BACKGROUND: Congenital scoliosis (CS) is a complex spinal malformation of unknown etiology with abnormal bone metabolism. Fibroblast growth factor 23 (FGF23), secreted by osteoblasts and osteocytes, can inhibit bone formation and mineralization. This research aims to investigate the relationship between CS and FGF23. METHODS: We collected peripheral blood from two pairs of identical twins for methylation sequencing of the target region. FGF23 mRNA levels in the peripheral blood of CS patients and age-matched controls were measured. Receiver operator characteristic (ROC) curve analyses were conducted to evaluate the specificity and sensitivity of FGF23. The expression levels of FGF23 and its downstream factors fibroblast growth factor receptor 3 (FGFr3)/tissue non-specific alkaline phosphatase (TNAP)/osteopontin (OPN) in primary osteoblasts from CS patients (CS-Ob) and controls (CT-Ob) were detected. In addition, the osteogenic abilities of FGF23-knockdown or FGF23-overexpressing Ob were examined. RESULTS: DNA methylation of the FGF23 gene in CS patients was decreased compared to that of their identical twins, accompanied by increased mRNA levels. CS patients had increased peripheral blood FGF23 mRNA levels and decreased computed tomography (CT) values compared with controls. The FGF23 mRNA levels were negatively correlated with the CT value of the spine, and ROCs of FGF23 mRNA levels showed high sensitivity and specificity for CS. Additionally, significantly increased levels of FGF23, FGFr3, OPN, impaired osteogenic mineralization and lower TNAP levels were observed in CS-Ob. Moreover, FGF23 overexpression in CT-Ob increased FGFr3 and OPN levels and decreased TNAP levels, while FGF23 knockdown induced downregulation of FGFr3 and OPN but upregulation of TNAP in CS-Ob. Mineralization of CS-Ob was rescued after FGF23 knockdown. CONCLUSIONS Our results suggested increased peripheral blood FGF23 levels, decreased bone mineral density in CS patients, and a good predictive ability of CS by peripheral blood FGF23 levels. FGF23 may contribute to osteopenia in CS patients through FGFr3/TNAP / OPN pathway.
Humans ; Osteopontin/genetics* ; Alkaline Phosphatase/metabolism* ; Receptor, Fibroblast Growth Factor, Type 3/metabolism* ; Scoliosis/genetics* ; Osteoblasts/metabolism* ; Calcinosis ; RNA, Messenger/metabolism* ; Bone Diseases, Metabolic/metabolism* ; Fibroblast Growth Factors/genetics*

Sympathetic cues via the adrenergic signaling critically regulate bone homeostasis and contribute to neurostress-induced bone loss, but the mechanisms and therapeutics remain incompletely elucidated. Here, we reveal an osteoclastogenesis-centered functionally important osteopenic pathogenesis under sympatho-adrenergic activation with characterized microRNA response and efficient therapeutics. We discovered that osteoclastic miR-21 was tightly regulated by sympatho-adrenergic cues downstream the β2-adrenergic receptor (β₂AR) signaling, critically modulated osteoclastogenesis in vivo by inhibiting programmed cell death 4 (Pdcd4), and mediated detrimental effects of both isoproterenol (ISO) and chronic variable stress (CVS) on bone. Intriguingly, without affecting osteoblastic bone formation, bone protection against ISO and CVS was sufficiently achieved by a (D-Asp₈)-lipid nanoparticle-mediated targeted inhibition of osteoclastic miR-21 or by clinically relevant drugs to suppress osteoclastogenesis. Collectively, these results unravel a previously underdetermined molecular and functional paradigm that osteoclastogenesis crucially contributes to sympatho-adrenergic regulation of bone and establish multiple targeted therapeutic strategies to counteract osteopenias under stresses.
Adrenergic Agents/pharmacology* ; Apoptosis Regulatory Proteins/pharmacology* ; Bone Diseases, Metabolic/metabolism* ; Humans ; Liposomes ; MicroRNAs/genetics* ; Nanoparticles ; Osteoclasts ; Osteogenesis/physiology* ; RNA-Binding Proteins/pharmacology*

OBJECTIVE: To investigate the effect of 275 nm and 310 nm ultraviolet irradiation on ovariectomized rats' bone metabolism. METHODS: Twenty four 3-month-old female Sprague-Dawley (SD) rat were randomly divided into control group, sham operated group, 275 nm ultraviolet (UV) irradiation group and 310 nm UV irradiation group. Each group contained 6 rats. The rats in the two irradiation groups were treated with bilateral ovariectomy. The rats in sham operated group received sham operation (They were given the same back incision and a bit of par-ovarian fat were removed). Control group received no disposition. About 24 weeks after operation, all the rats received detailed bone mineral density (BMD) detection again. Detection regions include cervical vertebra, lumbar vertebra, proximal femur, mid femur and distal femur. Next, osteopenia rats in 275 nm irradiation group were UV irradiated 275 nm with fixed illumination intensity (15 μW/cm²) everyday for 16 weeks. The osteopenia rats in 310 nm irradiation group were UV irradiated 310 nm with fixed illumination intensity (15 μW/cm²) everyday for 16 weeks. The backs of the rats were shaved regularly as irradiation area (6 cm×8 cm). After 16-week irradiation, all the rats' BMD of cervical vertebra, lumbar vertebra, proximal femur, mid femur and distal femur were measured. At the end of the trial, all the rats' blood specimens were obtained and serum 25(OH)D, procollagen type Ⅰ N-peptide (PINP) and osteocalcin (OC) were measured. RESULTS: Compared with control group [(238.78±26.74) mg/cm³], the BMD of the whole body were significantly lower in 275 nm [(193.34±13.28) mg/cm³] and 310 nm [(191.19±18.48) mg/cm³] irradiation groups (P=0.002, P=0.001). There were no significant difference between sham operated group [(227.20±14.32) mg/cm³] and control group. After 16-week ultraviolet irradiation, the BMD of the whole body were significantly increased in 275 nm [(193.34±13.28) mg/cm³ vs. (221.68±25.52) mg/cm³, P=0.005] and 310 nm groups [(191.19±18.48) mg/cm³ vs. (267.48±20.54) mg/cm³, P < 0.001] after corresponding irradiation. The BMD of the four body regions (lumbar vertebra, proximal femur, mid femur and distal femur) had significantly increased after irradiation in 275 nm irradiation group. For 310 nm irradiation group, the BMD in cervical vertebra, lumbar vertebra, proximal femur, mid femur and distal femur also had increased significantly after 310 nm ultraviolet irradiation. The concentration of serum 25(OH)D and OC was higher in 275 nm irradiation group than in control group [(46.78±5.59) μg/L vs. (21.32±6.65) μg/L, P=0.002;(2.05±0.53) U/L vs. (1.32±0.07) U/L, P=0.022]. Compared with the control, the concentration of serum 25(OH)D [(58.05±12.74) μg/L], OC [(2.04±0.53) U/L] and PINP [(176.16±24.18) U/L] was significantly higher (P < 0.001, P=0.015, P=0.005) in 310 nm irradiation group. However, there were no significantly difference between sham operated group and the control. CONCLUSION Both 275 nm and 310 nm ultraviolet could improve rats' vitamin D synthesis. Both 275 nm and 310 nm ultraviolet could improve osteopenia rats' bone condition. The irradiation of 310 nm might be more effective on bone condition improvement.
Animals ; Bone Density ; Bone Diseases, Metabolic/metabolism* ; Female ; Femur/metabolism* ; Humans ; Osteocalcin/metabolism* ; Ovariectomy ; Rats ; Rats, Sprague-Dawley

BACKGROUND: Despite the beneficial effect of fibroblast growth factor 21 (FGF21) on metabolic disease, there are concerns about adverse effects on bone metabolism, supported by animal studies. However, a recent human study showed the positive association between serum FGF21 level and bone mineral density (BMD) in healthy premenopausal women. We undertook this study to examine the association between FGF21 level and BMD in healthy postmenopausal Korean women who are susceptible to osteoporosis. METHODS: We used data of 115 participants from a cohort of healthy postmenopausal women (>50 years old) to examine the association between serum FGF21 level and BMD. The clinical characteristics were obtained from the participants, and blood testing and serum FGF21 testing were undertaken. BMD of the lumbar spine, femoral neck and total hip area, and bone markers were used in the analyses. RESULTS: The mean age of the participants was 60.2±7.2 years. Serum FGF21 levels showed negative correlation with BMD and T-scores in all three areas, but there were no statistically significant differences. Multivariate analyses with adjustment for age and body mass index also did not show significant association between serum FGF21 level and BMD. In addition, serum FGF21 level also showed no correlation with osteocalcin and C-telopeptide levels. CONCLUSION: In our study, serum FGF21 level showed no significant correlation with BMD and T-scores.
Animals ; Body Mass Index ; Bone Density* ; Cohort Studies ; Female ; Femur Neck ; Fibroblast Growth Factors* ; Fibroblasts* ; Hematologic Tests ; Hip ; Humans ; Metabolic Diseases ; Metabolism ; Multivariate Analysis ; Osteocalcin ; Osteoporosis ; Spine

STUDY DESIGN: Retrospective cohort study. PURPOSE: To assess bone mineral density (BMD) and bone metabolism ≥27 years after surgery in female patients who underwent spinal fusion for adolescent idiopathic scoliosis (AIS) during adolescence and to determine their associations with physical performance. OVERVIEW OF LITERATURE: There are no studies investigating postsurgical BMD in middle-aged AIS patients. METHODS: This study included 23 patients who provided informed consent among 229 female patients with AIS who underwent spinal fusion from 1968 until 1988. Average age at the time of observation was 48.8 years. BMD was measured at the left femoral neck, and the levels of two bone metabolism markers–procollagen type 1 N-terminal propeptide (P1NP) and tartrate-resistant acid phosphatase 5b (TRACP-5b)–were measured from blood samples. Physical performance was measured using grip strength, sit-ups, sit-and-reach, side step, and standing long jump. RESULTS: Mean BMD was 0.784 g/cm2. According to the World Health Organization diagnostic criteria, one subject (4.3%) had osteoporosis, whereas nine subjects (39.1%) had osteopenia. In patients with osteoporosis or osteopenia, P1NP and TRACP-5b levels were high, and BMD loss was because of high metabolic turnover. All calculated standard scores for physical performance were lower in the study cohort than in healthy individuals. There was a positive correlation between BMD and the standard score for grip strength, whereas there were weak positive correlations between BMD and the standard scores for side step and standing long jump. CONCLUSIONS: In female AIS patients who underwent spinal fusion in adolescence, 4.3% and 39.1% had osteoporosis and osteopenia, respectively, ≥27 years after surgery. Exercise performance of these patients was poor compared with the national standards. In these patients, increased physical activity should be encouraged to prevent BMD loss in middle age.
Acid Phosphatase ; Adolescent* ; Bone Density* ; Bone Diseases, Metabolic ; Cohort Studies ; Female* ; Femur Neck ; Hand Strength ; Humans ; Informed Consent ; Metabolism ; Middle Aged ; Motor Activity ; Osteoporosis ; Retrospective Studies ; Scoliosis* ; Spinal Fusion ; World Health Organization

OBJECTIVETo investigate the influencing factors and pathogenesis of osteopenia in the patients with hemophilia.

METHODSTwenty-three patients with hemophilia were admitted in the hospital affiliated to North China University of Science and technology from March to August 2015, including 13 severe cases, 10 mild and moderate cases. All the patients accepted the detection of serum I collagen cross-linking N terminal peptide (NTX I), osteoprotegerin (OPG), bone alkaline phosphatase (BALP), basic fibroblast growth factor (bFGF), insulin-like growth factor (IGF) and transforming growth factor-β1 (TGF-β1), the score scale of activity ability was recorded according to the criteria published by the U.S. Center for disease prevention and control in 2002, and 21 patients received the measurement of bone mineral density. According to the World Health Organization (WHO) definition, the clinical significance of bone mineral density (BMD) was assessed by measuring the Z level.

RESULTSZ level>-2 was recorded in 10 cases, Z≤-2 was recorded in 11 cases; the levels of body mass index (BMI) and human bone alkaline phosphatase (BALP) reflecting bone formation in 11 cases (Z≤-2) were lower than there in 10 cases (Z>-2) (P<0.05); the levels of BALP (r=0.489, P<0.05), IGF (r=0.538, P<0.05) and BMI (r=0.572, P<0.01) positively correlated significantly with BMD (P<0.05); the levels of bFGF (r=0.570, P<0.01) and OPG (r=0.505, P<0.05) positively correlated with NTX I, indicating bone destruction (P<0.05); the score of activity ability of severe patients was significantly lower than that of mild and moderate cases (P<0.05), BMD levels of these 2 groups were not statistically different (P>0.05).

CONCLUSIONThe BMD level does not correlate with the clinial grouping of hemophilia, the low body mass index may be a risk factor for bone lose; the mechanism of hemophilia patient's bone lose may be related with the decrease of osteogenic activity, the IGF can prevent bone lose in hemophilia, the bFGF and OPG can promote bone metabolism of the patients with hemophilia.

Alkaline Phosphatase ; metabolism ; Biomarkers ; Bone Density ; Bone Diseases, Metabolic ; pathology ; Bone and Bones ; pathology ; Collagen Type I ; metabolism ; Fibroblast Growth Factor 2 ; metabolism ; Hemophilia A ; pathology ; Humans ; Osteogenesis ; Osteoprotegerin ; metabolism ; Peptides ; metabolism ; Somatomedins ; metabolism ; Transforming Growth Factor beta1 ; metabolism

Vascular calcification, abnormal mineralization of the vessel wall, is frequently associated with aging, atherosclerosis, diabetes mellitus, and chronic kidney disease. Vascular calcification is a key risk factor for many adverse clinical outcomes, including ischemic cardiac events and subsequent cardiovascular mortality. Vascular calcification was long considered to be a passive degenerative process, but it is now recognized as an active and highly regulated process similar to bone formation. However, despite numerous studies on the pathogenesis of vascular calcification, the mechanisms driving this process remain poorly understood. Pyruvate dehydrogenase kinases (PDKs) play an important role in the regulation of cellular metabolism and mitochondrial function. Recent studies show that PDK4 is an attractive therapeutic target for the treatment of various metabolic diseases. In this review, we summarize our current knowledge regarding the mechanisms of vascular calcification and describe the role of PDK4 in the osteogenic differentiation of vascular smooth muscle cells and development of vascular calcification. Further studies aimed at understanding the molecular mechanisms of vascular calcification will be critical for the development of novel therapeutic strategies.
Aging ; Atherosclerosis ; Bone Morphogenetic Proteins ; Diabetes Mellitus ; Metabolic Diseases ; Metabolism ; Mitochondria ; Mortality ; Muscle, Smooth, Vascular ; Osteogenesis ; Oxidoreductases* ; Phosphotransferases* ; Pyruvic Acid* ; Renal Insufficiency, Chronic ; Risk Factors ; Vascular Calcification*

Vitamin D deficiency is a global health problem that increases risk for metabolic bone diseases in children and adults as well as many chronic illnesses including autoimmune diseases, type 2 diabetes, cardiovascular disease, infectious disease, and cancer. This has raised important questions concerning the physiological and clinical impact of low vitamin D levels during pregnancy, with implications for functions of vitamin D. The review describes the pathways that are required for metabolism and function of vitamin D, the various clinical complications that have been linked to impaired vitamin D status during pregnancy, and effects of vitamin D supplementation on maternal and neonatal outcomes.
Adult ; Autoimmune Diseases ; Bone Diseases, Metabolic ; Cardiovascular Diseases ; Child ; Chronic Disease ; Communicable Diseases ; Diabetes, Gestational ; Female ; Humans ; Metabolism ; Pre-Eclampsia ; Pregnancy* ; Vitamin D Deficiency* ; Vitamin D* ; Vitamins*

BACKGROUND: The average dietary sodium intake of Koreans is 2.6 times higher than the World Health Organization's recommended amount. The effect of a diet high in sodium on the skeletal system, especially osteoporosis, has not previously been examined in Korean postmenopausal women with low bone mass. We assessed the daily sodium intake, and determined the impact of sodium intake on urinary calcium excretion and bone resorption marker. METHODS: A retrospective review of medical records was performed for 86 postmenopausal subjects who were initially diagnosed with osteopenia or osteoporosis at the health promotion center. They were subsequently referred to the Division of Endocrinology and Metabolism between 2010 and 2013. All subjects completed a modified food frequency questionnaire. Twenty-four hour urine collection for sodium, calcium and creatinine excretion, and serum C-terminal telopeptides of type I collagen (CTX-I) were also obtained. RESULTS: The average amount of daily sodium and calcium intake were 3,466 mg and 813 mg, respectively. Average dietary sodium intake and 24-hour urinary sodium excretion showed significant positive linear correlation (r=0.29, P=0.006). There was also a significant positive linear correlation between 24-hour urine sodium and calcium excretion (r=0.42, P<0.001); CTX-I and 24-hour urinary calcium excretion (r=0.29, P=0.007). CONCLUSIONS: Excessive sodium intake assessed by 24-hour urine specimen is associated with high calcium excretion in urine. High calcium excretion is also related to increasing bone resorption marker.
Bone Diseases, Metabolic ; Bone Resorption* ; Calcium* ; Collagen Type I ; Creatinine ; Diet ; Endocrinology ; Female ; Health Promotion ; Humans ; Medical Records ; Metabolism ; Osteoporosis ; Retrospective Studies ; Sodium ; Sodium, Dietary* ; Urine Specimen Collection ; World Health ; World Health Organization ; Surveys and Questionnaires

OBJECTIVETo determine the influence of maximal androgen blockade (MAB) on bone mineral density (BMD) in men with prostate cancer.

METHODSWe enrolled 40 men with prostate cancer treated by MAB for 7 to 12 months. We obtained the laboratory results of PSA, testosterone, serum calcium and phosphorus, 24-h urine calcium and phosphorus, alkaline phosphatase, and parathyroid hormone, measured the BMD of the lumbar spine and femoral neck by dual energy X-ray absorptiometry, recorded pain scores, and compared the results before and after the treatment.

RESULTSBefore MAB treatment, 5 (12.5%) of the patients met the BMD criteria of lumbar spine (L2-4) osteopenia, 8 (20%) lumbar spine (L2-4) osteoporosis, 13 (32.5%) left femoral neck osteopenia, and 15 (37.5%) left femoral neck osteoporosis. The PSA and testosterone levels were decreased from (52.9 +/- 69.9) microg/L and (18.9 +/- 6.5) nmol/L before MAB to (1.5 +/- 1.6) microg/L and (1.9 +/- 1.3) nmol/L after it (P<0.05). There were no statistically significant differences before and after MAB in the levels of serum calcium and phosphorus, 24-h urine calcium and phosphorus, alkaline phosphatase, and parathyroid hormone (P>0.05), nor in the BMD levels of the lumbar spine ([1.1 +/- 0.1] vs [1.1 +/- 0.2] g/cm2) and femoral neck ([0.8 +/- 0.2] vs [0.8 +/- 0.1] g/cm2), nor in the pain score ([0.6 +/- 0.2] vs [0.7 +/- 0.1], P>0.05).

CONCLUSIONMAB treatment (range from 7 to 12 months) has no significant influence on BMD in men with prostate cancer, but BMD should be measured before MAB.

Aged ; Aged, 80 and over ; Alkaline Phosphatase ; analysis ; Androgen Antagonists ; administration & dosage ; adverse effects ; therapeutic use ; Bone Density ; drug effects ; Bone Diseases, Metabolic ; etiology ; Calcium ; blood ; urine ; Humans ; Male ; Middle Aged ; Osteoporosis ; etiology ; Parathyroid Hormone ; analysis ; Phosphorus ; urine ; Prostatic Neoplasms ; drug therapy ; metabolism ; Testosterone ; blood