scholarly journals Is it possible to predict a risk of osteoporosis in patients with juvenile idiopathic arthritis? A study of serum levels of markers of bone turnover

2018 ◽  
Vol 65 (2) ◽  
pp. 297-302 ◽  
Author(s):  
Marta Janicka-Szczepaniak ◽  
Krzysztof Orczyk ◽  
Katarzyna Szymbor ◽  
Danuta Chlebna-Sokół ◽  
Elzbieta Smolewska
Keyword(s):  
Alkaline Phosphatase ◽  
Juvenile Idiopathic Arthritis ◽  
Bone Turnover ◽  
Fracture Risk ◽  
Serum Levels ◽  
Bone Alkaline Phosphatase ◽  
Common Finding ◽  
Treatment Needs ◽  
Mineral Density ◽  
Markers Of Bone Turnover

Background: Low bone mineral density is a common finding in children with systemic connective tissue diseases, including juvenile idiopathic arthritis (JIA). The influence of the ongoing process of bone remodeling on the disease course merits further investigation. The aim of the study was to assess the clinical relevance of markers of bone turnover and their potential role as predictors of higher fracture risk and, by extension, risk of osteoporosis.Materials and methods: Blood samples were collected from 59 patients diagnosed with JIA in order to determine serum levels of the following markers of bone turnover: Beta-Crosslaps, osteocalcin, bone alkaline phosphatase, osteoprotegerin and receptor activator for nuclear factor kappa-B ligand. The values were analyzed with laboratory parameters and results of dual X-ray absorptiometry (DXA).Results: Osteoprotegerin and bone alkaline phosphatase levels were age-dependent. Beta‑Crosslaps values were significantly higher in patients with positive JADAS27 score (p=0.0410). Osteoprotegerin levels were higher in patients treated with biological agentsthan only withdisease-modifying anti-rheumatic drugs (p=0.0273). There was no relation between markers of bone turnover and sex, DXA results, dosage of glucocorticosteroids and disease duration.Conclusions:Authors postulate performing DXA measurements every 6 months in patients with higher disease activity. The potential lower fracture risk in children with JIA within biological treatment needs future assessment. Age- and sex-adjusted reference rates of markers of bone turnover for Central Europe need to be developed in order to assess individual values properly.

scholarly journals Biomarkers of bone health and osteoporosis risk

2008 ◽  
Vol 67 (2) ◽  
pp. 157-162 ◽  
Author(s):  
Richard Eastell ◽  
Rosemary A. Hannon
Keyword(s):  
Bone Turnover ◽  
Fracture Risk ◽  
Risk Reduction ◽  
Hormone Replacement ◽  
Osteoporosis Treatment ◽  
Bone Alkaline Phosphatase ◽  
Type I ◽  
Mineral Density ◽  
Markers Of Bone Turnover ◽  
Fracture Risk Reduction

The assay features of biochemical markers of bone turnover have markedly improved in the past few years. The most sensitive and specific markers of bone formation include serum bone alkaline phosphatase, total osteocalcin (including the intact molecule and the large N-mid fragment) and the procollagen type I N-terminal propeptide assay. Among the various markers of bone resorption, measurements of the urinary excretion of N- and C-terminal cross-linked telopeptides) and of serum C-terminal cross-linked telopeptides are the most sensitive and specific. Markers of bone turnover can be used to predict the rate of bone loss in post-menopausal women and can also be used to assess the risk of fractures. In osteoporosis-treatment studies (with alendronate, risedronate, raloxifene) markers of bone turnover appear even more strongly associated with fracture risk reduction than bone mineral density (BMD). These observations support the use of markers of bone turnover as surrogates for fracture risk reduction, perhaps even more so than BMD. Bone markers can also be used to monitor the efficacy of antiresorptive therapy such as hormone-replacement therapy, raloxifene and bisphosphonates in individual patients. Furthermore, they have also proved to be helpful in monitoring the response to nutritional interventions and have the advantage over BMD in that they provide information about mechanism of effect and changes are often observed much more rapidly.

Reduced Bone Mineral Density in Factor VIII Deficient Mice and the Role of Inflammatory Cytokines

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 21-21 ◽  
Author(s):  
Meghan S. Liel ◽  
Robert Klein ◽  
Michael Recht ◽  
Daniel L. Greenberg ◽  
Jason Taylor
Keyword(s):  
Bone Mineral Density ◽  
Bone Turnover ◽  
Inflammatory Cytokines ◽  
Bone Health ◽  
Inflammatory Cytokine ◽  
Serum Levels ◽  
Mineral Density ◽  
Markers Of Bone Turnover ◽  
Skeletal Phenotype ◽  
Deficient Mice

Abstract Abstract 21 Background: Low bone mineral density (BMD) and increased risk of fracture are increasingly being identified in patients with hemophilia. Multiple clinical studies have shown that both children and adults with hemophilia have significantly decreased BMD, with up to 70% of adult patients affected. Decreased BMD in this population has previously been attributed to inactivity due to hemophilic arthropathy and comorbid conditions including infection with HIV and hepatitis C. The factor VIII (FVIII) knockout (KO) mouse model has been extensively characterized with respect to bleeding and the development of inhibitors. However, the skeletal status of these animals has not been described. Therefore, the purpose of this study is to examine the skeletal phenotype of FVIII deficient mice and measure serum markers of bone turnover and regulation. Methods: We compared the skeletal phenotype of 11 male FVIII KO mice and 8 matched wild-type (WT) controls at 20 weeks of age. BMD was measured using dual energy x-ray absorptiometry (DXA), bone geometry was examined by μCT and, after sacrifice, femoral breaking strength was measured by three-point bending until failure (ultimate force). In a second group of 24 mice (12 KO and 12 WT), serum was obtained under uniform conditions at 20 weeks of age via cardiac puncture. Serum levels of receptor activator of nuclear factor kappa-B ligand (RANK-L), osteoprotegerin (OPG), interleukin 1α (IL-1α) and osteocalcin were measured using commercially available ELISAs. Alkaline phosphatase (alk phos) activity was measured using a colorimetric assay. The RANK-L/OPG system regulates bone turnover, osteocalcin and alk phos are markers of bone turnover and IL-1α is an inflammatory cytokine. Results: No differences in body weight, length, percent fat, or femoral length were observed between FVIII KO and WT mice (data not shown). No spontaneous bleeding was observed in any animal. As shown in Table I, KO mice had significantly decreased BMD, cortical thickness and stiffness compared to WT mice. This resulted in decreased resistance to fracture as measured via ultimate force. The data presented here demonstrate that adult FVIII KO male mice exhibit lower cortical bone mass resulting in femora less resistant to fracture compared with WT controls. Because FVIII KO mice do not have spontaneous joint hemorrhages and exhibit normal behavior and activity levels, these data suggest that there is an underlying connection between the coagulation system and bone metabolism that results in lower BMD and bone strength. To understand why KO mice have decreased BMD, we measured serum levels of regulators of bone metabolism, markers of bone turnover and inflammatory cytokines. There was no difference in RANK-L, OPG or the RANK-L/OPG ratio between the KO and WT mice. In addition, there was no observed difference in osteocalcin and alk phos. However, WT animals had significantly higher levels of IL-1α expression (P = 0.008). All of the KO animals had undetectable IL-1α levels under physiologic conditions whereas the mean IL-1α level in WT mice was 32.2 pg/ml. Thrombin production is reduced in hemophilia and thrombin has previously been shown to stimulate inflammatory cytokine production. Therefore, these data suggest that thrombin may be necessary for IL-1α production under non-stress conditions and that lower levels of IL-1α may be detrimental to bone health. Although increased inflammatory cytokines are typically associated with decreased BMD, prior research has shown that physiologic levels of cytokines are necessary to maintain bone health. Conclusions: These data provide compelling evidence that the link between FVIII deficiency and impaired skeletal health is real and independent of differences in physical activity and other medical co-morbidities. In addition, the decreased levels of IL-1α observed in KO mice suggest that inflammatory cytokines are involved in this pathophysiology. Ongoing work in our laboratory is aimed at further exploring these connections. Disclosures: No relevant conflicts of interest to declare.

Bone turnover and bone mineral density in young adult patients with panhypopituitarism before and after long-term growth hormone therapy

1995 ◽  
Vol 132 (1) ◽  
pp. 42-46 ◽  
Author(s):  
Rina Balducci ◽  
Vincenzo Toscano ◽  
Anna M Pasquino ◽  
Adele Mangiantini ◽  
Giovanna Municchi ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Growth Hormone ◽  
Alkaline Phosphatase ◽  
Bone Turnover ◽  
Bone Mineral ◽  
Serum Levels ◽  
Creatinine Ratio ◽  
Mineral Density ◽  
Urinary Hydroxyproline ◽  
Igf I

Balducci R, Toscano V, Pasquino AM, Mangiantini A, Municchi G, Armenise P, Terracina S, Prossomariti G, Boscherini B. Bone turnover and bone mineral density in young adult partients with panhypopituitarism before and after long-term growth hormone therapy. Eur J Endocrinol 1995;132:42–6. ISSN 0804–4643 We examined the effects of biosynthetic growth hormone (GH) on biochemical indices of bone turnover and on bone mineral density in a group of GH-deficient adults. Thirteen patients (eight males and five females) aged 24 ± 5 years (range 16–35) were studied before and 12 and 24 months after GH treatment (0.1 IU, kg− day−1, 6 days a week). Serum levels of insulin-like growth factor I (IGF-I), calcitonin, parathyroid hormone, alkaline phosphatase, intact osteocalcin, fasting urinary hydroxyproline/creatinine ratio and bone mineral density (BMD), measured at the lumbar spine by dualphoton absorptiometry, were evaluated. After 12 months of treatment, IGF-I, alkaline phosphatase, osteocalcin and the fasting urinary hydroxyproline/creatinine ratio increased significantly. However, after 24 months of therapy, serum levels of osteocalcin decreased to pretreatment values while IGF-I, fasting urinary hydroxyproline/creatinine ratio and alkaline phosphatase remained elevated significantly. No changes were found in parathyroid hormone and calcitonin plasma levels or in BMD either after 12 or 24 months of treatment. These data demonstrate that GH, at the dosage that we used, activates bone turnover during 24 months of therapy in adults with panhypopituitarism, even if a downward trend for osteocalcin became apparent at 24 months. However, this activation in bone turnover was not accompanied by an increase in BMD. We can hypothesize that GH, at the relatively high dosage used, may stimulate osteoclastic activity to a greater extent than osteoblastic activity. It is probable that the dose of GH replacement therapy in adults plays a key role R Balducci, Dipartimento di Sanita Pubblica, Universita "Tor Vergata", Via di Tor Vergata 38, 00173 Roma, Italy

Biochemical Markers of Bone Turnover and Fracture Prediction

2003 ◽  
Vol 9 (1) ◽  
pp. 10-16 ◽  
Author(s):  
Rosemary A Hannon ◽  
Richard Eastell
Keyword(s):  
Bone Mineral Density ◽  
Bone Resorption ◽  
Bone Turnover ◽  
Fracture Risk ◽  
Bone Mineral ◽  
Biochemical Markers ◽  
Mineral Density ◽  
Risk Of Fracture ◽  
Increased Risk ◽  
Markers Of Bone Turnover

Low bone mineral density is a strong risk factor for fractures in the older woman. Biochemical markers of bone turnover may predict fracture risk independently of bone mineral density. High levels of bone resorption markers are associated with increased risk of fracture in both retrospective and prospective studies, although the evidence for bone formation markers and fracture risk is equivocal. For example, the risk of fracture is increased up to two-fold in women with elevated levels of several markers of bone resorption. Prediction models have been developed to predict the 10–year risk of fracture using bone mineral density and biochemical markers of bone turnover and these could prove very useful in clinical practice.

scholarly journals High prevalence of vertebral fractures despite normal bone mineral density in patients with long-term controlled acromegaly

2011 ◽  
Vol 164 (4) ◽  
pp. 475-483 ◽  
Author(s):  
M J E Wassenaar ◽  
N R Biermasz ◽  
N A T Hamdy ◽  
M C Zillikens ◽  
J B J van Meurs ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Bone Turnover ◽  
Fracture Risk ◽  
Disease Control ◽  
Vertebral Fractures ◽  
Mineral Density ◽  
Markers Of Bone Turnover ◽  
High Prevalence

ObjectiveTo establish the prevalence of osteoporosis, vertebral fractures (VFs), and non-VFs in acromegaly patients with long-term controlled disease and factors potentially influencing fracture risk.DesignCase–control study.Patients and measurementsEighty-nine patients (46% male, mean age: 58 years) were included. We studied VFs and non-VFs, bone mineral density (BMD), and markers of bone turnover. In 48 patients, BMD assessment was also obtained 7 years prior to the current study. To compare VF prevalence, data from a sample of the Dutch population (n=3469) were used.ResultsVF prevalence was 59% (men 64% and women 54%), significantly increased when compared with controls (odds ratio up to 6.5), and independent of the duration of disease control, BMD, markers of bone turnover, and acromegalic disease characteristics. Mean number of VFs per patient was 3.4±0.3 (range 1–8). There was no relationship between the number and severity of fractures, parameters of bone turnover, and follow-up BMD measurements. BMD did not change during prolongation of follow-up by 7 years of controlled acromegaly.ConclusionThere is a very high prevalence of VFs in acromegaly patients with long-term controlled disease, independently of BMD. In view of the significant morbidity and mortality associated with VFs in general and the inability of BMD to predict fracture risk in acromegalic patients, we propose to include VF assessment, for example by lateral conventional radiographs of the spine in the screening of patients with acromegaly, both at diagnosis and during follow-up after establishment of disease control.

scholarly journals Plasma total versus bone alkaline phosphatase as markers of bone turnover in hemodialysis patients.

1996 ◽  
Vol 7 (3) ◽  
pp. 506-512
Author(s):  
P Ureña ◽  
M Hruby ◽  
A Ferreira ◽  
K S Ang ◽  
M C de Vernejoul
Keyword(s):  
Alkaline Phosphatase ◽  
Bone Formation ◽  
Bone Turnover ◽  
Bone Disease ◽  
Formation Rate ◽  
Bone Alkaline Phosphatase ◽  
Hemodialysis Patients ◽  
High Turnover ◽  
Bone Formation Rate ◽  
Markers Of Bone Turnover

Plasma total versus bone alkaline phosphatase as markers of bone turnover in hemodialysis patients. Plasma bone-specific alkaline phosphatase (bAP) has been demonstrated to be more reliable than total alkaline phosphatases (tAP) in providing information about bone turnover in patients with metabolic bone diseases. This study surveyed 42 hemodialysis patients who underwent a systematic transiliac bone biopsy for histomorphometry study. Plasma bAP was determined by using a new immunoassay (Tandem-R Ostase, Hybritech, Liège, Belgium). Plasma bAP values were compared with those of two other plasma markers of bone metabolism, namely tAP and intact parathyroid hormone (iPTH), for the correlations with bone histomorphometric parameters. Patients with high-turnover bone disease (HTBD) (N = 32) had significantly higher plasma bAP levels than patients with normal or low bone turnover (N/LTBD) (N = 10) (66.9 +/- 63.5 ng/mL versus 10.8 +/- 4.2 ng/mL, respectively). Bone formation and resorption were highly correlated in these patients, and plasma bAP levels were positively correlated with bone resorption parameters, including osteoclast surface (r = 0.39, P < 0.0001) and osteoclast number/mm2 (r = 0.36, P < 0.001), and with bone formation parameters, osteoblast surface (r = 0.50, P < 0.005), and bone formation rate (r = 0.91, P < 0.0001). The bone formation rate was better correlated with plasma bAP levels than with either plasma tAP or iPTH concentrations. Plasma bAP level equal or higher than 20 ng/mL, either alone or combined with plasma iPTH of 200 pg/mL, had the highest sensitivity, specificity, and predictability values for the diagnosis of high-turnover bone disease, and formally excluded patients with normal or LTBD. In conclusion, plasma bAP can be measured with a reliable immunoassay in hemodialysis patients. It represents a highly sensitive and specific biochemical marker of skeletal remodeling in these patients. Therefore, both serum iPTH and bAP are complementary in diagnoses of the type of renal osteodystrophy.

scholarly journals Longitudinal Association between Sex Hormone Levels, Bone Loss, and Bone Turnover in Elderly Men

2003 ◽  
Vol 88 (11) ◽  
pp. 5327-5333 ◽  
Author(s):  
Luigi Gennari ◽  
Daniela Merlotti ◽  
Giuseppe Martini ◽  
Stefano Gonnelli ◽  
Beatrice Franci ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Alkaline Phosphatase ◽  
Bone Loss ◽  
Bone Turnover ◽  
Bone Turnover Markers ◽  
Bone Alkaline Phosphatase ◽  
Mineral Density ◽  
Elderly Men ◽  
Hormone Levels ◽  
Turnover Markers

Abstract Male osteoporosis is an increasingly important health problem. It is known that sex steroid hormones play an important role in regulating bone turnover and bone mass in males as well as in females. However, the exact mechanism of bone loss in men remains unknown. In the present study, 200 elderly men (age range, 55–85 yr) were followed for 4 yr to evaluate the relationships between hormone levels, bone turnover markers, bone mineral density, and rates of bone loss. Femoral and lumbar bone mineral density, bone ultrasound parameters at the os calcis, serum testosterone (T), serum estradiol (E2), SHBG levels, and bone turnover markers (urinary crosslaps and bone alkaline phosphatase) were evaluated for each man at enrollment and 4 yr afterward. The free androgen index (FAI) and free estrogen index (FEI) as well as measures of the bioavailable sex hormones [calculated bioavailable E2 (c-bioE2) and T (c-bioT)] were calculated from total hormone levels and SHBG. In the total population, T, c-bioT, c-bioE2, FAI, and FEI, but not E2, decreased significantly with age, whereas SHBG increased significantly. Subjects with FEI, c-bioE2, and E2 levels below the median showed higher rates of bone loss at the lumbar spine and the femoral neck as well as higher speed-of-sounds decrease at the calcaneus with respect to men with FEI, c-bioE2, and E2 levels above the median. Serum bone alkaline phosphatase and urinary crosslaps were significantly higher in men with FEI, c-bioE2, and E2 in the lower quartile than in men with FEI, c-bioE2, and E2 levels in the higher quartile. No statistically significant differences were observed in relation to T, c-bioT, or FAI levels. Finally, the ratio between E2 and T, an indirect measure for aromatase activity, increased significantly with age and was higher in normal than in osteoporotic subjects. In conclusion, results from the present study indicate an important role of estrogens, and particularly of the ability to aromatize T to E2, in the regulation of bone loss and bone metabolism in elderly men.

scholarly journals Bone-Derived Serum Enzymes and Bone Density in Perimenopausal Caucasian Women

1993 ◽  
Vol 30 (2) ◽  
pp. 191-194 ◽  
Author(s):  
J D Johnston ◽  
S Koneru ◽  
T Kuwana ◽  
S B Rosalki
Keyword(s):  
Alkaline Phosphatase ◽  
Acid Phosphatase ◽  
Bone Density ◽  
Femoral Neck ◽  
Serum Levels ◽  
Bone Alkaline Phosphatase ◽  
Serum Enzymes ◽  
Tartrate Resistant Acid Phosphatase ◽  
Vertebral Bone ◽  
Caucasian Women

Serum levels of bone-origin alkaline phosphatase and of tartrate-resistant acid phosphatase were measured in Caucasian women aged 41–69 years who had volunteered for bone densitometry. Bone alkaline phosphatase and tartrate-resistant acid phosphatase were inversely correlated with vertebral bone density and with femoral neck bone density. Bone alkaline phosphatase and acid phosphatase were also significantly correlated, consistent with the concept of ‘coupling’ between osteoblast and osteoclast activity.

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