Automated HPLC Assay for Urinary Collagen Cross-links: Effect of Age, Menopause, and Metabolic Bone Diseases

Abstract Background: The pyridinium cross-links pyridinoline (PYD) and deoxypyridinoline (DPD) are established markers of bone resorption. We evaluated the analytical and clinical performance of a commercially available PYD HPLC assay and established reference intervals in children and adults. Methods: We used a commercially available reagent set (Chromsystems Instruments & Chemicals) to measure PYD and DPD in 319 healthy controls (156 premenopausal women, 80 healthy men, and 83 healthy children age 1 month to 14 years) and 397 patients with metabolic bone diseases (postmenopausal osteoporosis, n = 175; male osteoporosis, n = 176; hyperparathyroidism, n = 17; hyperthyroidism, n = 19; Paget disease, n = 10). Results: The mean intraassay and interassay CVs were <6% and <8% for both PYD and DPD, respectively. The reference interval was constant for premenopausal women in the age group 20–49 years. In men, cross-link values peaked at 20–29 years and decreased thereafter. Women with postmenopausal osteoporosis had significantly higher PYD (51%) and DPD (58%) values compared to premenopausal women. Similar results were found in osteoporotic men. In children the highest values were found in the first weeks and months after birth, followed by a decrease of 50%–60% at age 11–14 years. In metabolic bone diseases cross-link concentrations were significantly increased. The DPD:PYD ratio (mean value approximately 0.2) was remarkably constant in all populations evaluated. Conclusions: The automated HPLC assay is a precise and convenient method for PYD and DPD measurement. We established reference intervals for adult women and men and for children up to 14 years old. The cross-link concentrations we determined by use of this HPLC method confirm its clinical value in enabling identification of increased bone resorption in patients with metabolic bone diseases.

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Bisphosphonates in the treatment of metabolic bone diseases

Arquivos Brasileiros de Endocrinologia & Metabologia ◽

10.1590/s0004-27302010000200017 ◽

2010 ◽

Vol 54 (2) ◽

pp. 206-212 ◽

Cited By ~ 11

Author(s):

Henrique Pierotti Arantes ◽

André Gonçalves da Silva ◽

Marise Lazaretti-Castro

Keyword(s):

Bone Resorption ◽

Bone Diseases ◽

Low Bone Mass ◽

Metabolic Bone Diseases ◽

Treatment Of Osteoporosis ◽

Good Safety Profile ◽

Metabolic Bone ◽

Prevention And Treatment ◽

High Bone ◽

Osteonecrosis Of Jaw

Osteoporosis is a disease characterized by low bone mass associated with the deterioration of microarchitecture, due to an imbalance either in high bone resorption or low bone formation or in both, leading to a high risk of fractures. Bisphosphonates are medications which reduce the ability of osteoclasts to induce bone resorption and consequently improve the balance between resorption and formation. There are bisphosphonates approved for the prevention and treatment of osteoporosis. Administration can be oral (daily, weekly or monthly) or intravenous (quarterly or yearly). These medications are well tolerated and with the correct instructions of administration have a good safety profile. Serious side effects, such as, osteonecrosis of jaw is very rare. Bisphosphonates are the most prescribed medication for the treatment of osteoporosis.

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Alpinetin Inhibits RANKL-Induced Osteoclastogenesis and Ovariectomy-Induced Bone Loss by Modulating NFATc1 Transcription and Lysosomal Function

10.21203/rs.3.rs-132706/v1 ◽

2020 ◽

Author(s):

Rongxin He ◽

Jinwei Lu ◽

Yazhou Chen ◽

Yong Li ◽

Chenyi Ye ◽

...

Keyword(s):

Bone Resorption ◽

Bone Loss ◽

Bone Matrix ◽

Osteoclast Differentiation ◽

Estrogen Deficiency ◽

Bone Diseases ◽

Dependent Manner ◽

Metabolic Bone Diseases ◽

Lysosomal Function ◽

Metabolic Bone

Abstract BackgroundPostmenopausal osteoporosis is a chronic metabolic bone disease caused by excessive osteoclast activation, and osteoclasts are considered to be the sole participants in the degeneration and resorption of bone matrix for controlling bone integrity and continuity. The biological functions of osteoclasts depend critically on the number and activity of fused polykaryon. Hence, targeting osteoclast differentiation and activity can modulate bone resorption and alleviate osteoporosis. Alpinetin is widely used for excellent anti-inflammatory activities and little side-effect, but its role in osteoporosis remains unknown.ResultsIn this study, we investigated for the first time the ability of alpinetin to inhibit estrogen deficiency-induced bone loss. Alpinetin significantly reduced the expression levels of NFATc1 and its downstream genes, thereby inhibiting osteoclast differentiation in a concentration- and time-dependent manner. Additionally, alpinetin inhibited F-actin ring formation and bone resorption, as well as reduced the activation levels of NF-κB, ERK, and AKT signaling cascades. In mature osteoclasts, alpinetin remarkably inhibited integrin-mediated migration and lysosomal biogenesis and trafficking by modulating the PKCβ/TFEB and ATG5/LC3 axes. Importantly, alpinetin treatment in mice alleviated ovariectomy-induced bone volume loss. ConclusionOur findings strongly suggest that alpinetin plays a significant role in the regulation of NFATc1 production for the differentiation of osteoclasts and inhibits integrin-mediated cell migration and lysosomal function in mature osteoclasts, thus weaken the increased osteolytic ability due to estrogen deficiency. Alpinetin may represent a promising agent for the treatment of osteoporosis and other metabolic bone diseases.

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Homologous Radioimmunoassay of Human Osteocalcin

Clinical Chemistry ◽

10.1093/clinchem/38.10.2055 ◽

1992 ◽

Vol 38 (10) ◽

pp. 2055-2060 ◽

Cited By ~ 38

Author(s):

R Bouillon ◽

D Vanderschueren ◽

E Van Herck ◽

H K Nielsen ◽

M Bex ◽

...

Keyword(s):

Bone Turnover ◽

Premenopausal Women ◽

Bone Diseases ◽

Serum Osteocalcin ◽

Normal Children ◽

Metabolic Bone Diseases ◽

Mean Values ◽

Metabolic Bone ◽

Low Bone Turnover ◽

Human Osteocalcin

Abstract Osteocalcin or bone gamma-glutamic acid-containing protein (GLA protein) was isolated from human bone and used to develop a homologous radioimmunoassay of human osteocalcin. The effect of age on serum osteocalcin was studied in 380 normal children and adolescents and 330 normal adults. The mean (+/- SD) values in adults were higher in men [25 +/- 5 micrograms/L (4.3 +/- 0.8 nmol/L)] than in premenopausal women [20 +/- 6 micrograms/L (3.4 +/- 1.0 nmol/L); P < 0.01], but both were lower than in postmenopausal women [29 +/- 2 micrograms/L (5.0 nmol/L)]. The highest concentrations were seen in girls [ages 10-12 years: 99 +/- 38 micrograms/L (17.0 nmol/L)] and boys [ages 14-16 years: 107 +/- 57 micrograms/L (18.4 nmol/L)]. These mean values were substantially higher than those previously reported for results of heterologous osteocalcin radioimmunoassays but the correlation (r = 0.87, n = 77, P < 0.001) between both sets of results was excellent. In patients with metabolic bone diseases characterized by high or low bone turnover, the increase or decrease in serum osteocalcin observed was as expected. This homologous radioimmunoassay of human osteocalcin thus reflects bone turnover but reports serum concentrations higher than previously suspected.

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