Bone Turnover Markers in Children: From Laboratory Challenges to Clinical Interpretation

Ladang, Aurélie; Rauch, Frank; Delvin, Edgard; Cavalier, Étienne

doi:10.1007/s00223-022-00964-2

Cited by 9 publications

(5 citation statements)

References 160 publications

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“…Yet, assessing BAP does not offer a distinct advantage in infants, as the liver isozyme’s contribution to total ALP activity is minimal in children experiencing increased bone turnover. 3 Notably, ALP3, the bone type, was the dominant isoenzyme in all measurable cases in this study, validating the use of total ALP as a bone absorption marker during early infancy. Our results demonstrated that ALP and iPTH levels were elevated in response to vitamin D deficiency with a biphasic or negative linear pattern detected by the spline curve regression analysis.…”

Section: Discussionsupporting

confidence: 77%

Discordant responses of bone formation and absorption markers in Japanese infants with vitamin D deficiency: a comprehensive matched case–control study

Takahashi,

Ikeda,

Hara-Isono

et al. 2024

JBMR Plus

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Vitamin D deficiency during infancy has been associated with increased bone turnover rate and bone mineral loss. However, few studies have examined bone turnover markers (BTMs) for both bone formation and resorption in infants with vitamin D deficiency. Here, we analyzed serum concentrations of 25(OH)D, intact parathormone (iPTH), and BTMs including total alkaline phosphatase (ALP), tartrate-resistant acid phosphatase isoform 5b (TRACP-5b), and serum type I collagen N-telopeptide (NTx) as well as basic clinical characteristics of 456 infants (626 samples) aged less than 12 months born at Saitama City Hospital, Japan (latitude 35.9° North) between January 2021 and December 2022. 116 infants (147 samples) were classified as having vitamin D deficiency (25(OH)D < 12.0 ng/mL), and 340 infants (479 samples) had sufficient vitamin D levels (25(OH)D ≥ 12.0 ng/mL). In addition to 25(OH)D and ALP, both TRACP-5b and sNTx were measured in 331 infants (418 samples), while 90 infants (105 samples) had only TRACP-5b only measured and 101 infants (103 samples) had only sNTx measured. Statistical comparison of 104 subjects each in the vitamin D deficiency and sufficiency groups after matching for the background characteristics revealed that the vitamin D deficiency group had significantly higher levels of ALP and iPTH compared with the sufficiency group (p = <0.0001, 0.0012, respectively). However, no significant differences were found in TRACP-5b and NTx levels between the two groups (p = 0.19, 0.08, respectively). Our findings suggest discordant responses between bone formation and resorption markers in subclinical vitamin D deficiency during infancy.

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Section: Discussionsupporting

confidence: 77%

Discordant responses of bone formation and absorption markers in Japanese infants with vitamin D deficiency: a comprehensive matched case–control study

Takahashi,

Ikeda,

Hara-Isono

et al. 2024

JBMR Plus

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“…In addition, other factors, such as inflammation, infection, immobilization, malnutrition, and weight loss, may influence BTM by decreasing bone formation, while the effects on bone resorption may be variable. 18 , 57 Such conditions are common in children with leukemia and in children with solid tumors and may play a role in the suppression of bone remodeling. However, children with solid tumors do not have the same type of BM infiltration, which may explain the more suppressed bone turnover observed in children with leukemia.…”

Section: Discussionmentioning

confidence: 99%

“…The bone formation markers bone alkaline phosphatase (BALP), intact N-terminal propeptide of type I procollagen (PINP), and osteocalcin represent the activity of osteoblasts, whereas bone resorption markers, such as C-terminal cross-linked telopeptide of type I collagen (CTX) and tartrate-resistant acid phosphatase isoform 5b, reflect the activity of osteoclasts. 17 , 18 However, only a few studies have explored BTM in children with hemato-oncological diseases. 8 , 19–22 Investigating these markers is important for understanding the pathophysiology of skeletal complications in children with hemato-oncological diseases.…”

Section: Introductionmentioning

confidence: 99%

Demographic and disease-related factors impact bone turnover and vitamin D in children with hemato-oncological diseases

Jackmann,

Gustafsson,

Utriainen

et al. 2024

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Children with hemato-oncological diseases may have significant skeletal morbidity, not only during and after treatment but also at the time of diagnosis before cancer treatment. This study was designed to evaluate the vitamin D status and circulating bone metabolic markers and their determinants in children at the time of diagnostic evaluation for hemato-oncological disease. This cross-sectional study included 165 children (91 males, median age 6.9 years range 0.2–17.7 years). Of them, 76 patients were diagnosed with extracranial or intracranial solid tumors, 83 with leukemia, and 6 with bone marrow failure. Bone metabolism was assessed by measuring serum 25-hydroxyvitamin D, parathyroid hormone, bone alkaline phosphatase, intact N-terminal propeptide of type I procollagen, and C-terminal cross-linked telopeptide of type I collagen. Vitamin D deficiency was found in 30.9% of children. Lower 25-hydroxyvitamin D levels were associated with older age, lack of vitamin D supplementation, season outside summer, and a country of parental origin located between latitudes -45° and 45°. Children diagnosed with leukemia had lower levels of markers of bone formation and bone resorption than those who had solid tumors or bone marrow failure. In conclusion, vitamin D deficiency was observed in one-third of children with newly diagnosed cancer. Bone turnover markers were decreased in children with leukemia, possibly because of the suppression of osteoblasts and osteoclasts by leukemic cells. The identification of patients with suboptimal vitamin D status and compromised bone remodeling at cancer diagnosis may aid in the development of supportive treatment to reduce the adverse effects of cancer and its treatment.

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“…The serum levels of ALP, calcium, magnesium, and phosphorus were detected by Cobas8000c701 automatic biochemical analyzer (Roche). These bone metabolism markers with their clinical meaning are listed in Table S1 17,18 …”

Section: Methodsmentioning

confidence: 99%

Both epilepsy and anti‐seizure medications affect bone metabolism in children with self‐limited epilepsy with centrotemporal spikes

Shi

Lü

et al. 2023

Epilepsia

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ObjectiveBone metabolism can be influenced by a range of factors. We selected children with self‐limited epilepsy with centrotemporal spikes (SeLECTS) and lifestyles similar to those of healthy children to control for the confounding factors that may influence bone metabolism. We aimed to identify the specific effects of epilepsy and/or anti‐seizure medications (ASMs) on bone metabolism.MethodsPatients with SeLECTS were divided into an untreated group and a monotherapy group, and the third group was a healthy control group. We determined the levels of various biochemical markers of bone metabolism, including procollagen type I nitrogenous propeptide (PINP), alkaline phosphatase (ALP), osteocalcin (OC), collagen type I cross‐linked C‐telopeptide (CTX), calcium, magnesium, phosphorus, parathyroid hormone (PTH), and vitamin D3 (VD3).ResultsA total of 1487 patients (from 19 centers) were diagnosed with SeLECTS; 1032 were analyzed, including 117 patients who did not receive any ASMs (untreated group), 643 patients who received only one ASM (monotherapy group), and 272 children in the healthy control group. Except for VD3, other bone metabolism of the three groups were different (p < .001). Bone metabolism was significantly lower in the untreated group than the healthy control group (p < .05). There were significant differences between the monotherapy and healthy control group in the level of many markers. However, when comparing the monotherapy and untreated groups, the results were different; oxcarbazepine, levetiracetam, and topiramate had no significant effect on bone metabolism. Phosphorus and magnesium were significantly lower in the valproic acid group than the untreated group (adjusted p < .05, Cliff's delta .282–.768). CTX was significantly higher in the lamotrigine group than in the untreated group (adjusted p = .012, Cliff's delta = .316).SignificanceEpilepsy can affect many aspects of bone metabolism. After controlling epilepsy and other confounders that affect bone metabolism, we found that the effects of ASMs on bone metabolism differed. Oxcarbazepine, levetiracetam, and topiramate did not affect bone metabolism, and lamotrigine corrected some of the abnormal markers of bone metabolism in patients with epilepsy.

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Bone Turnover Markers in Children: From Laboratory Challenges to Clinical Interpretation

Cited by 9 publications

References 160 publications

Discordant responses of bone formation and absorption markers in Japanese infants with vitamin D deficiency: a comprehensive matched case–control study

Discordant responses of bone formation and absorption markers in Japanese infants with vitamin D deficiency: a comprehensive matched case–control study

Demographic and disease-related factors impact bone turnover and vitamin D in children with hemato-oncological diseases

Both epilepsy and anti‐seizure medications affect bone metabolism in children with self‐limited epilepsy with centrotemporal spikes

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