Bone Related Hormones Research Articles

The Emerging Roles of Endocrine Hormones in Different Arthritic Disorders.

The relationship between endocrine hormones and the spectrum of rheumatic conditions has long been discussed in the literature, focusing primarily on sexual hormones, such as estrogens, androgens, prolactin (PRL). Estrogens are indeed involved in the pathogenesis of the main inflammatory arthritis thanks to their effects on the immune system, both stimulatory and inhibitory. The PRL system has been discovered in synovial tissue of rheumatoid arthritis (RA) and psoriatic arthritis (PsA), patients and has been propose as a new potential therapeutic target. Besides sexual hormones, in the last years scientific interest about the crosstalk of immune system with other class of hormones has grown. Hormones acting on the bone tissue (i.e. parathyroid hormone, vitamin D) and modulators of the Wnt pathway (i.e. Dickkopf-1) have been demonstrated to play active role in inflammatory arthritis course, defining a new field of research named osteoimmunology. PTH, which is one of the main determinants of Dkkopf-1, plays a crucial role in bone erosions in RA and a correlation between PTH, Trabecular Bone Score (TBS) and disease activity has been found in ankylosing spondylitis (AS). In PSA is under studying the interaction among IL-17 and bone metabolism. The purpose of this review is to discuss and summarize the recent data about the interaction between endocrine hormone and immune system in the main rheumatic disorders, covering in particular the role of bone-related hormones and cytokines. We will describe this relationship from a biochemical, diagnostic and therapeutic perspective, with a particular focus on RA, PsA and AS.

MON-375 A Sporadic Case of Camurati-Engelmann Disease: A Rare Sclerosing Bone Disorder

Background: Camurati-Engelmann disease (CED)is a rare sclerosing bone disorder. The skull and the diaphyses of the long tubular bones are mainly affected. The symptom developed in childhood and patients suffer from bone pain, easy fatigability, and decreased muscle mass and weakness. CED is caused by mutations in the transforming growth factorβ1 (TGFβ1)gene on chromosome 19q13.113.3. This condition is inherited in an autosomal dominant pattern. Case: A 20- year-old male. He has a so-called marfanoid habitus with long and narrow limbs. At the age of 19,he presented pain in lower limb, then walking became difficult. None of his relatives had similar symptoms. In biochemical tests,calcium, Phosphorus and bone-related hormones levels were all in the normal range. 25(OH)vitamin D levels were low probably due to his eating habits. On radiological evaluation, X-ray showed thickening of the bone cortex of the bilateral tibia. Bone scintigraphy revealed markedly increased tracer uptake in the bilateral temporal bone, femur, and tibia. Based on clinical and radiological features CED was suspected. Sequence analysis of the transforming growth factor β1 (TGFB1)gene revealed a previously reported pathological variant (p.R218H). Discussion: CED is a rare pan-ethnic condition with more than 300 published cases worldwide. Although this case was difficult to diagnose because there was no family history and the onset of adulthood not childhood, this disease was suspected due to the typical localization of affected bone lesions by bone scintigraphy and was diagnosed by genetic testing. The majority of CED are missense variants in exon 4 leading to single amino acid substitutions in the encoded protein. Exon 4 encodes a latency-associated peptide (LAP) that suppresses the activity of TGF-β1 protein. No consensus management guidelines have been developed to date. Treatment with corticosteroids may relieve the pain, improve the muscle weakness and fatigue. Recently, the efficacy of losartan has been reported in some patients. Conclusion: Here we report a de novo case of CED diagnosed by genetic testing. Osteosclerotic diseases are very rare and are often difficult to diagnose. Genetic testing plays an important role in confirming the diagnosis.

Does idiopathic hypercalciuria affect bone metabolism during childhood? A prospective case-control study.

A limited number of studies have evaluated biochemical bone metabolism markers in children with idiopathic hypercalciuria, which in adults has been linked with osteopenia. Our aim was to investigate in children with idiopathic hypercalciuria biochemical markers of bone formation and resorption and the osteoprotegerin (OPG) and soluble receptor activator of nuclear factor kB ligand (sRANKL) system which is involved in the osteoclastogenesis process. A prospective study was conducted on 50 children with idiopathic hypercalciuria and 50 healthy age-, sex-, and Tanner stage-matched control subjects. Following the diagnosis, patients were requested to follow a 3-month dietary recommendation for idiopathic hypercalciuria. In patients, at diagnosis and at 3months of follow-up, and in controls, bone-related hormones and serum/urine biochemical parameters were studied. The bone formation markers (total ALP and osteocalcin) and the bone resorption markers (β-Crosslaps) and the OPG and sRANKL levels were determined. No differences were found in the bone formation markers or OPG and sRANKL between the children with idiopathic hypercalciuria and controls. The β-Crosslaps and the β-Crosslaps/osteocalcin ratio were higher in the patients at diagnosis than in controls (p = 0.019 and p = 0.029, respectively), with a trend to decrease after the 3-month dietary intervention. The initially increased 24-h urinary Ca in the patients decreased after the 3-month dietary intervention (p = 0.002). Children with idiopathic hypercalciuria had biochemical markers compatible with normal bone formation but increased bone resorption. After a 3-month dietary intervention, the trend observed towards decrease in the serum β-Crosslaps may reflect a beneficial response.

Effects of prepartum dietary cation-anion difference and source of vitamin D in dairy cows: Vitamin D, mineral, and bone metabolism

Pregnant Holstein cows, 28 nulliparous and 51 parous, were blocked by parity and milk yield and randomly allocated to receive diets that differed in dietary cation-anion difference (DCAD), +130 or -130 mEq/kg, and supplemented with either calcidiol or cholecalciferol at 3 mg/11 kg of dry matter from 255 d of gestation until parturition. Blood was sampled thrice weekly prepartum, and on d 0, 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, and 30 postpartum to evaluate effects of the diets on vitamin D, mineral and bone metabolism, and acid-base status. Blood pH and concentrations of minerals, vitamin D metabolites, and bone-related hormones were determined, as were mineral concentrations and losses in urine and colostrum. Supplementing with calcidiol increased plasma concentrations of 25-hydroxyvitamin D3, 3-epi 25-hydroxyvitamin D3, 25-hydroxyvitamin D2, 1,25-dihydroxyvitamin D3, and 24,25-dihydroxyvitamin D3 compared with supplementing with cholecalciferol. Cows fed the diet with negative DCAD had lesser concentrations of vitamin D metabolites before and after calving than cows fed the diet with positive DCAD, except for 25-hydroxyvitamin D2. Feeding the diet with negative DCAD induced a compensated metabolic acidosis that attenuated the decline in blood ionized Ca (iCa) and serum total Ca (tCa) around calving, particularly in parous cows, whereas cows fed the diet with positive DCAD and supplemented with calcidiol had the greatest 1,25-dihydroxyvitamin D3 concentrations and the lowest iCa and tCa concentrations on d 1 and 2 postpartum. The acidogenic diet or calcidiol markedly increased urinary losses of tCa and tMg, and feeding calcidiol tended to increase colostrum yield and increased losses of tCa and tMg in colostrum. Cows fed the diet with negative DCAD had increased concentrations of serotonin and C-terminal telopeptide of type 1 collagen prepartum compared with cows fed the diet with positive DCAD. Concentrations of undercarboxylated and carboxylated osteocalcin and those of adiponectin did not differ with treatment. These results provide evidence that dietary manipulations can induce metabolic adaptations that improve mineral homeostasis with the onset of lactation that might explain some of the improvements observed in health and production when cows are fed diets with negative DCAD or supplemented with calcidiol.

FGF Suppresses Poldip2 Expression in Osteoblasts.

Osteoporosis is one of the most prevalent ageing-associated diseases that are soaring in the modern world. Although various aspects of the disease have been investigated to understand the bases of osteoporosis, the pathophysiological mechanisms underlying bone loss is still incompletely understood. Poldip2 is a molecule that has been shown to be involved in cell migration of vascular cells and angiogenesis. However, expression of Poldip2 and its regulation in bone cells were not known. Therefore, we examined the Poldip2 mRNA expression and the effects of bone regulators on the Poldip2 expression in osteoblasts. We found that Poldip2 mRNA is expressed in osteoblastic MC3T3-E1 cells. As FGF controls osteoblasts and angiogenesis, FGF regulation was investigated in these cells. FGF suppressed the expression of Poldip2 in MC3T3-E1 cells in a time dependent manner. Protein synthesis inhibitor but not transcription inhibitor reduced the FGF effects on Poldip2 gene expression in MC3T3-E1 cells. As for bone-related hormones, dexamethasone was found to enhance the expression of Poldip2 in osteoblastic MC3T3-E1 cells whereas FGF still suppressed such dexamethasone effects. With respect to function, knockdown of Poldip2 by siRNA suppressed the migration of MC3T3-E1 cells. Poldip2 was also expressed in the primary cultures of osteoblast-enriched cells and FGF also suppressed its expression. Finally, Poldip2 was expressed in femoral bone in vivo and its levels were increased in aged mice compared to young adult mice. These data indicate that Poldip2 is expressed in osteoblastic cells and is one of the targets of FGF. J. Cell. Biochem. 118: 1670-1677, 2017. © 2016 Wiley Periodicals, Inc.

Physical activity benefits bone density and bone-related hormones in adult men with cervical spinal cord injury

Severe bone loss is a recognized complication of chronic spinal cord injury (SCI). Physical exercise contributes to bone health; however, its influence on bone mass of cervical SCI individuals has not been investigated. The aim of this study was to investigate the influence of physical activity on bone mass, bone metabolism, and vitamin D status in quadriplegics. Total, lumbar spine (L1-L4), femur and radius bone mineral density (BMD) were assessed in active (n = 15) and sedentary (n = 10) quadriplegic men by dual energy X-ray absorptiometry. Concentrations of 25-hydroxyvitamin D [25(OH)D], PTH, IGF1, osteocalcin and NTx were measured in serum. After adjustments for duration of injury, total body mass, and habitual calcium intake, bone indices were similar between groups, except for L1-L4 BMD Z score that was higher in the sedentary group (P < 0.05). Hours of physical exercise per week correlated positively with 25(OH)D (r = 0.59; P < 0.05) and negatively with PTH (r = -0.50; P < 0.05). Femur BMD was negatively associated with the number of months elapsed between the injury and the onset of physical activity (r = -0.60; P < 0.05). Moreover, in the active subjects, both L1-L4 BMD Z score (r = 0.72; P < 0.01) and radius BMD (r = 0.59; P < 0.05) were positively associated with calcium intake. In this cross-sectional study, both the onset of physical activity after injury and the number of hours dedicated to exercise were able to influence bone density and bone-related hormones in quadriplegic men. Our results also suggest a positive combined effect of exercise and calcium intake on bone health of quadriplegic individuals.

The influence of physical activity on the bone mass through the bone metabolism in premenopausal adult Japanese women

Background Few studies have reported on the effects of the energy expenditure estimated from the frequency of exercise on bone mass, bone metabolic marker and bone related hormones in young females. The goal of this study is to examine the indices related to bone metabolism such as the bone metabolism markers and hormones and clarify their association with the bone mass through their relationship to exercises.

Biochemical markers of bone turnover associated with calcium supplementation in children with juvenile rheumatoid arthritis: Results of a double‐blind, placebo‐controlled intervention trial

To determine the effects of calcium supplementation on bone physiology in corticosteroid-free children with juvenile rheumatoid arthritis (JRA) by measuring serum and urinary bone-related hormones, minerals, and markers of bone formation and resorption. In this double-blind trial, patients were randomized to receive daily oral supplementation with 1,000 mg of calcium and 400 IU of vitamin D or with placebo and 400 IU of vitamin D for 24 months. The effect of calcium supplementation on bone physiology was determined periodically using markers of bone turnover. One hundred ninety-eight patients met the inclusion criteria and were followed up in the study. At baseline, there were no differences in markers of bone turnover between the groups. Patients with < or = 4 joints with active disease had higher serum levels of calcium and parathyroid hormone (PTH). Calcium-treated patients with < or =4 joints with active disease had lower levels of osteocalcin (OC). At followup, levels of 1,25-dihydroxyvitamin D3, PTH, OC, and urine phosphorus were lower in the group receiving calcium supplementation. Hypercalciuria, as determined by the urinary calcium-to-creatinine ratio, was not noted in 24-hour urine studies. Levels of markers of bone physiology were significantly decreased in children with JRA receiving calcium supplementation. The physiologic changes were noted as early as 12 months into calcium supplementation. The hypercalciuria noted on spot testing of the urinary calcium-to-creatinine ratio was not demonstrated on further evaluation, nor did it lead to renal pathology. These findings suggest that the calcium supplementation met physiologic needs and caused an increased calcium loss in urine.

The effects of exercise on bone density and hormones in lactating women

The objective of this study was to determine the effects of exercise on bone‐related hormones in lactating women. At 4wks postpartum (PP) women were randomized to either exercise group (EX, n=10) [weight bearing aerobic exercise (3d/wk, 45 min/d) and 3d/wk of resistance exercise] or control group (C, no exercise, n=10) for 16 wks with a 1‐yr PP follow‐up. Lumbar spine (LS) and hip bone mineral densities (BMD) were measured by DXA. Prolactin (Prl), estradiol (E2), growth hormone (GH), insulin‐like growth factor (IGF‐1), and its associated binding protein‐3 (IGFBP‐3) were analyzed using ELISA. RMANOVA was used to determine differences between groups. During the intervention, C lost significantly more LS BMD then EX (−7 ± 2% vs −5 ± 1%, p &lt; 0.01), but not hip BMD (−2 ± 3% vs −3 ± 2%). GH levels decreased in the C (2.2 ± 2.7 to 1.0 ± 1.6 μg/L) and increased in the EX (2.0 ± 2.7 to 4.0 ± 4.7 μg/L), p=0.1, with no change in IGF‐1 and IGFBP‐3. Prl levels declined in both groups during 1‐yr PP, whereas E2, GH, IGF‐1 and IGFBP‐3 levels remained stable in both groups. At 1‐yr PP, controlling for Prl levels, LS and hip BMD were within baseline values for EX (−1% and +0.4%, respectively) vs C (−4% and −2%), p=0.1. These results suggest exercise during lactation affects GH levels and given the role of GH in bone metabolism, may ultimately influence BMD.Supported by NC Agricultural Research Services

High bone turnover of type I collagen depends on fetal growth

The bone metabolic processes of proliferation and differentiation in preterm and term newborns have yet to be fully elucidated. Seventy-four umbilical cord blood samples were collected from preterm and term newborns delivered at 27 to 42 gestational weeks (GWs). Carboxy-terminal propeptide of type I procollagen (PICP), pyridinoline cross-linked telopeptide domain of type I collagen (ICTP), alkaline phosphatase (ALP), and bone-specific alkaline phosphatase (BAP) were measured. Calcitonin (CT), estrogen (E 2), intact parathyroid hormone, and insulin-like growth factor-I (IGF-I) were also examined in 20 or 23 randomly selected samples. We conducted cross-sectional regression analyses for bone metabolic markers, fetal growth markers including GWs, birth weight (BW), height (BH) and head circumference (HC), and bone related hormones. PICP and ICTP activities were very high, but decreased significantly with fetal growth based on GWs, BW, BH, and HC changes (GWs, BW, and BH to both PICP and ICTP, P < 0.0001; HC to ICTP, P < 0.0001; HC to PICP, P < 0.05), while BAP and ALP did not change significantly. E 2 and CT both showed a significant positive correlation with Ca ( P < 0.05), but neither hormone had any apparent correlation with PICP, ALP, BAP, or ICTP. These results suggest very active bone formation and resorption of type I collagen to be dependent on fetal growth and that fetal osteoblasts dominate the proliferation phase of development rather than the maturation phase. However, factors contributing to high bone turnover in the fetus remain to be elucidated.

Response of bone metabolism related hormones to a single session of strenuous exercise in active elderly subjects

Objective: To evaluate the effect of strenuous exercise on bone metabolism and related hormones in elderly subjects. Methods: Twenty one active elderly subjects (11 men and 10 women; mean age...

High phosphorus intake only slightly affects serum minerals, urinary pyridinium crosslinks and renal function in young women

Assessment of the physiological effects of a diet rich in phosphorus in young women. Control period I--commercial basic diet containing 1700 mg P and 1500 mg Ca/day for 4 weeks. Supplementation period--a 6 week high-phosphorus period of 3008 mg P and 1995 mg Ca/day. Control period II--4 weeks washout with basic diet as in period I. Institute of Nutritional Science, Friedrich Schiller University, Jena. Ten healthy women, aged 20-30y. Orange juice and tablets, containing supplements of Ca5(PO4)3OH and NaH2PO4, totalling 1436 mg elemental phosphorus per day. There was an increase of 10.7+/-13.7 pg/ml in serum PTH, a decrease of 0.6+/-0.6 ng/ml in serum osteocalcin, an increase of 73.6+/-136.6 nmol/mmol creatinine in urinary pyridinoline and of 19.3+/-36.0 nmol/ mmol creatinine in urinary deoxypyridinoline, and a decrease of 2.6+/-9.3 mg/l in urinary microalbumin. All changes were insignificant. There were no changes in serum levels of Ca, PO4 or Zn, in serum concentration of 1,25-(OH)2D3, and in urinary beta-2-microglobulin excretion. Phosphorus supplementation caused intestinal distress, soft stools or mild diarrhoea. In spite of a high phosphorus supplementation no significant changes in bone-related hormones, pyridinium crosslinks as markers of bone resorption and parameters of renal function in young women were found.

Diving into iliac bone: A 3-D trip along the Z-axis of iliac bone biopsies. A video on connectivity (with Euler numbers)

The bone metabolic processes of proliferation and differentiation in preterm and term newborns have yet to be fully elucidated. Seventy-four umbilical cord blood samples were collected from preterm and term newborns delivered at 27 to 42 gestational weeks (GWs). Carboxy-terminal propeptide of type I procollagen (PICP), pyridinoline cross-linked telopeptide domain of type I collagen (ICTP), alkaline phosphatase (ALP), and bone-specific alkaline phosphatase (BAP) were measured. Calcitonin (CT), estrogen (E2), intact parathyroid hormone, and insulin-like growth factor-I (IGF-I) were also examined in 20 or 23 randomly selected samples. We conducted cross-sectional regression analyses for bone metabolic markers, fetal growth markers including GWs, birth weight (BW), height (BH) and head circumference (HC), and bone related hormones. PICP and ICTP activities were very high, but decreased significantly with fetal growth based on GWs, BW, BH, and HC changes (GWs, BW, and BH to both PICP and ICTP, P < 0.0001; HC to ICTP, P < 0.0001; HC to PICP, P < 0.05), while BAP and ALP did not change significantly. E2 and CT both showed a significant positive correlation with Ca (P < 0.05), but neither hormone had any apparent correlation with PICP, ALP, BAP, or ICTP. These results suggest very active bone formation and resorption of type I collagen to be dependent on fetal growth and that fetal osteoblasts dominate the proliferation phase of development rather than the maturation phase. However, factors contributing to high bone turnover in the fetus remain to be elucidated.

Estradiol stimulates bone mineralization at physiological concentration in fetal mouse parietal bones

The bone metabolic processes of proliferation and differentiation in preterm and term newborns have yet to be fully elucidated. Seventy-four umbilical cord blood samples were collected from preterm and term newborns delivered at 27 to 42 gestational weeks (GWs). Carboxy-terminal propeptide of type I procollagen (PICP), pyridinoline cross-linked telopeptide domain of type I collagen (ICTP), alkaline phosphatase (ALP), and bone-specific alkaline phosphatase (BAP) were measured. Calcitonin (CT), estrogen (E2), intact parathyroid hormone, and insulin-like growth factor-I (IGF-I) were also examined in 20 or 23 randomly selected samples. We conducted cross-sectional regression analyses for bone metabolic markers, fetal growth markers including GWs, birth weight (BW), height (BH) and head circumference (HC), and bone related hormones. PICP and ICTP activities were very high, but decreased significantly with fetal growth based on GWs, BW, BH, and HC changes (GWs, BW, and BH to both PICP and ICTP, P < 0.0001; HC to ICTP, P < 0.0001; HC to PICP, P < 0.05), while BAP and ALP did not change significantly. E2 and CT both showed a significant positive correlation with Ca (P < 0.05), but neither hormone had any apparent correlation with PICP, ALP, BAP, or ICTP. These results suggest very active bone formation and resorption of type I collagen to be dependent on fetal growth and that fetal osteoblasts dominate the proliferation phase of development rather than the maturation phase. However, factors contributing to high bone turnover in the fetus remain to be elucidated.

Skeletal remodelling and bone related hormones in two adults with increased bone mass

Skeletal remodelling and bone related hormones in two adults with increased bone mass

Skeletal remodelling and bone related hormones in two adults with increased bone mass

This study of two cases documents increased bone mass in a 30-yr-old man and osteopetrosis in a 38-yr-old woman and examines the patients in terms of radiologic features, bone photon absorptiometry and bone biopsy analyses which include tetracycline kinetics. Both patients had elevated bone mass based on quantitative bone histology of iliac crest biopsies normal, or low PTH, and normal calcitonin values. However, they differed markedly from each other in other respects: One patient possessed significantly increased rates of bone formation and mineralization, had elevated serum alkaline phosphatase, increased total hydroxyproline over a 24 hour urine collection but displayed a normal amount of bone surface involved in resorption. The other subject had normal bone formation parameters, but had elevated serum acid phosphatase and a significantly elevated resorbing (crenated) surface. Although most theories ascribe the cause of osteopetrosis to decreased resorption, our study shows that increased bone formation, even when accompanied by normal resorption, can lead to the abnormal accumulation of bone mass. In this respect, the resorptive response of this patient was abnormal; the normal coupled relationship between bone formation and bone resorption, which ensures proper control of endosteal bone volume, had been lost.