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Pierre D Delmas - One of the best experts on this subject based on the ideXlab platform.
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biochemical markers of Bone Turnover
Journal of Bone and Mineral Research, 2009Co-Authors: Pierre D DelmasAbstract:The noninvasive assessment of Bone Turnover has received increasing attention over the past few years because of the need for sensitive markers in the clinical investigation of osteoporosis. Markers of Bone formation include the serum measurement of total and Bone-specific alkaline phosphatase, osteocalcin, and type I collagen extension peptides. Assessment of Bone resorption can be achieved with measurement of fasting urinary calcium and hydroxyproline, urinary hydroxylysine glycosides, urinary excretion of the pyridinium cross-links (pyridinoline and deoxypyridinoline), and plasma tartrate-resistant acid phosphatase activity. Several studies performed in a variety of metabolic Bone diseases have shown these markers to be of unequal sensitivity and specificity. In addition, some of them are not fully characterized. For assessment of the level of Bone Turnover in women with vertebral osteoporosis, serum osteocalcin and urinary pyridinoline appear to be the most sensitive markers so far. Programs combining Bone mass measurement and assessment of Bone Turnover by several markers in women at the time of menopause are being developed in an attempt to improve the assessment of the risk for osteoporosis. Efforts are being made to develop more convenient assays and to identify other markers of Bone Turnover. A battery of various specific markers is likely to improve the assessment of the complex and subtle abnormalities of Bone metabolism that characterize metabolic Bone diseases, especially the various aspects of osteoporosis.
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increased Bone Turnover in late postmenopausal women is a major determinant of osteoporosis
Journal of Bone and Mineral Research, 2009Co-Authors: Patrick Garnero, E Sornayrendu, M C Chapuy, Pierre D DelmasAbstract:Changes of Bone Turnover with aging are responsible for Bone loss and play a major role in osteoporosis. Although an increase of Bone Turnover has been documented at the time of menopause, the subsequent abnormalities of Bone resorption and formation and their potential role in determining Bone mass in the elderly have not been investigated. To address this issue, we have measured a battery of new sensitive and specific markers of Bone Turnover in a population-based study of 653 healthy women analyzed cross-sectionally, including 432 women postmenopausal from 1 to 40 years, and the data were correlated with Bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) at different skeletal sites. Bone formation was assessed by serum osteocalcin (OC), serum Bone-specific alkaline phosphatase (B-ALP), serum C-propeptide of type I collagen (PICP), and Bone resorption by the urinary excretion of two pyridinoline cross-linked peptides (NTX and CTX). Bone Turnover increased in perimenopausal women with both irregular menses and elevated serum follicle stimulating hormone (FSH). Menopause induced a 37–52% and 79–97% increase in the Bone formation and Bone resorption marker levels, respectively (p < 0.0001 except for PICP). In postmenopausal women, Bone formation markers did not decrease with age. When resorption markers were corrected by whole body Bone mineral content (BMC), the fraction of Bone resorbed per day was not correlated with age in postmenopausal women and remained elevated for up to 40 years after menopause. In premenopausal women, the Bone Turnover rate accounted for only 0–10% of the variation in whole body BMC, total hip, distal radius, and lumbar spine BMD. With increasing time after menopause, the importance of the Bone Turnover rate as a determinant of Bone mass increased at all sites and accounted for up to 52% of the BMD variance in elderly women. Thus, in women 20 years or more postmenopause, Bone Turnover was higher in those in the lowest quartile than in those in the highest quartile of BMD. In elderly women, 20 years since menopause and over, but not in younger ones, serum PTH was negatively correlated with serum 25-hydroxyvitamin D (r = −0.22,p < 0.05) and explained only 5–8% of the Bone Turnover variance (p < 0.01-0.001). These data indicate that the overall rates of both Bone formation and Bone resorption remain high in elderly women. The rate of Bone Turnover appears to play an increasing role as a determinant of Bone mass with increasing time since menopause with a high Bone Turnover rate being associated with a low Bone mass. Thus assessing Bone marker levels may be useful in the evaluation of osteoporosis risk. In elderly women, secondary hyperparathyroidism caused in part by reduced serum 25-hydroxyvitamin D appears to be a marginal determinant of an increased Bone Turnover rate.
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establishing a reference interval for Bone Turnover markers in 637 healthy young premenopausal women from the united kingdom france belgium and the united states
Journal of Bone and Mineral Research, 2009Co-Authors: Sarah J Glover, Dennis M. Black, Patrick Garnero, Pierre D Delmas, Jane A Cauley, Steven Boonen, Martin Gall, Oliver Schoenbornkellenberger, Michael Wagener, Richard EastellAbstract:Robust reference intervals are needed for the interpretation of Bone Turnover markers in large phase III fracture trials. The objectives of the study were to (1) estimate reference intervals for serum Bone alkaline phosphatase (Bone ALP), serum procollagen type I N propeptide (PINP), serum beta cross-linked C-telopeptides of type I collagen (S-betaCTX), and urinary cross-linked N-telopeptides of type I collagen (U-NTX) in healthy young premenopausal women; (2) examine geographical differences on Bone Turnover markers; and (3) assess factors known to influence Bone Turnover and test whether these explain any regional differences. We studied 637 eligible women from four countries that participated in the Horizon-PFT study (United Kingdom, France, Belgium, United States). The women were 30-39 yr of age (mean, 34.6 yr), with regular cyclic menses. Subjects completed a medical and lifestyle questionnaire. Two-sided 95% reference intervals were estimated on transformed values and transformed back to the original scale using the proposed methodology of the International Federation of Clinical Chemistry. S-betaCTX was significantly higher in France relative to the United Kingdom (p = 0.01), and PINP was higher in France (p < 0.001) and Belgium (p = 0.02) relative to the United Kingdom and significantly higher in France relative to the United States (p < 0.01) by ANOVA. Overall, one could associate low Bone Turnover markers with nonsmoking, use of a contraceptive pill, exercise, being close to the time of ovulation, and having high 25-hydroxyvitamin D levels. Countries differed by these characteristics, and once allowed for in the statistical model, any country differences were attenuated or removed.
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fracture risk reduction during treatment with teriparatide is independent of pretreatment Bone Turnover
Bone, 2006Co-Authors: Pierre D Delmas, Jeanyves Reginster, Gerald G Crans, Angelo A Licata, Peiqi Chen, Derek A Misurski, R B Wagman, Bruce H MitlakAbstract:Abstract Introduction Teriparatide is a Bone formation agent that increases Bone Turnover and mass, resulting in an increase in Bone strength and a decrease in fracture risk. Methods The primary purpose of this analysis was to evaluate the association between pretreatment Bone Turnover marker (BTM) concentrations and the absolute and relative fracture risks after adjusting for baseline femoral neck BMD, number of prevalent vertebral fractures, and age. Because femoral neck BMD is commonly attained in the assessment of patients at risk for osteoporosis, we examined the ability of a multivariate assessment including pretreatment BTM concentration and femoral neck BMD to predict future fracture risk after adjusting for the number of prevalent vertebral fractures. We examined data from the Fracture Prevention Trial, a study designed to determine the effect of teriparatide 20 mcg/day and teriparatide 40 mcg/day on vertebral and nonvertebral fracture risk in postmenopausal women with osteoporosis. BTM were analyzed in two subsets of women within the Fracture Prevention Trial, and included serum Bone-specific alkaline phosphatase (BSAP), serum carboxy-terminal extension peptide of procollagen type I (PICP), serum amino-terminal extension peptide of procollagen type I (PINP), urinary free deoxypyridinoline (DPD), and urinary N-terminal telopeptide (NTX). Results Teriparatide significantly reduced the risk of fracture [four BTM subset ( n = 520), placebo = 14.3%, teriparatide = 5.8%, P n = 771), placebo = 17.7%, teriparatide = 5.5%, P Conclusion Teriparatide-mediated relative fracture risk reduction was independent of pretreatment Bone Turnover, demonstrating that this therapy offers clinical benefit to patients across a range of disease severity.
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pretreatment levels of Bone Turnover and the antifracture efficacy of alendronate the fracture intervention trial
Journal of Bone and Mineral Research, 2005Co-Authors: Douglas C Bauer, Marc C Hochberg, Patrick Garnero, Susan K Ewing, Pierre D Delmas, Art Santora, Dennis M. BlackAbstract:The influence of pretreatment Bone Turnover on alendronate efficacy is not known. In the FIT, we examined the effect of pretreatment Bone Turnover on the antifracture efficacy of daily alendronate given to postmenopausal women. The nonspine fracture efficacy of alendronate was significantly greater among both osteoporotic and nonosteoporotic women with higher baseline levels of the Bone formation marker PINP. Introduction: Previous trials have shown that high Bone Turnover is associated with greater increases in BMD among bisphosphonate-treated women. The influence of pretreatment Bone Turnover levels on antifracture efficacy has not been well studied. Materials and Methods: We randomized women 55–80 years of age with femoral neck BMD T scores ≤ −1.6 to alendronate (ALN), 5–10 mg/day (n = 3105), or placebo (PBO; n = 3081). At baseline, 3495 women were osteoporotic (femoral neck BMD T score ≤ −2.5 or prevalent vertebral fracture), and 2689 were not osteoporotic (BMD T score > −2.5 and no prevalent vertebral fracture). Pretreatment levels of Bone-specific alkaline phosphatase (BSALP), N-terminal propeptide of type 1 collagen (PINP), and C-terminal cross-linked telopeptide of type 1 collagen (sCTx) were measured in all participants using archived serum (20% fasting). The risk of incident spine and nonspine fracture was compared in ALN- and PBO-treated subjects stratified into tertiles of baseline Bone marker level. Results and Conclusions: During a mean follow-up of 3.2 years, 492 nonspine and 294 morphometric vertebral fractures were documented. Compared with placebo, the reduction in nonspine fractures with ALN treatment differed significantly among those with low, intermediate, and high pretreatment levels of PINP levels (p = 0.03 for trend). For example, among osteoporotic women in the lowest tertile of pretreatment PINP ( 56.8 ng/ml). Results were similar among women without osteoporosis at baseline. Although they did not reach statistical significance, similar trends were observed with baseline levels of BSALP. Conversely, spine fracture treatment efficacy among osteoporotic women did not differ significantly according to pretreatment marker levels. Spine fracture treatment efficacy among nonosteoporotic women was related to baseline BSALP (p = 0.05 for trend). In summary, alendronate nonspine fracture efficacy is greater among both osteoporotic and nonosteoporotic women with high pretreatment PINP. If confirmed in other studies, these findings suggest that bisphosphonate treatment may be most effective in women with elevated Bone Turnover.
Richard Eastell - One of the best experts on this subject based on the ideXlab platform.
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diagnostic accuracy of biomarkers and imaging for Bone Turnover in renal osteodystrophy
Journal of The American Society of Nephrology, 2018Co-Authors: Syazrah Salam, F Gossiel, Orla Gallagher, Margaret Paggiosi, Arif Khwaja, Richard EastellAbstract:Background Renal osteodystrophy is common in advanced CKD, but characterization of Bone Turnover status can only be achieved by histomorphometric analysis of Bone biopsy specimens (gold standard test). We tested whether Bone biomarkers and high-resolution peripheral computed tomography (HR-pQCT) parameters can predict Bone Turnover status determined by histomorphometry.Methods We obtained fasting blood samples from 69 patients with CKD stages 4-5, including patients on dialysis, and 68 controls for biomarker analysis (intact parathyroid hormone [iPTH], procollagen type 1 N-terminal propeptide [PINP], Bone alkaline phosphatase [bALP], collagen type 1 crosslinked C-telopeptide [CTX], and tartrate-resistant acid phosphatase 5b [TRAP5b]) and scanned the distal radius and tibia of participants by HR-pQCT. We used histomorphometry to evaluate Bone biopsy specimens from 43 patients with CKD.Results Levels of all biomarkers tested were significantly higher in CKD samples than control samples. For discriminating low Bone Turnover, bALP, intact PINP, and TRAP5b had an areas under the receiver operating characteristic curve (AUCs) of 0.82, 0.79, and 0.80, respectively, each significantly better than the iPTH AUC of 0.61. Furthermore, radius HR-pQCT total volumetric Bone mineral density and cortical Bone volume had AUCs of 0.81 and 0.80, respectively. For discriminating high Bone Turnover, iPTH had an AUC of 0.76, similar to that of all other biomarkers tested.Conclusions The biomarkers bALP, intact PINP, and TRAP5b and radius HR-pQCT parameters can discriminate low from nonlow Bone Turnover. Despite poor diagnostic accuracy for low Bone Turnover, iPTH can discriminate high Bone Turnover with accuracy similar to that of the other biomarkers, including CTX.
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diagnosis of endocrine disease Bone Turnover markers are they clinically useful
European Journal of Endocrinology, 2018Co-Authors: Richard Eastell, F Gossiel, K E Naylor, Jennifer Walsh, Tom Pigott, Nicola PeelAbstract:Bone Turnover markers (BTMs) are useful in clinical practice as they are inexpensive, and they have proven useful for treatment monitoring and identification of poor adherence. BTMs cannot be used in individual patients for identifying accelerated Bone loss or an increase in fracture risk or in deciding on the optimal therapy. They are useful for monitoring both anti-resorptive and anabolic treatment. Response can be defined as a result that exceeds an absolute target, or by a change greater than the least significant change; if such a response is not present, then poor compliance or secondary osteoporosis are likely causes. A baseline BTM measurement is not always made; in that case, a value of BTM on anti-resorptive treatment that is low or low normal or above the reference interval for anabolic therapy may be taken to indicate a satisfactory response. We provide an approach to using these Bone Turnover markers in clinical practice by describing algorithms for anti-resorptive and anabolic therapy and describing the changes we observe in the clinical practice setting.
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use of Bone Turnover markers in postmenopausal osteoporosis
The Lancet Diabetes & Endocrinology, 2017Co-Authors: Richard Eastell, Pawel SzulcAbstract:Summary Bone Turnover comprises two processes: the removal of old Bone (resorption) and the laying down of new Bone (formation). N-terminal propeptide of type I procollagen (PINP) and C-telopeptide of type I collagen (CTX-I) are markers of Bone formation and resorption, respectively, that are recommended for clinical use. Bone Turnover markers can be measured on several occasions in one individual with good precision. However, these markers are subject to several sources of variability, including feeding (resorption decreases) and recent fracture (all markers increase for several months). Bone Turnover markers are not used for diagnosis of osteoporosis and do not improve prediction of Bone loss or fracture within an individual. In untreated women, very high Bone Turnover marker concentrations suggest secondary causes of high Bone Turnover (eg, Bone metastases or multiple myeloma). In people with osteoporosis, Bone Turnover markers might be useful to assess the response to anabolic and antiresorptive therapies, to assess compliance to therapy, or to indicate possible secondary osteoporosis. Much remains to be learnt about how Bone Turnover markers can be used to monitor the effect of stopping bisphosphonate therapy (eg, to identify a threshold above which restarting therapy should be considered). More studies are needed to investigate the use of Bone Turnover markers for assessment of the Bone safety of new medications.
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response of Bone Turnover markers to three oral bisphosphonate therapies in postmenopausal osteoporosis the trio study
Osteoporosis International, 2016Co-Authors: K E Naylor, F Gossiel, Margaret Paggiosi, Richard Jacques, Nicola Peel, E V Mccloskey, Jennifer Walsh, Richard EastellAbstract:Summary We used Bone Turnover markers to identify women who responded to bisphosphonate treatment for osteoporosis. Response was more likely with alendronate and ibandronate than risedronate. There was a greater decrease in Bone markers if baseline Bone Turnover markers were higher and if the patient took more than 80 % of her medication.
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Bone Turnover markers use in osteoporosis
Nature Reviews Rheumatology, 2012Co-Authors: K E Naylor, Richard EastellAbstract:Analyzing Bone Turnover markers—an approach boosted by the advent of automated analysis—can guide clinical decision making and the development of new therapies in osteoporosis. How such markers are, ought to be, and might be, used to understand osteoporosis and to optimize its treatment form the focus of this Review. Biochemical markers of Bone Turnover (Bone Turnover markers, BTMs) can be used to study changes in Bone remodelling in osteoporosis. Investigators and clinicians should be aware of the appropriate sample collection and storage conditions for optimum measurements of these markers. Improvements in the variability of BTM measurements have resulted from the development of assays for automated analysers, and from international consensus regarding their use. Appropriate reference intervals should be used for the optimum interpretation of results. BTMs can provide information that is useful for the management of patients with osteoporosis, for both the initial clinical assessment and for guiding and monitoring of treatment. BTMs are clinically useful to determine possible causes of secondary osteoporosis by identifying patients with high Bone Turnover and rapid Bone loss. In the follow-up of treatment response, BTM levels respond rapidly to both anabolic and antiresorptive treatments. BTM changes can also be used for understanding the mechanism of action of drugs in development and identifying the correct dose; they are also potentially useful as surrogate biomarkers for fracture.
Patrick Garnero - One of the best experts on this subject based on the ideXlab platform.
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increased Bone Turnover in late postmenopausal women is a major determinant of osteoporosis
Journal of Bone and Mineral Research, 2009Co-Authors: Patrick Garnero, E Sornayrendu, M C Chapuy, Pierre D DelmasAbstract:Changes of Bone Turnover with aging are responsible for Bone loss and play a major role in osteoporosis. Although an increase of Bone Turnover has been documented at the time of menopause, the subsequent abnormalities of Bone resorption and formation and their potential role in determining Bone mass in the elderly have not been investigated. To address this issue, we have measured a battery of new sensitive and specific markers of Bone Turnover in a population-based study of 653 healthy women analyzed cross-sectionally, including 432 women postmenopausal from 1 to 40 years, and the data were correlated with Bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) at different skeletal sites. Bone formation was assessed by serum osteocalcin (OC), serum Bone-specific alkaline phosphatase (B-ALP), serum C-propeptide of type I collagen (PICP), and Bone resorption by the urinary excretion of two pyridinoline cross-linked peptides (NTX and CTX). Bone Turnover increased in perimenopausal women with both irregular menses and elevated serum follicle stimulating hormone (FSH). Menopause induced a 37–52% and 79–97% increase in the Bone formation and Bone resorption marker levels, respectively (p < 0.0001 except for PICP). In postmenopausal women, Bone formation markers did not decrease with age. When resorption markers were corrected by whole body Bone mineral content (BMC), the fraction of Bone resorbed per day was not correlated with age in postmenopausal women and remained elevated for up to 40 years after menopause. In premenopausal women, the Bone Turnover rate accounted for only 0–10% of the variation in whole body BMC, total hip, distal radius, and lumbar spine BMD. With increasing time after menopause, the importance of the Bone Turnover rate as a determinant of Bone mass increased at all sites and accounted for up to 52% of the BMD variance in elderly women. Thus, in women 20 years or more postmenopause, Bone Turnover was higher in those in the lowest quartile than in those in the highest quartile of BMD. In elderly women, 20 years since menopause and over, but not in younger ones, serum PTH was negatively correlated with serum 25-hydroxyvitamin D (r = −0.22,p < 0.05) and explained only 5–8% of the Bone Turnover variance (p < 0.01-0.001). These data indicate that the overall rates of both Bone formation and Bone resorption remain high in elderly women. The rate of Bone Turnover appears to play an increasing role as a determinant of Bone mass with increasing time since menopause with a high Bone Turnover rate being associated with a low Bone mass. Thus assessing Bone marker levels may be useful in the evaluation of osteoporosis risk. In elderly women, secondary hyperparathyroidism caused in part by reduced serum 25-hydroxyvitamin D appears to be a marginal determinant of an increased Bone Turnover rate.
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biochemical markers of Bone Turnover hip Bone loss and fracture in older men the mros study
Journal of Bone and Mineral Research, 2009Co-Authors: Douglas C Bauer, Richard Eastell, Patrick Garnero, Stephanie L Harrison, Jane A Cauley, K Ensrud, Eric S OrwollAbstract:We used data from the Osteoporotic Fractures in Men (MrOS) study to test the hypothesis that men with higher levels of Bone Turnover would have accelerated Bone loss and an elevated risk of fracture. MrOS enrolled 5995 subjects >65 yr; hip BMD was measured at baseline and after a mean follow-up of 4.6 yr. Nonspine fractures were documented during a mean follow-up of 5.0 yr. Using fasting serum collected at baseline and stored at –190°C, Bone Turnover measurements (type I collagen N-propeptide [PINP]; β C-terminal cross-linked telopeptide of type I collagen [βCTX]; and TRACP5b) were obtained on 384 men with nonspine fracture (including 72 hip fractures) and 947 men selected at random. Among randomly selected men, total hip Bone loss was 0.5%/yr among those in the highest quartile of PINP (>44.3 ng/ml) and 0.3%/yr among those in the lower three quartiles (p = 0.01). Fracture risk was elevated among men in the highest quartile of PINP (hip fracture relative hazard = 2.13; 95% CI: 1.23, 3.68; nonspine relative hazard = 1.57, 95% CI: 1.21, 2.05) or βCTX (hip fracture relative hazard = 1.76, 95 CI: 1.04, 2.98; nonspine relative hazard = 1.29, 95% CI: 0.99, 1.69) but not TRACP5b. Further adjustment for baseline hip BMD eliminated all associations between Bone Turnover and fracture. We conclude that higher levels of Bone Turnover are associated with greater hip Bone loss in older men, but increased Turnover is not independently associated with the risk of hip or nonspine fracture.
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establishing a reference interval for Bone Turnover markers in 637 healthy young premenopausal women from the united kingdom france belgium and the united states
Journal of Bone and Mineral Research, 2009Co-Authors: Sarah J Glover, Dennis M. Black, Patrick Garnero, Pierre D Delmas, Jane A Cauley, Steven Boonen, Martin Gall, Oliver Schoenbornkellenberger, Michael Wagener, Richard EastellAbstract:Robust reference intervals are needed for the interpretation of Bone Turnover markers in large phase III fracture trials. The objectives of the study were to (1) estimate reference intervals for serum Bone alkaline phosphatase (Bone ALP), serum procollagen type I N propeptide (PINP), serum beta cross-linked C-telopeptides of type I collagen (S-betaCTX), and urinary cross-linked N-telopeptides of type I collagen (U-NTX) in healthy young premenopausal women; (2) examine geographical differences on Bone Turnover markers; and (3) assess factors known to influence Bone Turnover and test whether these explain any regional differences. We studied 637 eligible women from four countries that participated in the Horizon-PFT study (United Kingdom, France, Belgium, United States). The women were 30-39 yr of age (mean, 34.6 yr), with regular cyclic menses. Subjects completed a medical and lifestyle questionnaire. Two-sided 95% reference intervals were estimated on transformed values and transformed back to the original scale using the proposed methodology of the International Federation of Clinical Chemistry. S-betaCTX was significantly higher in France relative to the United Kingdom (p = 0.01), and PINP was higher in France (p < 0.001) and Belgium (p = 0.02) relative to the United Kingdom and significantly higher in France relative to the United States (p < 0.01) by ANOVA. Overall, one could associate low Bone Turnover markers with nonsmoking, use of a contraceptive pill, exercise, being close to the time of ovulation, and having high 25-hydroxyvitamin D levels. Countries differed by these characteristics, and once allowed for in the statistical model, any country differences were attenuated or removed.
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pretreatment levels of Bone Turnover and the antifracture efficacy of alendronate the fracture intervention trial
Journal of Bone and Mineral Research, 2005Co-Authors: Douglas C Bauer, Marc C Hochberg, Patrick Garnero, Susan K Ewing, Pierre D Delmas, Art Santora, Dennis M. BlackAbstract:The influence of pretreatment Bone Turnover on alendronate efficacy is not known. In the FIT, we examined the effect of pretreatment Bone Turnover on the antifracture efficacy of daily alendronate given to postmenopausal women. The nonspine fracture efficacy of alendronate was significantly greater among both osteoporotic and nonosteoporotic women with higher baseline levels of the Bone formation marker PINP. Introduction: Previous trials have shown that high Bone Turnover is associated with greater increases in BMD among bisphosphonate-treated women. The influence of pretreatment Bone Turnover levels on antifracture efficacy has not been well studied. Materials and Methods: We randomized women 55–80 years of age with femoral neck BMD T scores ≤ −1.6 to alendronate (ALN), 5–10 mg/day (n = 3105), or placebo (PBO; n = 3081). At baseline, 3495 women were osteoporotic (femoral neck BMD T score ≤ −2.5 or prevalent vertebral fracture), and 2689 were not osteoporotic (BMD T score > −2.5 and no prevalent vertebral fracture). Pretreatment levels of Bone-specific alkaline phosphatase (BSALP), N-terminal propeptide of type 1 collagen (PINP), and C-terminal cross-linked telopeptide of type 1 collagen (sCTx) were measured in all participants using archived serum (20% fasting). The risk of incident spine and nonspine fracture was compared in ALN- and PBO-treated subjects stratified into tertiles of baseline Bone marker level. Results and Conclusions: During a mean follow-up of 3.2 years, 492 nonspine and 294 morphometric vertebral fractures were documented. Compared with placebo, the reduction in nonspine fractures with ALN treatment differed significantly among those with low, intermediate, and high pretreatment levels of PINP levels (p = 0.03 for trend). For example, among osteoporotic women in the lowest tertile of pretreatment PINP ( 56.8 ng/ml). Results were similar among women without osteoporosis at baseline. Although they did not reach statistical significance, similar trends were observed with baseline levels of BSALP. Conversely, spine fracture treatment efficacy among osteoporotic women did not differ significantly according to pretreatment marker levels. Spine fracture treatment efficacy among nonosteoporotic women was related to baseline BSALP (p = 0.05 for trend). In summary, alendronate nonspine fracture efficacy is greater among both osteoporotic and nonosteoporotic women with high pretreatment PINP. If confirmed in other studies, these findings suggest that bisphosphonate treatment may be most effective in women with elevated Bone Turnover.
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change in Bone Turnover and hip non spine and vertebral fracture in alendronate treated women the fracture intervention trial
Journal of Bone and Mineral Research, 2004Co-Authors: Douglas C Bauer, Dennis M. Black, Desmond E Thompson, Marc C Hochberg, Patrick Garnero, John J Orloff, Susan K Ewing, Pierre D DelmasAbstract:We used data from the Fracture Intervention Trial to assess the relationship change in Bone Turnover after 1 year of alendronate or placebo treatment and subsequent hip, non-spine, and spine fracture risk among 6186 postmenopausal women. In the alendronate group (n = 3105), greater reductions in one or more biochemical marker were associated with a lower risk of fracture. Introduction: There are few data on the relationship between short-term change in biochemical markers of Bone Turnover and non-spine fracture risk among bisphosphonate-treated women, and the clinical use of such measurements is unknown. Materials and Methods: We measured biochemical markers of Bone Turnover (Bone-specific alkaline phosphatase [Bone ALP], intact N-terminal propeptide of type I collagen, and C-terminal crosslinked telopeptide of type 1 collagen) and BMD of the spine and hip at baseline and after 1 year of alendronate or placebo. During a mean follow-up of 3.6 years, 72 hip, 786 non-spine, and 336 vertebral fractures were documented. Results and Conclusions: Each 1 SD reduction in 1-year change in Bone ALP was associated with fewer spine (odds ratio = 0.74; CI: 0.63, 0.87), non-spine (relative hazard [RH] = 0.89; CI: 0.78, 1.00; p < 0.050), and hip fractures (RH = 0.61; CI: 0.46, 0.78). Alendronate-treated women with at least a 30% reduction in Bone ALP had a lower risk of non-spine (RH = 0.72; CI: 0.55, 0.92) and hip fractures (RH = 0.26; CI: 0.08, 0.83) relative to those with reductions <30%. We conclude that greater reductions in Bone Turnover with alendronate therapy are associated with fewer hip, non-spine, and vertebral fractures, and the effect is at least as strong as that observed with 1-year change in BMD.
Jakob Staruplinde - One of the best experts on this subject based on the ideXlab platform.
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effects of a whey protein pre meal on Bone Turnover in participants with and without type 2 diabetes a post hoc analysis of a randomised controlled crossover trial
Diabetic Medicine, 2020Co-Authors: Ann Bjornshave, Simon Lykkeboe, Bolette Hartmann, Jens J Holst, Kjeld Hermansen, Jakob StaruplindeAbstract:Aims Whey protein may improve Bone Turnover and have anti-osteoporotic effects. The aim of the present randomized, controlled, cross-over trial was to evaluate the effects of a whey protein pre-meal on Bone Turnover in people with type 2 diabetes and controls. Methods Two groups, matched on sex, age, and body mass index, comprising 12 participants with and 12 participants without type 2 diabetes were randomly given a pre-meal of whey protein (20g) or water, which was consumed 15 min before a fat-rich meal or a fat-rich meal supplemented with 20g whey protein. During a 360-min period, postprandial responses in Bone Turnover were examined. Results Osteocalcin, P-procollagen type 1 amino terminal propeptide (P1NP), C-terminal cross-linked telopeptide of type-I collagen (CTX), and parathyroid hormone (PTH) were lower at baseline and PTH, osteocalcin, and P1NP were lower during the entire postprandial phase in participants with type 2 diabetes than in participants without type 2 diabetes. We observed similar postprandial responses in Bone Turnover markers between persons with and without type 2 diabetes. We observed no effect of the whey protein or the water pre-meal on Bone Turnover markers. The changes were unrelated to secretion of hormones of the gut-Bone axis. Conclusion Osteocalcin, P1NP, CTX, and PTH all decreased following meal ingestion. We observed no convincing effect of a whey protein pre-meal on Bone Turnover. However, these results confirm that people with type 2 diabetes have low Bone Turnover and that the decreased Bone formation markers are also extend into the postprandial responses.
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mechanisms in endocrinology diabetes mellitus a state of low Bone Turnover a systematic review and meta analysis
European Journal of Endocrinology, 2017Co-Authors: Katrine Hygum, Jakob Staruplinde, Peter Vestergaard, Torben Harslof, Bente L LangdahlAbstract:OBJECTIVE To investigate the differences in Bone Turnover between diabetic patients and controls. DESIGN A systematic review and meta-analysis. METHODS A literature search was conducted using the databases Medline at PubMed and EMBASE. The free text search terms 'diabetes mellitus' and 'Bone Turnover', 'sclerostin', 'RANKL', 'osteoprotegerin', 'tartrate-resistant acid' and 'TRAP' were used. Studies were eligible if they investigated Bone Turnover markers in patients with diabetes compared with controls. Data were extracted by two reviewers. RESULTS A total of 2881 papers were identified of which 66 studies were included. Serum levels of the Bone resorption marker C-terminal cross-linked telopeptide (-0.10 ng/mL (-0.12, -0.08)) and the Bone formation markers osteocalcin (-2.51 ng/mL (-3.01, -2.01)) and procollagen type 1 amino terminal propeptide (-10.80 ng/mL (-12.83, -8.77)) were all lower in patients with diabetes compared with controls. Furthermore, s-tartrate-resistant acid phosphatase was decreased in patients with type 2 diabetes (-0.31 U/L (-0.56, -0.05)) compared with controls. S-sclerostin was significantly higher in patients with type 2 diabetes (14.92 pmol/L (3.12, 26.72)) and patients with type 1 diabetes (3.24 pmol/L (1.52, 4.96)) compared with controls. Also, s-osteoprotegerin was increased among patients with diabetes compared with controls (2.67 pmol/L (0.21, 5.14)). CONCLUSIONS Markers of both Bone formation and Bone resorption are decreased in patients with diabetes. This suggests that diabetes mellitus is a state of low Bone Turnover, which in turn may lead to more fragile Bone. Altered levels of sclerostin and osteoprotegerin may be responsible for this.
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biochemical Bone Turnover markers in diabetes mellitus a systematic review
Bone, 2016Co-Authors: Jakob Staruplinde, Peter VestergaardAbstract:Abstract Background Diabetes mellitus is associated with an increased risk of fractures, which is not explained by Bone mineral density. Other markers as Bone Turnover markers (BTMs) may be useful. Aim To assess the relationship between BTMs, diabetes, and fractures. Methods A systematic literature search was conducted in August 2014. The databases searched were Medline at Pubmed and Embase. Medline at Pubmed was searched by “Diabetes Mellitus” (MESH) and “Bone Turnover markers” and Embase was searched using the Emtree by “Diabetes Mellitus” and “Bone Turnover”, resulting in 611 studies. The eligibility criteria for the studies were to assess BTM in either type 1 diabetes (T1D) or type 2 diabetes (T2D) patients. Results Of the 611 eligible studies, removal of duplicates and screening by title and abstract lead to 114 potential studies for full-text review. All these studies were full-text screened for eligibility and 45 studies were included. Two additional studies were added from other sources. Among the 47 studies included there were 1 meta-analysis, 29 cross-sectional studies, 13 randomized controlled trials, and 4 longitudinal studies. Both T1D and T2D were studied. Most studies reported fasting BTM and excluded renal disease. Conclusion Markers of Bone resorption and formation seem to be lower in diabetes patients. Bone specific alkaline phosphatase is normal or increased, which suggests that the matrix becomes hypermineralized in diabetes patients. The BTMs: C-terminal cross-link of collagen, insulin-like growth factor-1, and sclerostin may potentially predict fractures, but longitudinal trials are needed. This article is part of a Special Issue entitled Bone and diabetes.
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sclerostin levels associated with inhibition of the wnt β catenin signaling and reduced Bone Turnover in type 2 diabetes mellitus
The Journal of Clinical Endocrinology and Metabolism, 2012Co-Authors: Agostino Gaudio, F Privitera, Katia Battaglia, Venerando Torrisi, Maria Helga Sidoti, Ivana Pulvirenti, Elena Canzonieri, Giovanni Tringali, C E FioreAbstract:Context: Patients with type 2 diabetes (T2DM) have low Bone Turnover, poor Bone quality, and circulating levels of sclerostin significantly higher than non-T2DM controls. There are no data on the possible association of sclerostin with β-catenin, a key component of the Wnt/β-catenin canonical signaling. Objectives: The aim of the study was to evaluate the circulating β-catenin levels in T2DM patients and to analyze their relationship with sclerostin and Bone Turnover markers. Design: This was a cross-sectional study. Setting and Patients: The study was conducted at a clinical research center. Forty T2DM postmenopausal women were studied and compared with 40 healthy controls. Bone status was assessed by dual-energy x-ray absorptiometry measurements (Bone mineral density) and by measuring Bone alkaline phosphatase and carboxy-terminal telopeptide of type 1 collagen. Sclerostin and β-catenin were evaluated by an immunoenzymetric assay. Results: Consistent with previous reports in T2DM subjects, we found scle...