 25(OH)D3 (p=0.025), b-ALP (p<0.001), OC (p=0.004) and PINP (p=0.029) prior to the test. On the other hand, within individual groups, between the values pre and post the stress test, there were statistically significant differences for the average level of: b-ALP (p<0.001), NTx1 (p<0.001), OPG (p=0.001) and PINP (p=0.002). A single-session maximum physical effort can become an effective tool to initiate positive changes in bone turnover markers.

Daily yogurt consumption does not affect bone turnover markers in men and postmenopausal women of Caribbean Latino descent: a randomized controlled trial

BackgroundCaribbean Latino adults are at high risk for osteoporosis yet remain underrepresented in bone research. This increased risk is attributed to genetics, diet, and lifestyle known to drive inflammation and microbial dysbiosis.ObjectiveThe primary objective of this study was to determine whether consuming 5 oz of yogurt daily for 8wks improves bone turnover markers (BTMs) among Caribbean Latino adults > 50 years; and secondarily to determine the impact on the gut microbiota and markers of intestinal integrity and inflammation.MethodsFollowing a 4wk baseline period, participants were randomized to an 8wk whole fat yogurt intervention (n = 10) daily, containing only Streptococcus thermophilus and Lactobacillus bulgaricus, or to an untreated control group that did not consume yogurt (n = 10). Blood and stool samples collected at week-0 and week-8 were used to assess BTMs, inflammation, intestinal integrity biomarkers, and gut microbiota composition, short chain fatty acids (SCFAs), respectively. Data were evaluated for normality and statistical analyses were performed.ResultsParticipants were 55% women, with a mean age of 70 ± 9 years, BMI 30 ± 6 kg/m2, and serum C-reactive protein 4.8 ± 3.6 mg/L, indicating chronic low-grade inflammation. Following 8wks of yogurt intake, absolute change in BTMs did not differ significantly between groups (P = 0.06–0.78). Secondarily, absolute change in markers of inflammation, intestinal integrity, and fecal SCFAs did not differ significantly between groups (P range 0.13–1.00). Yogurt intake for 8wks was significantly associated with microbial compositional changes of rare taxa (P = 0.048); however, no significant alpha diversity changes were observed.ConclusionsIn this study, daily yogurt did not improve BTMs, inflammation, intestinal integrity, nor SCFAs. However, yogurt did influence beta diversity, or the abundance of rare taxa within the gut microbiota of the yogurt group, compared to controls. Additional research to identify dietary approaches to reduce osteoporosis risk among Caribbean Latino adults is needed.Trial registrationThis study is registered to ClinicalTrials.gov, NCT05350579 (28/04/2022).

Effects of TSH suppressive therapy on bone mineral density (BMD) and bone turnover markers (BTMs) in patients with differentiated thyroid cancer in Northeast China: a prospective controlled cohort study.

This study aimed to evaluate the effects of thyroid-stimulating hormone (TSH) suppressive therapy on bone mineral density (BMD) and bone turnover markers (BTMs) in differentiated thyroid cancer (DTC) patients after postoperative 1-2 years in Northeast China. Five male, sixteen premenopausal, and eight postmenopausal female DTC patients receiving TSH suppressive therapy after thyroidectomy were enrolled. Patients were matched with healthy controls in a ratio of 1:2. All participants completed postoperative 1-year follow-up, and postmenopausal women completed 2-year follow-up. We measured BMD of the lumbar spine (LS), femoral neck (FN), and total hip (TH) using dual-energy X-ray absorptiometry (DXA). Bone formation marker P1NP and bone resorption marker β-CTX were also evaluated. Fracture risks were assessed by FRAX. There was no difference in BMD and BTMs between DTC patients and controls in the male group at 1-year follow-up. In the premenopausal women, the baseline P1NP was significantly lower in DTC patients than in the controls. The LS-BMD, FN-BMD, and TH-BMD in DTC patients were all higher than those in controls at 1-year follow-up. The difference in FN-BMD was not significant after adjusting for baseline P1NP. In the postmenopausal women, no differences in BMD and BTMs were observed between DTC patients and controls at the 1-year and 2-year follow-up. Our study indicated that postoperative 1-year TSH suppressive therapy did not show detrimental effects on BMD and BTMs in men, premenopausal, and postmenopausal DTC patients. The 2-year postoperative TSH suppressive therapy did not lead to additional loss of bone mass in postmenopausal DTC patients.

Relationship of Bone Status with Serum Uric Acid and Bilirubin in Men with Type 2 Diabetes: A Cross-Sectional Study.

BackgroundAccumulating evidence has shown that serum uric acid and bilirubin are associated with some chronic diseases, owing to their antioxidant capacity, but the previous research produced discrepant results regarding the relation between uric acid, as well as bilirubin, and bone health. This study was designed to assess the relationship of serum uric acid and total bilirubin with bone mineral density and bone turnover markers in men with type 2 diabetes.Material/MethodsIn total, 631 male patients with type 2 diabetes were included. Data of patients’ medical history, biochemical index, bone mineral density of the lumbar vertebra, femoral neck, and total hip, and bone turnover markers including osteocalcin (OC), amino-terminal propeptide of type I procollagen (PINP), type I collagen carboxy-terminal peptide (CTX), and parathyroid hormone were collected and retrospectively analyzed.ResultsBoth serum uric acid and total bilirubin were positively related to bone mineral density of the lumbar vertebra (β=0.179, p<0.001; β=0.095, p=0.030), femoral neck (β=0.133, p=0.002; β=0.089, p=0.029), and total hip (β=0.142, p=0.001; β=0.087, p=0.032), respectively. Serum uric acid concentration was negatively related to bone turnover markers (OC: r=−0.148, p=0.037; PINP: r=−0.139, p=0005; CTX: r=−0.200, p=0.005). Each unit increase of serum uric acid and total bilirubin was associated with a 0.4% and 5.6% lower risk of osteoporosis or osteopenia (OR=0.996, 95% CI=0.994–0.998; OR=0.944, 95% CI=0.899–0.992), respectively. The risk of osteoporosis and osteopenia in patients with low-tertile concentrations of serum uric acid and total bilirubin was increased (OR=3.486, 95% CI=1.535–7.913).ConclusionsIn men with type 2 diabetes, serum uric acid level and total bilirubin were significantly associated with bone mineral density and were protective factors against osteoporosis and osteopenia.

Trabecular bone score and bone turnover markers in men with DISH: Data from the Camargo Cohort study

ObjectiveDiffuse idiopathic skeletal hyperostosis (DISH) has been associated with an increased risk of vertebral fracture. To date, no studies have investigated the relationship between DISH and bone microstructure assessed by the trabecular bone score (TBS). MethodsCross-sectional study, nested in a prospective population-based cohort. All men (968) aged≥50 years were included. Clinical covariates, DISH, TBS, serum bone turnover markers and bone mineral density (BMD) were analyzed. ResultsMean age of participants was 65 ± 9 years. 207 (21.6%) had DISH. DISH subjects were older, had higher body mass index (BMI) and abdominal perimeter, lower glomerular filtration rate (GFR), and higher prevalence of metabolic syndrome (MetS) than non-DISH (NDISH) subjects. Bone mineral density at the lumbar spine (LS-BMD) was significantly higher in the DISH group. TBS values were 1.317 [1.303–1.331] for DISH and 1.334 [1.327–1.341] for NDISH subjects, after adjusting by age, BMI, abdominal perimeter, arterial hypertension, diabetes mellitus, MetS, GFR, serum alkaline phosphatase (ALP), LS and femoral neck BMD (p = 0.03). Serum ALP levels were higher in DISH subjects, showing an inverse correlation with TBS that remained significant after adjusting by age and BMI. ConclusionsTBS values were significantly lower in men with DISH irrespective of age, BMI and BMD, suggesting that the presence of DISH might be related to a worse trabecular microstructure.

Bone Turnover Markers in Men and Women with Impaired Fasting Glucose and Diabetes.

Bone turnover markers (BTMs) are reduced in diabetes, but whether BTM changes occur in impaired fasting glucose (IFG) is unknown. The aim of this study was to investigate whether BTMs are altered in IFG and diabetes compared to normoglycaemia. For men and women (n = 2222) in the Geelong Osteoporosis Study, IFG was defined as fasting plasma glucose (FPG) 5.5-6.9mmol/L and diabetes as FPG ≥ 7.0mmol/L, use of antihyperglycemic medication and/or self-report. Serum C-terminal telopeptide (CTx) and procollagen type 1 N-terminal propeptide (P1NP) were measured. After natural log transformation to normalise the data, multivariable regression was used to examine the relationship between glycaemia status and bone turnover markers (BTMs), before and after adjusting for other confounders. There were 643 men and 682 women with normoglycaemia, 355 men and 391 women with IFG and 97 men and 54 women with diabetes. Men with IFG or diabetes had lower adjusted ln(CTx) and ln(P1NP) compared to normoglycaemia (all p < 0.05). Women with IFG or diabetes had lower adjusted ln(CTx) and ln(P1NP) (all p < 0.05) except for ln(P1NP) when comparing diabetes with normoglycaemia, which showed a trend for lower ln(P1NP) (p = 0.053). In both sexes, an age*glycaemia interaction term indicated between-group differences in BTMs diminished with increasing age. No other confounders were identified. Bone turnover was lower in those with either IFG or diabetes compared to normoglycaemia.

Effect of acute downhill running on bone markers in responders and non-responders.

The aim of the current study was to compare the effects of acute flat running (FR) and downhill running (DHR) on bone turnover markers in men. Fourteen healthy young active men performed three exercise tests in a counterbalanced order, including rest condition, FR, and DHR, at 60% maximal aerobic capacity on a treadmill with 0 and - 12% inclines. Blood samples were taken in the pre-exercise, immediately post-exercise, and 24-h post-exercise periods, and bone markers included total procollagen type 1 amino-terminal pro-peptide (total PINP) and N-MID osteocalcin. Total P1NP significantly increased after exercise independent of the form of muscle contraction (p > 0.05). N-MID osteocalcin increased after DHR by 17% compared to after pre-exercise, but the difference did not reach significance (p = 0.07; partial eta square, 0.21). Biomarker responses to exercise were dependent on the exercise form and independent of hormone type in half of the participants who were classified as responders. Physiological parameters and changes in muscle voluntary contraction did not explain the differences between responders and non-responders. The effect of acute DHR on bone turnover is determined by biomarker type and participant characteristics. Future studies should discriminate between the characteristics of responders and those of non-responders.

Effect of soy on bone turn-over markers in men with type 2 diabetes and hypogonadism \u2013 a randomised controlled study

Type 2 diabetes (T2DM) is associated with increased risk of fractures. Soy supplementation has been shown to have a beneficial effect on bone turnover markers (BTM) in postmenopausal women. However, the effect of soy supplementation on BTM in T2DM and particularly in men is unclear. We performed an analysis of a randomized double blind parallel study of 200 men with T2DM treated with soy, either with or without isoflavones. Outcome measures were type I collagen crosslinked beta C-telopeptide (βCTX), and type 1 procollagen-N-propeptide (P1NP). The men, with a total testosterone <12 nmol/L, were treated with 15 g soy protein containing 66 mg of isoflavones (SPI) or 15 g soy protein alone without isoflavones (SP) daily for three months. There was a 15% reduction in βCTX after three months of SPI compared to SP supplementation. There was no significant difference in P1NP with either SPI or SP supplementation. There was a significant linear correlation between the reduction in βCTX in the SPI group with the reduction in HbA1c (r2 = 0.42; p = 0.04) and HOMA-IR (r2 = 0.54; p = 0.02). Our study indicates that there was a significant reduction in bone resorption following 3 months of SPI supplementation that correlated with an improvement of glycemic control in men with T2DM.

Bone Turnover in Young Adult Men: Cross-Sectional Determinants and Associations With Prospectively Assessed Bone Loss.

Biochemical markers of bone turnover are higher in young adult men than in middle-aged men or young adult women. Nonetheless, little is known about the determinants and clinical significance hereof. The present study examined determinants of serum bone turnover markers in men around peak bone mass age, and explored whether bone turnover at this age predicts subsequent changes in bone mass. We used cross-sectional and longitudinal data from 973 and 428 healthy men, respectively, aged 25 to 45 years at baseline, including baseline procollagen type I amino-terminal propeptide (P1NP), osteocalcin, and C-terminal telopeptide of type I collagen (CTX) from fasting serum samples, baseline questionnaire-assessed physical activity levels, and baseline and follow-up dual-energy X-ray absorptiometry-derived areal bone mineral density (aBMD) and body composition. Mean follow-up time was 12.4 ± 0.4 years. At baseline, all bone turnover markers were inversely associated with total body fat mass (β ≤ -0.20, p < 0.001), and positively with physical activity during sports activities (β ≥ 0.09, p ≤ 0.003), and, albeit not independently from fat mass, total body lean mass (β ≥ 0.20, p ≤ 0.003). Mean annual aBMD changes in the longitudinal cohort were -0.19% ± 0.24% at the total body, -0.14% ± 0.42% at the spine, -0.49% ± 0.47% at the femoral neck, and -0.25% ± 0.37% at the total hip (all p < 0.001). Higher bone turnover markers at baseline were associated with larger decreases in aBMD at all measurement sites (β ≤ -0.08, p ≤ 0.081 for P1NP; β ≤ -0.16, p ≤ 0.002 for osteocalcin; and β ≤ -0.21, p < 0.001 for CTX). In conclusion, our findings show that sports activities and body composition, primarily fat mass, are the main identified determinants of bone turnover in men around peak bone mass age. Further, bone turnover at this age is an important determinant of subsequent changes in bone mass, with higher levels of bone turnover markers being associated with greater decreases in aBMD. © 2017 American Society for Bone and Mineral Research.

Influence of vitamin D deficiency on bone turnover markers in men of different age

Influence of vitamin D deficiency on bone turnover markers in men of different age

Malay

Bone turnover markers (BTMs) are useful in the assessment of bone health status. However, the infl uence of age, ethnicity and body anthropometry on the level of BTMs in men remains understudied. This study aimed to determine the influence of these factors on the level of BTM, namely osteoclacin (OC) and C-terminal telopeptides of type 1 collagen (CTX-1) among Malay and Chinese men (N = 407) aged 20 years and above in Klang Valley. The subjects were recruited using purposive sampling method. Their height, body weight and body mass index were measured. Their blood was collected in the morning for serum OC and CTX-1 analysis using enzyme-linked immunoasorbent assays. Results showed that OC and CTX-1 levels were significantly higher in Malay compared to Chinese men (p 0.005). There were significant and negative correlations between OC and body mass index and weight, which were significant for men aged 20-39 years only (p 0.05). As a conclusion, levels of BTMs in Malaysian men could be infl uenced by age, ethnicity and body anthropometry. Thus, these factors should be taken into consideration in the evaluation of bone health status of men using BTMs. DOI : http://dx.doi.org/10.17576/jskm-1201-2014-02

Effect of the ERα agonist GTx-758 on bone turnover markers in men with advanced prostate cancer.

222 Background: Men with advanced prostate cancer are being treated with androgen deprivation therapy (ADT) for longer periods of time. The use of ADT can be limited by estrogen deficiency side effects, including a loss of bone and a higher incidence of fractures. GTx-758 is an ERα agonist that lowers serum free testosterone greater than an LHRH agonist. Herein we compare the effects of GTx-758 and leuprolide on markers of bone turnover, C-terminal telopeptides and bone specific alkaline phosphatase, in men with advanced prostate cancer treated with ADT. Methods: In a Phase II study (G200705), men with advanced prostate cancer (n=159) received 1000 mg or 2000 mg of GTx-758 daily or leuprolide. Serum samples were collected and analyzed by a reference laboratory. C-terminal telopeptides (pg/ml) and bone specific alkaline phosphatase (U/L) were measured as indicators of bone turnover. All p values describe the comparison of the GTx-758 treatment groups to the leuprolide treated men at day 120. Results: Men receiving the 1000 mg and 2000 mg doses of GTx-758 had lower C-terminal telopeptide levels with a mean percentage change of -56.9 ± 12.5 and -54.8 ± 23.1, respectively, as compared with an increase of 46.0 ± 48.9 percentage in the men receiving the leuprolide (p&lt;0.001). Similarly, bone specific alkaline phosphatase levels were lower in men treated with GTx-758, with mean percentage changes of-28.5 ± 11.7 and -19.8 ± 14.7, respectively, compared with an increase of 8.1 ± 24.3 percent in the leuprolide treated group (p&lt;0.001). As a result of an increased risk of venous thromboembolic events (VTEs) at these higher doses of GTx-758, the trial was stopped prior to its completion and not all of the men on the study reached the 120 day treatment dates (71 evaluable). Conclusions: Patients receiving GTx-758 experienced a significant decrease in markers of bone turnover indicating potential improvement and not a loss of bone on ADT. Since changes in bone mineral density are a major side effect that can negatively affect the quality of life in men on ADT, the improvements in bone turnover observed in men treated with GTx-758 could be significant. A Phase II clinical trial utilizing lower doses of GTx-758 (G200712) is currently being performed. Clinical trial information: NCT01326312.

Relative value of the lumbar spine and hip bone mineral density and bone turnover markers in men with ankylosing spondylitis

The purpose of this study is to evaluate bone mineral density (BMD) and bone turnover markers in men with ankylosing spondylitis (AS) and to determine their relationship with clinical features and disease activity. Serum carboxi terminal cross-linked telopeptide of type I collagen (CTX), osteocalcin (OC) levels, and BMD of lumbar spine and proximal femur were evaluated in 44 males with AS, 18-60 years of age, and compared with those of 39 age-matched healthy men. Men with AS had a significantly lower BMD at the femoral neck and total hip as compared to age-matched controls (all p < 0.01). Osteopaenia or osteoporosis was found in 59.5% AS patients at the lumbar spine and in 47.7% at the femoral neck. Mean serum levels of OC and CTX were similar in AS patients and controls. There were no significant differences in BMD and bone turnover markers when comparing subgroups stratified according to disease duration or presence of peripheral arthritis. No correlations were found between disease activity markers and BMD or OC and CTX. In a cohort of relatively young males with AS, we found a high incidence of osteopaenia and osteoporosis. Disease activity and duration did not show any significant influence on BMD or serum levels of OC and CTX.

Effect of Zoledronic Acid on Bone Mineral Density in Men with Prostate Cancer Receiving Gonadotropin-Releasing Hormone Analog

Background. Loss of bone density with androgen deprivation therapy for prostate cancer is well recognized. We assessed the effects of quarterly infusion of zoledronic acid on bone mineral density (BMD) and markers of bone turnover over a one-year period in men receiving gonadotropin-releasing hormone analog (GnRH-a) for prostate cancer. Methods. 41 subjects were randomly assigned to treatment with zoledronic acid (4 mg) IV infusion or placebo every 3 months. The primary endpoint was the change in the lumbar spine BMD after 12 months of treatment. Results. The change in vertebral BMD in the zoledronic acid group (+7.93 ± 1.4%) was significantly (P < .05) greater than the change in the placebo group (+0.82 ± 1.7%) as was the change in left femoral neck BMD (+5.05 ± 1.4% for the zoledronic acid group versus −0.48 ± 1.4% for the placebo group). The decrease in biochemical markers of bone turnover was significantly (P < .05) greater in the zoledronic acid group compared to the placebo group. Conclusion. Quarterly infusion of zoledronic acid for 1 year improved vertebral and left femoral neck BMD with a decrease in bone turnover markers in men on GnRH-a treatment. Zoledronic acid treatment appears to be promising in men with low BMD receiving GnRH-a treatment.

Relationship among dietary estimates of net endogenous acid production, bone mineral density and biochemical markers of bone turnover in an Iranian general population

Chronic, low-grade metabolic acidosis due to Western diets may be a risk factor for osteoporosis. The severity can be determined in part by net endogenous acid production (NEAP). In a population-based study, a total of 1028 healthy men and women aged 20–72 years were evaluated for dietary intakes and NEAP estimates with a validated food frequency questionnaire. Dual-energy X-ray absorptiometry (DXA) was used to determine BMD of the lumbar spine (L2–L4), distal third of radius, and proximal femur. Serum CrossLaps, degradation products of the C-terminal telopeptides of type I collagen, and osteocalcin were measured by highly specific ELISA methods. Lower estimates of energy-adjusted rates of NEAP were associated with greater femoral neck BMD ( p = 0.01) in premenopausal women and with greater BMDs at the distal radius ( p = 0.001) and lumbar spine ( p = 0.04) in postmenopausal women. Compared with women in the highest quartile of the estimates of the energy-adjusted rates of NEAP, pre- and postmenopausal women in the lowest quartile had significantly greater means of osteocalcin [9.12 (SD ± 1.62) vs. 5.24 (SD ± 1.41) ng/ml, p = 0.02 and 11.74 (SD ± 1.69) vs. 7.79 (SD ± 2.63) ng/ml, p = 0.002, respectively]. Analysis by quartiles of the estimates of energy-adjusted rates of NEAP did not reveal a relationship between BMD and bone turnover markers in men. In conclusion, we found that a high energy-adjusted rate of NEAP was associated with a significantly lower BMD in women but not in men and the energy-adjusted rate of NEAP had a negative relationship with bone formation.

Sex steroids and bone turnover markers in men with symptomatic vertebral fractures

Sex steroids play an important role in the maintenance of bone density in men and women, but the circulating, biologically active unbound fraction is influenced by the concentration of sex hormone binding globulin (SHBG). SHBG increases with advancing age in men and leads to a reduction in serum free testosterone and oestradiol, which may then affect bone turnover, bone mineral density (BMD) and the risk of fractures. We have therefore measured total and unbound sex steroids, SHBG, bone turnover markers and BMD in 57 men with symptomatic low trauma vertebral fractures and 57 age-matched male control subjects. Fasting blood and urine samples were collected from all subjects, who also underwent BMD measurement of the lumbar spine and hip. Serum testosterone, oestradiol, SHBG, bone specific alkaline phosphatase (bone ALP) and urine free deoxypyridinoline/creatinine ratio (fDPD/Cr) were measured. Free sex steroid concentrations were calculated using their ratio with SHBG and albumin and bioavailable testosterone was measured using radioimmunoassay. The two groups were then compared and regression models developed to determine the best predictors of BMD and fracture. Men with vertebral fractures had significantly lower weight and BMD at all sites than control subjects ( p < 0.0001). Serum total testosterone and oestradiol did not differ between the two groups, but calculated free androgen and free oestradiol indices were lower in the fracture group than the control subjects ( p = 0.04), due to higher SHBG (46.6 versus 36.1 nmol/L: p = 0.005). The men with vertebral fractures had significantly higher mean bone ALP (15.8 versus 11.8 μg/L: p = 0.002) and fDPD/Cr (5.5 versus 4.0 nmol/mmol: p = 0.03). Stepwise multiple regression analysis in both fracture and control groups found body weight to be the best predictor of BMD. In the fracture group weight predicted between 19.7 and 30.7% of the variance in BMD and in control subjects this was between 12.3 and 13.2%. SHBG contributed to the model for hip BMD in the fracture group alone, so that weight and SHBG together accounted for 32 to 42.9% of the variance. A model combining BMD at the spine, total femur and femoral neck with height loss best predicted fracture. In conclusion, men with symptomatic vertebral fractures have higher SHBG and lower calculated free sex steroid indices, increased bone turnover and lower BMD. Whilst body weight was the best predictor of BMD, symptomatic vertebral fracture was best predicted by BMD and height loss.

Racial and Ethnic Differences in Bone Turnover Markers in Men

Whereas racial and ethnic differences in fracture risk and bone mineral density (BMD) in men have been well described, the influence of race and ethnicity on biochemical markers of bone turnover is less clear. To examine the relationship between bone turnover, BMD, and race and ethnicity in men, we measured BMD, serum intact osteocalcin (OC), and serum C-terminal telopeptides of type 1 collagen (CTx) in 1029 men (aged 30-79 yr) enrolled in the Boston Area Community Health/Bone Survey, a population-based random sample of Black, Hispanic, and White. Men with diseases or on medications known to affect bone metabolism were excluded from the analysis. Mean serum levels of OC and CTx were adjusted for age, month and time of blood sample, and 25-hydroxyvitamin D. Compared with Black men, adjusted mean OC levels were 17.6 and 20.5% higher in Hispanic (P = 0.02) and White men (P < 0.01), respectively. There was no significant difference between White and Hispanic men. Adjusted mean CTx levels were 14.3% higher in White men, compared with Black men (P = 0.04), but no other differences were significant. OC declined by 0.4%/yr from age 30 to 65 yr and increased thereafter by 2.1%/yr. The age trend in CTx appeared to follow a pattern consistent with a quadratic function of age. Model-estimated annual percent changes within age decade were as follows: 30-39 yr, -2.5%; 40-49 yr, -1.4%; 50-59 yr, -0.3%; 60-69 yr, +0.9%; 70-79 yr, +1.7%. There was no variation in the shape of the age trend in OC or CTx by race or ethnic group. Correlations between bone turnover markers and BMD (adjusted for age, height, weight, serum 25-hydroxyvitamin D, and PTH and month and time of blood sample) were generally weak. Bone turnover markers are lower in Black men, compared with White and Hispanic men. Age trends in bone turnover markers are not influenced by race or ethnicity. Future studies in this cohort and others are needed to explore further these reported differences in bone metabolism among Black, Hispanic, and White men.

Serial Markers of Bone Turnover in Men with Metastatic Prostate Cancer Treated with Zoledronic Acid for Detection of Bone Metastases Progression

ObjectivesThis study assessed the usefulness of serial measurements of bone turnover markers in men with metastatic prostate cancer treated with zoledronic acid to detect disease progression. MethodsSerum measurements of total alkaline phosphatase (tALP), bone-specific alkaline phosphatase (bALP), cross-linked N-terminal (NTx) and cross-linked C-terminal (CTx) telopeptides of type I collagen, amino-terminal procollagen propeptides of type I collagen (PINP), C-terminal telopeptides of type I collagen (ICTP), and prostate-specific antigen (PSA) were performed in 77 prostate cancer patients suffering from bone metastases and treated with zoledronic acid up to 15 mo. Fifty patients were with and 27 patients without objective evidence of metastatic bone progression during the administration of zoledronic acid. ResultsThe baseline bone marker concentrations were not significantly different between the groups. After administration of zoledronic acid all bone markers except of ICTP decreased compared with baseline. CTx showed the greatest decrease. In patients with metastatic bone progression PINP, tALP, bALP, and ICTP were significantly higher at weeks 24, 36, 48, and 60 after starting treatment with zoledronic acid compared with patients without progression. In addition to the information of prostate-specific antigen as a monitoring parameter, the bone formation marker showed a better distinction between patients with and without disease progression. ConclusionsSelected bone turnover markers provide valuable information regarding progression of bone metastasis in men with metastatic prostate cancer under bisphosphonate therapy. The clinical impact should be confirmed in prospective randomised studies.

Randomized phase II study of atrasentan alone or in combination with zoledronic acid in men with metastatic prostate cancer

Metastatic prostate cancer is characterized by the presence of osteoblastic bone metastases. Bone metastases account for most of the morbidity from this disease. Inhibition of osteoclast activity with the potent bisphosphonate zoledronic acid reduces skeletal complications and decreases serum levels of biochemical bone turnover markers compared with placebo. Atrasentan is an investigational agent that inhibits endothelin-1 receptor, resulting in decreased osteoblast activity. The effects of atrasentan alone versus combination therapy with atrasentan and zoledronic acid were investigated on bone turnover markers in men with bone metastases from prostate cancer. Forty-four men were randomized to receive either atrasentan alone or combination therapy, and 33 completed at least 12 weeks of treatment and were included in the primary analysis. Treatment with the combination resulted in significantly lower serum levels of N-telopeptide, a marker of bone resorption, compared with treatment with atrasentan alone. There was no difference between groups in serum levels of bone-specific alkaline phosphatase, a marker of bone formation, at 12 weeks. Commonly observed adverse effects were edema, rhinitis, fatigue, and shortness of breath, most of which were NCI CTC (version 3.0) Grade 1. No Grade 4 or 5 treatment-related toxicities were observed. There was minimal clinical efficacy, with no objective responses and only 1 prostate-specific antigen (PSA) response. There is no evidence for additive or synergistic effects of combination therapy with atrasentan and zoledronic acid on bone turnover markers in men with metastatic prostate cancer.