Bone Metabolism-related Markers Research Articles

Thick Skin on the Dorsal Spine in Osteoproliferative Disease: Ossification of the Posterior Longitudinal Ligament and Diffuse Idiopathic Skeletal Hyperostosis.

Background Although the correlation between reduced skin thickness and reduced bone density has been investigated, no study has evaluated skin thickness and osteoproliferative diseases, including ossification of the posterior longitudinal ligament (OPLL) and diffuse idiopathic skeletal hyperostosis (DISH). Methodology This retrospective cohort study consisted of 99 consecutive patients aged ≥60 years treated for spinal surgery at our hospital between January 2022 and March 2023. Skin thickness was measured at the dorsal side of the cervical, thoracic, and lumbar vertebrae on the sagittal cross-section image of whole-spine CT. Based on the median value, skin thickness was categorized into two groups based on a median thickness of 4 mm. Bone mineral density (BMD) was assessed. The sum of the vertebral body and intervertebral bridging osteophytes of the anterior longitudinal and posterior longitudinal ligament were defined as the OALL index and OPLL index. Serum levels of bone metabolism-related markers, such as tartrate-resistant acid phosphatase type 5b, procollagen I N-propeptide, 25-hydroxyvitamin D, and periostin, were measured. To assess the association between skin thickness and imaging findings, we calculated the adjusted odds ratios, adjusting for age, sex, and body mass index (BMI) and using univariate and multivariate logistic regression analyses. Results No significant differences were found in skin thickness in the three dorsal regions of the cervical, thoracic, and lumbar spine (median = 3.3 mm versus 3.5 mm versus 3.4 mm, p = 0.357) and bone metabolism-related markers. Adjusting for age, sex, and BMI, cervical, thoracic, and lumbar skin thicknesses were related to DISH, the OPLL index, and the OPLL and OPLL index, respectively. Conclusions Skin thickness did not correlate with BMD but with the amount of spinal ossification. A correlation was found between skin thickness and vertebral and intervertebral ossification; vertebral osteophytes, OPLL, and DISH may be more common in thicker skin.

Variation of Bone Turnover Markers in Childhood and Adolescence.

To determine the bone metabolic marker changes from childhood to adolescence and to provide reference values for monitoring bone development in children in Southwest China. We surveyed 703 participants attending physical examinations from April 2019 and August 2021. Twenty-eight participants were excluded for lack of laboratory tests, and 14 people were excluded for diseases that might affect bone metabolism. A total of 661 children were selected for the study. According to the main developmental periods, the children were divided into preschool, preadolescence, and adolescence groups. Serum bone turnover markers including β-isomerized C-terminal telopeptide of type I collagen (β-CTx), N-terminal midfragment of osteocalcin (N-MID), and procollagen type 1 N-propeptide (P1NP) as well as growth and development indices such as serum calcium (Ca), phosphorus (Pi), alkaline phosphatase (ALP), and vitamin D were measured. The changes in bone metabolism-related markers and the correlations between the indices were analyzed. During the development in boys, the levels of β-CTx and N-MID increased with age from preschool to adolescence, while the levels of P1NP decreased and then increased. In girls, the levels of β-CTx and N-MID plateaued in early adolescence and showed little change in subsequent adolescence, while the levels of P1NP exhibited a downward trend. The correlations between bone metabolism markers and vitamin D were not significant. The levels of bone metabolism markers differed between boys and girls. Reference intervals can be used as essential tools to examine the levels of bone metabolism markers reasonably.

The probiotic Lactiplantibacillus plantarum attenuates ovariectomy-induced osteoporosis through osteoimmunological signaling.

Osteoporosis is characterized by low bone mass and bone tissue microarchitectural deterioration with increased fracture risk in numerous populations. Probiotics are reported to be a potential biotherapeutic for the prevention and treatment of osteoporosis. In this study, the IL-10 secretion properties of probiotics were simulated in vitro and the potential applications of the novel strain Lactiplantibacillus plantarum 622 were investigated in an in vivo osteoporosis model. Female Sprague-Dawley rats were ovariectomized (OVX) and orally administered Lp. plantarum GMNL-662 or alendronate for 14 weeks. The Lp. plantarum treatment group exhibited an increase in the level of fecal Lp. plantarum, Lactobacillus, and Lachnospiraceae. Bone marker analysis indicated improvements in the levels of osteocalcin and N-terminal telopeptides in the Lp. plantarum treatment group. Compared with the OVX control group, the Lp. plantarum treatment group exhibited marked improvements in femur bone mineral density, trabecular bone volume, trabecular number, and lumbar vertebrae. Moreover, biomechanical three-point bending testing indicated considerably higher improvements in femur maximum load, stiffness, and energy to maximum load in the Lp. plantarum treatment group than in the OVX control group. Quantitative polymerase chain reaction analysis indicated reduced expression levels of OVX-induced IL-1, IL-6, TNFα, and RANKL and increased expression levels of IL-10, TGF-β, and osteoprotegerin in the Lp. Plantarum treatment group. In summary, Lp. plantarum GMNL-662 exhibits high probiotic potential and potentially influences osteoimmunity through the modulation of proinflammatory cytokines and bone metabolism-related markers.

Resveratrol Ameliorates High Altitude Hypoxia-Induced Osteoporosis by Suppressing the ROS/HIF Signaling Pathway.

Hypoxia at high-altitude leads to osteoporosis. Resveratrol (RES), as an antioxidant, has been reported to promote osteoblastogenesis and suppress osteoclastogenesis. However, the therapeutic effect of RES against osteoporosis induced by high-altitude hypoxia remains unclear. Thus, this study was intended to investigate the potential effects of RES on high-altitude hypoxia-induced osteoporosis both in vivo and in vitro. Male Wistar rats were given RES (400 mg/kg) once daily for nine weeks under hypoxia, while the control was allowed to grow under normoxia. Bone mineral density (BMD), the levels of bone metabolism-related markers, and the changes on a histological level were measured. Bone marrow-derived mesenchymal stem cells (BMSCs) and RAW264.7 were incubated with RES under hypoxia, with a control growing under normoxia, followed by the evaluation of proliferation and differentiation. The results showed that RES inhibited high-altitude hypoxia-induced reduction in BMD, enhanced alkaline phosphatase (ALP), osteocalcin (OCN), calcitonin (CT) and runt-related transcription factor 2 (RUNX2) levels, whereas it reduced cross-linked carboxy-terminal telopeptide of type I collagen (CTX-I) levels and tartrate-resistant acid phosphatase (TRAP) activity in vivo. In addition, RES attenuated histological deteriorations in the femurs. In vitro, RES promoted osteoblastogenesis and mineralization in hypoxia-exposed BMSCs, along with promotion in RUNX2, ALP, OCN and osteopontin (OPN) levels, and inhibited the proliferation and osteoclastogenesis of RAW264.7. The promotion effects of RES on osteoblastogenesis were accompanied by the down-regulation of reactive oxygen species (ROS) and hypoxia inducible factor-1α (HIF-1α) induced by hypoxia. These results demonstrate that RES can alleviate high-altitude hypoxia-induced osteoporosis via promoting osteoblastogenesis by suppressing the ROS/HIF-1α signaling pathway. Thus, we suggest that RES might be a potential treatment with minimal side effects to protect against high-altitude hypoxia-induced osteoporosis.

Impact of Vitamin D and Calcium Supplementation on Bone Mineral Density and Bone Metabolism Among Thai Adolescents With Perinatally Acquired Human Immunodeficiency Virus (HIV) Infection: A Randomized Clinical Trial.

To evaluate the impact of vitamin D and calcium supplementation (VitD/Ca) on lumbar spine bone mineral density (LSBMD) and bone metabolism among Thai adolescents with perinatally acquired HIV (PHIVA). A multicenter, randomized, active-control, open-labeled trial was conducted. PHIVA (aged 10-20 years) who were on stable cART were enrolled. Baseline LSBMD status was defined as low (z-score ≤ -2) and normal (> -2). Eligible PHIVA were randomly assigned to receive standard-dose (400 IU/1200 mg/day) or high-dose (400 IU/1200 mg/day plus ergocalciferol 20 000 IU/week) VitD/Ca supplementation for 48 weeks (ratio 1:1, stratified by baseline LSBMD). Study outcomes were changes in LSBMD, LSBMD z-scores, and bone metabolism-related biomarkers (25-hydroxyvitamin D [25(OH)D], intact parathyroid hormone [iPTH], C-terminal telopeptide [CTX], procollagen type I amino-terminal propeptide [PINP]) from baseline to week 48. Among 200 enrolled PHIVA, median age was 16 (IQR:14-18) years; 61% were on NNRTI-based cART. Median 25(OH)D level was 25.5 (IQR: 20.8-33.0) ng/mL. After 48-week VitD/Ca supplementation, LSBMD significantly increased in both treatment groups (high-dose: median: +0.07 [IQR: +0.04 to +0.11] g/cm2; P < .001; standard-dose: +0.09 [+0.03 to +0.13] g/cm2; P < .001). Notably, the change in LSBMD z-scores was significantly greater in high-dose versus standard-dose groups (median: +0.4 [IQR: -0.1 to +0.9] vs +0.1 [-0.4 to +0.7]; P = .02). Levels of 25(OH)D increased, whereas iPTH, CTX, and PINP declined significantly in both groups (P < .05), but no between-group differences were demonstrated. Over 48-week VitD/Ca supplementation, significant increases in LSBMD, and significant decreases in bone metabolism-related markers were observed among our Thai PHIVA in both treatment groups. The improvement in LSBMD z-score was more enhanced with high-dose VitD/Ca supplementation than standard-dose. High-dose VitD/Ca supplementation might be considered to promote bone health in this population. NCT02426840.

Prevention of bone loss by using Lactobacillus-fermented milk products in a rat model of glucocorticoid-induced secondary osteoporosis

Secondary osteoporosis is a common side effect of glucocorticoid treatments. The anti-osteoporotic role of two fermented milk products (FMPs), produced with Lactobacillus plantarum A41 and Lactobacillus fermentum SRK414, in alleviating secondary osteoporotic symptoms induced by dexamethasone (Dex) injection in rats was investigated. The two FMPs could prevent Dex-induced bone loss in rats. The two FMPs normalised altered gene expression levels of bone metabolism-related markers (osteoprotegerin, osteocalcin, bone sialoprotein, receptor activator of nuclear factor kappa-B ligand, and tartrate-resistant acid phosphatase). Furthermore, they regulated gene expression levels of bone morphogenetic protein 2-related and cell apoptosis markers in the tibia and calcium metabolism-related markers in the ileum. Additionally, these treatments modulated faecal bacterial populations by increasing Lactobacillus colonies. FMPs fermented by L. plantarum A41 and L. fermentum SRK414 were capable of preventing glucocorticoid-induced secondary osteoporosis via regulation of intestinal microbiota and gene expression levels of bone cell apoptosis related markers.

Effects of dihydrotestosterone on osteoblast activity in curdlan-administered SKG mice and osteoprogenitor cells in patients with ankylosing spondylitis

BackgroundAnkylosing spondylitis (AS) is characteristically male-predominant, and progressive spinal ankylosis affects male patients more severely; however, the hormonal effects in males with AS are poorly understood.MethodsIn the present study, the regulatory effects of dutasteride, a 5-α reductase inhibitor that blocks the conversion of testosterone to dihydrotestosterone (DHT), were examined in curdlan-administered male SKG mice to determine spinal bone formation, bone metabolism-related markers, and interleukin (IL)-17A cytokine and T cell populations. In addition, the effects of DHT on primary osteoprogenitors from the facet joints of AS patients were assessed based on osteoblast-related parameters. DHT level was measured, and the correlation with modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) was analyzed in AS patients.ResultsIn curdlan-administered SKG mice, dutasteride treatment resulted in an increased accumulation of hydroxyapatite in the spine which was positively correlated with serum IL-17A levels. In the analysis of bone metabolism-related molecules, a decrease in sclerostin levels was observed in the sera in the dutasteride group. Continuous exposure to DHT resulted in fewer calcium deposits in AS osteoprogenitors during osteoblast differentiation. DHT-treated AS osteoprogenitors showed decreased osteocalcin and increased DKK1 and SOST1 mRNA expression, supporting the results of the in vivo experiments. Treatment with dutasteride upregulated bone formation in the spine of curdlan-administered SKG mice and DHT treatment downregulated osteoblast differentiation in vitro.ConclusionsTreatment with dutasteride affected the bone formation in the spine of curdlan-treated SKG mice, and DHT treatment attenuated osteoblast differentiation in vitro. Therefore, contrary to what could be expected if osteoblasts contributed to spinal ankylosis, DHT inhibition might increase rather than decrease the progression of spinal ankylosis despite the higher levels of DHT observed in many AS patients.

Strontium ranelate improves alveolar bone healing in estrogen-deficient rats.

This study evaluated the impact of strontium ranelate on tooth-extraction wound healing in estrogen-deficient and estrogen-sufficient rats. Ninety-six Wistar rats (90 days of age) were allocated into one of the following groups: sham-surgery+water (estrogen-sufficient); ovariectomy+water (estrogen-deficient), sham-surgery+strontium ranelate (625mg/kg/d) (strontium/estrogen-sufficient); ovariectomy+strontium ranelate (625mg/kg/d) (strontium/estrogen-deficient). Water or strontium ranelate were administrated from the 14th day post-ovariectomy/sham surgery until euthanasia. Maxillary first molars were extracted at 21 days after sham/ovariectomy surgery. Rats were euthanized at 10, 20, and 30 days post-extractions. The following parameters were analyzed inside tooth-extraction wound: proportion of newly formed bone (bone healing/BH), number of cells stained for tartrate-resistant acid phosphatase (TRAP) and immunohistochemical staining for five bone metabolism-related markers (osteocalcin [OCN], osteopontin [OPN], bone sialoprotein [BSP], osteoprotegerin [OPG] and receptor activator of NF-КB ligand [RANKL]). The estrogen-deficient group presented lower BH than all other groups at 20 and 30 days post-extraction (P<0.05). The number of TRAP-stained cells was higher in the estrogen-deficient group than in estrogen-sufficient group at 30 days post-extraction (P<0.05). The strontium /estrogen-sufficient group exhibited stronger staining for OCN, when compared to the estrogen-sufficient and estrogen-deficient groups (P<0.05). Both strontium ranelate-treated groups presented higher staining of OPN and BSP than both untreated groups (P<0.05). The strontium/estrogen-sufficient group demonstrated stronger staining for OPG than the estrogen-deficient group (P<0.05). The estrogen-sufficient group and both groups treated with strontium ranelate showed lower expression of RANKL than the estrogen-deficient group (P<0.05). Strontium ranelate benefited BH and the expression of bone markers in tooth-extraction wound in estrogen-deficient rats whereas its benefits in estrogen-sufficient rats were modest.

Involvement of PI3K/Akt/β-catenin signaling in schisandrin B-mitigated bone deterioration in an experimental rat model of estrogen deficiency.

Schisandrin B (SchB) has been reported to perform a wide range of biological functions, including antioxidant activity, anti-inflammatory activity and stimulation of osteoblast proliferation. However, the function and mechanism of SchB in ovariectomy (OVX)-induced osteoporosis are still unknown. The present study was designed to investigate the anti-osteoporotic activity of SchB in an experimental rat model of estrogen deficiency, which is usually used to mimic human postmenopausal osteoporosis (PMO). OVX rats were orally treated with low (10 mg/kg) or high (50 mg/kg) doses of SchB for 8 weeks. Bone metabolism-related markers were measured by ELISA. The levels of protein expression were determined by western blotting analysis. Hematoxylin and eosin (H&E) and safranin O staining were performed to analyze trabecular bone and cartilage degeneration. Tartrate-resistant acid phosphatase (TRAP) staining was used to evaluate osteoclast differentiation. SchB administration markedly increased serum Ca levels and bone Ca content and decreased urinary calcium excretion in OVX-operated rats. In addition, high-dosage SchB treatment blocked osteoclastogenesis and improved trabecular bone and cartilage degeneration in the tibia of OVX-operated rats. Furthermore, high-dosage SchB treatment dramatically elevated the protein expression of phospho-PI3K, phospho-Akt and β-catenin in OVX-operated rats. SchB exerted anti-osteoporotic activity in OVX-operated rats by accelerating the phosphorylation of PI3K and Akt, subsequently upregulating the expression of β-catenin.

The change of bone mineral density and bone metabolism after gastrectomy for gastric cancer: a meta-analysis.

Survivorship care, including bone health, has become an important issue in gastric cancer. We performed a meta-analysis of the available observational studies to determine whether and how osteoporosis risk is increased after gastrectomy in patients with gastric cancer. A total of 1204 patients (802 men) from 19 cohort studies were included. We evaluated the prevalence of osteoporosis in postgastrectomy patients, comparing the incidence according to the type of gastrectomy and sex. Additionally, we evaluated changes in bone mineral density (BMD) and bone metabolism-related markers pre- to postoperatively and between patients who underwent gastrectomy and matched controls. Proportion meta-analysis was performed and pooled odds ratios (ORs) were calculated. The pooled incidence estimate was 36% [95% confidence interval (CI), 32-40]. The incidence of osteoporosis was significantly higher in women than in men (OR = 1.90, p < 0.001) but was similar between partial and total gastrectomy groups (OR = 0.983, p = 0.939). BMD was significantly decreased, and calcium, phosphorous, and parathyroid hormone levels were significantly increased in patients after gastrectomy compared to those before gastrectomy. BMD and calcium and 25OH-vitamin D levels were significantly decreased, and parathyroid hormone and 1,25OH-vitamin D levels were significantly increased in the gastrectomy group compared to that in the control group. We found that BMD is significantly decreased after gastrectomy in patients with gastric cancer. Vitamin D deficiency and secondary hyperparathyroidism are suggested to be common mechanism underlying BMD impairment. After resection, patients should undergo long-term nutritional and bone health surveillance, in addition to their oncological follow-up.

Periodontal Disease in Patients Receiving Dialysis.

Chronic kidney disease (CKD) is characterized by kidney damage with proteinuria, hematuria, and progressive loss of kidney function. The final stage of CKD is known as end-stage renal disease, which usually indicates that approximately 90% of normal renal function is lost, and necessitates renal replacement therapy for survival. The most widespread renal replacement therapy is dialysis, which includes peritoneal dialysis (PD) and hemodialysis (HD). However, despite the development of novel medical instruments and agents, both dialysis procedures have complications and disadvantages, such as cardiovascular disease due to excessive blood fluid and infections caused by impaired immunity. Periodontal disease is chronic inflammation induced by various pathogens and its frequency and severity in patients undergoing dialysis are higher compared to those in healthy individuals. Therefore, several investigators have paid special attention to the impact of periodontal disease on inflammation-, nutrient-, and bone metabolism-related markers; the immune system; and complications in patients undergoing dialysis. Furthermore, the influence of diabetes on the prevalence and severity of manifestations of periodontal disease, and the properties of saliva in HD patients with periodontitis have been reported. Conversely, there are few reviews discussing periodontal disease in patients with dialysis. In this review, we discuss the available studies and review the pathological roles and clinical significance of periodontal disease in patients receiving PD or HD. In addition, this review underlines the importance of oral health and adequate periodontal treatment to maintain quality of life and prolong survival in these patients.

Anti-inflammatory and Anti-osteoporotic Potential of Lactobacillus plantarum A41 and L. fermentum SRK414 as Probiotics

This study involves an investigation on the probiotic properties of lactic acid bacteria and their potential applications in an in vitro model of lipopolysaccharide (LPS)-stimulated inflammation and dexamethasone-induced osteoporosis. Nine strains were pre-screened from 485 lactic acid bacteria based on their survival at a low pH and in a solution containing bile salts. All candidates were capable of surviving in an environment with low pH and with bile salts and could successfully colonize the intestine. Furthermore, their functional properties, such as anti-oxidation and anti-inflammation, were evaluated. Of the nine probiotic candidates, Lactobacillus plantarum A41 and L. fermentum SRK414 exhibited the highest anti-oxidative capacity. Moreover, only L. plantarum A41 and L. fermentum SRK414 could increase gut barrier function by upregulating the mRNA expression of tight junction proteins and inhibit the expression of inflammatory mediators induced by LPS-stimulated inflammation. Interestingly, these two strains were also capable of regulating several bone metabolism-related markers playing a role in bone homeostasis and osteoblast differentiation. In brief, L. plantarum A41 and L. fermentum SRK414 exhibited high probiotic potential and potentially impact immune-related bone health by modulating pro-inflammatory cytokines and bone metabolism-related markers.

Doxercalciferol Alleviates Bone Deteriorations and Cartilage Degeneration in Aging Mice.

Age-related bone deteriorations are the common endocrine disorders in the elderly population, leading to an increased risk of fractures. Therefore, effective treatment strategies provide a way to prevent bone loss and improve the quality of life in the elderly population. The present study aimed to investigate the anti-osteoporotic effects of doxercalciferol (DOX) in aging mice. Bone metabolism-related markers were measured by ELISA assay. The expression of bone formation and resorption-related genes was performed by RT-qPCR analysis. Hematoxylin and eosin (H&E) and Safranin O staining were performed to analyze the trabecular bone and cartilage degeneration. Aging resulted in urine ca2+ excretion, a decrease in bone ca2+ content and reduction of biomechanical strength in mice. We also found that the level of PTH was increased in aging mice, while DOX administration markedly down-regulated serum PTH in aging mice. H&E and Safranin O staining showed that DOX protected against aging-induced bone loss and cartilage regeneration in the tibia from aging mice. Furthermore, DOX treatment resulted in an increase in Runx2, osterix and Col1a1 mRNA expression and a decrease in Ctsk, MMP-9 and CAII mRNA expression in the tibia from aging mice. These findings indicated that DOX had a beneficial effect on age-related bone deteriorations in aging mice by promoting osteoblast activity and cartilage regeneration and inhibiting osteoclast-specific genes expression.

Combined Effects of Phytoestrogen Genistein and Silicon on Ovariectomy-Induced Bone Loss in Rat.

This study was performed to evaluate the effect of concomitant supplementation of genistein and silicon on bone mineral density and bone metabolism-related markers in ovariectomized rat. Three-month-old Sprague Dawley female rats were subjected to bilateral ovariectomy (OVX) or sham surgery, and then the OVX rats were randomly divided into four groups: OVX-GEN, OVX-Si, OVX-GEN-Si, and OVX. Genistein and silicon supplementation was started immediately after OVX and continued for 10weeks. In the OVX-GEN group, 5mg genistein per gram body weight was injected subcutaneously. The OVX-Si group was given soluble silicon daily in demineralized water (Si 20mg/kg body weight/day). The OVX-GEN-Si group was given subcutaneous injections of 5mg genistein per gram body weight, at the same time, given soluble silicon daily (Si 20mg/kg body weight/day). The results showed that the genistein supplementation in the OVX rats significantly prevented the loss of uterus weight; however, the silicon supplementation showed no effect on the uterus weight loss. The lumbar spine and femur bone mineral density was significantly decreased after OVX surgery; however, this decrease was inhibited by the genistein and/or silicon, and the BMD of the lumbar spine and femur was the highest in the OVX-GEN-Si-treated group. Histomorphometric analyses showed that the supplementation of genistein and/or silicon restored bone volume and trabecular thickness of femoral trabecular bone in the OVX group. Besides, the treatment with genistein and silicon for 10weeks increased the serum levels of calcium and phosphorus in the OVX rats; serum calcium and serum phosphorus in the OVX-GEN-Si group were higher than those in the OVX-GEN and OVX-Si group (P<0.05). At the same time, the treatment with genistein and/or silicon decreased serum alkaline phosphatase (ALP) and osteocalcin, which were increased by ovariectomy; serum ALP and osteocalcin in the OVX-GEN-Si group were lower than those in the OVX-GEN and OVX-Si groups (P<0.05). The results above indicate that genistein and silicon have synergistic effects on bone formation in ovariectomized rats.

Impact of Tenofovir Disoproxil Fumarate on Bone Metabolism and Bone Mass among Perinatally HIV-Infected Asian Adolescents

This study aimed to determine the effect of tenofovir disoproxil fumarate (TDF) on bone metabolism and bone mass in HIV-infected adolescents. This was a sub-study of a cross-sectional multicentre bone health trial that enrolled perinatally HIV-infected Thai and Indonesian adolescents (10-18 years) with viral suppression on antiretroviral therapy. Participants were classified into two groups as TDF users and non-users. Bone metabolism-related markers (25-hydroxyvitamin D [25-OHD], intact parathyroid hormone [iPTH], bone turnover biomarkers), and lumbar spine dual-energy X-ray absorptiometry were assessed. Bone mineral density (BMD)/bone mineral apparent density (BMAD) Z-scores were calculated. Of 394 adolescents, 136 (34.5%) and 258 (65.5%) were TDF users and non-users, respectively. Among TDF users, median age (IQR) was 16.1 (14.7-17.4) years and TDF treatment duration (IQR) was 2.3 (1.4-3.1) years. Among TDF non-users, median age (IQR) was 14.3 (12.6-16.4) years. BMD and BMAD Z-scores comparing TDF users with non-users were -0.8 and -0.6 (P=0.27), and -0.3 and -0.2 (P=0.58), respectively. The association between TDF use and iPTH elevation was intensified in adolescents with suboptimal vitamin D levels (25-OHD <30 ng/ml; P=0.001). TDF administration was positively associated with bone resorption marker (P=0.04) and negatively associated with bone formation marker (P=0.04). With data up to 4 years, neither association between TDF use and bone mass loss (BMD: P=0.09; BMAD: P=0.22), nor variation of bone mass Z-scores by TDF treatment duration (BMD: P=0.34; BMAD: P=0.58) was demonstrated. Recent TDF administration was correlated with PTH elevation and bone turnover dysregulation but not with bone mass reduction in our cohort. A study with extended follow-up to ascertain TDF-associated bone mass deterioration is warranted.

The Association between Coffee Consumption and Bone Status in Young Adult Males according to Calcium Intake Level.

The purpose of this study was to investigate the association between coffee consumption and bone status (bone mineral density and bone metabolism-related markers) according to calcium intake level in Korean young adult males. Healthy and nonsmoking males (19-26 years, n = 330) participated in this study. Anthropometric measurements, dietary habits, and nutrient intakes were surveyed. Bone status of the calcaneus was measured by using quantitative ultrasound (QUS). Bone metabolism-related markers including serum total alkaline phosphatase activity (TALP), N-mid osteocalcin (OC), and type 1 collagen C-terminal telopeptide (1CTP) were analyzed. The subjects were divided into two groups based on daily calcium intake level: a calcium-sufficient group (calcium intake ≥ 75% RI, n = 171) and a calcium-deficient group (calcium intake < 75% RI, n = 159). Each group was then further divided into three subgroups based on daily average coffee consumption: no-coffee, less than one serving of coffee per day, and one or more servings of coffee per day. There were no significant differences in height, body weight, body mass index, energy intake, or calcium intake among the three coffee consumption subgroups. QUS parameters and serum 1CTP, TALP, and OC were not significantly different among either the two calcium-intake groups or the three coffee consumption subgroups. Our results may show that current coffee consumption level in Korean young men is not significantly associated with their bone status and metabolism according to the calcium intake level.

Association of osteoporosis susceptibility genes with bone mineral density and bone metabolism related markers in Koreans: the Chungju Metabolic Disease Cohort (CMC) study.

In this study, we evaluated the association between bone mineral density (BMD) and 10 single-nucleotide polymorphisms (SNPs) within eight osteoporosis susceptibility genes that were previously identified in genome-wide association studies (GWASs). A total of 494 men and 493 postmenopausal women participating in the Chungju Metabolic Disease cohort study in Korea were included. The following 10 SNPs were genotyped: ZBTB40 rs6426749, MEF2C rs1366594, ESR1 rs2941740, TNFRSF11B rs3134070, TNFRSF11B rs2073617, SOX6 rs711785, LRP5 rs599083, TNFSF11 rs227438, TNFSF11 rs9594782, and FOXL1 rs10048146; and the association between these SNPs and bone metabolism-related markers was assessed. Two SNPs, TNFSF11 rs2277438 and FOXL1 rs1004816, were associated with lumbar spine BMD. TNFSF11 rs2277438 in men and SOX6 rs7117858 and FOXL1 rs10048146 in postmenopausal women were found to be associated with lumbar BMD. ZBTB40 rs6426749, MEF2C rs1366594, and LRP5 rs599083 showed significant associations with femur neck BMD. These three SNPs in men and MEF2C rs1366594 and ESR1 rs2941740 in postmenopausal women were associated with femur neck BMD. A significant association between MEF2C rs1366594 and serum calcium levels was observed in men. Serum phosphorus levels were related to SOX6 rs7117858. Serum PTH levels were significantly associated with TNFRSF11B rs3134070 in men, and SOX6 rs711858 in postmenopausal women. In conclusion, our study independently confirmed associations between several SNPs: ZBTB40, MEF2C, ESR1, SOX6, LRP5, TNFSF11, and FOXL1 and bone marrow density in the Korean population.

Influence of conjugated linoleic acid (c9, t11-CLA and t10, c12-CLA) on mRNA expression of bone metabolism related markers of bone marrow cells

Objective To observe the effect of conjugated linoleic acid (c9,t11-CLA and t10,c12-CLA) on the mRNA expression of peroxisome proliferator activated receptorγ2 (PPARγ2),receptor activator of NF-κB ligand ( RANKL),alkaline phosphatase ( ALP),osteoprotegerin ( OPG),receptor activator of NF-κB (RANK) and tartrate-resistant acid phosphatase (TRAP) of bone marrow cells,and study the effect of c9,t11-CLA and t10,c12-CLA on bone metabolism.Methods Bone marrow cells of Wistar rats were cultured in vitro and then the cells were cultured in DMEM with c9,t11-CLA or t10,c12-CLA at different concentrations (the final concentration was 0,12.5,25.0,50.0 μmol/L,respectively) for 24 h.Reverse transcription-polymerase chain reaction (RT-PCR) was performed to detect the mRNA expression of PPARγ2,RANKL,ALP,OPG,RANK and TRAP.Results Semi-quantitative RT-PCR analysis showed that c9,t11-CLA down-regulated the mRNA expression of RANK and TRAP in a dose-dependent manner,and statistically significant difference was found in interclass comparison (P ＜ 0.05,P ＜ 0.01 ),while it had no effect on the mRNA expression of RANKL,ALP,OPG and PPARγ2.The results also showed that t10,c12-CLA up-regulated the mRNA expression of RANKL and OPG in a dose-dependent manner and down-regnlated the mRNA expression of RANK,TRAP and PPARγ2 in a dose-dependent manner,statistically significant difference was found in interclass comparison ( P ＜ 0.05,P ＜ 0.01 ),while it had no effect on the mRNA expression of ALP.Conclusion Our findings suggest that c9,t11-CLA and t10,c12-CLA can suppress the expression of osteoclastogenesis genes and t10,c12-CLA can also promote the expression of osteogenic genes,which suggests a possible benecial effect on bone formation. Key words: Peroxisome proliferator activated receptoryγ; Conjugated linoleic acid; Osteoporosis