scholarly journals Predictive Power of Bone Turnover Biomarkers to Estimate Bone Mineral Density after Kidney Transplantation with or without Denosumab: A post hoc Analysis of the POSTOP Study

2020 ◽  
Vol 45 (5) ◽  
pp. 758-767
Author(s):  
Nadine Heimgartner ◽  
Nicole Graf ◽  
Diana Frey ◽  
Lanja Saleh ◽  
Rudolf P. Wüthrich ◽  
...  

Background: Low bone mineral density (BMD) represents a major risk factor for bone fractures in patients with chronic kidney disease (CKD) as well as after kidney transplantation. However, modalities to solidly predict patients at fracture risk are yet to be defined. Better understanding of bone turnover biomarkers (BTMs) may close this diagnostic gap. This study strives to correlate BTMs to BMD in kidney transplant recipients. Methods: Changes in BTMs – procollagen type I N-terminal propeptide (P1NP), bone-specific alkaline phosphatase (BSAP), β-isomer of the C-terminal telopeptide of type I collagen, and urine deoxypyridinoline/Cr – at the time of transplant and 3 months were correlated to changes in BMD measured by dual-energy X-ray absorptiometry at the time of transplant, 6, and 12 months, respectively. Half of the collective was treated with denosumab twice yearly in addition to the standard treatment with calcium and vitamin D. Results: Changes in bone formation markers BSAP and P1NP within 3 months showed a significant negative correlation to changes in BMD at the hip within 6 months in denosumab-naïve patients. This correlation was abrogated by denosumab treatment. Conclusions: Changes in BSAP and P1NP showed promise in short-term prediction of BMD. We suggest further trials expanding on the knowledge of these BTMs with assessment of fracture risk, sequential measurements of BTMs within the first 6 months, and the additional use of computed tomography to assess BMD.

Author(s):  
Claudia Harper ◽  
Andrea L. Pattinson ◽  
Hamish A. Fernando ◽  
Jessica Zibellini ◽  
Radhika V. Seimon ◽  
...  

AbstractBackground:New evidence suggests that obesity is deleterious for bone health, and obesity treatments could potentially exacerbate this.Materials and methods:This narrative review, largely based on recent systematic reviews and meta-analyses, synthesizes the effects on bone of bariatric surgery, weight loss pharmaceuticals and dietary restriction.Results and conclusions:All three obesity treatments result in statistically significant reductions in hip bone mineral density (BMD) and increases in bone turnover relative to pre-treatment values, with the reductions in hip BMD being strongest for bariatric surgery, notably Roux-en Y gastric bypass (RYGB, 8%–11% of pre-surgical values) and weakest for dietary restriction (1%–1.5% of pre-treatment values). Weight loss pharmaceuticals (orlistat or the glucagon-like peptide-1 receptor agonist, liraglutide) induced no greater changes from pre-treatment values than control, despite greater weight loss. There is suggestive evidence that liraglutide may increase bone mineral content (BMC) – but not BMD – and reduce fracture risk, but more research is required to clarify this. All three obesity treatments have variable effects on spine BMD, probably due to greater measurement error at this site in obesity, suggesting that future research in this field could focus on hip rather than spine BMD. Various mechanisms have been proposed for BMD loss with obesity treatments, notably reduced nutritional intake/absorption and insufficient exercise, and these are potential avenues for protection against bone loss. However, a pressing outstanding question is whether this BMD reduction contributes to increased fracture risk, as has been observed after RYGB, and whether any such increase in fracture risk outweighs the risks of staying obese (unlikely).


Cartilage ◽  
2017 ◽  
Vol 9 (3) ◽  
pp. 255-262 ◽  
Author(s):  
Jadwiga Ambroszkiewicz ◽  
Joanna Gajewska ◽  
Grazyna Rowicka ◽  
Witold Klemarczyk ◽  
Magdalena Chelchowska

Objective There is scant research examining the prevalence of thinness in early childhood, despite its potential negative consequences for health and development across the life course. The objective of this study was to assess bone status through measurement of bone mineral density and biochemical bone turnover markers, with special attention paid to carboxylated (c-OC) as well as undercarboxylated (uc-OC) forms of osteocalcin, in the groups of thin and normal-weight children. Design The study included 80 healthy prepubertal children (median age 7.0 years), who were divided (according to Cole’s international cutoffs) into 2 subgroups: thin children ( n = 40, body mass index [BMI] = 13.5 kg/m2) and normal-weight children ( n = 40, BMI = 16.1 kg/m2). Bone mineral density (BMD) and bone mineral content (BMC) were assessed by dual-energy x-ray absorptiometry method. Serum concentrations of C-terminal telopeptide of collagen type I (CTX), total osteocalcin (OC), and c-OC, and uc-OC forms of osteocalcin were determined using enzyme-linked immunosorbent assays. Results In thin children, we observed higher levels of bone resorption marker CTX compared with normal-weight peers. Total osteocalcin concentrations were comparable in both groups of children; however, in thin children we observed higher median values of uc-OC (34.40 vs. 29.30 ng/mL, P < 0.05) and similar c-OC levels (25.65 vs. 28.80 ng/mL). The ratio of c-OC to uc-OC was significantly lower ( P < 0.05) in thin than in normal-weight children. Total BMD and BMC were significantly decreased ( P < 0.0001) in thin children compared with normal-weight peers (0.724 ± 0.092 vs. 0.815 ± 0.060 g/cm2 and 602.7 ± 159.2 vs. 818.2 ± 220.1 g, respectively). Conclusion Increased concentrations of CTX and uc-OC might lead to disturbances in bone turnover and a decrease in bone mineral density in thin children.


2019 ◽  
Vol 10 (Vol.10, No.3) ◽  
pp. 243-251
Author(s):  
Alina Deniza CIUBEAN ◽  
Laszlo IRSAY ◽  
Rodica Ana UNGUR ◽  
Viorela Mihaela CIORTEA ◽  
Ileana Monica BORDA ◽  
...  

Introduction: Osteoporosis has a strong genetic contribution, and several genes have been shown to influence bone mineral density. Variants in the human genome are considered important causes of differences in drug responses observed in clinical practice. In terms of bone mineral density, about 26–53% of patients do not respond to amino-bisphosphonate therapies, of which alendronate is the most widely used. Material and method: The current study is prospective, observational, analytical, longitudinal and cohort type. It included 25 postmenopausal women treated with alendronate for 1 year. Bone mineral density at lumbar spine and proximal femur was measured and bone turnover markers (C-terminal telopeptide of type I collagen and procollagen 1N-terminal propeptide) were evaluated at 0 and 12 months of treatment. Six single nucleotide polymorphisms in osteoporosis-candidate genes were genotyped (FDPS rs2297480, LRP5 rs3736228, SOST rs1234612, VKORC1 rs9934438, GGPS1 rs10925503 and RANKL rs2277439). Treatment response was evaluated by percentage changes in bone mineral density and bone turnover markers. Results: The heterozygous CT of FDPS rs2297480 showed lower increases in BMD values in the lumbar spine region and the homozygous CC of the GGPS1 rs10925503 showed lower increases in terms of BMD at the total hip region. No association was found for LRP5 rs3736228, SOST rs1234612, VKORC1 rs9934438 and RANKL rs2277439. Conclusions: Romanian postmenopausal women with osteoporosis carrying the CT genotype of FDPS rs2297480 or the CC genotype of GGPS1 rs10925503 could have an unsatisfactory response to alendronate treatment. Key words: osteoporosis; genetic polymorphism; alendronate; bone mineral density; bone turnover markers,


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 555-555 ◽  
Author(s):  
E. McCloskey ◽  
R. Hannon ◽  
G. Lakner ◽  
G. Clack ◽  
A. Miyamoto ◽  
...  

555 Background: The LEAP trial is an open, randomized, multicenter, Phase I pharmacodynamic study comparing the effects of the AIs L, E and A on safety parameters, such as serum markers of bone formation and resorption, lipid profiles, and adrenal function in healthy postmenopausal women with normal bone mineral density at the spine and hip. Elevated bone biochemical levels indicate high turnover of bone, and correlate with a loss in bone mineral density. It has been suggested that there are differences between the effect of the steroidal AIs (E) and non-steroidal AIs (A and L) on bone turnover, with steroidal AIs having a less negative effect. Methods: Healthy volunteersfrom the UK and Hungarywere randomized to receive A (1 mg/day), L (2.5 mg/day), or E (25 mg/day) orally, once daily for 24 weeks. Changes from baseline in log-transformed bone alkaline phosphatase (ALP), serum C-telopeptide crosslinks (CTX), parathyroid hormone (PTH) and propeptide of type I procollagen (PINP) at 24 weeks on A, were compared with those on L and E by ANCOVA, adjusting for treatment, baseline measurement, BMI, smoking status and baseline estradiol. No adjustments were made for multiple comparisons. Results: A total of 102 healthy volunteers were recruited, with 90 participants evaluable at 24 weeks (29 A, 29 L, 32 E). Participant demographics were similar between the treatment groups in terms of age, years since menopause, and history of hysterectomy and oophorectomy. Bone biochemical measurement changes are presented in the table . With the exception of PTH, where there is a greater decrease in PTH with E than with A (p=0.04), there were no statistically significant differences between the AIs. Conclusions: The steroidal and non-steroidal AIs appear to have similar effects on bone biochemical measurements, and thus bone turnover. All three licensed AIs result in increases in bone turnover. [Table: see text] [Table: see text]


2006 ◽  
Vol 50 (4) ◽  
pp. 579-585 ◽  
Author(s):  
Juliet Compston

Bone quality describes aspects of bone composition and structure that contribute to bone strength independently of bone mineral density. These include bone turnover, microarchitecture, mineralisation, microdamage and the composition of bone matrix and mineral. New techniques to assess these components of bone quality are being developed and should produce important insights into determinants of fracture risk in untreated and treated disease.


2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Wei-Wei Hu ◽  
Zeng Zhang ◽  
Jin-Wei He ◽  
Wen-Zhen Fu ◽  
Chun Wang ◽  
...  

The reference ranges of bone turnover markers (BTMs) were important during the treatment of osteoporosis, and the associations with bone mineral density (BMD) were controversial. The aim of this study was to establish the reference ranges of N-terminal procollagen of type l collagen (P1NP), osteocalcin (OC), and beta C-terminal cross-linked telopeptides of type I collagen (β-CTX) in Shanghai area and to investigate the relationships between BTMs and BMD in postmenopausal women. 2,799 subjects recruited in Shanghai City were measured BTMs to establish the reference ranges. Additional 520 healthy postmenopausal women were also measured BTMs, these women measured BMD in addition. BTMs were measured using the Roche electrochemiluminescence system. We used the age range of 35 to 45-year-olds to calculate reference intervals. The reference range of OC was 4.91 to 13.90 ng/mL for women and 5.58 to 16.57 ng/mL for men, P1NP was 13.72 to 32.90 ng/mL for women and 16.89 to 42.43 ng/mL for men, andβ-CTX was 0.112 to 0.210 ng/mL for women and 0.100 to 0.378 ng/mL for men. BTMs significantly negatively correlated with lumbar spine and femoral and total hip in postmenopausal women ( = −0.157~−0.217,P< 0.001). We established the normal reference ranges of P1NP, OC, andβ-CTX in the Shanghai area. This study also found that BTMs correlated with BMD and suggested that BTMs were the key determining factors of early BMD decreases.


2017 ◽  
Vol 29 (4) ◽  
pp. 513-519 ◽  
Author(s):  
Ammar Nebigh ◽  
Mohamed Elfethi Abed ◽  
Rihab Borji ◽  
Sonia Sahli ◽  
Slaheddine Sellami ◽  
...  

The aim of this study was to examine the relationship between bone mass and bone turnover markers with lean mass (LM) in pubescent soccer players. Two groups participated in this study, which included 65 elite young soccer players who trained for 6–8 hours per week and 60 controls. Bone mineral density; bone mineral content in the whole body, lower limbs, lumbar spine, and femoral neck; biochemical markers of osteocalcin; bone-specific alkaline phosphatase; C-telopeptide type I collagen; and total LM were assessed. Young soccer players showed higher bone mineral density and bone mineral content in the whole body and weight-bearing sites (P < .001). Indeed, the total LM correlated with whole-body bone mineral density and bone mineral content (P < .001). There were significant differences within the bone formation markers and osteocalcin (formation)/C-telopeptide type I collagen (resorption) ratio between young soccer players compared with the control group, but no significant difference in C-telopeptide type I collagen was observed between the 2 groups. This study showed a significant positive correlation among bone-specific alkaline phosphatase, osteocalcin, and total LM (r = .29; r = .31; P < .05) only for the young soccer players. Findings of this study highlight the importance of soccer practice for bone mineral parameters and bone turnover markers during the puberty stage.


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